[Federal Register Volume 80, Number 152 (Friday, August 7, 2015)]
[Proposed Rules]
[Pages 47565-47828]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-17596]



[[Page 47565]]

Vol. 80

Friday,

No. 152

August 7, 2015

Part II





Department of Labor





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 Occupational Safety and Health Administration





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29 CFR Part 1910





 Occupational Exposure to Beryllium and Beryllium Compounds; Proposed 
Rule

Federal Register / Vol. 80 , No. 152 / Friday, August 7, 2015 / 
Proposed Rules

[[Page 47566]]


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DEPARTMENT OF LABOR

Occupational Safety and Health Administration

29 CFR Part 1910

[Docket No. OSHA-H005C-2006-0870]
RIN 1218-AB76


Occupational Exposure to Beryllium and Beryllium Compounds

AGENCY: Occupational Safety and Health Administration (OSHA), 
Department of Labor.

ACTION: Proposed rule; request for comments.

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SUMMARY: The Occupational Safety and Health Administration (OSHA) 
proposes to amend its existing exposure limits for occupational 
exposure in general industry to beryllium and beryllium compounds and 
promulgate a substance-specific standard for general industry 
regulating occupational exposure to beryllium and beryllium compounds. 
This document proposes a new permissible exposure limit (PEL), as well 
as ancillary provisions for employee protection such as methods for 
controlling exposure, respiratory protection, medical surveillance, 
hazard communication, and recordkeeping. In addition, OSHA seeks 
comment on a number of alternatives, including a lower PEL, that could 
affect construction and maritime, as well as general industry.

DATES: Written comments. Written comments, including comments on the 
information collection determination described in Section IX of the 
preamble (OMB Review under the Paperwork Reduction Act of 1995), must 
be submitted (postmarked, sent, or received) by November 5, 2015.
    Informal public hearings. The Agency will schedule an informal 
public hearing on the proposed rule if requested during the comment 
period. The location and date of the hearing, procedures for interested 
parties to notify the Agency of their intention to participate, and 
procedures for participants to submit their testimony and documentary 
evidence will be announced in the Federal Register if a hearing is 
requested.

ADDRESSES: Written comments. You may submit comments, identified by 
Docket No. OSHA-H005C-2006-0870, by any of the following methods:
    Electronically: You may submit comments and attachments 
electronically at http://www.regulations.gov, which is the Federal e-
Rulemaking Portal. Follow the instructions on-line for making 
electronic submissions. When uploading multiple attachments into 
Regulations.gov, please number all of your attachments because 
www.Regulations.gov will not automatically number the attachments. This 
will be very useful in identifying all attachments in the beryllium 
rule. For example, Attachment 1_title of your document, Attachment 2_
title of your document, Attachment 3_title of your document, etc. 
Specific instructions on uploading all documents are found in the 
Facts, Answer, Questions portion and the commenter check list on 
Regulations.gov Web page.
    Fax: If your submissions, including attachments, are not longer 
than 10 pages, you may fax them to the OSHA Docket Office at (202) 693-
1648.
    Mail, hand delivery, express mail, messenger, or courier service: 
You may submit your comments to the OSHA Docket Office, Docket No. 
OSHA-H005C-2006-0870, U.S. Department of Labor, Room N-2625, 200 
Constitution Avenue NW., Washington, DC 20210, telephone (202) 693-2350 
(OSHA's TTY number is (877) 889-5627). Deliveries (hand, express mail, 
messenger, or courier service) are accepted during the Docket Office's 
normal business hours, 8:15 a.m.-4:45 p.m., E.S.T.
    Instructions: All submissions must include the Agency name and the 
docket number for this rulemaking (Docket No. OSHA-H005C-2006-0870). 
All comments, including any personal information you provide, are 
placed in the public docket without change and may be made available 
online at http://www.regulations.gov. Therefore, OSHA cautions you 
about submitting personal information such as Social Security numbers 
and birthdates.
    If you submit scientific or technical studies or other results of 
scientific research, OSHA requests (but is not requiring) that you also 
provide the following information where it is available: (1) 
Identification of the funding source(s) and sponsoring organization(s) 
of the research; (2) the extent to which the research findings were 
reviewed by a potentially affected party prior to publication or 
submission to the docket, and identification of any such parties; and 
(3) the nature of any financial relationships (e.g., consulting 
agreements, expert witness support, or research funding) between 
investigators who conducted the research and any organization(s) or 
entities having an interest in the rulemaking. If you are submitting 
comments or testimony on the Agency's scientific or technical analyses, 
OSHA requests that you disclose: (1) The nature of any financial 
relationships you may have with any organization(s) or entities having 
an interest in the rulemaking; and (2) the extent to which your 
comments or testimony were reviewed by an interested party before you 
submitted them. Disclosure of such information is intended to promote 
transparency and scientific integrity of data and technical information 
submitted to the record. This request is consistent with Executive 
Order 13563, issued on January 18, 2011, which instructs agencies to 
ensure the objectivity of any scientific and technological information 
used to support their regulatory actions. OSHA emphasizes that all 
material submitted to the rulemaking record will be considered by the 
Agency to develop the final rule and supporting analyses.
    Docket: To read or download comments and materials submitted in 
response to this Federal Register notice, go to Docket No. OSHA-H005C-
2006-0870 at http://www.regulations.gov, or to the OSHA Docket Office 
at the address above. All comments and submissions are listed in the 
http://www.regulations.gov index; however, some information (e.g., 
copyrighted material) is not publicly available to read or download 
through that Web site. All comments and submissions are available for 
inspection at the OSHA Docket Office.
    Electronic copies of this Federal Register document are available 
at http://www.regulations.gov. Copies also are available from the OSHA 
Office of Publications, Room N-3101, U.S. Department of Labor, 200 
Constitution Avenue NW., Washington, DC 20210; telephone (202) 693-
1888. This document, as well as news releases and other relevant 
information, is also available at OSHA's Web site at http://www.osha.gov.
    OSHA has not provided the document ID numbers for all submissions 
in the record for this beryllium proposal. The proposal only contains a 
reference list for all submissions relied upon. The public can find all 
document ID numbers in an Excel spreadsheet that is posted on OSHA's 
rulemaking Web page (see www.osha.gov/berylliumrulemaking). The public 
will be able to locate submissions in the record in the public docked 
Web page: http://www.regulations.gov. To locate a particular submission 
contained in http://www.regulations.gov, the public should enter the 
full document ID number in the search bar.

FOR FURTHER INFORMATION CONTACT: For general information and press 
inquiries, contact Frank Meilinger, Director, Office of Communications, 
Room N-3647,

[[Page 47567]]

OSHA, U.S. Department of Labor, 200 Constitution Avenue NW., 
Washington, DC 20210; telephone: (202) 693-1999; email: 
[email protected] . For technical inquiries, contact: William 
Perry or Maureen Ruskin, Directorate of Standards and Guidance, Room N-
3718, OSHA, U.S. Department of Labor, 200 Constitution Avenue NW., 
Washington, DC 20210; telephone (202) 693-1955 or fax (202) 693-1678; 
email: [email protected].

SUPPLEMENTARY INFORMATION: 
    The preamble to the proposed standard on occupational exposure to 
beryllium and beryllium compounds follows this outline:

Executive Summary

I. Issues and Alternatives
II. Pertinent Legal Authority
III. Events Leading to the Proposed Standards
IV. Chemical Properties and Industrial Uses
V. Health Effects
VI. Preliminary Risk Assessment
VII. Response to Peer Review
VIII. Significance of Risk
IX. Summary of the Preliminary Economic Analysis and Initial 
Regulatory Flexibility Analysis
X. OMB Review under the Paperwork Reduction Act of 1995
XI. Federalism
XII. State-Plan States
XIII. Unfunded Mandates Reform Act
XIV. Protecting Children from Environmental Health and Safety Risks
XV. Environmental Impacts
XVI. Consultation and Coordination with Indian Tribal Governments
XVII. Public Participation
XVIII. Summary and Explanation of the Proposed Standard
    (a) Scope and Application
    (b) Definitions
    (c) Permissible Exposure Limits (PELs)
    (d) Exposure Assessment
    (e) Beryllium Work Areas and Regulated Areas
    (f) Methods of Compliance
    (g) Respiratory Protection
    (h) Personal Protective Clothing and Equipment
    (i) Hygiene Areas and Practices
    (j) Housekeeping
    (k) Medical Surveillance
    (l) Medical Removal
    (m) Communication of Hazards to Employees
    (n) Recordkeeping
    (o) Dates
XIX. References

Executive Summary

    OSHA currently enforces permissible exposure limits (PELs) for 
beryllium in general industry, construction, and shipyards. These PELs 
were adopted in 1971, shortly after the Agency was created, and have 
not been updated since then. The time-weighted average (TWA) PEL for 
beryllium is 2 micrograms per cubic meter of air ([mu]g/m\3\) as an 8-
hour time-weighted average. OSHA is proposing a new TWA PEL of 0.2 
[mu]g/m\3\ in general industry. OSHA is also proposing other elements 
of a comprehensive health standard, including requirements for exposure 
assessment, preferred methods for controlling exposure, respiratory 
protection, personal protective clothing and equipment (PPE), medical 
surveillance, medical removal, hazard communication, and recordkeeping.
    OSHA's proposal is based on the requirements of the Occupational 
Safety and Health Act (OSH Act) and court interpretations of the Act. 
For health standards issued under section 6(b)(5) of the OSH Act, OSHA 
is required to promulgate a standard that reduces significant risk to 
the extent that it is technologically and economically feasible to do 
so. See Section II of this preamble, Pertinent Legal Authority, for a 
full discussion of OSHA legal requirements.
    OSHA has conducted an extensive review of the literature on adverse 
health effects associated with exposure to beryllium. The Agency has 
also assessed the risk of beryllium-related diseases at the current TWA 
PEL, the proposed TWA PEL and the alternative TWA PELs. These analyses 
are presented in this preamble at Section V, Health Effects, Section 
VI, Preliminary Risk Assessment, and Section VIII, Significance of 
Risk. As discussed in Section VIII of this preamble, Significance of 
Risk, the available evidence indicates that worker exposure to 
beryllium at the current PEL poses a significant risk of chronic 
beryllium disease (CBD) and lung cancer, and that the proposed standard 
will substantially reduce this risk.
    Section 6(b) of the OSH Act requires OSHA to determine that its 
standards are technologically and economically feasible. OSHA's 
examination of the technological and economic feasibility of the 
proposed rule is presented in the Preliminary Economic Analysis and 
Initial Regulatory Flexibility Analysis (PEA) (OSHA, 2014), and is 
summarized in Section IX of this preamble, Summary of the Preliminary 
Economic Analysis and Initial Regulatory Flexibility Analysis. OSHA has 
preliminarily concluded that the proposed PEL of 0.2 [mu]g/m\3\ is 
technologically feasible for all affected industries and application 
groups. Thus, OSHA preliminarily concludes that engineering and work 
practices will be sufficient to reduce and maintain beryllium exposures 
to the proposed PEL of 0.2 [mu]g/m\3\ or below in most operations most 
of the time in the affected industries. For those few operations within 
an industry or application group where compliance with the proposed PEL 
cannot be achieved even when employers implement all feasible 
engineering and work practice controls, the proposed standard would 
require employers to supplement controls with respirators.
    OSHA developed quantitative estimates of the compliance costs of 
the proposed rule for each of the affected industry sectors. The 
estimated compliance costs were compared with industry revenues and 
profits to provide a screening analysis of the economic feasibility of 
complying with the revised standard and an evaluation of the potential 
economic impacts. Industries with unusually high costs as a percentage 
of revenues or profits were further analyzed for possible economic 
feasibility issues. After performing these analyses, OSHA has 
preliminarily concluded that compliance with the requirements of the 
proposed rule would be economically feasible in every affected industry 
sector.
    The Regulatory Flexibility Act, as amended by the Small Business 
Regulatory Enforcement Fairness Act (SBREFA), requires that OSHA either 
certify that a rule would not have a significant economic impact on a 
substantial number of small entities or prepare a regulatory 
flexibility analysis and hold a Small Business Advocacy Review (SBAR) 
Panel prior to proposing the rule. OSHA has determined that a 
regulatory flexibility analysis is needed and has provided this 
analysis in Chapter IX of the PEA (OSHA, 2014). A summary is provided 
in Section IX of this preamble, Summary of the Preliminary Economic 
Analysis and Initial Regulatory Flexibility Analysis. OSHA also 
previously held a SBAR Panel for this rule. The recommendations of the 
Panel and OSHA's response to them are summarized in Section IX of this 
preamble.
    Executive Orders 13563 and 12866 direct agencies to assess all 
costs and benefits of available regulatory alternatives. Executive 
Order 13563 emphasizes the importance of quantifying both costs and 
benefits, of reducing costs, of harmonizing rules, and of promoting 
flexibility. This rule has been designated an economically significant 
regulatory action under section 3(f)(1) of Executive Order 12866. 
Accordingly, this proposed rule has been reviewed by the Office of 
Management and Budget. The remainder of this section summarizes the key 
findings of the analysis with respect to costs and benefits of the 
proposed standard, presents alternatives

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to the proposed standard, and requests comments on a number of issues.
    Table I-1, which is derived from material presented in the PEA, 
provides a summary of OSHA's best estimate of the costs and benefits of 
this proposed rule. As shown, this proposed rule is estimated to 
prevent 96 fatalities and 50 non-fatal beryllium-related illnesses 
annually once it is fully effective, and the monetized annualized 
benefits of the proposed rule are estimated to be $576 million using a 
3-percent discount rate and $255 million using a 7-percent discount 
rate. Also as shown in Table I-1, the estimated annualized cost of the 
rule is $37.6 million using a 3-percent discount rate and $39.1 million 
using a 7-percent discount rate. This proposed rule is estimated to 
generate net benefits of $538 million annually using a 3-percent 
discount rate and $216 million annually using a 7-percent discount 
rate. These estimates are for informational purposes only and have not 
been used by OSHA as the basis for its decision concerning the choice 
of a PEL or of other ancillary requirements for this proposed beryllium 
rule. The courts have ruled that OSHA may not use benefit-cost analysis 
or a criterion of maximizing net benefits as a basis for setting OSHA 
health standards.\1\
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    \1\ Am. Textile Mfrs. Inst., Inc. v. Nat'l Cotton Council of 
Am., 452 U.S. 490, 513 (1981); Pub. Citizen Health Research Group v. 
U.S. Dep't of Labor, 557 F.3d 165, 177 (3d Cir. 2009).

 Table I-1--Annualized Costs, Benefits and Net Benefits of OSHA's Proposed Beryllium Standard of 0.2 [mu]g/m\3\
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                  Discount rate                                            3%                       7%
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Annualized Costs
    Engineering Controls.........................                            $9,540,189              $10,334,036
    Respirators..................................                               249,684                  252,281
    Exposure Assessment..........................                             2,208,950                2,411,851
    Regulated Areas and Beryllium Work Areas.....                               629,031                  652,823
    Medical Surveillance.........................                             2,882,076                2,959,448
    Medical Removal..............................                               148,826                  166,054
    Exposure Control Plan........................                             1,769,506                1,828,766
    Protective Clothing and Equipment............                             1,407,365                1,407,365
    Hygiene Areas and Practices..................                               389,241                  389,891
    Housekeeping.................................                            12,574,921               12,917,944
    Training.....................................                             5,797,535                5,826,975
Total Annualized Costs (Point Estimate)..........                            37,597,325               39,147,434
Annual Benefits: Number of Cases Prevented
    Fatal Lung Cancer............................          4.0
    CBD-Related Mortality........................         92.0
    Total Beryllium Related Mortality............         96.0              572,981,864              253,743,368
Morbidity........................................         49.5                2,844,770                1,590,927
Monetized Annual Benefits (midpoint estimate)....                           575,826,633              255,334,295
        Net Benefits.............................                           538,229,308              216,186,861
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Source: OSHA, Directorate of Standards and Guidance, Office of Regulatory Analysis.

    Both the costs and benefits of Table I-1 reflect the incremental 
costs and benefits associated with achieving full compliance with the 
proposed standard. They do not include costs and benefits associated 
with employers' current exposure control measures or other aspects of 
the proposed standard they have already implemented. For example, for 
employers whose exposures are already below the proposed PEL, OSHA's 
estimated costs and benefits for the proposed standard do not include 
the costs of their exposure control measures or the benefits of these 
employers' compliance with the proposed PEL. The costs and benefits of 
Table I-1 also do not include costs and benefits associated with 
achieving compliance with existing requirements, to the extent that 
some employers may currently not be fully complying with applicable 
regulatory requirements.

I. Issues and Alternatives

    In addition to the proposed standard itself, this preamble 
discusses more than two dozen regulatory alternatives, including 
various sub-alternatives, to the proposed standard and requests 
comments and information on a variety of topics pertinent to the 
proposed standard. The regulatory alternatives OSHA is considering 
include alternatives to the proposed scope of the standard, regulatory 
alternatives to the proposed TWA PEL of 0.2 [mu]g/m\3\ and proposed 
STEL of 2 [mu]g/m\3\, a regulatory alternative that would modify the 
proposed methods of compliance, and regulatory alternatives that affect 
proposed ancillary provisions. The Agency solicits comment on the 
proposed phase-in schedule for the various provisions of the standard. 
Additional requests for comments and information follow the summaries 
of regulatory alternatives, under the ``Issues'' heading.

Regulatory Alternatives

    OSHA believes that inclusion of regulatory alternatives serves two 
important functions. The first is to explore the possibility of less 
costly ways (than the proposed standard) to provide an adequate level 
of worker protection from exposure to beryllium. The second is tied to 
the Agency's statutory requirement, which underlies the proposed 
standard, to reduce significant risk to the extent feasible. Each 
regulatory alternative presented here is described and analyzed more 
fully elsewhere in this preamble or in the PEA. Where appropriate, the 
alternative is included in this preamble at the end of the relevant 
section of Section XVIII, Summary and Explanation of the Proposed 
Standard, to facilitate comparison of the alternative to the proposed 
standard. For example, alternative PELs under consideration by the 
Agency are presented in the discussion of paragraph (c) in Section 
XVIII. In addition, all

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alternatives are discussed in the PEA, Chapter VIII: Regulatory 
Alternatives (OSHA, 2014). The costs and benefits of each regulatory 
alternative are presented both in Section IX of this preamble and in 
Chapter VIII of the PEA.
    The more than two dozen regulatory alternatives, including various 
sub-alternatives regulatory alternatives under consideration are 
summarized below, and are organized into the following categories: 
alternatives to the proposed scope of the standard; alternatives to the 
proposed PELs; alternatives to the proposed methods of compliance; 
alternatives to the proposed ancillary provisions; and the timing of 
the standard.
Scope
    OSHA has examined three alternatives that would alter the groups of 
employers and employees covered by this rulemaking. Regulatory 
Alternative #1a would expand the scope of the proposed standard to 
include all operations in general industry where beryllium exists only 
as a trace contaminant; that is, where the materials used contain no 
more than 0.1% beryllium by weight. Regulatory Alternative #1b is 
similar to Regulatory Alternative #1a, but exempts operations where the 
employer can show that employees' exposures will not meet or exceed the 
action level or exceed the STEL. Where the employer has objective data 
demonstrating that a material containing beryllium or a specific 
process, operation, or activity involving beryllium cannot release 
beryllium in concentrations at or above the proposed action level or 
above the proposed STEL under any expected conditions of use, that 
employer would be exempt from the proposed standard except for 
recordkeeping requirements pertaining to the objective data. 
Alternative #1a and Alternative #1b, like the proposed rule, would not 
cover employers or employees in construction or shipyards.
    Regulatory Alternative #2a would expand the scope of the proposed 
standard to also include employers in construction and maritime. For 
example, this alternative would cover abrasive blasters, pot tenders, 
and cleanup staff working in construction and shipyards who have the 
potential for airborne beryllium exposure during blasting operations 
and during cleanup of spent media. Regulatory Alternative #2b would 
update Sec. Sec.  1910.1000 Tables Z-1 and Z-2, 1915.1000 Table Z, and 
1926.55 Appendix A so that the proposed TWA PEL and STEL would apply to 
all employers and employees in general industry, shipyards, and 
construction, including occupations where beryllium exists only as a 
trace contaminant. However, all other provisions of the standard would 
be in effect only for employers and employees that fall within the 
scope of the proposed rule. More detailed discussion of Regulatory 
Alternatives #1a, #1b, #2a, and #2b appears in Section IX of this 
preamble and in Chapter VIII of the PEA (OSHA, 2014). In addition, 
Section XVIII of this preamble, Summary and Explanation, includes a 
discussion of paragraph (a) that describes the scope of the proposed 
rule, issues with the proposed scope, and Regulatory Alternatives #1a, 
#1b, #2a, and #2b.
    Another regulatory alternative that would impact the scope of 
affected industries, extending eligibility for medical surveillance to 
employees in shipyards, construction, and parts of general industry 
excluded from the scope of the proposed standard, is discussed along 
with other medical surveillance alternatives later in this section 
(Regulatory Alternative #21) and in the discussion of paragraph (k) in 
this preamble at Section XVIII, Summary and Explanation of the Proposed 
Standard.
Permissible Exposure Limits
    OSHA has examined several regulatory alternatives that would modify 
the TWA PEL or STEL for the proposed rule. Under Regulatory Alternative 
#3, OSHA would adopt a STEL of 5 times the proposed PEL. Thus, this 
alternative STEL would be 1.0 [mu]g/m\3\ if OSHA adopts a PEL of 0.2 
[mu]g/m\3\; it would be 0.5 [mu]g/m\3\ if OSHA adopts a PEL of 0.1 
[mu]g/m\3\; and it would be 2.5 [micro]g/m\3\ if OSHA adopts a PEL of 
0.5 [micro]g/m\3\ (see Regulatory Alternatives #4 and #5). Under 
Regulatory Alternative #4, the proposed PEL would be lowered from 0.2 
[mu]g/m\3\ to 0.1 [mu]g/m\3\. Under Regulatory Alternative #5, the 
proposed PEL would be raised from 0.2 [mu]g/m\3\ to 0.5 [mu]g/m\3\. In 
addition, for informational purposes, OSHA examined a regulatory 
alternative that would maintain the TWA PEL at 2.0 [mu]g/m\3\, but all 
of the other proposed provisions would be required with their triggers 
remaining the same as in the proposed rule. This alternative is not one 
OSHA could legally adopt because the absence of a more protective 
requirement for engineering controls would not be consistent with 
section 6(b)(5) of the OSH Act. More detailed discussion of these 
alternatives to the proposed PEL appears in Section IX of this preamble 
and in Chapter VIII of the PEA (OSHA, 2014). In addition, in Section 
XVIII of this preamble, Summary and Explanation of the Proposed 
Standard, the discussion of proposed paragraph (c) describes the 
proposed TWA PEL and STEL, issues with the proposed exposure limits, 
and Regulatory Alternatives #3, #4, and #5.
Methods of Compliance
    The proposed standard would require employers to implement 
engineering and work practice controls to reduce employees' exposures 
to or below the TWA PEL and STEL. Where engineering and work practice 
controls are insufficient to reduce exposures to or below the TWA PEL 
and STEL, employers would still be required to implement them to reduce 
exposure as much as possible, and to supplement them with a respiratory 
protection program. In addition, for each operation where there is 
airborne beryllium exposure, the employer must ensure that one or more 
of the engineering and work practice controls listed in paragraph 
(f)(2) are in place, unless all of the listed controls are infeasible, 
or the employer can demonstrate that exposures are below the action 
level based on two samples taken seven days apart. Regulatory 
Alternative #6 would eliminate the engineering and work practice 
controls provision currently specified in paragraph (f)(2). This 
regulatory alternative does not eliminate the need for engineering 
controls to lower exposure levels to or below the TWA PEL and STEL; 
rather, it dispenses with the mandatory use of certain engineering 
controls that must be installed above the action level but at or below 
the TWA PEL.
    More detailed discussion of Regulatory Alternative #6 appears in 
Section IX of this preamble and in Chapter VIII of the PEA (OSHA, 
2014). In addition, the discussion of paragraph (f) in Section XVIII of 
this preamble, Summary and Explanation, provides a more detailed 
explanation of the proposed methods of compliance, issues with the 
proposed methods of com pli ance, and Regulatory Alternative #6.
Ancillary Provisions
    The proposed rule contains several ancillary provisions, including 
requirements for exposure assessment, personal protective clothing and 
equipment (PPE), medical surveillance, medical removal, training, and 
regulated areas or access control. OSHA has examined a variety of 
regulatory alternatives involving changes to one or more of these 
ancillary provisions. OSHA has preliminarily determined that several of 
these ancillary provisions will increase the benefits of the proposed 
rule, for example, by helping to ensure the TWA PEL is not exceeded

[[Page 47570]]

or by lowering the risks to workers given the significant risk 
remaining at the proposed TWA PEL. However, except for Regulatory 
Alternative #7 (involving the elimination of all ancillary provisions), 
OSHA did not estimate changes in monetized benefits for the regulatory 
alternatives that affect ancillary provisions. Two regulatory 
alternatives that involve all ancillary provisions are presented below 
(#7 and #8), followed by regulatory alternatives for exposure 
monitoring (#9, #10, and #11), for regulated areas (#12), for personal 
protective clothing and equipment (#13), for medical surveillance (#14 
through #21), and for medical removal (#22).
All Ancillary Provisions
    During the Small Business Regulatory Fairness Act (SBREFA) process 
conducted in 2007, the SBAR Panel recommended that OSHA analyze a PEL-
only standard as a regulatory alternative. The Panel also recommended 
that OSHA consider applying ancillary provisions of the standard so as 
to minimize costs for small businesses where exposure levels are low 
(OSHA, 2008b). In response to these recommendations, OSHA analyzed 
Regulatory Alternative #7, a PEL-only standard, and Regulatory 
Alternative #8, which would only apply ancillary provisions of the 
beryllium standard at exposures above the proposed PEL of 0.2 [micro]g/
m\3\ or the proposed STEL of 2 [micro]g/m\3\. Regulatory Alternative #7 
would update the Z tables for Sec.  1910.1000, so that the proposed TWA 
PEL and STEL would apply to all workers in general industry. All other 
provisions of the proposed standard would be dropped.
    As indicated previously, OSHA has preliminarily determined that 
there is significant risk remaining at the proposed PEL of 0.2 [mu]g/
m\3\. However, the available evidence on feasibility suggests that 0.2 
[mu]g/m\3\ may be the lowest feasible PEL (see Chapter IV of the PEA, 
OSHA 2014). Therefore, the Agency believes that it is necessary to 
include ancillary provisions in the proposed rule to further reduce the 
remaining risk. In addition, the recommended standard provided to OSHA 
by representatives of the primary beryllium manufacturing industry and 
the Steelworkers Union further supports the importance of ancillary 
provisions in protecting workers from the harmful effects of beryllium 
exposure (Materion and USW, 2012).
    Under Regulatory Alternative #8, several ancillary provisions that 
the current proposal would require under a variety of exposure 
conditions (e.g., dermal contact; any airborne exposure; exposure at or 
above the action level) would instead only apply where exposure levels 
exceed the TWA PEL or STEL. Regulatory Alternative #8 affects the 
following provisions of the proposed standard:

--Exposure monitoring. Whereas the proposed standard requires annual 
monitoring where exposure levels are at or above the action level and 
at or below the TWA PEL, Alternative #8 would require annual exposure 
monitoring only where exposure levels exceed the TWA PEL or STEL;
-- Written exposure control plan. Whereas the proposed standard 
requires written exposure control plans to be maintained in any 
facility covered by the standard, Alternative #8 would require only 
facilities with exposures above the TWA PEL or STEL to maintain a plan;
--PPE. Whereas the proposed standard requires PPE for employees under a 
variety of conditions, such as exposure to soluble beryllium or visible 
contamination with beryllium, Alternative #8 would require PPE only for 
employees exposed above the TWA PEL or STEL;
--Housekeeping. Whereas the proposed standard's housekeeping 
requirements apply across a wide variety of beryllium exposure 
conditions, Alternative #8 would limit housekeeping requirements to 
areas with exposures above the TWA PEL or STEL.
--Medical Surveillance. Whereas the proposed standard's medical 
surveillance provisions require employers to offer medical surveillance 
to employees with signs or symptoms of beryllium-related health effects 
regardless of their exposure level, Alternative #8 would make 
surveillance available to such employees only if they were exposed 
above the TWA PEL or STEL.

More detailed discussions of Regulatory Alternatives #7 and #8, 
including a description of the considerations pertinent to these 
alternatives, appear in Section IX of this preamble and in Chapter VIII 
of the PEA (OSHA, 2014).
Exposure Monitoring
    OSHA has examined three regulatory alternatives that would modify 
the proposed standard's provisions on exposure monitoring, which 
require periodic monitoring annually where exposures are at or above 
the action level and at or below the TWA PEL. Under Regulatory 
Alternative #9, employers would be required to perform periodic 
exposure monitoring every 180 days where exposures are at or above the 
action level or above the STEL, and at or below the TWA PEL. Under 
Regulatory Alternative #10, employers would be required to perform 
periodic exposure monitoring every 180 days where exposures are at or 
above the action level or above the STEL, including where exposures 
exceed the TWA PEL. Under Regulatory Alternative #11, employers would 
be required to perform periodic exposure monitoring every 180 days 
where exposures are at or above the action level or above the STEL, and 
every 90 days where exposures exceed the TWA PEL. More detailed 
discussions of Regulatory Alternatives #9, #10, and #11 appear in 
Section IX of this preamble and in Chapter VIII of the PEA (OSHA, 
2014). In addition, the discussion of proposed paragraph (d) in Section 
XVIII of this preamble, Summary and Explanation of the Proposed 
Standard, provides a more detailed explanation of the proposed 
requirements for exposure monitoring, issues with exposure monitoring, 
and the considerations pertinent to Regulatory Alternatives #9, #10, 
and #11.
Regulated Areas
    The proposed standard would require employers to establish and 
maintain two types of areas: beryllium work areas, wherever employees 
are, or can reasonably be expected to be, exposed to any level of 
airborne beryllium; and regulated areas, wherever employees are, or can 
reasonably be expected to be, exposed to airborne beryllium at levels 
above the TWA PEL or STEL. Employers are required to demarcate 
beryllium work areas, but are not required to restrict access to 
beryllium work areas or provide respiratory protection or other forms 
of PPE within work areas that are not also regulated areas. Employers 
must demarcate regulated areas, restrict access to them, post warning 
signs and provide respiratory protection and other PPE within regulated 
areas, as well as medical surveillance for employees who work in 
regulated areas for more than 30 days in a 12-month period. During the 
SBREFA process conducted in 2007, the SBAR Panel recommended that OSHA 
consider dropping or limiting the provision for regulated areas (OSHA, 
2008b). In response to this recommendation, OSHA analyzed Regulatory 
Alternative #12, which would not require employers to establish 
regulated areas. More detailed discussion of Regulatory Alternative #12 
appears in Section IX of this preamble and in Chapter VIII of the PEA 
(OSHA, 2014). In addition, the discussion of

[[Page 47571]]

paragraph (e) in Section XVIII of this preamble, Summary and 
Explanation, provides a more detailed explanation of the proposed 
requirements for regulated areas, issues with regulated areas, and 
considerations pertinent to Regulatory Alternative #12.
Personal Protective Clothing and Equipment (PPE)
    Regulatory Alternative #13 would modify the proposed requirements 
for PPE, which require PPE where exposure exceeds the TWA PEL or STEL; 
where employees' clothing or skin may become visibly contaminated with 
beryllium; and where employees may have skin contact with soluble 
beryllium compounds. The requirement to use PPE where work clothing or 
skin may become ``visibly contaminated'' with beryllium differs from 
prior standards that do not require contamination to be visible in 
order for PPE to be required. In the case of beryllium, which OSHA has 
preliminarily concluded can sensitize through dermal exposure, the 
exposure levels capable of causing adverse health effects and the PELs 
in effect are so low that beryllium surface contamination is unlikely 
to be visible (see this preamble at section V, Health Effects). OSHA is 
therefore considering Regulatory Alternative #13, which would require 
appropriate PPE wherever there is potential for skin contact with 
beryllium or beryllium-contaminated surfaces. More detailed discussion 
of Regulatory Alternative #13 is provided in Section IX of this 
preamble and in Chapter VIII of the PEA (OSHA, 2014). In addition, the 
discussion of paragraph (h) in Section XVIII of this preamble, Summary 
and Explanation, provides a more detailed explanation of the proposed 
requirements for PPE, issues with PPE, and the considerations pertinent 
to Regulatory Alternative #13.
Medical Surveillance
    The proposed requirements for medical surveillance include: (1) 
Medical examinations, including a test for beryllium sensitization, for 
employees who are exposed to beryllium above the proposed PEL for 30 
days or more per year, who are exposed to beryllium in an emergency, or 
who show signs or symptoms of CBD; and (2) low-dose helical tomography 
(low-dose computed tomography, hereafter referred to as ``CT scans''), 
for employees who were exposed above the proposed PEL for more than 30 
days in a 12-month period for 5 years or more. This type of CT scan is 
a method of detecting tumors, and is commonly used to diagnose lung 
cancer. The proposed standard would require periodic medical exams to 
be provided for employees in the medical surveillance program annually, 
while tests for beryllium sensitization and CT scans would be provided 
to eligible employees biennially.
    OSHA has examined eight regulatory alternatives (#14 through #21) 
that would modify the proposed rule's requirements for employee 
eligibility, the types of exam that must be offered, and the frequency 
of periodic exams. Medical surveillance was a subject of special 
concern to SERs during the SBREFA process, and the SBREFA Panel offered 
many comments and recommendations related to medical surveillance for 
OSHA's consideration. Some of the Panel's concerns have been addressed 
in this proposal, which was modified since the SBREFA Panel was 
convened (see this preamble at Section XVIII, Summary and Explanation 
of the Proposed Standard, for more detailed discussion). Several of the 
alternatives presented here (#16, #18, and #20) also respond to 
recommendations by the SBREFA Panel to reduce burdens on small 
businesses by dropping or reducing the frequency of medical 
surveillance requirements. OSHA also seeks to ensure that the 
requirements of the final standard offer workers adequate medical 
surveillance while limiting the costs to employers. Thus, OSHA requests 
feedback on several additional alternatives and on a variety of issues 
raised later in this section of the preamble.
    Regulatory Alternatives #14, #15, and #21 would expand eligibility 
for medical surveillance to a broader group of employees than would be 
eligible in the proposed standard. Under Regulatory Alternative #14, 
medical surveillance would be available to employees who are exposed to 
beryllium above the proposed PEL, including employees exposed for fewer 
than 30 days per year. Regulatory Alternative #15 would expand 
eligibility for medical surveillance to employees who are exposed to 
beryllium above the proposed action level, including employees exposed 
for fewer than 30 days per year. Regulatory Alternative #21 would 
extend eligibility for medical surveillance as set forth in proposed 
paragraph (k) to all employees in shipyards, construction, and general 
industry who meet the criteria of proposed paragraph (k)(1) (or any of 
the alternative criteria under consideration). However, all other 
provisions of the standard would be in effect only for employers and 
employees that fall within the scope of the proposed rule.
    Regulatory Alternatives #16 and #17 would modify the proposed 
standard's requirements to offer beryllium sensitization testing to 
eligible employees. Under Regulatory Alternative #16, employers would 
not be required to offer employees testing for beryllium sensitization. 
Regulatory Alternative #17 would increase the frequency of periodic 
sensitization testing, from the proposed standard's biennial 
requirement to annual testing. Regulatory Alternatives #18 and #19 
would similarly modify the proposed standard's requirements to offer CT 
scans to eligible employees. Regulatory Alternative #18 would drop the 
CT scan requirement from the proposed rule, whereas Regulatory 
Alternative #19 would increase the frequency of periodic CT scans from 
biennial to annual scans. Finally, under Regulatory Alternative #20, 
all periodic components of the medical surveillance exams would be 
available biennially to eligible employees. Instead of requiring 
employers to offer eligible employees a medical examination every year, 
employers would be required to offer eligible employees a medical 
examination every other year. The frequency of testing for beryllium 
sensitization and CT scans would also be biennial for eligible 
employees, as in the proposed standard.
    More detailed discussions of Regulatory Alternatives #14, #15, #16, 
#17, #18, #19, #20, and #21 appear in Section IX of this preamble and 
in Chapter VIII of the PEA (OSHA, 2014). In addition, Section XVIII of 
this preamble, Summary and Explanation, paragraph (k) provides a more 
detailed explanation of the proposed requirements for medical 
surveillance, issues with medical surveillance, and the considerations 
pertinent to Regulatory Alternatives #14 through #21.
Medical Removal Protection (MRP)
    The proposed requirements for medical removal protection provide an 
option for medical removal to an employee who is working in a job with 
exposure at or above the action level and is diagnosed with CBD or 
confirmed positive for beryllium sensitization. If the employee chooses 
removal, the employer must either remove the employee to comparable 
work in a work environment where exposure is below the action level, or 
if comparable work is not available, must place the employee on paid 
leave for 6 months or until such time as comparable work becomes 
available. In either case, the employer must maintain for 6 months the 
employee's base earnings, seniority,

[[Page 47572]]

and other rights and benefits that existed at the time of removal. 
During the SBREFA process, the Panel recommended that OSHA give careful 
consideration to the impacts that an MRP requirement could have on 
small businesses (OSHA, 2008b). In response to this recommendation, 
OSHA analyzed Regulatory Alternative #22, which would not require 
employers to offer MRP. More detailed discussion of Regulatory 
Alternative #22 appears in Section IX of this preamble and in Chapter 
VIII of the PEA (OSHA, 2014). In addition, the discussion of paragraph 
(l) in section XVIII of this preamble, Summary and Explanation, 
provides a more detailed explanation of the proposed requirements for 
MRP, issues with MRP, and considerations pertinent to Regulatory 
Alternative #22.
Timing of the Standard
    The proposed standard would become effective 60 days following 
publication of the final standard in the Federal Register. The 
effective date is the date on which the standard imposes compliance 
obligations on employers. However, the standard would not become 
enforceable by OSHA until 90 days following the effective date for 
exposure monitoring, work areas and regulated areas, written exposure 
control plan, respiratory protection, other personal protective 
clothing and equipment, hygiene areas and practices (except change 
rooms), housekeeping, medical surveillance, and medical removal. The 
proposed requirement for change rooms would not be enforceable until 
one year after the effective date, and the requirements for engineering 
controls would not be enforceable until two years after the effective 
date. In summary, employers will have some period of time after the 
standard becomes effective to come into compliance before OSHA will 
begin enforcing it: 90 days for most provisions, one year for change 
rooms, and two years for engineering controls. Beginning 90 days 
following the effective date, during periods necessary to install or 
implement feasible engineering controls where exposure exceed the TWA 
PEL or STEL, employers must provide employees with respiratory 
protection as described in the proposed standard under section (g), 
Respiratory Protection.
    OSHA invites comment and suggestions for phasing in requirements 
for engineering controls, medical surveillance, and other provisions of 
the standard. A longer phase-in time would have several advantages, 
such as reducing initial costs of the standard or allowing employers to 
coordinate their environmental and occupational safety and health 
control strategies to minimize potential costs. However, a longer 
phase-in would also postpone and reduce the benefits of the standard. 
Suggestions for alternatives may apply to specific industries (e.g., 
industries where first-year or annualized cost impacts are highest), 
specific size-classes of employers (e.g., employers with fewer than 20 
employees), combinations of these factors, or all firms covered by the 
rule.
    OSHA requests comments on these regulatory alternatives, including 
the Agency's choice of regulatory alternatives (and whether there are 
other regulatory alternatives the Agency should consider) and the 
Agency's analysis of them. In addition, OSHA requests comments and 
information on a number of specific topics and issues pertinent to the 
proposed standard. These are summarized below.

Regulatory Issues

    In this section, we solicit public feedback on issues associated 
with the proposed standard and request information that would help the 
Agency craft the final standard. In addition to the issues specified 
here, OSHA also raises issues for comment on technical questions and 
discussions of economic issues in the PEA (OSHA, 2014). OSHA requests 
comment on all relevant issues, including health effects, risk 
assessment, significance of risk, technological and economic 
feasibility, and the provisions of the proposed regulatory text. In 
addition, OSHA requests comments on all of the issues raised by the 
Small Business Advocacy Review (SBAR) Panel, as summarized in the SBAR 
report (OSHA, 2008b)
    We present these issues and requests for information in the first 
chapter of the preamble to assist readers as they review the preamble 
and consider any comments they may want to submit. The issues are 
presented here in summary form. However, to fully understand the 
questions in this section and provide substantive input in response to 
them, the sections of the preamble relevant to these issues should be 
reviewed. These include: Section V, Health Effects; Section VI, the 
Preliminary Risk Assessment; Section VIII, Significance of Risk; 
Section IX, Summary of the Preliminary Economic Analysis and Initial 
Regulatory Flexibility Analysis; and Section XVIII, Summary and 
Explanation of the Proposed Standard.
    OSHA requests that comments be organized, to the extent possible, 
around the following issues and numbered questions. Comment on 
particular provisions should contain a heading setting forth the 
section and the paragraph in the proposed standard that the comment 
addresses. Comments addressing more than one section or paragraph will 
have correspondingly more headings.
    Submitting comments in an organized manner and with clear reference 
to the issue raised will enable all participants to easily see what 
issues the commenter addressed and how they were addressed. Many 
commenters, especially small businesses, are likely to confine their 
comments to the issues that affect them, and they will benefit from 
being able to quickly identify comments on these issues in others' 
submissions. The Agency welcomes comments concerning all aspects of 
this proposal. However, OSHA is especially interested in responses, 
supported by evidence and reasons, to the following questions:

Health Effects

    1. OSHA has described a variety of studies addressing the major 
adverse health effects that have been associated with exposure to 
beryllium. Using currently available epidemiologic and experimental 
studies, OSHA has made a preliminary determination that beryllium 
presents risks of lung cancer; sensitization; CBD at 0.1 [micro]g/m\3\; 
and at higher exposures acute beryllium disease, and hepatic, renal, 
cardiovascular and ocular diseases. Is this determination correct? Are 
there additional studies or other data OSHA should consider in 
evaluating any of these health outcomes?
    2. Has OSHA adequately identified and documented all critical 
health impairments associated with occupational exposure to beryllium? 
If not, what other adverse health effects should be added? Are there 
additional studies or other data OSHA should consider in evaluating any 
of these health outcomes?
    3. Are there any additional studies, other data, or information 
that would affect the information discussed or significantly change the 
determination of material health impairment?
    Please submit any relevant information, data, or additional studies 
(or citations to studies), and explain your reasons for recommending 
any studies you suggest.

Risk Assessment and Significance of Risk

    4. OSHA has developed an analysis of health risks associated with 
occupational beryllium exposure, including an analysis of sensitization 
and CBD based on a selection of recent

[[Page 47573]]

studies in the epidemiological literature, a data set on a population 
of beryllium machinists provided by the National Jewish Medical 
Research Center (NJMRC), and an assessment of lung cancer risk using an 
analysis provided by NIOSH. Did OSHA rely on the best available 
evidence in its risk assessment? Are there additional studies or other 
data OSHA should consider in evaluating risk for these health outcomes? 
Please provide the studies, citations to studies, or data you suggest.
    5. OSHA preliminarily concluded that there is significant risk of 
material health impairment (lung cancer or CBD) from a working lifetime 
of occupational exposure to beryllium at the current TWA PEL of 2 
[micro]g/m\3\, which would be substantially reduced by the proposed TWA 
PEL of 0.2 [micro]g/m\3\ and the alternative TWA PEL of 0.1 [micro]g/
m\3\. OSHA's preliminary risk assessment also concludes that there is 
still significant risk of CBD and lung cancer at the proposed PEL and 
the alternative PELs, although substantially less than at the current 
PEL. Are these preliminary conclusions reasonable, based on the best 
available evidence? If not, please provide a detailed explanation of 
your position, including data to support your position and a detailed 
analysis of OSHA's risk assessment if appropriate.
    6. Please provide comment on OSHA's analysis of risk for beryllium 
sensitization, CBD and lung cancer. Are there important gaps or 
uncertainties in the analysis, such that the Agency's preliminary 
conclusions regarding significance of risk at the current, proposed, 
and alternative PELs may be in error? If so, please provide a detailed 
explanation and suggestions for how OSHA's analysis should be corrected 
or improved.
    7. OSHA has made a preliminary determination that the available 
data are not sufficient or suitable for risk analysis of effects other 
than beryllium sensitization, CBD and lung cancer. Do you have, or are 
you aware of, studies or data that would be suitable for a risk 
assessment for these adverse health effects? Please provide the 
studies, citations to studies, or data you suggest.

(a) Scope

    8. Has OSHA defined the scope of the proposed standard 
appropriately? Does it currently include employers who should not be 
covered, or exclude employers who should be covered by a comprehensive 
beryllium standard? Are you aware of employees in construction or 
maritime, or in general industry who deal with beryllium only as a 
trace contaminant, who may be at significant risk from occupational 
beryllium exposure? Please provide the basis for your response and any 
applicable supporting information.

(b) Definitions

    9. Has OSHA defined the Beryllium lymphocyte proliferation test 
appropriately? If not, please provide the definition that you believe 
is appropriate. Please provide rationale and citations supporting your 
comments.
    10. Has OSHA defined CBD Diagnostic Center appropriately? In 
particular, should a CBD diagnostic center be required to analyze 
biological samples on-site, or should diagnostic centers be allowed to 
send samples off-site for analysis? Is the list of tests and procedures 
a CBD Diagnostic Center is required to be able to perform appropriate? 
Should any of the tests or procedures be removed from the definition? 
Should other tests or procedures be added to the definition? Please 
provide rationale and information supporting your comments.

(d) Exposure Monitoring

    11. Do you currently monitor for beryllium exposures in your 
workplace? If so, how often? Please provide the reasoning for the 
frequency of your monitoring. If periodic monitoring is performed at 
your workplace for exposures other than beryllium, with what frequency 
is it repeated?
    12. Is it reasonable to allow discontinuation of monitoring based 
on one sample below the action level? Should more than one result below 
the action level be required to discontinue monitoring?

(e) Work Areas and Regulated Areas

    The proposed standard would require employers to establish and 
maintain two types of areas: beryllium work areas, wherever employees 
are, or can reasonably be expected to be, exposed to any level of 
airborne beryllium; and regulated areas, wherever employees are, or can 
reasonably be expected to be, exposed to airborne beryllium at levels 
above the TWA PEL or STEL. Employers are required to demarcate 
beryllium work areas, but are not required to restrict access to 
beryllium work areas or provide respiratory protection or other forms 
of PPE within work areas with exposures at or below the TWA PEL or 
STEL. Employers must also demarcate regulated areas, including posting 
warning signs; restrict access to regulated areas; and provide 
respiratory protection and other PPE within regulated areas.
    13. Does your workplace currently have regulated areas? If so, how 
are regulated areas demarcated?
    14. Please describe work settings where establishing regulated 
areas could be problematic or infeasible. If establishing regulated 
areas is problematic, what approaches might be used to warn employees 
in such work settings of high risk areas?

(f) Methods of Compliance

    Paragraph (f)(2) of the proposed standard would require employers 
to implement engineering and work practice controls to reduce 
employees' exposures to or below the TWA PEL and STEL. Where 
engineering and work practice controls are insufficient to reduce 
exposures to or below the TWA PEL and STEL, employers would still be 
required to implement them to reduce exposure as much as possible, and 
to supplement them with a respiratory protection program. In addition, 
for each operation where there is airborne beryllium exposure, the 
employer must ensure that at least one of the engineering and work 
practice controls listed in paragraph (f)(2) is in place, unless all of 
the listed controls are infeasible, or the employer can demonstrate 
that exposures are below the action level based on no fewer than two 
samples taken seven days apart.
    15. Do you usually use engineering or work practices controls 
(local exhaust ventilation, isolation, substitution) to reduce 
beryllium exposures? If so, which controls do you use?
    16. Are the controls and processes listed in paragraph (f)(2)(i)(A) 
appropriate for controlling beryllium exposures? Are there additional 
controls or processes that should be added to paragraph (f)(2)(i)(A)?

(g) Respiratory Protection

    17. OSHA's asbestos standard (CFR 1910.1001) requires employers to 
provide each employee with a tight-fitting, powered air-purifying 
respirator (PAPR) instead of a negative pressure respirator when the 
employee chooses to use a PAPR and it provides adequate protection to 
the employee. Should the beryllium standard similarly require employers 
to provide PAPRs (instead of allowing a negative pressure respirator) 
when requested by the employee? Are there other circumstances where a 
PAPR should be specified as the appropriate respiratory protection? 
Please provide the basis for your response and any applicable 
supporting information.

[[Page 47574]]

(h) Personal Protective Clothing and Equipment

    18. Do you currently require specific PPE or respirators when 
employees are working with beryllium? If so, what type?
    19. The proposal requires PPE wherever work clothing or skin may 
become visibly contaminated with beryllium; where employees' skin can 
reasonably be expected to be exposed to soluble beryllium compounds; or 
where employee exposure exceeds or can reasonably be expected to exceed 
the TWA PEL or STEL. The requirement to use PPE where work clothing or 
skin may become ``visibly contaminated'' with beryllium differs from 
prior standards which do not require contamination to be visible in 
order for PPE to be required. Is ``visibly contaminated'' an 
appropriate trigger for PPE? Is there reason to require PPE where 
employees' skin can be exposed to insoluble beryllium compounds? Please 
provide the basis for your response and any applicable supporting 
information.

(i) Hygiene Areas and Practices

    20. The proposal requires employers to provide showers in their 
facilities if (A) Exposure exceeds or can reasonably be expected to 
exceed the TWA PEL or STEL; and (B) Beryllium can reasonably be 
expected to contaminate employees' hair or body parts other than hands, 
face, and neck. Is this requirement reasonable and adequately 
protective of beryllium-exposed workers? Should OSHA amend the 
provision to require showers in facilities where exposures exceed the 
PEL or STEL, without regard to areas of bodily contamination?

(j) Housekeeping

    21. The proposed rule prohibits dry sweeping or brushing for 
cleaning surfaces in beryllium work areas unless HEPA-filtered 
vacuuming or other methods that minimize the likelihood and level of 
exposure have been tried and were not effective. Please comment on this 
provision. What methods do you use to clean work surfaces at your 
facility? Are HEPA-filtered vacuuming or other methods to minimize 
beryllium exposure used to clean surfaces at your facility? Have they 
been effective? Are there any circumstances under which dry sweeping or 
brushing are necessary? Please explain your response.
    22. The proposed rule requires that materials designated for 
recycling that are visibly contaminated with beryllium particulate 
shall be cleaned to remove visible particulate, or placed in sealed, 
impermeable enclosures. However, small particles (<10 [mu]g) may not be 
visible to the naked eye, and there are studies suggesting that small 
particles may penetrate the skin, beyond which beryllium sensitization 
can occur (Tinkle et al., 2003). OSHA requests feedback on this 
provision. Should OSHA require that all material to be recycled be 
decontaminated regardless of perceived surface cleanliness? Should OSHA 
require that all material disposed or discarded be in enclosures 
regardless of perceived surface cleanliness? Please provide explanation 
or data to support your comments.

 (k) Medical Surveillance

    The proposed requirements for medical surveillance include: (1) 
Medical examinations, including a test for beryllium sensitization, for 
employees who are exposed to beryllium above the proposed PEL for 30 
days or more per year, who are exposed to beryllium in an emergency, or 
who show signs or symptoms of CBD; and (2) CT scans for employees who 
were exposed above the proposed PEL for more than 30 days in a 12-month 
period for 5 years or more. The proposed standard would require 
periodic medical exams to be provided for employees in the medical 
surveillance program annually, while tests for beryllium sensitization 
and CT scans would be provided to eligible employees biennially.
    23. Is medical surveillance being provided for beryllium-exposed 
employees at your worksite? If so:
    a. Do you provide medical surveillance to employees under another 
OSHA standard or as a matter of company policy? What OSHA standard(s) 
does the program address?
    b. How many employees are included, and how do you determine which 
employees receive medical surveillance (e.g., by exposure level, other 
factors)?
    c. Who administers and implements the medical surveillance (e.g., 
company doctor, nurse practitioner, physician assistant, or nurse; or 
outside doctor, nurse practitioner, physician assistant, or nurse)?
    d. What examinations, tests, or evaluations are included in the 
medical surveillance program, and with what frequency are they 
administered? Does your program include a surveillance program 
specifically for beryllium-related health effects (e.g., the BeLPT or 
other tests for beryllium sensitization)?
    e. If your facility offers the BeLPT, please provide feedback and 
data on your experience with the BeLPT, including the analytical or 
interpretive procedure you use and its role in your facility's exposure 
control program. Has identification of sensitized workers led to 
interventions to reduce exposures to sensitized individuals, or in the 
facility generally? If a worker is found to be sensitized, do you track 
worker health and possible progression of disease beyond sensitization? 
If so, how is this done?
    f. What difficulties and benefits (e.g., health, reduction in 
absenteeism, or financial) have you experienced with your medical 
surveillance program? If applicable, please discuss benefits and 
difficulties you have experienced with the use of the BeLPT, providing 
detailed information or examples if possible.
    g. What are the costs of your medical surveillance program? How do 
your costs compare with OSHA's estimated unit costs for the physical 
examination and employee time involved in the medical surveillance 
program? Are OSHA's baseline assumptions and cost estimates for medical 
surveillance consistent with your experiences providing medical 
surveillance to your employees?
    24. Please review paragraph (k) of the proposed rule, Medical 
Surveillance, and comment on the frequency and contents of medical 
surveillance in the proposed rule. Is 30 days from initial assignment a 
reasonable time at which to provide a medical exam? Should there be a 
requirement for beryllium sensitization testing at time of employment? 
Should there be a requirement for beryllium sensitization testing at an 
employee's exit exam, regardless of when the employee's most recent 
sensitization test was administered? Are the tests required and the 
testing frequencies specified appropriate? Should sensitized employees 
have the opportunity to be examined at a CBD Diagnostic Center more 
than once following a confirmed positive BeLPT? Are there additional 
tests or alternate testing schedules you would suggest? Should the skin 
be examined for signs and symptoms of beryllium exposure or other 
medical issues, as well as for breaks and wounds? Please explain the 
basis for your position and provide data or studies if applicable.
    25. Please provide comments on the proposed requirements regarding 
referral of a sensitized employee to a CBD diagnostic center, which 
specify referral to a diagnostic center ``mutually agreed upon'' by the 
employer and employee. Is this requirement for mutual agreement 
necessary and appropriate? How should a diagnostic center be chosen if 
the employee and employer cannot come to agreement? Should OSHA 
consider alternate language, such as referral for CBD

[[Page 47575]]

evaluation at a diagnostic center in a reasonable location?
    26. In the proposed rule, OSHA specifies that all medical 
examinations and procedures required by the standard must be performed 
by or under the direction of a licensed physician. Are physicians 
available in your geographic area to provide medical surveillance to 
workers who are covered by the proposed rule? Are other licensed health 
care professionals available to provide medical surveillance? Do you 
have access to other qualified personnel such as qualified X-ray 
technicians, and pulmonary specialists? Should the proposal be amended 
to allow examination by, or under the direction of, a physician or 
other licensed health care professional (PLHCP)? Please explain your 
position. Please note what you consider your geographic area in 
responding to this question.
    27. The proposed standard requires the employer to obtain the 
Licensed Physician's Written Medical Opinion from the PLHCP within 30 
days of the examination. Should OSHA revise the medical surveillance 
provisions of the proposed standard to allow employees to choose what, 
if any, medical information goes to the employer from the PLHCP? For 
example, the employer could instead be required to obtain a 
certification from the PLCHP within 30 days of the examination stating 
(1) when the examination took place, (2) that the examination complied 
with the standard, and (3) that the PLHCP provided the employee a copy 
of the Licensed Physician's Written Medical Opinion required by the 
standard. The PLHCP would need the employee's written consent to send 
the employer the Licensed Physician's Written Medical Opinion or any 
other medical information about the employee. This approach might lead 
to corresponding changes in proposed paragraphs (f)(1) (written 
exposure control program), (l) (medical removal) and (n) 
(recordkeeping) to reflect that employers will not automatically be 
receiving any medical information about employees as a result of the 
medical surveillance required by the proposed standard, but would 
instead only receive medical information the employee chooses to share 
with the employer. Please comment on the relative merits of the 
proposed standard's requirement that employers obtain the PLHCP's 
written opinion or an alternative that would provide employees with 
greater discretion over the information that goes to employers, and 
explain the basis for your position and the potential impact on the 
benefits of medical surveillance.
    28. Appendix A to the proposed standard reviews procedures for 
conducting and interpreting the results of BeLPT testing for beryllium 
sensitization. Is there now, or should there be, a standard method for 
BeLPT laboratory procedure? If yes, please describe the existing or 
proposed method. Is there now, or should there be, a standard algorithm 
for interpreting BeLPT results to determine sensitization? Please 
describe the existing or proposed laboratory method or interpretation 
algorithm. Should OSHA require that BeLPTs performed to comply with the 
medical surveillance provisions of this rule adhere to the Department 
of Energy (DOE) analytical and interpretive specifications issued in 
2001? Should interpretation of laboratory results be delegated to the 
employee's occupational physician or PLHCP?
    29. Should OSHA require the clinical laboratories performing the 
BeLPT to be accredited by the College of American Pathologists or 
another accreditation organization approved under the Clinical 
Laboratory Improvement Amendments (CLIA)? What other standards, if any, 
should be required for clinical laboratories providing the BeLPT?
    30. Are there now, or are there being developed, alternative tests 
to the BeLPT you would suggest? Please explain the reasons for your 
suggestion. How should alternative tests for beryllium sensitization be 
evaluated and validated? How should OSHA determine whether a test for 
beryllium sensitization is more reliable and accurate than the BeLPT? 
Please see Appendix A to the proposed standard for a discussion of the 
accuracy of the BeLPT.
    31. The proposed rule requires employers to provide OSHA with the 
results of BeLPTs performed to comply with the medical surveillance 
provisions upon request, provided that the employer obtains a release 
from the tested employee. Will this requirement be unduly burdensome 
for employers? Are there alternative organizations that would be 
appropriate to send test results to?

 (l) Medical Removal Protection

    The proposed requirements for medical removal protection provide an 
option for medical removal to an employee who is working in a job with 
exposure at or above the action level and is diagnosed with CBD or 
confirmed positive for beryllium sensitization. If the employee chooses 
removal, the employer must remove the employee to comparable work in a 
work environment where exposure is below the action level, or if 
comparable work is not available, must place the employee on paid leave 
for 6 months or until such time as comparable work becomes available. 
In either case, the employer must maintain for 6 months the employee's 
base earnings, seniority, and other rights and benefits that existed at 
the time of removal.
    32. Do you provide MRP at your facility? If so, please comment on 
the program's benefits, difficulties, and costs, and the extent to 
which eligible employees make use of MRP.
    33. OSHA has included requirements for medical removal protection 
(MRP) in the proposed rule, which includes provisions for medical 
removal for employees with beryllium sensitization or CBD, and an 
extension of removed employees' rights and benefits for six months. Are 
beryllium sensitization and CBD appropriate triggers for medical 
removal? Are there other medical conditions or findings that should 
trigger medical removal? For what amount of time should a removed 
employee's benefits be extended?

(p) Appendices

    34. Some OSHA health standards include appendices that address 
topics such as the hazards associated with the regulated substance, 
health screening considerations, occupational disease questionnaires, 
and PLHCP obligations. In this proposed rule, OSHA has included a non-
mandatory appendix to describe and discuss the BeLPT (Appendix A), and 
a non-mandatory appendix presenting a non-exhaustive list of 
engineering controls employers may use to comply with paragraph (f) 
(Appendix B). What would be the advantages and disadvantages of 
including each appendix in the final rule? What would be the advantages 
and disadvantages of providing this information in guidance materials?
    35. What additional information, if any, should be included in the 
appendices? What additional information, if any, should be provided in 
guidance materials?

General

    36. The current beryllium proposal includes triggers that require 
employers to initiate certain provisions, programs, and activities to 
protect workers from beryllium exposure. All employers covered under an 
OSHA health standard are required to initiate certain activities such 
as initial monitoring to evaluate the potential hazard to employees. 
OSHA health standards typically include ancillary provisions with 
various triggers indicating when an

[[Page 47576]]

employer covered under the standard would need to comply with a 
provision. The most common triggers are ones based an exposure level 
such as the PEL or action level. These exposure level triggers are 
sometimes combined with a minimum duration of exposure (e.g., >= 30 
days per year). Other triggers may include reasonably anticipated 
exposure, medical surveillance findings, certain work activities, or 
simply the presence of the regulated substance in the workplace.
    For the current Proposal, exposures to beryllium above the TWA PEL 
or STEL trigger the provisions for regulated areas, additional or 
enhanced engineering or work practice controls to reduce airborne 
exposures to or below the TWA PEL and STEL, personal protective 
clothing and equipment, medical surveillance, showers, and respiratory 
protection if feasible engineering and work practice controls cannot 
reduce airborne exposures to or below the TWA PEL and STEL. Exposures 
at or above the action level in turn trigger the provisions for 
periodic exposure monitoring, and medical removal eligibility (along 
with a diagnosis of CBD or confirmed positive for beryllium 
sensitization). Finally, an employer covered under the scope of the 
proposed standard must establish a beryllium work area where employees 
are, or can reasonably be expected to be, exposed to airborne beryllium 
regardless of the level of exposure. In beryllium work areas, employers 
must implement a written exposure control plan, provide washing 
facilities and change rooms (change rooms are only necessary if 
employees are required to remove their personal clothing), and follow 
housekeeping provisions. The employers must also implement at least one 
of the engineering and work practice controls listed in paragraph 
(f)(2) of the proposed standard. An employer is exempt from this 
requirement if he or she can demonstrate that such controls are not 
feasible or that exposures are below the action level.
    Certain provisions are triggered by one condition and other 
provisions are triggered only if multiple conditions are present. For 
example, medical removal is only triggered if an employee has CBD or is 
confirmed positive AND the employee is exposed at or above the action 
level.
    OSHA is requesting comment on the triggers in the proposed 
beryllium standard. Are the triggers OSHA has proposed appropriate? 
OSHA is also requesting comment on these triggers relative to the 
regulatory alternatives affecting the scope and PELs as described in 
this preamble in section I, Issues and Alternatives. For example, are 
the triggers in the proposed standard appropriate for Alternative #1a, 
which would expand the scope of the proposed standard to include all 
operations in general industry where beryllium exists only as a trace 
contaminant (less than 0.1% beryllium by weight)? Are the triggers 
appropriate for the alternatives that change the TWA PEL, STEL, and 
action level? Please specify the trigger and the alternative, if 
applicable, and why you agree or disagree with the trigger.

Relevant Federal Rules Which May Duplicate, Overlap, or Conflict With 
the Proposed Rule

    37. In Section IX--Preliminary Economic Analysis under the Initial 
Regulatory Flexibility Analysis, OSHA identifies, to the extent 
practicable, all relevant Federal rules which may duplicate, overlap, 
or conflict with the proposed rule. One potential area of overlap is 
with the U.S. Department of Energy (DOE) beryllium program. In 1999, 
DOE established a chronic beryllium disease prevention program (CBDPP) 
to reduce the number of workers (DOE employees and DOE contractors) 
exposed to beryllium at DOE facilities (10 CFR part 850, published at 
64 FR 68854-68914 (Dec. 8, 1999)). In establishing this program, DOE 
has exercised its statutory authority to prescribe and enforce 
occupational safety and health standards. Therefore pursuant to section 
4(b)(1) of the OSH Act, 29 U.S.C. 653(b)(1), the DOE facilities are 
exempt from OSHA jurisdiction.
    Nevertheless, under 10 CFR 850.22, DOE has included in its CBDPP 
regulation a requirement for compliance with the current OSHA 
permissible exposure limit (PEL), and any lower PEL that OSHA 
establishes in the future. Thus, although DOE has preempted OSHA's 
standard from applying at DOE facilities and OSHA cannot exercise any 
authority at those facilities, DOE relies on OSHA's PEL in implementing 
its own program. However, DOE's decision to tie its own standard to 
OSHA's PEL has little consequence to this rulemaking because the 
requirements in DOE's beryllium program (controls, medical 
surveillance, etc.) are triggered by DOE's action level of 0.2 
[micro]g/m\3\, which is much lower than DOE's existing PEL and the same 
as OSHA's proposed PEL. DOE's action level is not tied to OSHA's 
standard, so 10 CFR 850.22 would not require the CBDPP's action level 
or any non-PEL requirements to be automatically adjusted as a result of 
OSHA's rulemaking. For this reason, DOE has indicated to OSHA that 
OSHA's proposed rule would not have any impact on DOE's CBDPP, 
particularly since 10 CFR 850.25(b), Exposure reduction and 
minimization, requires DOE contractors to reduce exposures to below the 
DOE's action level of 0.2 [micro]g/m\3\, if practicable.
    DOE has expressed to OSHA that DOE facilities are already in 
compliance with 10 CFR 850 and its action level of 0.2 [micro]g/
m\3\,\2\ so the only potential impact on DOE's CBDPP that could flow 
from OSHA's rulemaking would be if OSHA ultimately adopted a PEL of 0.1 
[micro]g/m\3\, as discussed in alternative #4, instead of the proposed 
PEL of 0.2 [micro]g/m\3\, and DOE did not make any additional 
adjustments to its standards. Even in that hypothetical scenario, the 
impact would still be limited because of the odd result that DOE's PEL 
would drop below its own action level, while the action level would 
continue to serve as the trigger for most of DOE's program 
requirements.
---------------------------------------------------------------------------

    \2\ This would mean the prevailing beryllium exposures at DOE 
facilities are at or below 0.2 [micro]g/m\3\.
---------------------------------------------------------------------------

    DOE also has noted some potential overlap with a separate DOE 
provision in 10 CFR part 851, which requires its contractors to comply 
with DOE's CBDPP (10 CFR 851.23(a)(1)) and also with all OSHA standards 
under 29 CFR part 1910 except ``Ionizing Radiation'' (Sec.  1910.1096) 
(10 CFR 851.23(a)(3)). These requirements, which DOE established in 
2006 (71 FR 6858 (February 9, 2006)), make sense in light of OSHA's 
current regulation because OSHA's only beryllium protection is a PEL, 
so compliance with 10 CFR 851.23(a)(1) and (3) merely make OSHA's 
current PEL the relevant level for purposes of the CBDPP. However, its 
function would be less clear if OSHA adopts a beryllium standard as 
proposed. OSHA's proposed beryllium standard would establish additional 
substantive protections beyond the PEL. Consequently, notwithstanding 
the CBDPP's preemptive effect on the OSHA beryllium standard as a 
result of 29 U.S.C. 653(b)(1), 10 CFR 851.23(a)(3) could be read to 
require DOE contractors to comply with all provisions in OSHA's 
proposal (if finalized), including the ancillary provisions, creating a 
dual regulatory scheme for beryllium protection at DOE facilities.
    DOE officials have indicated that this is not their intent. 
Instead, their intent is that DOE contractors comply solely with the 
CBDPP provisions in 10 CFR part 850 for protection from beryllium.

[[Page 47577]]

Based on its discussions with DOE officials, OSHA anticipates that DOE 
will clarify that its contractors do not need to comply with any 
ancillary provisions in a beryllium standard that OSHA may promulgate.
    OSHA can envision several potential scenarios developing from its 
rulemaking, ranging from OSHA retaining the proposed PEL of 0.2 
[micro]g/m\3\ and action level of 0.1 [micro]g/m\3\ in the final rule 
to adopting the PEL of 0.1 [micro]g/m\3\, as discussed in alternative 
#4. Because OSHA's beryllium standard does not apply directly to DOE 
facilities, and the only impact of its rules on those facilities is the 
result of DOE's regulatory choices, there is also a range of actions 
that DOE could take to minimize any potential impact of any change to 
OSHA's rules, including (1) taking no action at all, (2) simply 
clarifying the CBDPP, as described above, to mean that OSHA's beryllium 
standard (other than its PEL) does not apply to contractors, or (3) 
revising both parts 850 and 851 to completely disassociate DOE's 
regulation of beryllium at DOE facilities from OSHA's regulation of 
beryllium.
    OSHA is aware that, in the preamble to its 1999 CBDPP rule, DOE 
analyzed the costs for implementing the CBDPP for action levels of 0.1 
[micro]g/m\3\, 0.2 [micro]g/m\3\, and 0.5 [micro]g/m\3\ (64 FR 68875, 
December 8, 1999). DOE estimated costs for periodic exposure 
monitoring, notifying workers of the results of such monitoring, 
exposure reduction and minimization, regulated areas, change rooms and 
showers, respiratory protection, protective clothing, and disposal of 
protective clothing. All of these provisions are triggered by DOE's 
action level (64 FR 68874, December 8, 1999). Although DOE's rule is 
not identical to OSHA's proposed standard, OSHA believes that DOE's 
costs are sufficiently representative to form the basis of a 
preliminary estimate of the costs that could flow from OSHA's standard, 
if finalized.
    Based on the range of potential scenarios and the prior DOE cost 
estimates, OSHA estimates that the annual cost impact on DOE facilities 
could range from $0 to $4,065,768 (2010 dollars). The upper end of the 
cost range would reflect the unlikely scenario in which OSHA 
promulgates a final PEL of 0.1 [micro]g/m\3\, 10 CFR 851.23(a)(3) is 
found to compel DOE contractors to comply with OSHA's comprehensive 
beryllium standard in addition to DOE's CBDPP, and DOE takes no action 
to clarify that OSHA's beryllium standard does not apply to DOE 
contractors. The lower end of the cost range assumes OSHA promulgates 
its rule as proposed with a PEL of 0.2 [micro]g/m\3\ and action level 
of 0.1 [micro]g/m\3\, and DOE clarifies that it intends its contractors 
to follow DOE's CBDPP and not OSHA's beryllium standard, so that the 
ancillary provisions of OSHA's beryllium standard do not apply to DOE 
facilities. Additionally, OSHA assumes that DOE contractors are in 
compliance with DOE's current rule and therefore took the difference in 
cost between implementation of an action level of 0.2 [micro]g/m\3\ and 
an action level of 0.1 [micro]g/m\3\ for the above estimates. Finally, 
OSHA used the GDP price deflator to present the cost estimate in 2010 
dollars.
    OSHA requests comment on the potential overlap of DOE's rule with 
OSHA's proposed rule.

II. Pertinent Legal Authority

    The purpose of the Occupational Safety and Health Act, 29 U.S.C. 
651 et seq. (``the Act''), is to ``. . . assure so far as possible 
every working man and woman in the nation safe and healthful working 
conditions and to preserve our human resources.'' 29 U.S.C. 651(b).
    To achieve this goal Congress authorized the Secretary of Labor 
(the Secretary) to promulgate and enforce occupational safety and 
health standards. 29 U.S.C. 654(b) (requiring employers to comply with 
OSHA standards), 655(a) (authorizing summary adoption of existing 
consensus and federal standards within two years of the Act's 
enactment), and 655(b) (authorizing promulgation, modification or 
revocation of standards pursuant to notice and comment).
    The Act provides that in promulgating health standards dealing with 
toxic materials or harmful physical agents, such as this proposed 
standard regulating occupational exposure to beryllium, the Secretary, 
shall set the standard which most adequately assures, to the extent 
feasible, on the basis of the best available evidence that no employee 
will suffer material impairment of health or functional capacity even 
if such employee has regular exposure to the hazard dealt with by such 
standard for the period of his working life. See 29 U.S.C. 655(b)(5).
    The Supreme Court has held that before the Secretary can promulgate 
any permanent health or safety standard, he must make a threshold 
finding that significant risk is present and that such risk can be 
eliminated or lessened by a change in practices. Industrial Union 
Dept., AFL-CIO v. American Petroleum Institute, 448 U.S. 607, 641-42 
(1980) (plurality opinion) (``The Benzene case''). Thus, section 
6(b)(5) of the Act requires health standards to reduce significant risk 
to the extent feasible. Id.
    The Court further observed that what constitutes ``significant 
risk'' is ``not a mathematical straitjacket'' and must be ``based 
largely on policy considerations.'' The Benzene case, 448 U.S. at 655. 
The Court gave the example that if,

    . . . the odds are one in a billion that a person will die from 
cancer . . . the risk clearly could not be considered significant. 
On the other hand, if the odds are one in one thousand that regular 
inhalation of gasoline vapors that are 2% benzene will be fatal, a 
reasonable person might well consider the risk significant. [Id.]

    OSHA standards must be both technologically and economically 
feasible. United Steelworkers v. Marshall, 647 F.2d 1189, 1264 (D.C. 
Cir. 1980) (``The Lead I case''). The Supreme Court has defined 
feasibility as ``capable of being done.'' Am. Textile Mfrs. Inst. v. 
Donovan, 452 U.S. 490, 509-510 (1981) (``The Cotton Dust case''). The 
courts have further clarified that a standard is technologically 
feasible if OSHA proves a reasonable possibility,

    . . . within the limits of the best available evidence . . . 
that the typical firm will be able to develop and install 
engineering and work practice controls that can meet the PEL in most 
of its operations. [See The Lead I case, 647 F.2d at 1272]

    With respect to economic feasibility, the courts have held that a 
standard is feasible if it does not threaten massive dislocation to or 
imperil the existence of the industry. Id. at 1265. A court must 
examine the cost of compliance with an OSHA standard,

    . . . in relation to the financial health and profitability of 
the industry and the likely effect of such costs on unit consumer 
prices . . . [T]he practical question is whether the standard 
threatens the competitive stability of an industry, . . . or whether 
any intra-industry or inter-industry discrimination in the standard 
might wreck such stability or lead to undue concentration. [Id. 
(citing Indus. Union Dep't, AFL-CIO v. Hodgson, 499 F.2d 467 (D.C. 
Cir. 1974))]

The courts have further observed that granting companies reasonable 
time to comply with new PELs may enhance economic feasibility. The Lead 
I case at 1265. While a standard must be economically feasible, the 
Supreme Court has held that a cost-benefit analysis of health standards 
is not required by the Act because a feasibility analysis is required. 
The Cotton Dust case, 453 U.S. at 509.

    Finally, sections 6(b)(7) and 8(c) of the Act authorize OSHA to 
include among a standard's requirements labeling, monitoring, medical 
testing, and other information-gathering and -transmittal provisions. 
29 U.S.C. 655(b)(7), 657(c).

[[Page 47578]]

III. Events Leading to the Proposed Standards

    The first occupational exposure limit for beryllium was set in 1949 
by the Atomic Energy Commission (AEC), which required that beryllium 
exposure in the workplaces under its jurisdiction be limited to 2 
[micro]g/m\3\ as an 8-hour time-weighted average (TWA), and 25 
[micro]g/m\3\ as a peak exposure never to be exceeded (Department of 
Energy, 1999). These exposure limits were adopted by all AEC 
installations handling beryllium, and were binding on all AEC 
contractors involved in the handling of beryllium.
    In 1956, the American Industrial Hygiene Association (AIHA) 
published a Hygienic Guide which supported the AEC exposure limits. In 
1959, the American Conference of Governmental Industrial Hygienists 
(ACGIH[supreg]) also adopted a Threshold Limit Value (TLV[supreg]) of 2 
[micro]g/m\3\ as an 8-hour TWA (Borak, 2006).
    In 1971, OSHA adopted, under Section 6(a) of the Occupational 
Safety and Health Act of 1970, and made applicable to general industry, 
a national consensus standard (ANSI Z37.29-1970) for beryllium and 
beryllium compounds. The standard set a permissible exposure limit 
(PEL) for beryllium and beryllium compounds at 2 [micro]g/m\3\ as an 8-
hour TWA; 5 [micro]g/m\3\ as an acceptable ceiling concentration; and 
25 [micro]g/m\3\ as an acceptable maximum peak above the acceptable 
ceiling concentration for a maximum duration of 30 minutes in an 8-hour 
shift (OSHA, 1971).
    Section 6(a) stipulated that in the first two years after the 
effective date of the Act, OSHA was to promulgate ``start-up'' 
standards, on an expedited basis and without public hearing or comment, 
based on national consensus or established Federal standards that 
improved employee safety or health. Pursuant to that authority, in 
1971, OSHA promulgated approximately 425 PELs for air contaminants, 
including beryllium, derived principally from Federal standards 
applicable to government contractors under the Walsh-Healey Public 
Contracts Act, 41 U.S.C. 35, and the Contract Work Hours and Safety 
Standards Act (commonly known as the Construction Safety Act), 40 
U.S.C. 333. The Walsh-Healey Act and Construction Safety Act standards, 
in turn, had been adopted primarily from ACGIH[supreg]'s TLV[supreg]s.
    The National Institute for Occupational Safety and Health (NIOSH) 
issued a document entitled Criteria for a Recommended Standard: 
Occupational Exposure to Beryllium (Criteria Document) in June 1972. 
OSHA reviewed the findings and recommendations contained in the 
Criteria Document along with the AEC control requirements for beryllium 
exposure. OSHA also considered existing data from animal and 
epidemiological studies, and studies of industrial processes of 
beryllium extraction, refinement, fabrication, and machining. In 1975, 
OSHA asked NIOSH to update the evaluation of the existing data 
pertaining to the carcinogenic potential of beryllium. In response to 
OSHA's request, the Director of NIOSH stated that, based on animal data 
and through all possible routes of exposure including inhalation, 
``beryllium in all likelihood represents a carcinogenic risk to man.''
    In October 1975, OSHA proposed a new beryllium standard for all 
industries based on information that beryllium caused cancer in animal 
experiments (40 FR 48814 (October 17, 1975)). Adoption of this proposal 
would have lowered the 8-hour TWA exposure limit from 2 [micro]g/m\3\ 
to 1 [micro]g/m\3\. In addition, the proposal included ancillary 
provisions for such topics as exposure monitoring, hygiene facilities, 
medical surveillance, and training related to the health hazards from 
beryllium exposure. The rulemaking was never completed.
    In 1977, NIOSH recommended an exposure limit of 0.5 [micro]g/m\3\ 
and identified beryllium as a potential occupational carcinogen. In 
December 1998, ACGIH published a Notice of Intended Change for its 
beryllium exposure limit. The notice proposed a lower TLV of 0.2 
[micro]g/m\3\ over an 8-hour TWA based on evidence of CBD and 
sensitization in exposed workers.
    In 1999, the Department of Energy (DOE) issued a Chronic Beryllium 
Disease Prevention Program (CBDPP) Final Rule for employees exposed to 
beryllium in its facilities (DOE, 1999). The DOE rule set an action 
level of 0.2 [mu]g/m\3\, and adopted OSHA's PEL of 2 [mu]g/m\3\ or any 
more stringent PEL OSHA might adopt in the future. The DOE action level 
triggers workplace precautions and control measures such as periodic 
monitoring, exposure reduction or minimization, regulated areas, 
hygiene facilities and practices, respiratory protection, protective 
clothing and equipment, and warning signs (DOE, 1999).
    Also in 1999, OSHA was petitioned by the Paper, Allied-Industrial, 
Chemical and Energy Workers International Union (PACE) (OSHA, 2002) and 
by Dr. Lee Newman and Ms. Margaret Mroz, from the National Jewish 
Medical Research Center (NJMRC) (OSHA, 2002), to promulgate an 
Emergency Temporary Standard (ETS) for beryllium in the workplace. In 
2001, OSHA was petitioned for an ETS by Public Citizen Health Research 
Group and again by PACE (OSHA, 2002). In order to promulgate an ETS, 
the Secretary of Labor must prove (1) that employees are exposed to 
grave danger from exposure to a hazard, and (2) that such an emergency 
standard is necessary to protect employees from such danger (29 U.S.C. 
655(c)). The burden of proof is on the Department and because of the 
difficulty of meeting this burden, the Department usually proceeds when 
appropriate with 6(b) rulemaking rather than a 6(c) ETS. Thus, instead 
of granting the ETS requests, OSHA instructed staff to further collect 
and analyze research regarding the harmful effects of beryllium.
    On November 26, 2002, OSHA published a Request for Information 
(RFI) for ``Occupational Exposure to Beryllium'' (OSHA, 2002). The RFI 
contained questions on employee exposure, health effects, risk 
assessment, exposure assessment and monitoring methods, control 
measures and technological feasibility, training, medical surveillance, 
and impact on small business entities. In the RFI, OSHA expressed 
concerns about health effects such as CBD, lung cancer, and beryllium 
sensitization. OSHA pointed to studies indicating that even short-term 
exposures below OSHA's PEL of 2 [micro]g/m\3\ could lead to CBD. The 
RFI also cited studies describing the relationship between beryllium 
sensitization and CBD (67 FR at 70708). In addition, OSHA stated that 
beryllium had been identified as a carcinogen by organizations such as 
NIOSH, the International Agency for Research on Cancer (IARC), and the 
Environmental Protection Agency (EPA); and cancer had been evidenced in 
animal studies (67 FR at 70709).
    On November 15, 2007, OSHA convened a Small Business Advocacy 
Review Panel for a draft proposed standard for occupational exposure to 
beryllium. OSHA convened this panel under Section 609(b) of the 
Regulatory Flexibility Act (RFA), as amended by the Small Business 
Regulatory Enforcement Fairness Act of 1996 (SBREFA) (5 U.S.C. 601 et 
seq.).
    The Panel included representatives from OSHA, the Solicitor's 
Office of the Department of Labor, the Office of Advocacy within the 
Small Business Administration, and the Office of Information and 
Regulatory Affairs of the Office of Management and Budget. Small Entity 
Representatives (SERs) made oral and written comments on the

[[Page 47579]]

draft rule and submitted them to the panel.
    The SBREFA Panel issued a report which included the SERs' comments 
on January 15, 2008. SERs expressed concerns about the impact of the 
ancillary requirements such as exposure monitoring and medical 
surveillance. Their comments addressed potential costs associated with 
compliance with the draft standard, and possible impacts of the 
standard on market conditions, among other issues. In addition, many 
SERs sought clarification of some of the ancillary requirements such as 
the meaning of ``routine'' contact or ``contaminated surfaces.''
    The SBREFA Panel issued a number of recommendations, which OSHA 
carefully considered. In section XVIII of this preamble, Summary and 
Explanation, OSHA has responded to the Panel's recommendations and 
clarified the requirements about which SERs expressed confusion. OSHA 
also examined the regulatory alternatives recommended by the SBREFA 
Panel. The regulatory alternatives examined by OSHA are listed in 
section I of this preamble, Issues and Alternatives. The alternatives 
are discussed in greater detail in section XVIII of this preamble, 
Summary and Explanation, and in the PEA (OSHA, 2014). In addition, the 
Agency intends to develop interpretive guidance documents following the 
publication of a final rule.
    In 2010, OSHA hired a contractor to oversee an independent 
scientific peer review of a draft preliminary beryllium health effects 
evaluation (OSHA, 2010a) and a draft preliminary beryllium risk 
assessment (OSHA, 2010b). The contractor identified experts familiar 
with beryllium health effects research and ensured that these experts 
had no conflict of interest or apparent bias in performing the review. 
The contractor selected five experts with expertise in such areas as 
pulmonary and occupational medicine, CBD, beryllium sensitization, the 
BeLPT, beryllium toxicity and carcinogenicity, and medical 
surveillance. Other areas of expertise included animal modeling, 
occupational epidemiology, biostatistics, risk and exposure assessment, 
exposure-response modeling, beryllium exposure assessment, industrial 
hygiene, and occupational/environmental health engineering.
    Regarding the health effects evaluation, the peer reviewers 
concluded that the health effect studies were described accurately and 
in sufficient detail, and OSHA's conclusions based on the studies were 
reasonable. The reviewers agreed that the OSHA document covered the 
significant health endpoints related to occupational beryllium 
exposure. Peer reviewers considered the preliminary conclusions 
regarding beryllium sensitization and CBD to be reasonable and well 
presented in the draft health evaluation section. All reviewers agreed 
that the scientific evidence supports sensitization as a necessary 
condition in the development of CBD. In response to reviewers' 
comments, OSHA made revisions to more clearly describe certain sections 
of the health effects evaluation. In addition, OSHA expanded its 
discussion regarding the BeLPT.
    Regarding the preliminary risk assessment, the peer reviewers were 
highly supportive of the Agency's approach and major conclusions. The 
peer reviewers stated that the key studies were appropriate and their 
selection clearly explained in the document. They regarded the 
preliminary analysis of these studies to be reasonable and 
scientifically sound. The reviewers supported OSHA's conclusion that 
substantial risk of sensitization and CBD were observed in facilities 
where the highest exposure generating processes had median full-shift 
exposures around 0.2 [micro]g/m\3\ or higher, and that the greatest 
reduction in risk was achieved when exposures for all processes were 
lowered to 0.1 [micro]g/m\3\ or below.
    In February 2012 the Agency received for consideration a draft 
recommended standard for beryllium (Materion and USW, 2012). This draft 
proposal was the product of a joint effort between two stakeholders: 
Materion Corporation, a leading producer of beryllium and beryllium 
products in the United States, and the United Steelworkers, an 
international labor union representing workers who manufacture 
beryllium alloys and beryllium-containing products in a number of 
industries. The United Steelworkers and Materion sought to craft an 
OSHA-like model beryllium standard that would have support from both 
labor and industry. OSHA has considered this proposal along with other 
information submitted during the development of the Notice of Proposed 
Rulemaking for beryllium.

IV. Chemical Properties and Industrial Uses

Chemical and Physical Properties

    Beryllium (Be; CAS Number 7440-41-7) is a silver-grey to greyish-
white, strong, lightweight, and brittle metal. It is a Group IIA 
element with an atomic weight of 9.01, atomic number of 4, melting 
point of 1,287 [deg]C, boiling point of 2,970[deg]C, and a density of 
1.85 at 20 [deg]C (NTP 2014). It occurs naturally in rocks, soil, coal, 
and volcanic dust (ATSDR, 2002). Beryllium is insoluble in water and 
soluble in acids and alkalis. It has two common oxidation states, Be(0) 
and Be(+2). There are several beryllium compounds with unique CAS 
numbers and chemical and physical properties. Table IV-1 describes the 
most common beryllium compounds.

                                              Table IV--1, Properties of Beryllium and Beryllium Compounds
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                Synonyms and     Molecular     Melting point
         Chemical name            CAS No.       trade names        weight        ([deg]C)         Description    Density  (g/cm3)        Solubility
--------------------------------------------------------------------------------------------------------------------------------------------------------
Beryllium metal...............    7440-41-7  Beryllium;              9.0122  1287............  Grey, close-      1.85 (20 [deg]C)  Soluble in most
                                              beryllium-9,                                      packed,                             dilute acids and
                                              beryllium                                         hexagonal,                          alkali; decomposes
                                              element;                                          brittle metal.                      in hot water;
                                              beryllium                                                                             insoluble in mercury
                                              metallic.                                                                             and cold water.
Beryllium chloride............    7787-47-5  Beryllium              79.92    399.2...........  Colorless to      1.899 (25         Soluble in water,
                                              dichloride.                                       slightly          [deg]C).          ethanol, diethyl
                                                                                                yellow;                             ether and pyridine;
                                                                                                orthorhombic,                       slightly soluble in
                                                                                                deliquescent                        benzene, carbon
                                                                                                crystal.                            disulfide and
                                                                                                                                    chloroform;
                                                                                                                                    insoluble in
                                                                                                                                    acetone, ammonia,
                                                                                                                                    and toluene.

[[Page 47580]]

 
Beryllium fluoride............    7787-49-7  Beryllium              47.01    555.............  Colorless or      1.986...........  Soluble in water,
                                (12323-05-6   difluoride.                                       white,                              sulfuric acid,
                                          )                                                     amorphous,                          mixture of ethanol
                                                                                                hygroscopic                         and diethyl ether;
                                                                                                solid.                              slightly soluble in
                                                                                                                                    ethanol; insoluble
                                                                                                                                    in hydrofluoric
                                                                                                                                    acid.
Beryllium hydroxide...........   13327-32-7  Beryllium              43.3     138 (decomposes   White,            1.92............  Soluble in hot
                                (1304-49-0)   dihydroxide.                    to beryllium      amorphous,                          concentrated acids
                                                                              oxide).           amphoteric                          and alkali; slightly
                                                                                                powder.                             soluble in dilute
                                                                                                                                    alkali; insoluble in
                                                                                                                                    water.
Beryllium sulfate.............   13510-49-1  Sulfuric acid,        105.07    550-600 [deg]C    Colorless         2.443...........  Forms soluble
                                              beryllium salt                  (decomposes to    crystal.                            tetrahydrate in hot
                                              (1:1).                          beryllium                                             water; insoluble in
                                                                              oxide).                                               cold water.
Beryllium sulfate tetrhydrate.    7787-56-6  Sulfuric acid;        177.14    100 [deg]C......  Colorless,        1.713...........  Soluble in water;
                                              beryllium salt                                    tetragonal                          slightly soluble in
                                              (1:1),                                            crystal.                            concentrated
                                              tetrahydrate.                                                                         sulfuric acid;
                                                                                                                                    insoluble in
                                                                                                                                    ethanol.
Beryllium Oxide...............    1304-56-9  Beryllia;              25.01    2508-2547 [deg]C  Colorless to      3.01 (20 [deg]C)  Soluble in
                                              beryllium                                         white,                              concentrated acids
                                              monoxide                                          hexagonal                           and alkali;
                                              thermalox TM.                                     crystal or                          insoluble in water.
                                                                                                amorphous,
                                                                                                amphoteric
                                                                                                powder.
Beryllium carbonate...........    1319-43-3  Carbonic acid,        112.05    No data.........  White powder....  No data.........  Soluble in acids and
                                              beryllium salt,                                                                       alkali; insoluble in
                                              mixture with                                                                          cold water;
                                              beryllium                                                                             decomposes in hot
                                              hydroxide.                                                                            water.
Beryllium nitrate trihydrate..    7787-55-5  Nitric acid,          187.97    60..............  White to faintly  1.56............  Very soluble in water
                                              beryllium salt,                                   yellowish,                          and ethanol.
                                              trihydrate.                                       deliquescent
                                                                                                mass.
Beryllium phosphate...........   13598-15-7  Phosphoric acid,      104.99    No data.........  Not reported....  Not reported....  Slightly soluble in
                                              beryllium salt                                                                        water.
                                              (1:1).
--------------------------------------------------------------------------------------------------------------------------------------------------------
ATSDR, 2002.

    The physical and chemical properties of beryllium were realized 
early in the 20th century, and it has since gained commercial 
importance in a wide range of industries. Beryllium is lightweight, 
hard, spark resistant, non-magnetic, and has a high melting point. It 
lends strength, electrical and thermal conductivity, and fatigue 
resistance to alloys (NTP, 2014). Beryllium also has a high affinity 
for oxygen in air and water, which can cause a thin surface film of 
beryllium oxide to form on the bare metal, making it extremely 
resistant to corrosion. These properties make beryllium alloys highly 
suitable for defense, nuclear, and aerospace applications (IARC, 1993).
    There are approximately 45 mineralized forms of beryllium. In the 
United States, the predominant mineral form mined commercially and 
refined into pure beryllium and beryllium alloys is bertrandite. 
Bertrandite, while containing less than 1% beryllium compared to 4% in 
beryl, is easily and efficiently processed into beryllium hydroxide 
(IARC, 1993). Imported beryl is also converted into beryllium hydroxide 
as the United States has very little beryl that can be economically 
mined (USGS, 2013a).

Industrial Uses

    Materion Corporation, formerly called Brush Wellman, is the only 
producer of primary beryllium in the United States. Beryllium is used 
in a variety of industries, including aerospace, defense, 
telecommunications, automotive, electronic, and medical specialty 
industries. Pure beryllium metal is used in a range of products such as 
X-ray transmission windows, nuclear reactor neutron reflectors, nuclear 
weapons, precision instruments, rocket propellants, mirrors, and 
computers (NTP, 2014). Beryllium oxide is used in components such as 
ceramics, electrical insulators, microwave oven components, military 
vehicle armor, laser structural components, and automotive ignition 
systems (ATSDR, 2002). Beryllium oxide ceramics are used to produce 
sensitive electronic items such as lasers and satellite heat sinks.
    Beryllium alloys, typically beryllium/copper or beryllium/aluminum, 
are manufactured as high beryllium content or low beryllium content 
alloys. High content alloys contain greater than 30% beryllium. Low 
content alloys are typically less than 3% beryllium. Beryllium alloys 
are used in automotive electronics (e.g., electrical connectors and 
relays and audio components), computer components, home appliance 
parts, dental appliances (e.g., crowns), bicycle frames, golf clubs, 
and other articles (NTP, 2014; Ballance et al., 1978; Cunningham et 
al., 1998; Mroz, et al., 2001). Electrical components and conductors 
are stamped and formed from beryllium alloys. Beryllium-copper

[[Page 47581]]

alloys are used to make switches in automobiles (Ballance et al., 1978, 
2002; Cunningham et al., 1998) and connectors, relays, and switches in 
computers, radar, satellite, and telecommunications equipment (Mroz et 
al., 2001). Beryllium-aluminum alloys are used in the construction of 
aircraft, high resolution medical and industrial X-ray equipment, and 
mirrors to measure weather patterns (Mroz et al., 2001). High content 
and low content beryllium alloys are precision machined for military 
and aerospace applications. Some welding consumables are also 
manufactured using beryllium.
    Beryllium is also found as a trace metal in materials such as 
aluminum ore, abrasive blasting grit, and coal fly ash. Abrasive 
blasting grits such as coal slag and copper slag contain varying 
concentrations of beryllium, usually less than 0.1% by weight. The 
burning of bituminous and sub-bituminous coal for power generation 
causes the naturally occurring beryllium in coal to accumulate in the 
coal fly ash byproduct. Scrap and waste metal for smelting and refining 
may also contain beryllium. A detailed discussion of the industries and 
job tasks using beryllium is included in the Preliminary Economic 
Analysis (OSHA, 2014).
    Occupational exposure to beryllium can occur from inhalation of 
dusts, fume, and mist. Beryllium dusts are created during operations 
where beryllium is cut, machined, crushed, ground, or otherwise 
mechanically sheared. Mists can also form during operations that use 
machining fluids. Beryllium fume can form while welding with or on 
beryllium components, and from hot processes such as those found in 
metal foundries.
    Occupational exposure to beryllium can also occur from skin, eye, 
and mucous membrane contact with beryllium particulate or solutions.

V. Health Effects

    Beryllium-associated health effects, including acute beryllium 
disease (ABD), beryllium sensitization (also referred to in this 
preamble as ``sensitization''), chronic beryllium disease (CBD), and 
lung cancer, can lead to a number of highly debilitating and life-
altering conditions including pneumonitis, loss of lung capacity 
(reduction in pulmonary function leading to pulmonary dysfunction), 
loss of physical capacity associated with reduced lung capacity, 
systemic effects related to pulmonary dysfunction, and decreased life 
expectancy (NIOSH, 1972).
    This Health Effects section presents information on beryllium and 
its compounds, the fate of beryllium in the body, research that relates 
to its toxic mechanisms of action, and the scientific literature on the 
adverse health effects associated with beryllium exposure, including 
ABD, sensitization, CBD, and lung cancer. OSHA considers CBD to be a 
progressive illness with a continuous spectrum of symptoms ranging from 
no symptomatology at its earliest stage following sensitization to mild 
symptoms such as a slight almost imperceptible shortness of breath, to 
loss of pulmonary function, debilitating lung disease, and, in many 
cases, death. This section also discusses the nature of these 
illnesses, the scientific evidence that they are causally associated 
with occupational exposure to beryllium, and the probable mechanisms of 
action with a more thorough review of the supporting studies.

A. Beryllium and Beryllium Compounds

1. Particle Physical/Chemical Properties
    Beryllium (Be; CAS No. 7440-41-7) is a steel-grey, brittle metal 
with an atomic number of 4 and an atomic weight of 9.01 (Group IIA of 
the periodic table). Because of its high reactivity, beryllium is not 
found as a free metal in nature; however, there are approximately 45 
mineralized forms of beryllium. Beryllium compounds and alloys include 
commercially valuable metals and gemstones.
    Beryllium has two oxidative states: Be(0) and Be(2\+\) Agency for 
Toxic Substance and Disease Registry (ATSDR) 2002). It is likely that 
the Be(2\+\) state is the most biologically reactive and able to form a 
bond with peptides leading to it becoming antigenic (Snyder et al., 
2003). This will be discussed in more detail in the Beryllium 
Sensitization section below. Beryllium has a high charge-to-radius 
ratio and in addition to forming various types of ionic bonds, 
beryllium has a strong tendency for covalent bond formation (e.g., it 
can form organometallic compounds such as 
Be(CH3)2 and many other complexes) (ATSDR, 2002; 
Greene et al., 1998). However, it appears that few, if any, toxicity 
studies exist for the organometallic compounds. Additional physical/
chemical properties for beryllium compounds that may be important in 
their biological response are summarized in Table 1 below. This 
information was obtained from their International Chemical Safety Cards 
(ICSC) (beryllium metal (ICSC 0226), beryllium oxide (ICSC 1325), 
beryllium sulfate (ICSC 1351), beryllium nitrate (ICSC 1352), beryllium 
carbonate (ICSC 1353), beryllium chloride (ICSC 1354), beryllium 
fluoride (ICSC 1355)) and from the hazardous substance data bank (HSDB) 
for beryllium hydroxide (CASRN: 13327-32-7), and beryllium phosphate 
(CASRN: 13598-15-7). Additional information on chemical and physical 
properties as well as industrial uses for beryllium can be found in 
this preamble at Section IV, Chemical Properties and Industrial Uses.

                                            Table 1--Physical/Chemical Properties of Beryllium and Compounds
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                  Solubility in water at
           Compound name              Physical  appearance      Chemical formula     Molecular mass     Acute physical hazards           20 [deg]C
--------------------------------------------------------------------------------------------------------------------------------------------------------
Beryllium Metal....................  Grey to White Powder..  Be....................             9.0  Combustible; Finely          None.
                                                                                                      dispersed particles--
                                                                                                      Explosive.
Beryllium Oxide....................  White Crystals or       BeO...................            25.0  Not combustible or           Very sparingly
                                      Powder.                                                         explosive.                   soluble.
Beryllium Carbonate................  White Powder..........  Be2CO3(OH)/Be2CO5H2...          181.07  Not combustible or           None.
                                                                                                      explosive.
Beryllium Sulfate..................  Colorless Crystals....  BeSO4.................           105.1  Not combustible or           Slightly soluble.
                                                                                                      explosive.
Beryllium Nitrate..................  White to Yellow Solid.  BeN2O6/Be(NO3)2.......           133.0  Enhances combustion of       Very soluble (1.66 x
                                                                                                      other substances.            10\6\ mg/L).
Beryllium Hydroxide................  White amorphous powder  Be(OH)2...............            43.0  Not reported...............  Slightly soluble 0.8 x
                                      or crystalline solid.                                                                        10-4 mol/L
                                                                                                                                  (3.44 mg/L).
Beryllium Chloride.................  Colorless to Yellow     BeCl2.................            79.9  Not combustible or           Soluble.
                                      Crystals.                                                       explosive.
Beryllium Fluoride.................  Colorless Lumps.......  BeF2..................            47.0  Not combustible or           Very soluble.
                                                                                                      explosive.

[[Page 47582]]

 
Beryllium Phosphate................  White solid...........  Be3(PO4)2.............           271.0  Not reported...............  Soluble.
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: International Chemical Safety Cards (except beryllium phosphate and hydroxide--HSDB).

    Beryllium shows a high affinity for oxygen in air and water, 
resulting in a thin surface film of beryllium oxide on the bare metal. 
If the surface film is disturbed, it may become airborne or dermal 
exposure may occur. The solubility, particle surface area, and particle 
size of some beryllium compounds are examined in more detail below. 
These properties have been evaluated in many toxicological studies. In 
particular, the properties related to the calcination (firing 
temperatures) and differences in crystal size and solubility are 
important aspects in their toxicological profile.
2. Factors Affecting Potency and Effect of Beryllium Exposure
    The effect and potency of beryllium and its compounds, as for any 
toxicant, immunogen, or immunotoxicant, may be dependent upon the 
physical state in which they are presented to a host. For occupational 
airborne materials and surface contaminants, it is especially critical 
to understand those physical parameters in order to determine the 
extent of exposure to the respiratory tract and skin since these are 
generally the initial target organs for either route of exposure.
    For example, large particles may have less of an effect in the lung 
than smaller particles due to reduced potential to stay airborne to be 
inhaled or be deposited along the respiratory tract. In addition, once 
inhalation occurs particle size is critical in determining where the 
particle will deposit along the respiratory tract. Solubility also has 
an important part in determining the toxicity and bioavailability of 
airborne materials as well. Respiratory tract retention and skin 
penetration are directly influenced by the solubility and reactivity of 
airborne material.
    These factors may be responsible, at least in part, for the process 
by which beryllium sensitization progresses to CBD in exposed workers. 
Other factors influencing beryllium-induced toxicity include the 
surface area of beryllium particles and their persistence in the lung. 
With respect to dermal exposure, the physical characteristics of the 
particle are important as well since they can influence skin absorption 
and bioavailability. This section addresses certain physical 
characteristics (i.e., solubility, particle size, particle surface 
area) that are important in influencing the toxicity of beryllium 
materials in occupational settings.
a. Solubility
    Solubility may be an important determinant of the toxicity of 
airborne materials, influencing the deposition and persistence of 
inhaled particles in the respiratory tract, their bioavailability, and 
the likelihood of presentation to the immune system. A number of 
chemical agents, including metals that contact and penetrate the skin, 
are able to induce an immune response, such as sensitization (Boeniger, 
2003; Mandervelt et al., 1997). Similar to inhaled agents, the ability 
of materials to penetrate the skin is also influenced by solubility 
since dermal absorption may occur at a greater rate for soluble 
materials than insoluble materials (Kimber et al., 2011).
    This section reviews the relevant information regarding solubility, 
its importance in a biological matrix and its relevance to 
sensitization and beryllium lung disease. The weight of evidence 
presented below suggests that both soluble and non-soluble forms of 
beryllium can induce a sensitization response and result in progression 
of lung disease.
    Beryllium salts, including the chloride (BeCl2), 
fluoride (BeF2), nitrate (Be(NO3)2), 
phosphate (Be3(PO4)2), and sulfate 
(tetrahydrate) (BeSO4 [middot] 4H2O) salts, are 
all water soluble. However, soluble beryllium salts can be converted to 
less soluble forms in the lung (Reeves and Vorwald, 1967). Aqueous 
solutions of the soluble beryllium salts are acidic as a result of the 
formation of Be(OH2)4 2\+\, the tetrahydrate, 
which will react to form insoluble hydroxides or hydrated complexes 
within the general physiological range of pH values (between 5 and 8) 
(EPA, 1998). This may be an important factor in the development of CBD 
since lower-solubility forms of beryllium have been shown to persist in 
the lung for longer periods of time and persistence in the lung may be 
needed in order for this disease to occur (NAS, 2008).
    Beryllium oxide (BeO), hydroxide (Be(OH)2), carbonate 
(Be2CO3(OH)2), and sulfate (anhydrous) 
(BeSO4) are either insoluble, slightly soluble, or 
considered to be sparingly soluble (almost insoluble or having an 
extremely slow rate of dissolution). The solubility of beryllium oxide, 
which is prepared from beryllium hydroxide by calcining (heating to a 
high temperature without fusing in order to drive off volatile 
chemicals) at temperatures between 500 and 1,750 [deg]C, has an inverse 
relationship with calcination temperature. Although the solubility of 
the low-fired crystals can be as much as 10 times that of the high-
fired crystals, low-fired beryllium oxide is still only sparingly 
soluble (Delic, 1992). In a study that measured the dissolution 
kinetics (rate to dissolve) of beryllium compounds calcined at 
different temperatures, Hoover et al., compared beryllium metal to 
beryllium oxide particles and found them to have similar solubilities. 
This was attributed to a fine layer of beryllium oxide that coats the 
metal particles (Hoover et al., 1989). A study conducted by Deubner et 
al., (2011) determined ore materials to be more soluble than beryllium 
oxide at pH 7.2 but similar in solubility at pH 4.5. Beryllium 
hydroxide was more soluble than beryllium oxide at both pHs (Deubner et 
al., 2011).
    Investigators have also attempted to determine how biological 
fluids can dissolve beryllium materials. In two studies, insoluble 
beryllium, taken up by activated phagocytes, was shown to be ionized by 
myeloperoxidases (Leonard and Lauwerys, 1987; Lansdown, 1995). The 
positive charge resulting from ionization enabled the beryllium to bind 
to receptors on the surface of cells such as lymphocytes or antigen-
presenting cells which could make it more biologically active (NAS, 
2008). In a study utilizing phagolysosomal-simulating fluid (PSF) with 
a pH of 4.5, both beryllium metal and beryllium oxide dissolved at a 
greater rate than that previously reported in water or SUF (simulant 
fluid) (Stefaniak et al., 2006), and the rate of dissolution of the 
multi-constituent (mixed) particles was greater than that of the 
single-constituent beryllium oxide powder. The authors speculated that 
copper in the particles rapidly dissolves, exposing the small 
inclusions of beryllium oxide, which have higher specific surface areas 
(SSA)

[[Page 47583]]

and therefore dissolve at a higher rate. A follow-up study by the same 
investigational team (Duling et al., 2012) confirmed dissolution of 
beryllium oxide by PSF and determined the release rate was biphasic 
(initial rapid diffusion followed by a latter slower surface reaction-
driven release). During the latter phase, dissolution half-times were 
1,400 to 2,000 days. The authors speculated this indicated bertrandite 
was persistent in the lung (Duling et al., 2012).
    In a recent study investigating the dissolution and release of 
beryllium ions for 17 beryllium-containing materials (ore, hydroxide, 
metal, oxide, alloys, and processing intermediates) using artificial 
human airway epithelial lining fluid, Stefaniak et al., (2011) found 
release of beryllium ions within 7 days (beryl ore melter dust). The 
authors calculated dissolution half-times ranging from 30 days 
(reduction furnace material) to 74,000 days (hydroxide). Stefaniak et 
al., (2011) speculated that despite the rapid mechanical clearance, 
billions of beryllium ions could be released in the respiratory tract 
via dissolution in airway lining fluid (ALF). Under this scenario 
beryllium-containing particles depositing in the respiratory tract 
dissolving in ALF could provide beryllium ions for absorption in the 
lung and interact with immune cells in the respiratory tract (Stefaniak 
et al., 2011).
    Huang et al., (2011) investigated the effect of simulated lung 
fluid (SLF) on dissolution and nanoparticle generation and beryllium-
containing materials. Bertrandite-containing ore, beryl-containing ore, 
frit (a processing intermediate), beryllium hydroxide (a processing 
intermediate) and silica (used as a control), were equilibrated in SLF 
at two pH values (4.5 and 7.2) to reflect inter- and intra-cellular 
environments in the lung tissue. Concentrations of beryllium, aluminum, 
and silica ions increased linearly during the first 20 days in SLF, 
rose slowly thereafter, reaching equilibrium over time. The study also 
found nanoparticle formation (in the size range of 10-100 nm) for all 
materials (Huang et al., 2011).
    In an in vitro skin model, Sutton et al., (2003) demonstrated the 
dissolution of beryllium compounds (insoluble beryllium hydroxide, 
soluble beryllium phosphate) in a simulated sweat fluid. This model 
showed beryllium can be dissolved in biological fluids and be available 
for cellular uptake in the skin. Duling et al., (2012) confirmed 
dissolution and release of ions from bertrandite ore in an artificial 
sweat model (pH 5.3 and pH 6.5).
b. Particle Size
    The toxicity of beryllium as exemplified by beryllium oxide also is 
dependent, in part, on the particle size, with smaller particles (<10 
[mu]m) able to penetrate beyond the larynx (Stefaniak et al., 2008). 
Most inhalation studies and occupational exposures involve quite small 
(<1-2 [mu]m) beryllium oxide particles that can penetrate to the 
pulmonary regions of the lung (Stefaniak et al., 2008). In inhalation 
studies with beryllium ores, particle sizes are generally much larger, 
with deposition occurring in several areas throughout the respiratory 
tract for particles <10 [mu]m.
    The temperature at which beryllium oxide is calcined influences its 
particle size, surface area, solubility, and ultimately its toxicity 
(Delic, 1992). Low-fired (500 [deg]C) beryllium oxide is predominantly 
made up of poorly crystallized small particles, while higher firing 
temperatures (1000--1750 [deg]C) result in larger particle sizes 
(Delic, 1992).
    In order to determine the extent to which particle size plays a 
role in the toxicity of beryllium in occupational settings, several key 
studies are reviewed and detailed below. The findings on particle size 
have been related, where possible, to work process and biologically 
relevant toxicity endpoints of either sensitization or CBD.
    Numerous studies have been conducted evaluating the particle size 
generated during basic industrial and machining operations. In a study 
by Cohen et al., (1983), a multi-cyclone sampler was utilized to 
measure the size mass distribution of the beryllium aerosol at a 
beryllium-copper alloy casting operation. Briefly, Cohen et al., (1983) 
found variable particle size generation based on the operations being 
sampled with particle size ranging from 3 to 16 [mu]m. Hoover et al., 
(1990) also found variable particle sizes being generated based on 
operations. In general, Hoover et al., (1990) found that milling 
operations generated smaller particle sizes than sawing operations. 
Hoover et al., (1990) also found that beryllium metal generated higher 
concentrations than metal alloys. Martyny et al., (2000) characterized 
generation of particle size during precision beryllium machining 
processes. The study found that more than 50 percent of the beryllium 
machining particles collected in the breathing zone of machinists were 
less than 10 [mu]m in aerodynamic diameter with 30 percent of that 
fraction being particles of less than 0.6 [mu]m. A study by Thorat et 
al., (2003) found similar results with ore mixing, crushing, powder 
production and machining ranging from 5.0 to 9.5 [mu]m. Kent et al., 
(2001) measured airborne beryllium using size-selective samplers in 
five furnace areas at a beryllium processing facility. A statistically 
significant linear trend was reported between the above alveolar-
deposited particle mass concentration and prevalence of CBD and 
sensitization in the furnace production areas. The study authors 
suggested that the concentration of alveolar-deposited particles (e.g., 
<3.5 [mu]m) may be a better predictor of sensitization and CBD than the 
total mass concentration of airborne beryllium.
    A recent study by Virji et al. (2011) evaluated particle size 
distribution, chemistry and solubility in areas with historically 
elevated risk of sensitization and CBD at a beryllium metal powder, 
beryllium oxide, and alloy production facility. The investigators 
observed that historically, exposure-response relationships have been 
inconsistent when using mass concentration to identify process-related 
risk, possibly due to incomplete particle characterization. Two 
separate exposure surveys were conducted in March 1999 and June-August 
1999 using multi-stage personal impactor samplers (to determine 
particle size distribution) and personal 37 mm closed face cassette 
(CFC) samplers, both located in workers' breathing zones. One hundred 
and ninety eight time-weighted-average (TWA) personal impactor samples 
were analyzed for representative jobs and processes. A total of 4,026 
CFC samples were collected over the 5-month collection period and 
analyzed for mass concentration, particle size, chemical content and 
solubility and compared to process areas with high risk of 
sensitization and CBD. The investigators found that total beryllium 
concentration varied greatly between workers and among process areas. 
Analysis of chemical form and solubility also revealed wide variability 
among process areas, but high risk process areas had exposures to both 
soluble and insoluble forms of beryllium. Analysis of particle size 
revealed most process areas had particles ranging from 5-14 [micro]m 
mass median aerodynamic diameter (MMAD). Rank order correlating jobs to 
particle size showed high overall consistency (Spearman r=0.84) but 
moderate correlation (Pearson r=0.43). The investigators concluded that 
consideration of relevant aspects of exposure such as particle size

[[Page 47584]]

distribution, chemical form, and solubility will likely improve 
exposure assessments (Virji et al., 2011)
c. Particle Surface Area.
    Particle surface area has been postulated as an important metric 
for beryllium exposure. Several studies have demonstrated a 
relationship between the inflammatory and tumorigenic potential of 
ultrafine particles and their increased surface area (Driscoll, 1996; 
Miller, 1995; Oberdorster et al., 1996). While the exact mechanism 
explaining how particle surface area influences its biological activity 
is not known, a greater particle surface area has been shown to 
increase inflammation, cytokine production, anti-oxidant defenses and 
apoptosis (Elder et al., 2005; Carter et al., 2006; Refsne et al., 
2006).
    Finch et al., (1988) found that beryllium oxide calcined at 500 
[deg]C had 3.3 times greater specific surface area (SSA) than beryllium 
oxide calcined at 1000 [deg]C, although there was no difference in size 
or structure of the particles as a function of calcining temperature. 
The beryllium-metal aerosol (airborne beryllium particles), although 
similar to the beryllium oxide aerosols in aerodynamic size, had an SSA 
about 30 percent that of the beryllium oxide calcined at 1000 [deg]C. 
As discussed above, a later study by Delic (1992) found calcining 
temperatures had an effect on SSA as well as particle size.
    Several studies have investigated the lung toxicity of beryllium 
oxide calcined at different temperatures and generally had found that 
those calcined at lower temperatures have greater toxicity and effect 
than materials calcined at higher temperatures. This may be because 
beryllium oxide fired at the lower temperature has a loosely formed 
crystalline structure with greater specific surface area than the fused 
crystal structure of beryllium oxide fired at the higher temperature. 
For example, beryllium oxide calcined at 500 [deg]C has been found to 
have stronger pathogenic effects than material calcined at 1,000 
[deg]C, as shown in several of the beagle dog, rat, mouse and guinea 
pig studies discussed in the section on CBD pathogenesis that follows 
(Finch et al., 1988; Polak et al., 1968; Haley et al., 1989; Haley et 
al., 1992; Hall et al., 1950). Finch et al. have also observed higher 
toxicity of beryllium oxide calcined at 500 [deg]C, an observation they 
attribute to the greater surface area of beryllium particles calcined 
at the lower temperature (Finch et al., 1988). These authors found that 
the in vitro cytotoxicity to Chinese hamster ovary (CHO) cells and 
cultured lung epithelial cells of 500 [deg]C beryllium oxide was 
greater than that of 1,000 [deg]C beryllium oxide, which in turn was 
greater than that of beryllium metal. However, when toxicity was 
expressed in terms of particle surface area, the cytotoxicity of all 
three forms was similar. Similar results were observed in a study 
comparing the cytotoxicity of beryllium metal particles of various 
sizes to cultured rat alveolar macrophages, although specific surface 
area did not entirely predict cytotoxicity (Finch et al., 1991).
    Stefaniak et al., (2003b) investigated the particle structure and 
surface area of particles (powder and process-sampled) of beryllium 
metal, beryllium oxide, and copper-beryllium alloy. Each of these 
samples was separated by aerodynamic size, and their chemical 
compositions and structures were determined with x-ray diffraction and 
transmission electron microscopy, respectively. In summary, beryllium-
metal powder varied remarkably from beryllium oxide powder and alloy 
particles. The metal powder consisted of compact particles, in which 
SSA decreases with increasing surface diameter. In contrast, the alloys 
and oxides consisted of small primary particles in clusters, in which 
the SSA remains fairly constant with particle size. SSA for the metal 
powders varied based on production and manufacturing process with 
variations among samples as high as a factor of 37. Stefaniak et al. 
(2003b) found lesser variation in SSA for the alloys or oxides. This is 
consistent with data from other studies summarized above showing that 
process may affect particle size and surface area. Particle size and/or 
surface area may explain differences in the rate of BeS and CBD 
observed in some epidemiological studies. However, these properties 
have not been consistently characterized in most studies.

B. Kinetics and Metabolism of Beryllium

    Beryllium enters the body by inhalation, ingestion, or absorption 
through the skin. For occupational exposure, the airways and the skin 
are the primary routes of uptake.
 1. Exposure via the Respiratory System
    The respiratory tract, especially the lung, is the primary target 
of inhalation exposure in workers. Inhaled beryllium particles are 
deposited along the respiratory tract in a size dependent manner. In 
general, particles larger than 10 [mu]m tend to deposit in the upper 
respiratory tract or nasal region and do not appreciably penetrate 
lower in the tracheobronchial or pulmonary regions (Figure 1). 
Particles less than 10 [mu]m increasingly penetrate and deposit in the 
tracheobronchial and pulmonary regions with peak deposition in the 
pulmonary region occurring below 5 [mu]m in particle diameter. The CBD 
pathology of concern is found in the pulmonary region. For particles 
below 1 [mu]m, regional deposition changes dramatically. Ultrafine 
particles (generally considered to be 100 nm or lower) have a higher 
rate of deposition along the entire respiratory system (ICRP model, 
1994). Those particles depositing in the lung and along the entire 
respiratory tract may encounter immunologic cells or may move into the 
vascular system where they are free to leave the lung and can 
contribute to systemic beryllium concentrations.
BILLING CODE 4510-26-C

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[GRAPHIC] [TIFF OMITTED] TP07AU15.000

    Beryllium is removed from the respiratory tract by various 
clearance mechanisms. Soluble beryllium is removed from the respiratory 
tract via absorption. Sparingly soluble or insoluble beryllium may 
remain in the lungs for many years after exposure, as has been observed 
in workers (Schepers, 1962). Clearance mechanisms for sparingly soluble 
or insoluble beryllium particles include: In the nasal passage, 
sneezing, mucociliary transport to the throat, or dissolution; in the 
tracheobronchial region, mucociliary transport, coughing, phagocytosis, 
or dissolution; in the pulmonary or alveolar region, phagocytosis, 
movement through the interstitium (translocation), or dissolution 
(Schlesinger, 1997).
    Clearance mechanisms may occur slowly in humans, which is 
consistent with some animal studies. For example, subjects in the 
Beryllium Case Registry (BCR), which identifies and tracks cases of 
acute and chronic beryllium diseases, had elevated concentrations of 
beryllium in lung tissue (e.g., 3.1 [mu]g/g of dried lung tissue and 
8.5 [mu]g/g in a mediastinal node) more than 20 years after termination 
of short-term (generally between 2 and 5 years) occupational exposure 
to beryllium (Sprince et al., 1976).
    Clearance rates may depend on the solubility, dose, and size of the 
beryllium particles inhaled as well as the sex and species of the 
animal tested. As reviewed in a WHO Report (2001), more soluble 
beryllium compounds generally tend to be cleared from the respiratory 
system and absorbed into the bloodstream more rapidly than less soluble 
compounds (Van Cleave and Kaylor, 1955; Hart et al., 1980; Finch et 
al., 1990). Animal inhalation or intratracheal instillation studies 
administering soluble beryllium salts demonstrated significant 
absorption of approximately 20 percent of the initial lung burden, 
while sparingly soluble compounds such as beryllium oxide demonstrated 
that absorption was slower and less significant (Delic, 1992). 
Additional animal studies have demonstrated that clearance of soluble 
and sparingly soluble beryllium compounds was biphasic: A more rapid 
initial mucociliary transport phase of particles from the 
tracheobronchial tree to the gastrointestinal tract, followed by a 
slower phase via translocation to tracheobronchial lymph nodes, 
alveolar macrophages uptake, and beryllium particles dissolution 
(Camner et al., 1977; Sanders et al., 1978; Delic, 1992; WHO, 2001). 
Confirmatory studies in rats have shown the half-time for the rapid 
phase between 1-60 days, while the slow phase ranged from 0.6-2.3 
years. It was also shown that this process was influenced by the 
solubility of the beryllium compounds: Weeks/months for soluble 
compounds, months/years for sparingly soluble compounds (Reeves and 
Vorwald, 1967; Reeves et al., 1967; Zorn et al., 1977; Rhoads and 
Sanders, 1985). Studies in guinea-pigs and rats indicate that 40-50 
percent of the inhaled soluble beryllium salts are retained in the 
respiratory tract. Similar data could not be found for the sparingly or 
less soluble beryllium compounds or metal administered by this exposure 
route. (WHO, 2001; ATSDR, 2002).
    Evidence from animal studies suggests that greater amounts of 
beryllium deposited in the lung may result in slower clearance times. A 
comparative study of rats and mice using a single dose of inhaled 
aerosolized beryllium metal demonstrated that an acute inhalation 
exposure to beryllium metal can slow particle clearance and induce lung 
damage in rats (Haley et al., 1990) and mice (Finch et al., 1998a). In 
another study Finch et al. (1994) exposed male F344/N rats to beryllium 
metal at concentrations resulting in beryllium lung burdens of 1.8, 10, 
and 100 [micro]g. These exposure levels resulted in an estimated 
clearance half-life ranging

[[Page 47586]]

from 250-380 days for the three concentrations. For mice (Finch et al., 
1998a), lung clearance half-lives were 91-150 days (for 1.7- and 2.6-
[mu]g lung burden groups) or 360-400 days (for 12- and 34-[mu]g lung 
burden groups). While the lower exposure groups were quite different 
for rats and mice, the highest groups were similar in clearance half-
lives for both species.
    Beryllium absorbed from the respiratory system is mainly 
distributed to the tracheobronchial lymph nodes via the lymph system, 
bloodstream, and skeleton, which is the ultimate site of beryllium 
storage (Stokinger et al., 1953; Clary et al., 1975; Sanders et al., 
1975; Finch et al., 1990). Trace amounts are distributed throughout the 
body (Zorn et al., 1977; WHO, 2001). Studies in rats have demonstrated 
accumulation of beryllium chloride in the skeletal system following 
intraperitoneal injection (Crowley et al., 1949; Scott et al., 1950) 
and accumulation of beryllium phosphate and beryllium sulfate in both 
nonparenchymal and parenchymal cells of the liver after intravenous 
administration in rats (Skilleter and Price, 1978). Studies have also 
demonstrated intracellular accumulation of beryllium oxide in bone 
marrow throughout the skeletal system after intravenous administration 
to rabbits (Fodor, 1977; WHO, 2001).
    Systemic distribution of the more soluble compounds appears to be 
greater than that of the insoluble compounds (Stokinger et al., 1953). 
Distribution has also been shown to be dose dependent in research using 
intravenous administration of beryllium in rats; small doses were 
preferentially taken up in the skeleton, while higher doses were 
initially distributed preferentially to the liver. Beryllium was later 
mobilized from the liver and transferred to the skeleton (IARC, 1993). 
A half-life of 450 days has been estimated for beryllium in the human 
skeleton (ICRP, 1960). This indicates the skeleton may serve as a 
repository for beryllium that may later be reabsorbed by the 
circulatory system, making beryllium available to the immunological 
system.
2. Dermal Exposure
    Beryllium compounds have been shown to cause skin irritation and 
sensitization in humans and certain animal models (Van Orstrand et al., 
1945; de Nardi et al., 1953; Nishimura 1966; Epstein 1990; Belman, 
1969; Tinkle et al., 2003; Delic, 1992). The Agency for Toxic 
Substances and Disease Registry (ATSDR) estimated that less than 0.1 
percent of beryllium compounds are absorbed through the skin (ATSDR, 
2002). However, even minute contact and absorption across the skin may 
directly elicit an immunological sensitization response (Deubner et 
al., 2001; Toledo et al., 2011). Recent studies by Tinkle et al. (2003) 
showed that penetration of beryllium oxide particles was possible ex 
vivo for human intact skin at particle sizes of <= 1[mu]m, as confirmed 
by scanning electron microscopy. Using confocal microscopy, Tinkle et 
al. demonstrated that surrogate fluorescent particles up to 1 [mu]m in 
size could penetrate the mouse epidermis and dermis layers in a model 
designed to mimic the flexing and stretching of human skin in motion. 
Other poorly soluble particles, such as titanium dioxide, have been 
shown to penetrate normal human skin (Tan et al., 1996) suggesting the 
flexing and stretching motion as a plausible mechanism for dermal 
penetration of beryllium as well. As earlier summarized, insoluble 
forms of beryllium can be solubilized in biological fluids (e.g., 
sweat) making them available for absorption through intact skin (Sutton 
et al., 2003; Stefaniak et al., 2011; Duling et al., 2012).
    Although its precise role remains to be elucidated, there is 
evidence to indicate that dermal exposure can contribute to beryllium 
sensitization. As early as the 1940s it was recognized that dermatitis 
experienced by workers in primary beryllium production facilities was 
linked to exposures to the soluble beryllium salts. Except in cases of 
wound contamination, dermatitis was rare in workers whose exposures 
were restricted to exposure to poorly soluble beryllium-containing 
particles (Van Ordstrand et al., 1945). Further investigation by McCord 
in 1951 indicated that direct skin contact with soluble beryllium 
compounds, but not beryllium hydroxide or beryllium metal, caused 
dermal lesions (reddened, elevated, or fluid-filled lesions on exposed 
body surfaces) in susceptible persons. Curtis, in 1951, demonstrated 
skin sensitization to beryllium with patch testing using soluble and 
insoluble forms of beryllium in beryllium-na[iuml]ve subjects. These 
subjects later developed granulomatous skin lesions with the classical 
delayed-type contact dermatitis following repeat challenge (Curtis, 
1951). These lesions appeared after a latent period of 1-2 weeks, 
suggesting a delayed allergic reaction. The dermal reaction occurred 
more rapidly and in response to smaller amounts of beryllium in those 
individuals previously sensitized (Van Ordstrand et al., 1945). 
Contamination of cuts and scrapes with beryllium can result in the 
beryllium becoming embedded within the skin causing a granuloma to 
develop in the skin (Epstein, 1991). Introduction of soluble or 
insoluble beryllium compounds into or under the skin as a result of 
abrasions or cuts at work has been shown to result in chronic 
ulcerations with granuloma formation (Van Orstrand et al., 1945; 
Lederer and Savage, 1954). Beryllium absorption through bruises and 
cuts has been demonstrated as well (Rossman et al., 1991). In a study 
by Invannikov et al., (1982), beryllium chloride was applied directly 
to the skin of live animals with three types of wounds: abrasions 
(superficial skin trauma), cuts (skin and superficial muscle trauma), 
and penetration wounds (deep muscle trauma). The percentage of the 
applied dose absorbed into the systemic circulation during a 24-hour 
exposure was significant, ranging from 7.8 percent to 11.4 percent for 
abrasions, from 18.3 percent to 22.9 percent for cuts, and from 34 
percent to 38.8 percent for penetration wounds (WHO, 2001).
    A study by Deubner et al., (2001) concluded that exposure across 
damaged skin can contribute as much systemic loading of beryllium as 
inhalation (Deubner et al., 2001). Deubner et al., (2001) estimated 
dermal loading (amount of particles penetrating into the skin) in 
workers as compared to inhalation exposure. Deubner's calculations 
assumed a dermal loading rate for beryllium on skin of 0.43 [mu]g/
cm\2\, based on the studies of loading on skin after workers cleaned up 
(Sanderson et al., 1999), multiplied by a factor of 10 to approximate 
the workplace concentrations and the very low absorption rate of 0.001 
percent (taken from EPA estimates). It should be noted that these 
calculations did not take into account absorption of soluble beryllium 
salts that might occur across nasal mucus membranes, which may result 
from contact between contaminated skin and the nose (EPA, 1998).
    A study conducted by Day et al. (2007) evaluated the effectiveness 
of a dermal protection program implemented in a beryllium alloy 
facility in 2002. The investigators evaluated levels of beryllium in 
air, on workplace surfaces, on cotton gloves worn over nitrile gloves, 
and on the necks and faces of workers over a six day period. The 
investigators found a good correlation between air samples and work 
surface contamination at this facility. The investigators also found 
measurable levels of beryllium on the skin of workers as a result of 
work processes even from workplace areas

[[Page 47587]]

promoted as ``visually clean'' by the company housekeeping policy. 
Importantly, the investigators found that the beryllium contamination 
could be transferred from body region to body region (e.g., hand to 
face, neck to face). The investigators demonstrated multiple pathways 
of exposure which could lead to sensitization, increasing risk for 
developing CBD (Day, et al., 2007).
    The same group of investigators (Armstrong et al., 2014) extended 
their work on investigating multiple exposure pathways contributing to 
sensitization and CBD. The investigators evaluated four different 
beryllium manufacturing and processing facilities to assess the 
contribution of various exposure pathways on worker exposure. Airborne, 
work surface and cotton glove beryllium concentrations were evaluated. 
The investigators found strong correlations between air-surface 
concentrations, glove-surface concentrations, and air-glove 
concentrations at this facility. This work confirms findings from Day 
et al. (2007) demonstrating the importance of airborne beryllium 
concentrations to surface contamination and dermal exposure even at 
exposures below the current OSHA PEL (Armstrong et al., 2014).
3. Oral and Gastrointestinal Exposure
    According to the WHO Report (2001), gastrointestinal absorption of 
beryllium can occur by both the inhalation and oral routes of exposure. 
Through inhalation exposure, a fraction of the inhaled material is 
transported to the gastrointestinal tract by the mucociliary escalator 
or by the swallowing of the insoluble material deposited in the upper 
respiratory tract (WHO, 2001). Gastrointestinal absorption of beryllium 
can occur by both the inhalation and oral routes of exposure. In the 
case of inhalation, a portion of the inhaled material is transported to 
the gastrointestinal tract by the mucociliary escalator or by the 
swallowing of the insoluble material deposited in the upper respiratory 
tract (Schlesinger, 1997). Animal studies have shown oral 
administration of beryllium compounds to result in very limited 
absorption and storage (as reviewed by U.S. EPA, 1998). In animal 
ingestion studies using radio-labeled beryllium chloride in rats, mice, 
dogs, and monkeys, the vast majority of the ingested dose passed 
through the gastrointestinal tract unabsorbed and was excreted in the 
feces. In most studies, <1 percent of the administered radioactivity 
was absorbed into the bloodstream and subsequently excreted in the 
urine (Crowley et al., 1949; Furchner et al., 1973; LeFevre and Joel, 
1986). Research using soluble beryllium sulfate has shown that as the 
compound passes into the intestine, which has a higher pH than the 
stomach (approximate pH of 6 to 8 for the intestine, pH of 1 or 2 for 
the stomach), the beryllium is precipitated as the insoluble phosphate 
and thus is no longer available for absorption (Reeves, 1965; WHO, 
2001).
    Urinary excretion of beryllium has been shown to correlate with the 
amount of occupational exposure (Klemperer et al., 1951). Beryllium 
that is absorbed into the bloodstream is excreted primarily in the 
urine (Crowley et al., 1949; Scott et al., 1950; Furchner et al., 1973; 
Stiefel et al., 1980), whereas excretion of unabsorbed beryllium is 
primarily via the fecal route (Hart et al., 1980; Finch et al., 1990). 
A far higher percentage of the beryllium administered parenterally in 
various animal species was eliminated in the urine than in the feces 
(Crowley et al., 1949; Scott et al., 1950; Furchner et al., 1973), 
confirming that beryllium found in the feces following oral exposure is 
primarily unabsorbed material. A study using percutaneous incorporation 
of soluble beryllium nitrate in rats similarly demonstrated that more 
than 90 percent of the beryllium in the bloodstream was eliminated via 
urine (Zorn et al., 1977; WHO, 2001). More than 99 percent of ingested 
beryllium chloride was excreted in the feces (Mullen et al., 1972). 
Elimination half-times of 890-1,770 days (2.4-4.8 years) were 
calculated for mice, rats, monkeys, and dogs injected intravenously 
with beryllium chloride (Furchner et al., 1973). Mean daily excretion 
of beryllium metal was 4.6 x 10-5 percent of the dose 
administered by intratracheal instillation in baboons and 3.1 x 
10-5 percent in rats (Andre et al., 1987).
4. Metabolism
    Beryllium and its compounds are not metabolized or biotransformed, 
but soluble beryllium salts may be converted to less soluble forms in 
the lung (Reeves and Vorwald, 1967). As stated earlier, solubility is 
an important factor for persistence of beryllium in the lung. Insoluble 
beryllium, engulfed by activated phagocytes, can be ionized by an 
acidic environment and by myeloperoxidases (Leonard and Lauwerys, 1987; 
Lansdown, 1995; WHO, 2001), and this positive charge could potentially 
make it more biologically reactive because it may allow the beryllium 
to bind to a peptide or protein and be presented to the T cell receptor 
or antigen-presenting cell (Fontenot, 2000).
5. Preliminary Conclusion for Particle Characterization and Kinetics of 
Beryllium
    The forms and concentrations of beryllium across the workplace vary 
substantially based upon location, process, production and work task. 
Many factors influence the potency of beryllium including 
concentration, composition, structure, size and surface area of the 
particle.
    Studies have demonstrated that beryllium sensitization can occur 
via the skin or inhalation from soluble or poorly soluble beryllium 
particles. Beryllium must be presented to a cell in a soluble form for 
activation of the immune system (NAS, 2008), and this will be discussed 
in more detail in the section to follow. Poorly soluble beryllium can 
be solubilized via intracellular fluid, lung fluid and sweat (Sutton et 
al., 2003; Stefaniak et al., 2011). For beryllium to persist in the 
lung it needs to be insoluble. However, soluble beryllium has been 
shown to precipitate in the lung to form insoluble beryllium (Reeves 
and Vorwald, 1967).
    Some animal and epidemiological studies suggest that the form of 
beryllium may affect the rate of development of BeS and CBD. Beryllium 
in an inhalable form (either as soluble or insoluble particles or mist) 
can deposit in the respiratory tract and interact with immune cells 
located along the entire respiratory tract (Scheslinger, 1997). 
However, more study is needed to precisely determine the physiochemical 
characteristics of beryllium that influence toxicity and 
immunogenicity.

C. Acute Beryllium Diseases

    Acute beryllium disease (ABD) is a relatively rapid onset 
inflammatory reaction resulting from breathing high airborne 
concentrations of beryllium. It was first reported in workers 
extracting beryllium oxide (Van Ordstrand et al., 1943). Since the 
Atomic Energy Commission's adoption of occupational exposure limits for 
beryllium beginning in 1949, cases of ABD have been rare. According to 
the World Health Organization (2001), ABD is generally associated with 
exposure to beryllium levels at or above 100 [mu]g/m\3\ and may be 
fatal in 10 percent of cases. However, cases have been reported with 
beryllium exposures below 100 [micro]g/m\3\ (Cummings et al., 2009). 
The disease involves an inflammatory reaction that may include the 
entire respiratory tract, involving the nasal passages, pharynx, 
bronchial airways and alveoli. Other tissues including skin and 
conjunctivae may be affected as well. The clinical features of

[[Page 47588]]

ABD include a nonproductive cough, chest pain, cyanosis, shortness of 
breath, low-grade fever and a sharp drop in functional parameters of 
the lungs. Pathological features of ABD include edematous distension, 
round cell infiltration of the septa, proteinaceous materials, and 
desquamated alveolar cells in the lung. Monocytes, lymphocytes and 
plasma cells within the alveoli are also characteristic of the acute 
disease process (Freiman and Hardy, 1970).
    Two types of acute beryllium disease have been characterized in the 
literature: a rapid and severe course of acute fulminating pneumonitis 
generally developing within 48 to 72 hours of a massive exposure, and a 
second form that takes several days to develop from exposure to lower 
concentrations of beryllium (still above the levels set by regulatory 
and guidance agencies) (Hall, 1950; DeNardi et al., 1953; Newman and 
Kreiss, 1992). Evidence of a dose-response relationship to the 
concentration of beryllium is limited (Eisenbud et al., 1948; 
Stokinger, 1950; Sterner and Eisenbud, 1951). Recovery from either type 
of ABD is generally complete after a period of several weeks or months 
(DeNardi et al., 1953). However, deaths have been reported in more 
severe cases (Freiman and Hardy, 1970). There have been documented 
cases of progression to CBD (ACCP, 1965; Hall, 1950) suggesting the 
possibility of an immune component to this disease (Cummings et al., 
2009) as well. According to the BCR, in the United States, 
approximately 17 percent of ABD patients developed CBD (BCR, 2010). The 
majority of ABD cases occurred between 1932 and 1970 (Eisenbud, 1983; 
Middleton, 1998). ABD is extremely rare in the workplace today due to 
more stringent exposure controls implemented following occupational and 
environmental standards set in 1970-1972 (OSHA, 1971; ACGIH, 1971; 
ANSI, 1970) and 1974 (EPA, 1974).

D. Chronic Beryllium Disease

    This section provides an overview of the immunology and 
pathogenesis of BeS and CBD, with particular attention to the role of 
skin sensitization, particle size, beryllium compound solubility, and 
genetic variability in individuals' susceptibility to beryllium 
sensitization and CBD.
    Chronic beryllium disease (CBD), formerly known as ``berylliosis'' 
or ``chronic berylliosis,'' is a granulomatous disorder primarily 
affecting the lungs. CBD was first described in the literature by Hardy 
and Tabershaw (1946) as a chronic granulomatous pneumonitis. It was 
proposed as early as 1951 that CBD could be a chronic disease resulting 
from an immune sensitization to beryllium (Sterner and Eisenbud, 1951; 
Curtis, 1959; Nishimura, 1966). However, for a time, there remained 
some controversy as to whether CBD was a delayed-onset hypersensitivity 
disease or a toxicant-induced disease (NAS, 2008). Wide acceptance of 
CBD as a hypersensitivity lung disease did not occur until bronchoscopy 
studies and bronchoalveolar lavage (BAL) studies were performed 
demonstrating that BAL cells from CBD patients responded to beryllium 
challenge (Epstein et al., 1982; Rossman et al., 1988; Saltini et al., 
1989).
    CBD shares many clinical and histopathological features with 
pulmonary sarcoidosis, a granulomatous lung disease of unknown 
etiology. This includes such debilitating effects as airway 
obstruction, diminishment of physical capacity associated with reduced 
lung function, possible depression associated with decreased physical 
capacity, and decreased life expectancy. Without appropriate 
information, CBD may be difficult to distinguish from sarcoidosis. It 
is estimated that up to 6 percent of all patients diagnosed with 
sarcoidosis may actually have CBD (Fireman et al., 2003; Rossman and 
Kreiber, 2003). Among patients diagnosed with sarcoidosis in which 
beryllium exposure can be confirmed, as many as 40 percent may actually 
have CBD (Muller-Quernheim et al., 2006; Cherry et al., 2015).
    Clinical signs and symptoms of CBD may include, but are not limited 
to, a simple cough, shortness of breath or dypsnea, fever, weight loss 
or anorexia, skin lesions, clubbing of fingers, cyanosis, night sweats, 
cor pulmonale, tachycardia, edema, chest pain and arthralgia. Changes 
or loss of pulmonary function also occur with CBD such as decrease in 
vital capacity, reduced diffusing capacity, and restrictive breathing 
patterns. The signs and symptoms of CBD constitute a continuum of 
symptoms that are progressive in nature with no clear demarcation 
between any stages in the disease (Rossman, 1996; NAS, 2008). Besides 
these listed symptoms from CBD patients, there have been reported cases 
of CBD that remained asymptomatic (Muller-Querheim, 2005; NAS, 2008).
    Unlike ABD, CBD can result from inhalation exposure to beryllium at 
levels below the current OSHA PEL, can take months to years after 
initial beryllium exposure before signs and symptoms of CBD occur 
(Newman 1996, 2005 and 2007; Henneberger, 2001; Seidler et al., 2012; 
Schuler et al., 2012), and may continue to progress following removal 
from beryllium exposure (Newman, 2005; Sawyer et al., 2005; Seidler et 
al., 2012). Patients with CBD can progress to a chronic obstructive 
lung disorder resulting in loss of quality of life and the potential 
for decreased life expectancy (Rossman, et al., 1996; Newman et al., 
2005). The NAS report (2008) noted the general lack of published 
studies on progression of CBD from an early asymptomatic stage to 
functionally significant lung disease (NAS, 2008). The report 
emphasized that risk factors and time course for clinical disease have 
not been fully delineated. However, for people now under surveillance, 
clinical progression from immunological sensitization and early 
pathological lesions (i.e., granulomatous inflammation) prior to onset 
of symptoms to symptomatic disease appears to be slow, although more 
follow-up is needed (NAS, 2008). A study by Newman (1996) emphasized 
the need for prospective studies to determine the natural history and 
time course from BeS and asymptomatic CBD to full-blown disease 
(Newman, 1996). Drawing from his own clinical experience, Newman was 
able to identify the sequence of events for those with symptomatic 
disease as follows: Initial determination of beryllium sensitization; 
gradual emergence of chronic inflammation of the lung; pathologic 
alterations with measurable physiologic changes (e.g., pulmonary 
function and gas exchange); progression to a more severe lung disease 
(with extrapulmonary effects such as clubbing and cor pulmonale in some 
cases); and finally death in some cases (reported between 5.8 to 38 
percent) (NAS, 2008; Newman, 1996).
    In contrast to some occupationally related lung diseases, the early 
detection of chronic beryllium disease may be useful since treatment of 
this condition can lead not only to regression of the signs and 
symptoms, but also may prevent further progression of the disease in 
certain individuals (Marchand-Adam, 2008; NAS, 2008). The management of 
CBD is based on the hypothesis that suppression of the hypersensitivity 
reaction (i.e., granulomatous process) will prevent the development of 
fibrosis. However, once fibrosis has developed, therapy cannot reverse 
the damage.
    To date, there have been no controlled studies to determine the 
optimal treatment for CBD (Rossman, 1996; NAS 2008; Sood, 2009). 
Management of CBD is generally modeled after sarcoidosis treatment. 
Oral corticosteroid treatment can be initiated in patients with

[[Page 47589]]

evidence of disease (either by bronchoscopy or other diagnostic 
measures before progression of disease or after clinical signs of 
pulmonary deterioration occur). This includes treatment with other 
anti-inflammatory agents (NAS, 2008; Maier et al., 2012; Salvator et 
al., 2013) as well. It should be noted, however, that treatment with 
corticosteroids has side-effects of their own that need to be measured 
against the possibility of progression of disease (Gibson et al., 1996; 
Zaki et al., 1987). Alternative treatments such as azathiopurine and 
infliximab, while successful at treating symptoms of CBD, have been 
demonstrated to have side-effects as well (Pallavicino et al., 2013; 
Freeman, 2012).
1. Development of Beryllium Sensitization
    Sensitization to beryllium is an essential step for worker 
development of CBD. Sensitization to beryllium can result from 
inhalation exposure to beryllium (Newman et al., 2005; NAS, 2008), as 
well as from skin exposure to beryllium (Curtis, 1951; Newman et al., 
1996; Tinkle et al., 2003). Sensitization is currently detected using a 
laboratory blood test described in Appendix A. Although there may be no 
clinical symptoms associated with BeS, a sensitized worker's immune 
system has been activated to react to beryllium exposures such that 
subsequent exposure to beryllium can progress to serious lung disease 
(Kreiss et al., 1996; Kreiss et al., 1997; Kelleher et al., 2001; and 
Rossman, 2001). Since the pathogenesis of CBD involves a beryllium-
specific, cell-mediated immune response, CBD cannot occur in the 
absence of sensitization (NAS, 2008). Various factors, including 
genetic susceptibility, have been shown to influence risk of developing 
sensitization and CBD (NAS 2008) and will be discussed later in this 
section.
    While various mechanisms or pathways may exist for beryllium 
sensitization, the most plausible mechanisms supported by the best 
available and most current science are discussed below. Sensitization 
occurs via the formation of a beryllium-protein complex (an antigen) 
that causes an immunological response. In some instances, onset of 
sensitization has been observed in individuals exposed to beryllium for 
only a few months (Kelleher et al., 2001; Henneberger et al., 2001). 
This suggests the possibility that relatively brief, short-term 
beryllium exposures may be sufficient to trigger the immune 
hypersensitivity reaction. Several studies (Newman et al., 2001; 
Henneberger et al., 2001; Rossman, 2001; Schuler et al., 2005; Donovan 
et al., 2007, Schuler et al., 2012) have detected a higher prevalence 
of sensitization among workers with less than one year of employment 
compared to some cross-sectional studies which, due to lack of 
information regarding initial exposure, cannot determine time of 
sensitization (Kreiss et al., 1996; Kreiss et al., 1997). While only 
very limited evidence has described humoral changes in certain patients 
with CBD (Cianciara et al., 1980), clear evidence exists for an immune 
cell-mediated response, specifically the T-cell (NAS, 2008). Figure 2 
delineates the major steps required for progression from beryllium 
contact to sensitization to CBD.
BILLING CODE 4510-26-P

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[GRAPHIC] [TIFF OMITTED] TP07AU15.001

BILLING CODE 4510-26-C
    Beryllium presentation to the immune system is believed to occur 
either by direct presentation or by antigen processing. It has been 
postulated that beryllium must be presented to the immune system in an 
ionic form for cell-mediated immune activation to occur (Kreiss et al., 
2007). Some soluble forms of beryllium are readily presented, since the 
soluble beryllium form disassociates into its ionic components. 
However, for insoluble forms, dissolution may need to occur. A study by 
Harmsen et al. (1986) suggested that a sufficient rate of dissolution 
of small amounts of poorly soluble beryllium compounds might occur in 
the lungs to allow persistent low-level beryllium presentation to the 
immune system. Stefaniak et al. (2005 and 2012) reported that insoluble 
beryllium particles phagocytized by macrophages were dissolved in 
phagolysomal fluid (Stefaniak et al., 2005; Stefaniak et al., 2012) and 
that the dissolution rate stimulated by phagolysomal fluid was 
different for various forms of beryllium (Stefaniak et al., 2006; 
Duling et al., 2012). Several studies have demonstrated that macrophage 
uptake of beryllium can induce aberrant apoptotic processes leading to 
the continued release of beryllium ions which will continually 
stimulate T-cell activation (Sawyer et al., 2000; Sawyer et al., 2004; 
Kittle et al., 2002). Antigen processing can be mediated by antigen-
presenting cells (APC). These may include macrophages, dendritic cells, 
or other antigen-presenting cells, although this has not been well 
defined in most studies (NAS, 2008).
    Because of their strong positive charge, beryllium ions have the 
ability to haptenate and alter the structure of peptides occupying the 
antigen-binding cleft of major histocompatibility complex (MHC) class 
II on antigen-presenting cells (APC). The MHC class II antigen-binding 
molecule for beryllium is the human leukocyte antigen (HLA) with 
specific alleles (e.g.,

[[Page 47591]]

HLA-DP, HLA-DR, HLA-DQ) associated with the progression to CBD (NAS, 
2008; Yucesoy and Johnson, 2011). Several studies have also 
demonstrated that the electrostatic charge of HLA may be a factor in 
binding beryllium (Snyder et al., 2003; Bill et al., 2005; Dai et al., 
2010). The strong positive ionic charge of the beryllium ion would have 
a strong attraction for the negatively charged patches of certain HLA 
alleles (Snyder et al., 2008; Dai et al., 2010). Alternatively, 
beryllium oxide has been demonstrated to bind to the MHC class II 
receptor in a neutral pH. The six carboxylates in the amino acid 
sequence of the binding pocket provide a stable bond with the Be-O-Be 
molecule when the pH of the substrate is neutral (Keizer et al., 2005). 
The direct binding of BeO may eliminate the biological requirement for 
antigen processing or dissolution of beryllium oxide to activate an 
immune response.
    Next in sequence is the beryllium-MHC-APC complex binding to a T-
cell receptor (TCR) on a na[iuml]ve T-cell which stimulates the 
proliferation and accumulation of beryllium-specific CD4\+\ (cluster of 
differentiation 4\+\) T-cells (Saltini et al., 1989 and 1990; Martin et 
al., 2011) as depicted in Figure 3. Fontenot et al. (1999) demonstrated 
that diversely different variants of TCR were expressed by CD4\+\ T-
cells in peripheral blood cells of CBD patients. However, the CD4\+\ T-
cells from the lung were more homologous in expression of TCR variants 
in CBD patients, suggesting clonal expansion of a subset of T-cells in 
the lung (Fontenot et al., 1999). This may also indicate a pathogenic 
potential for subsets of T-cell clones expressing this homologous TCR 
(NAS, 2008). Fontenot et al. (2006) reported beryllium self-
presentation by HLA-DP expressing BAL CD4\+\ T-cells. Self-presentation 
by BAL T-cells in the lung granuloma may result in activation-induced 
cell death, which may then lead to oligoclonality of the T-cell 
population characteristic of CBD (NAS, 2008).
[GRAPHIC] [TIFF OMITTED] TP07AU15.002

    As CD4\+\ T-cells proliferate, clonal expansion of various subsets 
of the CD4\+\ beryllium specific T-cells occurs (Figure 3). In the 
peripheral blood, the beryllium-specific CD4\+\ T cells require co-
stimulation with a co-stimulant CD28 (cluster of differentiation 28). 
During the proliferation and differentiation process CD4\+\ T-cells 
secrete pro-inflammatory cytokines that may influence this process 
(Sawyer et al., 2004; Kimber et al., 2011).
2. Development of CBD
    The continued persistence of residual beryllium in the lung leads 
to a T-cell maturation process. A large portion of beryllium-specific 
CD4\+\ T cells were shown to cease expression of CD28 mRNA and protein, 
indicating these cells no longer required co-stimulation with the CD28 
ligand (Fontenot et al., 2003). This change in phenotype correlated 
with lung inflammation (Fontenot et al., 2003). The CD4\+\ independent 
cells continued to secrete cytokines necessary for additional 
recruitment of inflammatory and immunological cells; however, they were 
less proliferative and less susceptible to cell death compared to the 
CD28 dependent cells (Fontenot et al., 2005; Mack et al., 2008). These 
beryllium-specific CD4\+\ independent cells are considered to be mature 
memory effector cells (Ndejembi et al., 2006; Bian et al., 2005). 
Repeat exposure to beryllium in the lung resulting in a mature 
population of T cell development independent of co-stimulation by CD28 
and development of a population of T effector memory cells 
(Tem cells) may be one of the mechanisms that lead to the 
more severe reactions observed specifically in the lung (Fontenot et 
al., 2005).
    CD4\+\ T cells created in the sensitization process recognize the 
beryllium antigen, and respond by proliferating and secreting cytokines 
and inflammatory mediators, including IL-2, IFN-[gamma], and TNF-
[alpha] (Tinkle et al., 1997a and b; Fontenot et al., 2002) and MIP-
1[alpha] and GRO-1 (Hong-Geller, 2006). This also results in the 
accumulation of various types of inflammatory cells including 
mononuclear cells (mostly CD4\+\ T cells) in the bronchoalveolar lavage 
fluid (BAL fluid) (Saltini et al., 1989, 1990).
    The development of granulomatous inflammation in the lung of CBD 
patients has been associated with the accumulation of beryllium 
responsive CD4\+\ Tem cells in BAL fluid (NAS, 2008). The 
subsequent release of pro-inflammatory cytokines, chemokines and 
reactive oxygen species by these cells may lead to migration of 
additional inflammatory/immune cells and the development of a 
microenvironment that contributes to the development of CBD (Sawyer et 
al., 2005; Tinkle et al., 1996; Hong-Geller et al., 2006; NAS, 2008).
    The cascade of events described above results in the formation of a 
noncaseating granulomatous lesion.

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Release of cytokines by the accumulating T cells leads to the formation 
of granulomatous lesions that are characterized by an outer ring of 
histiocytes surrounding non-necrotic tissue with embedded multi-
nucleated giant cells (Saltini et al., 1989, 1990).
    Over time, the granulomas spread and can lead to lung fibrosis and 
abnormal pulmonary function, with symptoms including a persistent dry 
cough and shortness of breath (Saber and Dweik, 2000). Fatigue, night 
sweats, chest and joint pain, clubbing of fingers (due to impaired 
oxygen exchange), loss of appetite or unexplained weight loss, and cor 
pulmonale have been experienced in certain patients as the disease 
progresses (Conradi et al., 1971; ACCP, 1965; Kriebel et al., 1988a and 
b). While CBD primarily affects the lungs, it can also involve other 
organs such as the liver, skin, spleen, and kidneys (ATSDR, 2002).
    As previously mentioned, the uptake of beryllium may lead to an 
aberrant apoptotic process with rerelease of beryllium ions and 
continual stimulation of beryllium-responsive CD4+ cells in 
the lung (Sawyer et al., 2000; Kittle et al., 2002; Sawyer et al., 
2004). Several research studies suggest apoptosis may be one mechanism 
that enhances inflammatory cell recruitment, cytokine production and 
inflammation, thus creating a scenario for progressive granulomatous 
inflammation (Palmer et al., 2008; Rana, 2008). Macrophages and 
neutrophils can phagocytize beryllium particles in an attempt to remove 
the beryllium from the lung (Ding, et al., 2009). Multiple studies 
(Sawyer et al., 2004; Kittle et al., 2002) using BAL cells (mostly 
macrophages and neutrophils) from patients with CBD found that in vitro 
stimulation with beryllium sulfate induced the production of TNF-
[alpha] (one of many cytokines produced in response to beryllium), and 
that production of TNF-[alpha] might induce apoptosis in CBD and 
sarcoidosis patients (Bost et al., 1994; Dai et al., 1999). The 
stimulation of CBD-derived macrophages by beryllium sulphate resulted 
in cells becoming apoptotic, as measured by propidium iodide. These 
results were confirmed in a mouse macrophage cell-line (p388D1) (Sawyer 
et al., 2000). However, other factors may influence the development of 
CBD and are outlined in the following section.
3. Genetic and Other Susceptibility Factors
    Evidence from a variety of sources indicates genetic susceptibility 
may play an important role in the development of CBD in certain 
individuals, especially at levels low enough not to invoke a response 
in other individuals. Early occupational studies proposed that CBD was 
an immune reaction based on the high susceptibility of some individuals 
to become sensitized and progress to CBD and the lack of CBD in others 
who were exposed to levels several orders of magnitude higher (Sterner 
and Eisenbud, 1951). Additional in vitro human research has identified 
genes coding for specific protein molecules on the surface of their 
immune cells that place carriers at greater risk of becoming sensitized 
to beryllium and developing CBD (McCanlies et al., 2004). Recent 
studies have confirmed genetic susceptibility to CBD involves either 
HLA variants, T-cell receptor clonality, tumor necrosis factor (TNF-
[alpha]) polymorphisms and/or transforming growth factor-beta (TGF-
[beta]) polymorphisms (Fontenot et al., 2000; Amicosante et al., 2005; 
Tinkle et al., 1996; Gaede et al., 2005; Van Dyke et al., 2011; 
Silveira et al., 2012).
    Single Nucleotide Polymorphisms (SNPs) have been studied with 
regard to genetic variations associated with increased risk of 
developing CBD. SNPs are the most abundant type of human genetic 
variation. Polymorphisms in MHC class II and pro-inflammatory genes 
have been shown to contribute to variations in immune responses 
contributing to the susceptibility and resistance in many diseases 
including auto-immunity, and beryllium sensitization and CBD (McClesky 
et al., 2009). Specific SNPs have been evaluated as a factor in Glu69 
variant from the HLA-DPB1 locus (Richeldi et al., 1993; Cai et al., 
2000; Saltini et al., 2001; Silviera et al., 2012; Dai et al., 2013), 
HLA-DRPhe[beta]47 (Amicosante et al., 2005).
    HLA-DPB1 with a glutamic acid at amino position 69 (Glu 69) has 
been shown to confer increased risk of beryllium sensitization and CBD 
(Richeldi et al., 1993; Saltini et al., 2001; Amicosante et al., 2005; 
Van Dyke et al., 2011; Silveira et al., 2012). Fontenot et al. (2000) 
demonstrated that beryllium presentation by certain alleles of the 
class II human leukocyte antigen-DP (HLA-DP) to CD4+ T cells is the 
mechanism underlying the development of CBD. Richeldi et al. (1993) 
reported a strong association between the MHC class II allele HLA-DP 1 
and the development of CBD in beryllium-exposed workers from a Tucson, 
AZ facility. This marker was found in 32 of the 33 workers who 
developed CBD, but in only 14 of 44 similarly exposed workers without 
CBD. The more common allele of the HLA-DP 1 variant is negatively 
charged at this site and could directly interact with the positively 
charged beryllium ion. The high percentage (~30 percent) of beryllium-
exposed workers without CBD who had this allele indicates that other 
factors also contribute to the development of CBD (EPA, 1998). 
Additional studies by Amicosante et al. (2005) using blood lymphocytes 
derived from beryllium-exposed workers found a high frequency of this 
gene in those sensitized to beryllium. In a study of 82 CBD patients 
(beryllium-exposed workers), Stubbs et al. (1996) also found a 
relationship between the HLA-DP 1 allele and BeS. The glutamate-69 
allele was present in 86 percent of sensitized subjects, but in only 48 
percent of beryllium-exposed, non-sensitized subjects. Some variants of 
the HLA-DPB1 allele convey higher risk of BeS and CBD than others. For 
example, HLA-DPB1*0201 yielded an approximately 3-fold increase in 
disease outcome relative to controls; HLA-DPB1*1901 yielded an 
approximately 5-fold increase, and HLA-DPB1*1701 an approximately 10-
fold increase (Weston et al., 2005; Snyder et al., 2008). By assigning 
odds ratios for specific alleles on the basis of previous studies 
discussed above, the researchers found a strong correlation (88 
percent) between the reported risk of CBD and the predicted surface 
electrostatic potential and charge of the isotypes of the genes. They 
were able to conclude that the alleles associated with the most 
negatively charged proteins carry the greatest risk of developing 
beryllium sensitization and CBD. This confirms the importance of 
beryllium charge as a key factor in haptogenic potential.
    In contrast, the HLA-DRB1 allele, which lacks Glu 69, has also been 
shown to increase the risk of developing sensitization and CBD 
(Amicosante et al., 2005; Maier et al., 2003). Bill et al. (2005) found 
that HLA-DR has a glutamic acid at position 71 of the [beta] chain, 
functionally equivalent to the Glu 69 of HLA-DP (Bill et al., 2005). 
Associations with BeS and CBD have also been reported with the HLA-DQ 
markers (Amicosante et al., 2005; Maier et al., 2003). Stubbs et al. 
also found a biased distribution of the MHC class II HLA-DR gene 
between sensitized and non-sensitized subjects. Neither of these 
markers was completely specific for CBD, as each study found beryllium 
sensitization or CBD among individuals without the genetic risk factor. 
While there remains uncertainty as to which of the MHC class II genes 
interact directly with the beryllium ion, antibody inhibition data 
suggest that the HLA-DR gene product may be involved in the

[[Page 47593]]

presentation of beryllium to T lymphocytes (Amicosante et al., 2002). 
In addition, antibody blocking experiments revealed that anti-HLA-DP 
strongly reduced proliferation responses and cytokine secretion by BAL 
CD4 T cells (Chou et al., 2005). In the study by Chou (2005), anti-HLA-
DR ligand antibodies mainly affected beryllium-induced proliferation 
responses with little impact on cytokines other than IL-2, thus 
implying that nonproliferating BAL CD4 T cells may still contribute to 
inflammation leading to the progression of CBD (Chou et al., 2005).
    TNF alpha (TNF-[alpha]) polymorphisms and TGF beta (TGF-[beta]) 
polymorphisms have also been shown to confer a genetic susceptibility 
for developing CBD in certain individuals. TNF-[alpha] is a pro-
inflammatory cytokine associated with a more severe pulmonary disease 
in CBD (NAS, 2008). Beryllium exposure has been shown to upregulate 
transcription factors AP-1 and NF-[kappa]B (Sawyer et al., 2007) 
inducing an inflammatory response by stimulating production of pro-
inflammatory cytokines such as TNF-[alpha] by inflammatory cells. 
Polymorphisms in the 308 position of the TNF-[alpha] gene have been 
demonstrated to increase production of the cytokine and increase 
severity of disease (Maier et al., 2001; Saltini et al., 2001; Dotti et 
al., 2004). While a study by McCanlies et al. (2007) found no 
relationship between TNF-[alpha] polymorphism and BeS or CBD, the 
inconsistency may be due to misclassification, exposure differences or 
statistical power (NAS, 2008).
    Other genetic variations have been shown to be associated with 
increased risk of beryllium sensitization and CBD (NAS, 2008). These 
include TGF-[beta] (Gaede et al., 2005), angiotensin-1 converting 
enzyme (ACE) (Newman et al., 1992; Maier et al., 1999) and an enzyme 
involved in glutathione synthesis (glutamate cysteine ligase) (Bekris 
et al., 2006). McCanlies et al. (2010) evaluated the association 
between polymorphisms in a select group of interleukin genes (IL-1A; 
IL-1B, IL-1RN, IL-2, IL-9, IL-9R) due to their role in immune and 
inflammatory processes. The study evaluated SNPs in three groups of 
workers from large beryllium manufacturing facilities in OH and AZ. The 
investigators found a significant association between variants IL-1A-
1142, IL-1A-3769 and IL-1A-4697 and CBD but not with beryllium 
sensitization. However, these still require confirmation in larger 
studies (NAS, 2008).
    In addition to the genetic factors which may contribute to the 
susceptibility and severity of disease, other factors such as smoking 
and gender may play a role in the development of CBD (NAS, 2008). A 
recent longitudinal cohort study by Mroz et al. (2009) of 229 
individuals identified with beryllium sensitization or CBD through 
workplace medical surveillance found that the prevalence of CBD among 
ever smokers was significantly lower than among never smokers (38.1 
percent versus 49.4 percent, p=0.025). BeS subjects that never smoked 
were found to be more likely to develop CBD over the course of the 
study compared to current smokers (12.6 percent versus 6.4 percent, 
p=0.10). The authors suggested smoking may confer a protective effect 
against development of lung granulomas as has been demonstrated with 
hypersensitivity pneumonitis (Mroz et al., 2009).
4. Beryllium Sensitization and CBD in the Workforce
    Sensitization to beryllium is currently detected in the workforce 
with the beryllium lymphocyte proliferation test (BeLPT), a laboratory 
blood test developed in the 1980s, also referred to as the LTT 
(Lymphocyte Transformation Test) or BeLT (Beryllium Lymphocyte 
Transformation Test). In this test, lymphocytes obtained from either 
bronchoalveolar lavage fluid (the BAL BeLPT) or from peripheral blood 
(the blood BeLPT) are cultured in vitro and exposed to beryllium 
sulfate to stimulate lymphocyte proliferation. The observation of 
beryllium-specific proliferation indicates beryllium sensitization. 
Hereafter, ``BeLPT'' generally refers to the blood BeLPT, which is 
typically used in screening for beryllium sensitization. This test is 
described in more detail in subsection D.5.b.
    CBD can be detected at an asymptomatic stage by a number of 
techniques including bronchoalveolar lavage and biopsy (Cordeiro et 
al., 2007; Maier, 2001). Bronchoalveolar lavage is a method of 
``washing'' the lungs with fluid inserted via a flexible fiberoptic 
instrument known as a bronchoscope, removing the fluid and analyzing 
the content for the inclusion of immune cells reactive to beryllium 
exposure, as described earlier in this section. Fiberoptic bronchoscopy 
can be used to detect granulomatous lung inflammation prior to the 
onset of CBD symptoms as well, and has been used in combination with 
the BeLPT to diagnose pre-symptomatic CBD in a number of recent 
screening studies of beryllium-exposed workers, which are discussed in 
the following section detailing diagnostic procedures. Of workers who 
were found to be sensitized and underwent clinical evaluation, 31-49 
percent of them were diagnosed with CBD (Kreiss et al., 1993; Newman et 
al., 1996, 2005, 2007; Mroz, 2009), however some estimate that with 
increased surveillance the percent could be much higher (Newman, 2005; 
Mroz, 2009). It has been estimated from ongoing surveillance studies of 
sensitized individuals with an average follow-up time of 4.5 years that 
31 percent of beryllium-sensitized employees were estimated to progress 
to CBD (Newman et al., 2005). A study of nuclear weapons facility 
employees enrolled in an ongoing medical surveillance program found 
that only 20 percent of sensitized workers employed less than 5 years 
eventually were diagnosed with CBD, while 40 percent of sensitized 
workers employed 10 years or more developed CBD (Stange et al., 2001). 
One limitation for all these studies is lack of long-term follow-up. It 
may be necessary to continue to monitor these workers in order to 
determine whether all BeS workers will develop CBD (Newman et al., 
2005).
    CBD has a clinical spectrum ranging from evidence of beryllium 
sensitization and granulomas in the lung with little symptomatology to 
loss of lung function and end stage disease which may result in the 
need for lung transplantation and decreased life expectancy. 
Unfortunately, there are very few published clinical studies describing 
the full range and progression of CBD from the beginning to the end 
stages and very few of the risk factors for progression of disease have 
been delineated (NAS, 2008). Clinical management of CBD is modeled 
after sarcoidosis where oral corticosteroid treatment is initiated in 
patients who have evidence of progressive lung disease, although 
progressive lung disease has not been well defined (NAS, 2008). In 
advanced cases of CBD, corticosteroids are the standard treatment (NAS, 
2008). No comprehensive studies have been published measuring the 
overall effect of removal of workers from beryllium exposure on 
sensitization and CBD (NAS, 2008) although this has been suggested as 
part of an overall treatment regime for CBD (Mapel et al., 2002; Sood 
et al., 2004; Maier et al., 2006; Sood, 2009; Maier et al., 2012). Sood 
et al. reported that cessation of exposure can sometimes have 
beneficial effects on lung function (Sood et al., 2004). However, this 
was based on anecdotal evidence from six patients with CBD, so more 
research is needed to better determine the relationship between

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exposure duration and disease progression
5. Human Epidemiological Studies
    This section describes the human epidemiological data supporting 
the mechanistic overview of beryllium-induced disease in workers. It 
has been divided into reviews of epidemiological studies performed 
prior to development and implementation of the BeLPT in the late 1980s 
and after wide use of the BeLPT for screening purposes. Use of the 
BeLPT has allowed investigators to screen for beryllium sensitization 
and CBD prior to the onset of clinical symptoms, providing a more 
sensitive and thorough analysis of the worker population. The 
discussion of the studies has been further divided by manufacturing 
processes that may have similar exposure profiles. Table A.1 in the 
Appendix summarizes the prevalence of beryllium sensitization and CBD, 
range of exposure measurements, and other salient information from the 
key epidemiological studies.
    It has been well-established that beryllium exposure, either via 
inhalation or skin, may lead to beryllium sensitization, or, with 
inhalation exposure, may lead to the onset and progression of CBD. The 
available published epidemiological literature discussed below provides 
strong evidence of beryllium sensitization and CBD in workers exposed 
to airborne beryllium well below the current OSHA PEL of 2 [mu]g/m\3\. 
Several studies demonstrate the prevalence of sensitization and CBD is 
related to the level of airborne exposure, including a cross-sectional 
survey of employees at a beryllium ceramics plant in Tucson, AZ 
(Henneberger et al., 2001), case-control studies of workers at the 
Rocky Flats nuclear weapons facility (Viet et al., 2000), and workers 
from a beryllium machining plant in Cullman, AL (Kelleher et al., 
2001). The prevalence of beryllium sensitization also may be related to 
dermal exposure. An increased risk of CBD has been reported in workers 
with skin lesions, potentially increasing the uptake of beryllium 
(Curtis, 1951; Johnson et al., 2001; Schuler et al., 2005). Three 
studies describe comprehensive preventive programs, which included 
expanded respiratory protection, dermal protection, and improved 
control of beryllium dust migration, that substantially reduced the 
rate of beryllium sensitization among new hires (Cummings et al., 2007; 
Thomas et al., 2009; Bailey et al., 2010; Schuler et al., 2012).
    Some of the epidemiological studies presented in this review suffer 
from challenges common to many published epidemiological studies: 
Limitations in study design (particularly cross-sectional); small 
sample size; lack of personal and/or short-term exposure data, 
particularly those published before the late 1990s; and incomplete 
information regarding specific chemical form and/or particle 
characterization. Challenges that are specific to beryllium 
epidemiological studies include: uncertainty regarding the contribution 
of dermal exposure; use of various BeLPT protocols; a variety of case 
definitions for determining CBD; and use of various exposure sampling/
assessment methods (e.g., daily weighted average (DWA), lapel 
sampling). Even with these limitations, the epidemiological evidence 
presented in this section clearly demonstrates that beryllium 
sensitization and CBD are continuing to occur from present-day 
exposures below OSHA's PEL. The available literature also indicates 
that the rate of BeS can be substantially lowered by reducing 
inhalation exposure and minimizing dermal contact.
a. Studies Conducted Prior to the BeLPT
    First reports of CBD came from studies performed by Hardy and 
Tabershaw (1946). Cases were observed in industrial plants that were 
refining and manufacturing beryllium metal and beryllium alloys and in 
plants manufacturing fluorescent light bulbs (NAS, 2008). From the late 
1940s through the 1960s, clusters of non-occupational CBD cases were 
identified around beryllium refineries in Ohio and Pennsylvania, and 
outbreaks in family members of beryllium factory workers were assumed 
to be from exposure to contaminated clothes (Hardy, 1980). It had been 
established that the risk of disease among beryllium workers was 
variable and generally rose with the levels of airborne concentrations 
(Machle et al., 1948). And while there was a relationship between air 
concentrations of beryllium and risk of developing disease both in and 
surrounding these plants, the disease rates outside the plants were 
higher than expected and not very different from the rate of CBD within 
the plants (Eisenbud et al., 1949; Lieben and Metzner, 1959). There 
remained considerable uncertainty regarding diagnosis due to lack of 
well-defined cohorts, modern diagnostic methods, or inadequate follow-
up. In fact, many patients with CBD may have been misdiagnosed with 
sarcoidosis (NAS, 2008).
    The difficulties in distinguishing lung disease caused by beryllium 
from other lung diseases led to the establishment of the BCR in 1952 to 
identify and track cases of ABD and CBD. A uniform diagnostic criterion 
was introduced in 1959 as a way to delineate CBD from sarcoidosis. 
Patient entry into the BCR required either: documented past exposure to 
beryllium or the presence of beryllium in lung tissue as well as 
clinical evidence of beryllium disease (Hardy et al., 1967); or any 
three of the six criteria listed below (Hasan and Kazemi, 1974). 
Patients identified using the above criteria were registered and added 
to the BCR from 1952 through 1983 (Eisenbud and Lisson, 1983).
    The BCR listed the following criteria for diagnosing CBD (Eisenbud 
and Lisson, 1983):
    (1) Establishment of significant beryllium exposure based on sound 
epidemiologic history;
    (2) Objective evidence of lower respiratory tract disease and 
clinical course consistent with beryllium disease;
    (3) Chest X-ray films with radiologic evidence of interstitial 
fibronodular disease;
    (4) Evidence of restrictive or obstructive defect with diminished 
carbon monoxide diffusing capacity (DLCO) by physiologic 
studies of lung function;
    (5) Pathologic changes consistent with beryllium disease on 
examination of lung tissue; and
    (6) Presence of beryllium in lung tissue or thoracic lymph nodes.
    Prevalence of CBD in workers during the time period between the 
1940s and 1950s was estimated to be between 1-10% (Eisenbud and Lisson, 
1983). In a 1969 study, Stoeckle et al. presented 60 case histories 
with a selective literature review utilizing the above criteria except 
that urinary beryllium was substituted for lung beryllium to 
demonstrate beryllium exposure. Stoeckle et al. (1969) were able to 
demonstrate corticosteroids as a successful treatment option in one 
case of confirmed CBD. This study also presented a 28 percent mortality 
rate from complications of CBD at the time of publication. However, 
even with the improved methodology for determining CBD based on the BCR 
criteria, these studies suffered from lack of well-defined cohorts, 
modern diagnostic techniques or adequate follow-up.
b. Criteria for Beryllium Sensitization and CBD Case Definition 
Following the Development of the BeLPT
    The criteria for diagnosis of CBD have evolved over time as more 
advanced

[[Page 47595]]

diagnostic technology, such as the (blood) BeLPT and BAL BeLPT, has 
become available. More recent diagnostic criteria have both higher 
specificity than earlier methods and higher sensitivity, identifying 
subclinical effects. Recent studies typically use the following 
criteria (Newman et al., 1989; Pappas and Newman, 1993; Maier et al., 
1999):
    (1) History of beryllium exposure;
    (2) Histopathological evidence of noncaseating granulomas or 
mononuclear cell infiltrates in the absence of infection; and
    (3) Positive blood or BAL BeLPT (Newman et al., 1989).
    The availability of transbronchial lung biopsy facilitates the 
evaluation of the second criterion, by making histopathological 
confirmation possible in almost all cases.
    A significant component for the identification of CBD is the 
demonstration of a confirmed abnormal BeLPT result in a blood or BAL 
sample (Newman, 1996). Since the development of the BeLPT in the 1980s, 
it has been used to screen beryllium-exposed workers for sensitization 
in a number of studies to be discussed below. The BeLPT is a non-
invasive in vitro blood test which measures the beryllium antigen-
specific T-cell mediated immune response and is the most commonly 
available diagnostic tool for identifying beryllium sensitization. The 
BeLPT measures the degree to which beryllium stimulates lymphocyte 
proliferation under a specific set of conditions, and is interpreted 
based upon the number of stimulation indices that exceed the normal 
value. The `cut-off' is based on the mean value of the peak stimulation 
index among controls plus 2 or 3 standard deviations. This methodology 
was modeled into a statistical method known as the ``least absolute 
values'' or ``statistical-biological positive'' method and relies on 
natural log modeling of the median stimulation index values (DOE, 2001; 
Frome, 2003). In most applications, two or more stimulation indices 
that exceed the cut-off constitute an abnormal test.
    Early versions of the BeLPT test had high variability, but the use 
of tritiated thymidine to identify proliferating cells has led to a 
more reliable test (Mroz et al., 1991; Rossman et al., 2001). In recent 
years, the peripheral blood test has been found to be as sensitive as 
the BAL assay, although larger abnormal responses have been observed 
with the BAL assay (Kreiss et al., 1993; Pappas and Newman, 1993). 
False negative results have also been observed with the BAL BeLPT in 
cigarette smokers who have marked excess of alveolar macrophages in 
lavage fluid (Kreiss et al., 1993). The BeLPT has also been a useful 
tool in animal studies to identify those species with a beryllium-
specific immune response (Haley et al., 1994).
    Screenings for beryllium sensitization have been conducted using 
the BeLPT in several occupational surveys and surveillance programs, 
including nuclear weapons facilities operated by the Department of 
Energy (Viet et al., 2000; Strange et al., 2001; DOE/HSS Report, 2006), 
a beryllium ceramics plant in Arizona (Kreiss et al., 1996; Henneberger 
et al., 2001; Cummings et al., 2007), a beryllium production plant in 
Ohio (Kreiss et al., 1997; Kent et al., 2001), a beryllium machining 
facility in Alabama (Kelleher et al., 2001; Madl et al., 2007), a 
beryllium alloy plant (Schuler et al., 2005, Thomas et al., 2009), and 
another beryllium processing plant (Rosenman et al., 2005) in 
Pennsylvania. In most of these studies, individuals with an abnormal 
BeLPT result were retested and were identified as sensitized (i.e., 
confirmed positive) if the abnormal result was repeated.
    There has been criticism regarding the reliability and specificity 
of the BeLPT as a screening tool (Borak et al., 2006). Stange et al. 
(2004) studied the reliability and laboratory variability of the BeLPT 
by splitting blood samples and sending samples to two laboratories 
simultaneously for BeLPT analysis. Stange et al. found the range of 
agreement on abnormal (positive BeLPT) results was 26.2--61.8 percent 
depending upon the labs tested (Stange et al., 2004). Borak et al. 
(2006) contended that the positive predictive value (PPV) (PPV is the 
portion of patients with positive test result correctly diagnosed) is 
not high enough to meet the criteria of a good screening tool. 
Middleton et al. (2008) used the data from the Stange et al. (2004) 
study to estimate the PPV and determined that the PPV of the BeLPT 
could be improved from 0.383 to 0.968 when an abnormal BeLPT result is 
confirmed with a second abnormal result (Middleton et al., 2008). 
However, an apparent false positive can occur in people not 
occupationally exposed to beryllium (NAS, 2008). An analysis of survey 
data from the general workforce and new employees at a beryllium 
manufacturer was performed to assess the reliability of the BeLPT 
(Donovan et al. 2007). Donovan et al. analyzed more than 10,000 test 
results from nearly 2400 participants over a 12-year period. Donovan et 
al. found that approximately 2 percent of new employees had at least 
one positive BeLPT at the time of hire and 1 percent of new hires with 
no known occupational exposure were confirmed positive at the time of 
hire with two BeLPTs. Since there are currently no alternatives to the 
BeLPT in a screening program many programs rely on a second test to 
confirm a positive result (NAS, 2008).
    The epidemiological studies presented in this section utilized the 
BeLPT as either a surveillance tool or a screening tool for determining 
sensitization status and/or sensitization/CBD prevalence in workers for 
inclusion in the published studies. Most epidemiological studies have 
reported rates of sensitization and disease based on a single screening 
of a working population (`cross-sectional' or 'population prevalence' 
rates). Studies of workers in a beryllium machining plant and a nuclear 
weapons facility have included follow-up of the population originally 
screened, resulting in the detection of additional cases of 
sensitization over several years (Newman et al., 2001, Stange et al., 
2001). OSHA regards the BeLPT as a reliable medical surveillance tool. 
The BeLPT is discussed in more detail in Non-Mandatory Appendix A to 
the proposed standard, Immunological Testing for the Determination of 
Beryllium Sensitization.
c. Beryllium Mining and Extraction
    Mining and extraction of beryllium usually involves the two major 
beryllium minerals, beryl (an aluminosilicate containing up to 4 
percent beryllium) and bertrandite (a beryllium silicate hydrate 
containing generally less than 1 percent beryllium) (WHO, 2001). The 
United States is the world leader in beryllium extraction and also 
leads the world in production and use of beryllium and its alloys (WHO, 
2001). Most exposures from mining and extraction come in the form of 
beryllium ore, beryllium salts, beryllium hydroxide (NAS 2008) or 
beryllium oxide (Stefaniak et al., 2008).
    Deubner et al. published a study of 75 workers employed at a 
beryllium mining and extraction facility in Delta, UT (Deubner et al., 
2001b). Of the 75 workers surveyed for sensitization with the BeLPT, 
three were identified as sensitized by an abnormal BeLPT result. One of 
those found to be sensitized was diagnosed with CBD. Exposures at the 
facility included primarily beryllium ore and salts. General area (GA), 
breathing zone (BZ), and personal lapel (LP) exposure samples were 
collected from 1970 to 1999. Jobs involving beryllium hydrolysis and 
wet-grinding activities had the highest air concentrations, with an 
annual median GA concentration ranging from 0.1 to 0.4 [mu]g/m\3\. 
Median BZ concentrations

[[Page 47596]]

were higher than either LP or GA. The average duration of exposure for 
beryllium sensitized workers was 21.3 years (27.7 years for the worker 
with CBD), compared to an average duration for all workers of 14.9 
years. However, these exposures were less than either the Elmore, OH, 
or Tucson, AZ, facilities described below, which also had higher 
reported rates of BeS and CBD. A study by Stefaniak et al. (2008) 
demonstrated that beryllium was present at the mill in three forms: 
mineral, poorly crystalline oxide, and hydroxide.
    There was no sensitization or CBD among those who worked only at 
the mine where exposure to beryllium resulted solely from working with 
bertrandite ore. The authors concluded that the results of this study 
indicated that beryllium ore and salts may pose less of a hazard than 
beryllium metal and beryllium hydroxide. These results are consistent 
with the previously discussed animal studies examining solubility and 
particle size.
d. Beryllium Metal Processing and Alloy Production
    Kreiss et al. (1997) conducted a study of workers at a beryllium 
production facility in Elmore, OH. The plant, which opened in 1953 and 
initially specialized in production of beryllium-copper alloy, later 
expanded its operations to include beryllium metal, beryllium oxide, 
and beryllium-aluminum alloy production; beryllium and beryllium alloy 
machining; and beryllium ceramics production, which was moved to a 
different factory in the early 1980s. Production operations included a 
wide variety of jobs and processes, such as work in arc furnaces and 
furnace rebuilding, alloy melting and casting, beryllium powder 
processing, and work in the pebble plant. Non-production work included 
jobs in the analytical laboratory, engineering research and 
development, maintenance, laundry, production-area management, and 
office-area administration. While the publication refers to the use of 
respiratory protection in some areas, such as the pebble plant, the 
extent of its use across all jobs or time periods was not reported. Use 
of dermal PPE was not reported.
    The authors characterized exposures at the plant using industrial 
hygiene (IH) samples collected between 1980 and 1993. The exposure 
samples and the plant's formulas for estimating workers' DWA exposures 
were used, together with study participants' work histories, to 
estimate their cumulative and average beryllium exposure levels. 
Exposure concentrations reflected the high exposures found historically 
in beryllium production and processing. Short-term BZ measurements had 
a median of 1.4, with 18.5 percent of samples exceeding OSHA's STEL of 
5.0 [mu]g/m\3\. Particularly high beryllium concentrations were 
reported in the areas of beryllium powder production, laundry, alloy 
arc furnace (approximately 40 percent of DWA estimates over 2.0 [mu]g/
m\3\) and furnace rebuild (28.6 percent of short-term BZ samples over 
the OSHA STEL of 5 [mu]g/m\3\). LP samples (n = 179), which were 
available from 1990 to 1992, had a median value of 1 [mu]g/m\3\.
    Of 655 workers employed at the time of the study, 627 underwent 
BeLPT screening. Blood samples were divided and split between two labs 
for analysis, with repeat testing for results that were abnormal or 
indeterminate. Thirty-one workers had an abnormal blood test upon 
initial testing and at least one of two subsequent tests was classified 
as sensitized. These workers, together with 19 workers who had an 
initial abnormal result and one subsequent indeterminate result, were 
offered clinical evaluation for CBD including the BAL-BeLPT and 
transbronchial lung biopsy. Nine with an initial abnormal test followed 
by two subsequent normal tests were not clinically evaluated, although 
four were found to be sensitized upon retesting in 1995. Of 47 workers 
who proceeded with evaluation for CBD (3 of the 50 initial workers with 
abnormal results declined to participate), 24 workers were diagnosed 
with CBD based on evidence of granulomas on lung biopsy (20 workers) or 
on other findings consistent with CBD (4 workers) (Kreiss et al., 
1997). After including five workers who had been diagnosed prior to the 
study, a total of 29 (4.6 percent) current workers were found to have 
CBD. In addition, the plant medical department identified 24 former 
workers diagnosed with CBD before the study.
    Kreiss et al. reported that the highest prevalence of sensitization 
and CBD occurred among workers employed in beryllium metal production, 
even though the highest airborne total mass concentrations of beryllium 
were generally among employees operating the beryllium alloy furnaces 
in a different area of the plant (Kreiss et al., 1997). Preliminary 
follow-up investigations of particle size-specific sampling at five 
furnace sites within the plant determined that the highest respirable 
(e.g., particles <10 [mu]m in diameter as defined by the authors) and 
alveolar-deposited (e.g., particles <1 [mu]m in diameter as defined by 
the authors) beryllium mass and particle number concentrations, as 
collected by a general area impactor device, were measured at the 
beryllium metal production furnaces rather than the beryllium alloy 
furnaces (Kent et al., 2001; McCawley et al., 2001). A statistically 
significant linear trend was reported between the above alveolar-
deposited particle mass concentration and prevalence of CBD and 
sensitization in the furnace production areas. The authors concluded 
that alveolar-deposited particles may be a more relevant exposure 
metric for predicting the incidence of CBD or sensitization than the 
total mass concentration of airborne beryllium.
    Bailey et al. (2010) evaluated the effectiveness of a workplace 
preventive program in lowering BeS at the beryllium metal, oxide, and 
alloy production plant studied by Kreiss et al. (1997). The preventive 
program included use of administrative and PPE controls (e.g., improved 
training, skin protection and other PPE, half-mask or air-purified 
respirators, medical surveillance, improved housekeeping standards, 
clean uniforms) as well as engineering controls (e.g., migration 
controls, physical separation of administrative offices from production 
facilities) implemented over the course of five years.
    In a cross-sectional/longitudinal hybrid study, Bailey et al. 
compared rates of sensitization in pre-program workers to those hired 
after the preventive program began. Pre-program workers were surveyed 
cross-sectionally in 1993-1994, and again in 1999 using the BeLPT to 
determine sensitization and CBD prevalence rates. The 1999 cross-
sectional survey was conducted to determine if improvements in 
engineering and administrative controls were successful, however, 
results indicated no improvement in reducing rates of sensitization or 
CBD.
    An enhanced preventive program including particle migration 
control, respiratory and dermal protection, and process enclosure was 
implemented in 2000, with continuing improvements made to the program 
in 2001, 2002-2004, and 2005. Workers hired during this period were 
longitudinally surveyed for sensitization using the BeLPT. Both the 
pre-program and program survey of worker sensitization status utilized 
split-sample testing to verify positive test results using the BeLPT. 
Of the total 660 workers employed at the production plant, 258 workers 
participated from the pre-program group while 290 participated from the 
program group (206 partial program, 84 full program). Prevalence 
comparisons of the pre-program and

[[Page 47597]]

program groups (partial and full) were performed by calculating 
prevalence ratios. A 95 percent confidence interval (95 percent CI) was 
derived using a cohort study method that accounted for the variance in 
survey techniques (cross-sectional versus longitudinal) (Bailey et al., 
2010). The sensitization prevalence of the pre-program group was 3.8 
times higher (95 percent CI, 1.5-9.3) than the program group, 4.0 times 
higher (95 percent CI, 1.4-11.6) than the partial program subgroup, and 
3.3 times higher (95 percent CI, 0.8-13.7) than the full program 
subgroup indicating that a comprehensive preventive program can reduce, 
but not eliminate, occurrence of sensitization among non-sensitized 
workers (Bailey et al., 2010).
    Rosenman et al. (2005) studied a group of several hundred workers 
who had been employed at a beryllium production and processing facility 
that operated in eastern Pennsylvania between 1957 and 1978. Of 715 
former workers located, 577 were screened for BeS with the BLPT and 544 
underwent chest radiography to identify cases of BeS and CBD. Workers 
were reported to have exposure to beryllium dust and fume in a variety 
of chemical forms including beryl ore, beryllium metal, beryllium 
fluoride, beryllium hydroxide, and beryllium oxide.
    Rosenman et al. used the plant's DWA formulas to assess workers' 
full-shift exposure levels, based on IH data collected between 1957-
1962 and 1971-1976, to calculate exposure metrics including cumulative, 
average, and peak for each worker in the study. The DWA was calculated 
based on air monitoring that consisted of GA and short-term task-based 
BZ samples. Workers' exposures to specific chemical and physical forms 
of beryllium were assessed, including insoluble beryllium (metal and 
oxide), soluble beryllium (fluoride and hydroxide), mixed soluble and 
insoluble beryllium, beryllium dust (metal, hydroxide, or oxide), fume 
(fluoride), and mixed dust and fume. Use of respiratory or dermal 
protection by workers was not reported. Exposures in the plant were 
high overall. Representative task-based IH samples ranged from 0.9 [mu] 
g/m\3\ to 84 [mu] g/m\3\ in the 1960s, falling to a range of 0.5-16.7 
[mu] g/m\3\ in the 1970s. A large number of workers' mean DWA estimates 
(25 percent) were above the OSHA PEL of 2.0 [mu] g/m\3\, while most 
workers had mean DWA exposures between 0.2 and 2.0 [mu] g/m\3\ (74 
percent) or below 0.02 [mu] g/m\3\ (1 percent) (Rosenman et al., Table 
11; revised erratum April, 2006).
    Blood samples for the BeLPT were collected from the former workers 
between 1996 and 2001 and were evaluated at a single laboratory. 
Individuals with an abnormal test result were offered repeat testing, 
and were classified as sensitized if the second test was also abnormal. 
Sixty workers with two positive BeLPTs and 50 additional workers with 
chest radiography suggestive of disease were offered clinical 
evaluation, including bronchoscopy with bronchial biopsy and BAL-BeLPT. 
Seven workers met both criteria. Only 56 (51 percent) of these workers 
proceeded with clinical evaluation, including 57 percent of those 
referred on the basis of confirmed abnormal BeLPT and 47 percent of 
those with abnormal radiographs.
    Of those workers who underwent bronchoscopy, 32 (5.5 percent) with 
evidence of granulomas were classified as ``definite'' CBD cases. 
Twelve (2.1 percent) additional workers with positive BAL-BeLPT or 
confirmed positive BeLPT and radiographic evidence of upper lobe 
fibrosis were classified as ``probable'' CBD cases. Forty workers (6.9 
percent) without upper lobe fibrosis who had confirmed abnormal BeLPT, 
but who were not biopsied or who underwent biopsy with no evidence of 
granuloma, were classified as sensitized without disease. It is not 
clear how many of the 40 workers underwent biopsy. Another 12 (2.1 
percent) workers with upper lobe fibrosis and negative or unconfirmed 
positive BeLPT were classified as ``possible'' CBD cases. Nine 
additional workers who were diagnosed with CBD before the screening 
were included in some parts of the authors' analysis.
    The authors reported a total prevalence of 14.5 percent for CBD 
(definite and probable) and sensitization. This rate, considerably 
higher than the overall prevalence of sensitization and disease in 
several other worker cohorts as described earlier in this section, 
reflects in part the very high exposures experienced by many workers 
during the plant's operation in the 1950s, 1960s and 1970s. A total of 
115 workers had mean DWAs above the OSHA PEL of 2 [mu] g/m\3\. Of 
those, 7 (6.0 percent) had definite or probable CBD and another 13 (11 
percent) were classified as sensitized without disease. The true 
prevalence of CBD in the group may be higher than reported, due to the 
low rate of clinical evaluation among sensitized workers.
    Although most of the workers in this study had high exposures, 
sensitization and CBD also were observed within the small subgroup of 
participants believed to have relatively low beryllium exposures. 
Thirty-three cases of CBD and 24 additional cases of sensitization 
occurred among 339 workers with mean DWA exposures below OSHA's PEL of 
2.0 [mu] g/m\3\ (Rosenman et al., Table 11, erratum 2006). Ten cases of 
sensitization and five cases of CBD were found among office and 
clerical workers, who were believed to have low exposures (levels not 
reported).
    Follow-up time for sensitization screening of workers in this study 
who became sensitized during their employment had a minimum of 20 years 
to develop CBD prior to screening. In this sense the cohort is 
especially well suited to compare the exposure patterns of workers with 
CBD and those sensitized without disease, in contrast to several other 
studies of workers with only recent beryllium exposures. Rosenman et 
al. characterized and compared the exposures of workers with definite 
and probable CBD, sensitization only, and no disease or sensitization 
using chi-squared tests for discrete outcomes and analysis of variance 
(ANOVA) for continuous variables (cumulative, mean, and peak exposure 
levels). Exposure-response relationships were further examined with 
logistic regression analysis, adjusting for potential confounders 
including smoking, age, and beryllium exposure from outside of the 
plant. The authors found that cumulative, peak, and duration of 
exposure were significantly higher for workers with CBD than for 
sensitized workers without disease (p <0.05), suggesting that the risk 
of progressing from sensitization to CBD is related to the level or 
extent of exposure a worker experiences. The risk of developing CBD 
following sensitization appeared strongly related to exposure to 
insoluble forms of beryllium, which are cleared slowly from the lung 
and increase beryllium lung burden more rapidly than quickly mobilized 
soluble forms. Individuals with CBD had higher exposures to insoluble 
beryllium than those classified as sensitized without disease, while 
exposure to soluble beryllium was higher among sensitized individuals 
than those with CBD.
    Cumulative, mean, peak, and duration of exposure were found to be 
comparable for workers with CBD and workers without sensitization or 
CBD (``normal'' workers). Cumulative, peak, and duration of exposure 
were significantly lower for sensitized workers without disease than 
for normal workers. Rosenman et al. suggested that genetic 
predisposition to sensitization and CBD may have obscured an exposure-
response relationship in this study, and plan to control for genetic 
risk factors in future studies. Exposure misclassification from the 
1950s and 1960s may have been another limitation in this study, 
introducing bias that

[[Page 47598]]

could have influenced the lack of exposure response. It is also unknown 
if the 25 percent who died from CBD-related conditions may have had 
higher exposures.
    A follow-up was conducted of the cross-sectional study of a 
population of workers first evaluated by Kreiss et al. (1997) and 
Rosenman et al. (2005) at a beryllium production and processing 
facility in eastern Pennsylvania by Schuler et al. (2012), and in a 
companion study by Virji et al. (2012). Schuler et al. evaluated the 
worker population employed in 1999 with six years or less work tenure 
in a cross-sectional study. The investigators evaluated the worker 
population by administering a work history questionnaire with a follow-
up examination for sensitization and CBD. A job-exposure matrix (JEM) 
was combined with work histories to create individual estimates of 
average, cumulative, and highest-job-related exposure for total, 
respirable, and sub-micron beryllium mass concentration. Of the 291 
eligible workers, 90.7 percent (264) participated in the study. 
Sensitization prevalence was 9.8 percent (26/264) with CBD prevalence 
of 2.3 percent (6/264). The investigators found a general pattern of 
increasing sensitization prevalence as the exposure quartile increased 
indicating an exposure-response relationship. The investigators found 
positive associations with both total and respirable mass concentration 
with sensitization (average and highest job) and CBD (cumulative). 
Increased sensitization prevalence was observed with metal oxide 
production alloy melting and casting, and maintenance. CBD was 
associated with melting and casting. The investigators summarized that 
both total and respirable mass concentration were relevant predictors 
of risk (Schuler et al., 2012).
    In the companion study by Virji et al. (2012), the investigators 
reconstructed historical exposure from 1994 to 1999 utilizing the 
personal sampling data collected in 1999 as baseline exposure estimates 
(BEE). The study evaluated techniques for reconstructing historical 
data to evaluate exposure-response relationships for epidemiological 
studies. The investigators constructed JEMs using the BEE and estimates 
of annual changes in exposure for 25 different process areas. The 
investigators concluded these reconstructed JEMs could be used to 
evaluate a range of exposure parameters from total, respirable and 
submicron mass concentration including cumulative, average, and highest 
exposure. These two studies demonstrate that high-quality exposure 
estimates can be developed both for total mass and respirable mass 
concentrations.
e. Beryllium Machining Operations
    Newman et al. (2001) and Kelleher et al. (2001) studied a group of 
235 workers at a beryllium metal machining plant. Since the plant 
opened in 1969, its primary operations have been machining and 
polishing beryllium metal and high-beryllium content composite 
materials, with occasional machining of beryllium oxide/metal matrix 
(`E-metal'), and beryllium alloys. Other functions include machining of 
metals other than beryllium; receipt and inspection of materials; acid 
etching; final inspection, quality control, and shipping of finished 
materials; tool making; and engineering, maintenance, administrative 
and supervisory functions (Newman et al., 2001; Madl et al., 2007). 
Machining operations, including milling, grinding, lapping, deburring, 
lathing, and electrical discharge machining (EDM), were performed in an 
open-floor plan production area. Most non-machining jobs were located 
in a separate, adjacent area; however, non-production employees had 
access to the machining area.
    Engineering and administrative measures, rather than PPE, were 
primarily used to control beryllium exposures at the plant (Madl et 
al., 2007). Based on interviews with long-standing employees of the 
plant, Kelleher et al. reported that work practices were relatively 
stable until 1994, when a worker was diagnosed with CBD and a new 
exposure control program was initiated. Between 1995 and 1999 new 
engineering and work practice controls were implemented, including 
removal of pressurized air hoses and discouragement of dry sweeping 
(1995), enclosure of deburring processes (1996), mandatory uniforms 
(1997), and installation or updating of local exhaust ventilation (LEV) 
in EDM, lapping, deburring, and grinding processes (1998) (Madl et al., 
2007). Throughout the plant's history, respiratory protection was used 
mainly for ``unusually large, anticipated exposures'' to beryllium 
(Kelleher et al., 2001), and was not routinely used otherwise (Newman 
et al., 2001).
    All workers at the plant participated in a beryllium disease 
surveillance program initiated in 1994, and were screened for beryllium 
sensitization with the BeLPT beginning in 1995. A BeLPT result was 
considered abnormal if two or more of six stimulation indices exceeded 
the normal range (see section on BeLPT testing above), and was 
considered borderline if one of the indices exceeded the normal range. 
A repeat BeLPT was conducted for workers with abnormal or borderline 
initial results. Workers were identified as beryllium sensitized and 
referred for a clinical evaluation, including bronchoalveolar lavage 
(BAL) and transbronchial lung biopsy, if the repeat test was abnormal. 
CBD was diagnosed upon evidence of sensititization with granulomas or 
mononuclear cell infiltrates in the lung tissue (Newman et al., 2001). 
Following the initial plant-wide screening, plant employees were 
offered BeLPT testing at two-year intervals. Workers hired after the 
initial screening were offered a BeLPT within 3 months of their hire 
date, and at 2-year intervals thereafter (Madl et al., 2007).
    Kelleher et al. performed a nested case-control study of the 235 
workers evaluated in Newman et al. (2001) to evaluate the relationship 
between beryllium exposure levels and risk of sensitization and CBD 
(Kelleher et al., 2001). The authors evaluated exposures at the plant 
using IH samples they had collected between 1996 and 1999, using 
personal cascade impactors designed to measure the mass of beryllium 
particles less than 6 [mu] m, particles less than 1 [mu]m in diameter, 
and total mass. The great majority of workers' exposures were below the 
OSHA PEL of 2 [mu] g/m\3\. However, a few higher levels were observed 
in machining jobs including deburring, lathing, lapping, and grinding. 
Based on a statistical comparison between their samples and historical 
data provided by the plant, the authors concluded that worker beryllium 
exposures across all time periods could be approximated using the 1996-
1999 data. They estimated workers' cumulative and `lifetime weighted' 
(LTW) beryllium exposure based on the exposure samples they collected 
for each job in 1996-1999 and company records of each worker's job 
history.
    Twenty workers with beryllium sensitization or CBD (cases) were 
compared to 206 workers (controls) for the case-control analysis from 
the study evaluating workers originally conducted by Newman et al. 
Thirteen workers were diagnosed with CBD based on lung biopsy evidence 
of granulomas and/or mononuclear cell infiltrates (11) or positive BAL 
results with evidence of lymphocytosis (2). Seven were evaluated for 
CBD and found to be sensitized only, thus twenty composing the case 
group. Nine of the remaining 215 workers first identified in original 
study (Newman et al., 2001) were

[[Page 47599]]

excluded due to incomplete job history information, leaving 206 workers 
in the control group.
    Kelleher et al.'s analysis included comparisons of the case and 
control groups' median exposure levels; calculation of odds ratios for 
workers in high, medium, and low exposure groups; and logistic 
regression testing of the association of sensitization or CBD with 
exposure level and other variables. Median cumulative exposures for 
total mass, particles <6 [mu] m, and particles <1 [mu]m were 
approximately three times higher among the cases than controls, 
although the relationships observed were not statistically significant 
(p values ~ 0.2). No clear difference between cases and controls was 
observed for the median LTW exposures. Odds ratios with sensitization 
and CBD as outcomes were elevated in high (upper third) and 
intermediate exposure groups relative to low (lowest third) exposure 
groups for both cumulative and LTW exposure, though the results were 
not statistically significant (p > 0.1). In the logistic regression 
analysis, only machinist work history was a significant predictor of 
case status in the final model. Quantitative exposure measures were not 
significant predictors of sensitization or disease risk.
    Citing an 11.5 percent prevalence of beryllium sensitization or CBD 
among machinists as compared with 2.9 percent prevalence among workers 
with no machinist work history, the authors concluded that the risk of 
sensitization and CBD is increased among workers who machine beryllium. 
Although differences between cases and controls in median cumulative 
exposure did not achieve conventional thresholds for statistical 
significance, the authors noted that cumulative exposures were 
consistently higher among cases than controls for all categories of 
exposure estimates and for all particle sizes, suggesting an effect of 
cumulative exposure on risk. The levels at which workers developed CBD 
and sensitization were predominantly below OSHA's current PEL of 2 [mu] 
g/m\3\, and no cases of sensitization or CBD were observed among 
workers with LTW exposure <0.02 [mu]g/m\3\. Twelve (60 percent) of the 
20 sensitized workers had LTW exposures > 0.20 [mu] g/m\3\.
    In 2007, Madl et al. published an additional study of 27 workers at 
the machining plant who were found to be sensitized or diagnosed with 
CBD between the start of medical surveillance in 1995 and 2005. As 
previously described, workers were offered a BeLPT in the initial 1995 
screening (or within 3 months of their hire date if hired after 1995) 
and at 2-year intervals after their first screening. Workers with two 
positive BeLPTs were identified as sensitized and offered clinical 
evaluation for CBD, including bronchoscopy with BAL and transbronchial 
lung biopsy. The criteria for CBD in this study were somewhat stricter 
than those used in the Newman et al. study, requiring evidence of 
granulomas on lung biopsy or detection of X-ray or pulmonary function 
changes associated with CBD, in combination with two positive BeLPTs or 
one positive BAL-BeLPT.
    Based on the history of the plant's control efforts and their 
analysis of historical IH data, Madl et al. identified three ``exposure 
control eras'': A relatively uncontrolled period from 1980-1995; a 
transitional period from 1996 to 1999; and a relatively well-controlled 
``modern'' period from 2000-2005. They found that the engineering and 
work practice controls instituted in the mid-1990s reduced workers' 
exposures substantially, with nearly a 15-fold difference in reported 
exposure levels between the pre-control and the modern period (Madl et 
al., 2007). Madl et al. estimated workers' exposures using LP samples 
collected between 1980 and 2005, including those collected by Kelleher 
et al., and work histories provided by the plant. As described more 
fully in the study, they used a variety of approaches to describe 
individual workers' exposures, including approaches designed to 
characterize the highest exposures workers were likely to have 
experienced. Their exposure-response analysis was based primarily on an 
exposure metric they derived by identifying the year and job of each 
worker's pre-diagnosis work history with the highest reported 
exposures. They used the upper 95th percentile of the LP samples 
collected in that job and year (in some cases supplemented with data 
from other years) to characterize the worker's upper-level exposures.
    Based on their estimates of workers' upper level exposures, Madl et 
al. concluded that workers with sensitization or CBD were likely to 
have been exposed to airborne beryllium levels greater than 0.2 [mu]g/
m\3\ as an 8-hour TWA at some point in their history of employment in 
the plant. They also concluded that most sensitization and CBD cases 
were likely to have been exposed to levels greater than 0.4 [mu]g/m\3\ 
at some point in their work at the plant. Madl et al. did not 
reconstruct exposures for workers at the plant who did not have 
sensitization or CBD and therefore could not determine whether non-
cases had upper-bound exposures lower than these levels. They found 
that upper-bound exposure estimates were generally higher for workers 
with CBD than for those who were sensitized but not diagnosed with CBD 
at the conclusion of the study (Madl et al., 2007). Because CBD is an 
immunological disease and beryllium sensitization has been shown to 
occur within a year of exposure for some workers, Madl et al. argued 
that their estimates of workers' short-term upper-bound exposures may 
better capture the exposure levels that led to sensitization and 
disease than estimates of long-term cumulative or average exposures 
such as the LTW exposure measure constructed by Kelleher et al. (Madl 
et al., 2007).
f. Beryllium Oxide Ceramics
    Kreiss et al. (1993) conducted a screening of current and former 
workers at a plant that manufactured beryllium ceramics from beryllium 
oxide between 1958 and 1975, and then transitioned to metalizing 
circuitry onto beryllium ceramics produced elsewhere. Of the plant's 
1,316 current and 350 retired workers, 505 participated who had not 
previously been diagnosed with CBD or sarcoidosis, including 377 
current and 128 former workers. Although beryllium exposure was not 
estimated quantitatively in this survey, the authors conducted a 
questionnaire to assess study participants' exposures qualitatively. 
Results showed that 55 percent of participants reported working in jobs 
with exposure to beryllium dust. Close to 25 percent of participants 
did not know if they had exposure to beryllium, and just over 20 
percent believed they had not been exposed.
    BeLPT tests were administered to all 505 participants in the 1989-
1990 screening period and evaluated at a single lab. Seven workers had 
confirmed abnormal BeLPT results and were identified as sensitized; 
these workers were also diagnosed with CBD based on findings of 
granulomas upon clinical evaluation. Radiograph screening led to 
clinical evaluation and diagnosis of two additional CBD cases, who were 
among three participants with initially abnormal BeLPT results that 
could not be confirmed on repeat testing. In addition, nine workers had 
been previously diagnosed with CBD, and another five were diagnosed 
shortly after the screening period, in 1991-1992.
    Eight (3.7 percent of the screening population) of the nine CBD 
cases identified in the screening population were hired before the 
plant stopped producing beryllium ceramics in 1975, and were among the 
216 participants who had reported having been near or

[[Page 47600]]

exposed to beryllium dust. Particularly high CBD rates of 11.1-15.8 
percent were found among screening participants who had worked in 
process development/engineering, dry pressing, and ventilation 
maintenance jobs believed to have high or uncontrolled dust exposure. 
One case (0.6 percent) of CBD was diagnosed among the 171 study 
participants who had been hired after the plant stopped producing 
beryllium ceramics. Although this worker was hired eight years after 
the end of ceramics production, he had worked in an area later found to 
be contaminated with beryllium dust. The authors concluded that the 
study results suggested an exposure-response relationship between 
beryllium exposure and CBD, and recommended beryllium exposure control 
to reduce workers' risk of CBD.
    Kreiss et al. later published a study of workers at a second 
ceramics plant located in Tucson, AZ (Kreiss et al., 1996), which since 
1980 had produced beryllium ceramics from beryllium oxide powder 
manufactured elsewhere. IH measurements collected between 1981 and 
1992, primarily GA or short-term BZ samples and a few (<100) LP 
samples, were available from the plant. Airborne beryllium exposures 
were generally low. The majority of area samples were below the 
analytical detection limit of 0.1 [mu]g/m\3\, while LP and short-term 
BZ samples had medians of 0.3 [mu]g/m\3\. However, 3.6 percent of 
short-term BZ samples and 0.7 percent of GA samples exceeded 5.0 [mu]g/
mg\3\, while LP samples ranged from 0.1 to 1.8 [mu]g/m\3\. Machining 
jobs had the highest beryllium exposure levels among job tasks, with 
short-term BZ samples significantly higher for machining jobs than for 
non-machining jobs (median 0.6 [mu]g/m\3\ vs. 0.3 [mu]g/mg\3\, p = 
0.0001). The authors used DWA formulas provided by the plant to 
estimate workers' full-shift exposure levels, and to calculate 
cumulative and average beryllium exposures for each worker in the 
study. The median cumulative exposure was 591.7 mg-days/m\3\ and the 
median average exposure was 0.35 [mu]g/m\3\.
    One hundred thirty-six of the 139 workers employed at the plant at 
the time of the Kreiss et al. (1996) study underwent BeLPT screening 
and chest radiographs in 1992. Blood samples were split between two 
laboratories. If one or both test results were abnormal, an additional 
sample was collected and split between the labs. Seven workers with an 
abnormal result on two draws were initially identified as sensitized. 
Those with confirmed abnormal BeLPTs or abnormal chest X-rays were 
offered clinical evaluation for CBD, including transbronchial lung 
biopsy and BAL BeLPT. CBD was diagnosed based on observation of 
granulomas on lung biopsy, in five of the six sensitized workers who 
accepted evaluation. An eighth case of sensitization and sixth case of 
CBD were diagnosed in one worker hired in October 1991 whose initial 
BeLPT was normal, but who was confirmed as sensitized and found to have 
lung granulomas less than two years later, after sustaining a 
beryllium-contaminated skin wound. The plant medical department 
reported 11 additional cases of CBD among former workers (Kreiss et 
al., 1996). The overall prevalence of sensitization in the plant was 
5.9 percent, with a 4.4 percent prevalence of CBD.
    Kreiss et al. reported that six (75 percent) of the eight 
sensitized workers were exposed as machinists during or before the 
period October 1985-March 1988, when measurements were first available 
for machining jobs. The authors reported that 14.3 percent of 
machinists were sensitized, compared to 1.2 percent of workers who had 
never been machinists (p <0.01). Workers' estimated cumulative and 
average beryllium exposures did not differ significantly for machinists 
and non-machinists, or for cases and non-cases. As in the previous 
study of the same ceramics plant published by Kreiss et al. in 1993, 
one case of CBD was diagnosed in a worker who had never been employed 
in a production job. This worker was employed in administration, a job 
with a median DWA of 0.1 [mu]g/m\3\ (range 0.1-0.3).
    In 1998, Henneberger et al. conducted a follow-up cross-sectional 
survey of 151 employees employed at the beryllium ceramics plant 
studied by Kreiss et al. (1996) (Henneberger et al., 2001). Employees 
were eligible who either had not participated in the Kreiss et al. 
survey (``short-term workers''--74 of those studied by Henneberger et 
al.), or who had participated and were not found to have sensitization 
or disease (``long-term workers''--77 of those studied by Henneberger 
et al.).
    The authors estimated workers' cumulative, average, and peak 
beryllium exposures based on the plant's formulas for estimating job-
specific DWA exposures, participants' work histories, and area and 
short-term task-specific BZ samples collected from the start of full 
production at the plant in 1981 to 1998. The long-term workers, who 
were hired before the 1992 study was conducted, had generally higher 
estimated exposures (median of average exposures--0.39 [mu]g/m\3\; 
mean--14.9 [mu]g/m\3\) than the short-term workers, who were hired 
after 1992 (median 0.28 [mu]g/m\3\, mean 6.1 [mu]g/m\3\).
    Fifteen cases of sensitization were found, including eight among 
short-term and seven among long-term workers. Eight of the 15 workers 
were found to have CBD. Of the workers diagnosed with CBD, seven (88 
percent) were long-term workers. One non-sensitized long-term worker 
and one sensitized long-term worker declined clinical examination.
    Henneberger et al. reported a higher prevalence of sensitization 
among long-term workers with ``high'' (greater than median) peak 
exposures compared to long-term workers with ``low'' exposures; 
however, this relationship was not statistically significant. No 
association was observed for average or cumulative exposures. The 
authors reported higher prevalence of sensitization (but not 
statistically significant) among short-term workers with ``high'' 
(greater than median) average, cumulative, and peak exposures compared 
to short-term workers with ``low'' exposures of each type.
    The cumulative incidence of sensitization and CBD was investigated 
in a cohort of 136 workers at the beryllium ceramics plant previously 
studied by the Kreiss and Henneberger groups (Schuler et al., 2008). 
The study cohort consisted of those who participated in the plant-wide 
BeLPT screening in 1992. Both current and former workers from this 
group were invited to participate in follow-up BeLPT screenings in 
1998, 2000, and 2002-03. A total of 106 of the 128 non-sensitized 
individuals in 1992 participated in the 11-year follow-up. 
Sensitization was defined as a confirmed abnormal BeLPT based on the 
split blood sample-dual laboratory protocol described earlier. CBD was 
diagnosed in sensitized individuals based on pathological findings from 
transbronchial biopsy and BAL fluid analysis. The 11-year crude 
cumulative incidence of sensitization and CBD was 13 percent (14 of 
106) and 8 percent (9 of 106) respectively. The cumulative prevalence 
was about triple the point prevalences determined in the initial 1992 
cross-sectional survey. The corrected cumulative prevalences for those 
that ever worked in machining were nearly twice that for non-
machinists. The data illustrate the value of longitudinal medical 
screening over time to obtain a more accurate estimate of the 
occurrence of sensitization and CBD among an exposed working 
population.
    Following the 1998 survey, the company continued efforts to reduce

[[Page 47601]]

exposures and risk of sensitization and CBD by implementing additional 
engineering, administrative, and PPE measures (Cummings et al., 2007). 
Respirator use was required in production areas beginning in 1999, and 
latex gloves were required beginning in 2000. The lapping area was 
enclosed in 2000, and enclosures were installed for all mechanical 
presses in 2001. Between 2000 and 2003, water-resistant or water-proof 
garments, shoe covers, and taped gloves were incorporated to keep 
beryllium-containing fluids from wet machining processes off the skin. 
The new engineering measures did not appear to substantially reduce 
airborne beryllium levels in the plant. LP samples collected between 
2000 and 2003 had a median of 0.18 [mu]g/m\3\, similar to the 1994-1999 
samples. However, respiratory protection requirements to control 
workers' airborne beryllium exposures were instituted prior to the 2000 
sample collections.
    To test the efficacy of the new measures instituted after 1998, in 
January 2000 the company began screening new workers for sensitization 
at the time of hire and at 3, 6, 12, 24, and 48 months of employment. 
These more stringent measures appear to have substantially reduced the 
risk of sensitization among new employees. Of 126 workers hired between 
2000 and 2004, 93 completed BeLPT testing at hire and at least one 
additional test at 3 months of employment. One case of sensitization 
was identified at 24 months of employment (1 percent). This worker had 
experienced a rash after an incident of dermal exposure to lapping 
fluid through a gap between his glove and uniform sleeve, indicating 
that he may have become sensitized via the skin. He was tested again at 
48 months of employment, with an abnormal result.
    A second worker in the 2000-2004 group had two abnormal BeLPT tests 
at the time of hire, and a third had one abnormal test at hire and a 
second abnormal test at 3 months. Both had normal BeLPTs at 6 months, 
and were not tested thereafter. A fourth worker had one abnormal BeLPT 
result at the time of hire, a normal result at 3 months, an abnormal 
result at 6 months, and a normal result at 12 months. Four additional 
workers had one abnormal result during surveillance, which could not be 
confirmed upon repeat testing.
    Cummings et al. calculated two sensitization rates based on these 
screening results: (1) a rate using only the sensitized worker 
identified at 24 months, and (2) a rate including all four workers who 
had repeated abnormal results. They reported a sensitization incidence 
rate (IR) of 0.7 per 1,000 person-months to 2.7 per 1,000 person-months 
for the workers hired between 2000 and 2004, using the sum of 
sensitization-free months of employment among all 93 workers as the 
denominator.
    The authors also estimated an incidence rate (IR) of 5.6 per 1,000 
person-months for workers hired between 1993 and the 1998 survey. This 
estimated IR was based on one BeLPT screening, rather than BeLPTs 
conducted throughout the workers' employment. The denominator in this 
case was the total months of employment until the 1998 screening. 
Because sensitized workers may have been sensitized prior to the 
screening, the denominator may overestimate sensitization-free time in 
the legacy group, and the actual sensitization IR for legacy workers 
may be somewhat higher than 5.6 per 1,000 person-months. Based on 
comparison of the IRs, the authors concluded that the addition of 
respirator use, dermal protection, and housekeeping improvements 
appeared to have reduced the risk of sensitization among workers at the 
plant, even though airborne beryllium levels in some areas of the plant 
had not changed significantly since the 1998 survey.
g. Copper-Beryllium Alloy Processing and Distribution
    Schuler et al. (2005) studied a group of 152 workers at a facility 
processing copper-beryllium alloys and small quantities of nickel-
beryllium alloys, and converting semi-finished alloy strip and wire 
into finished strip, wire and rod. Production activities included 
annealing, drawing, straightening, point and chamfer, rod and wire 
packing, die grinding, pickling, slitting, and degreasing. Periodically 
in the plant's history, they also did salt baths, cadmium plating, 
welding and deburring. Since the late 1980s, rod and wire production 
processes were physically segregated from strip metal production. 
Production support jobs included mechanical maintenance, quality 
assurance, shipping and receiving, inspection, and wastewater 
treatment. Administration was divided into staff primarily working 
within the plant and personnel who mostly worked in office areas 
(Schuler, et al., 2005). Workers' respirator use was limited, mostly to 
occasional tasks where high exposures were anticipated.
    Following the 1999 diagnosis of a worker with CBD, the company 
surveyed the workforce, offering all current employees BeLPT testing in 
2000 and offering sensitized workers clinical evaluation for CBD, 
including BAL and transbronchial biopsy. Of the facility's 185 
employees, 152 participated in the BeLPT screening. Samples were split 
between two laboratories, with additional draws and testing for 
confirmation if conflicting tests resulted in the initial draw. Ten 
participants (7 percent) had at least two abnormal BeLPT results. The 
results of nine workers who had abnormal BeLPT results from only one 
laboratory were not included because the authors believed it was 
experiencing technical problems with the test (Schuler et al., 2005). 
CBD was diagnosed in six workers (4 percent) on evidence of pathogenic 
abnormalities (e.g., granulomas) or evidence of clinical abnormalities 
consistent with CBD based on pulmonary function testing, pulmonary 
exercise testing, and/or chest radiography. One worker diagnosed with 
CBD had been exposed to beryllium during previous work at another 
copper-beryllium processing facility.
    Schuler et al. evaluated airborne beryllium levels at the plant 
using IH samples collected between 1969 and 2000, including 4,524 GA 
samples, 650 LP samples and 815 short-duration (3-5 min) high volume 
(SD-HV) BZ task-specific samples. Occupational exposures to airborne 
beryllium were generally low. Ninety-nine percent of all LP 
measurements were below the current OSHA PEL of 2.0 [mu]g/m\3\ (8-hr 
TWA); 93 percent were below the DOE action level of 0.2 [mu]g/m\3\; and 
the median value was 0.02 [mu]g/m\3\. The SD-HV BZ samples had a median 
value of 0.44 [mu]g/m\3\, with 90 percent below the OSHA Short-Term 
Exposure Limit (STEL) of 5.0 [mu]g/m\3\. The highest levels of 
beryllium were found in rod and wire production, particularly in wire 
annealing and pickling, the only production job with a median personal 
sample measurement greater than 0.1 [mu]g/m\3\ (median 0.12 [mu]g/m\3\; 
range 0.01-7.8 [mu]g/m\3\) (Schuler et al., Table 4). These 
concentrations were significantly higher than the exposure levels in 
the strip metal area (median 0.02, range 0.01-0.72 [mu]g/m\3\), in 
production support jobs (median 0.02, range <0.01-0.33 [mu]g/m\3\), 
plant administration (median 0.02, range <0.01-0.11 [mu]g/m\3\), and 
office administration jobs (median 0.01, range <0.01-0.06 [mu]g/m\3\).
    The authors reported that eight of the ten sensitized employees, 
including all six CBD cases, had worked in both major production areas 
during their tenure with the plant. The 7 percent prevalence (6 of 81 
workers) of CBD among employees who had ever worked in rod and wire was 
statistically

[[Page 47602]]

significantly elevated compared with employees who had never worked in 
rod and wire (p <0.05), while the 6 percent prevalence (6 of 94 
workers) among those who had worked in strip metal was not 
significantly elevated compared to non-strip metal workers (p > 0.1). 
Based on these results, together with the higher exposure levels 
reported for the rod and wire production area, Schuler et al. concluded 
that work in rod and wire was a key risk factor for CBD in this 
population. Schuler et al. also found a high prevalence (13 percent) of 
sensitization among workers who had been exposed to beryllium for less 
than a year at the time of the screening, a rate similar to that found 
by Henneberger et al. among beryllium ceramics workers exposed for one 
year or less (16 percent, Henneberger et al., 2001). All four workers 
who were sensitized without disease had been exposed 5 years or less; 
conversely, all six of the workers with CBD had first been exposed to 
beryllium at least five years prior to the screening (Schuler et al., 
Table 2).
    As has been seen in other studies, beryllium sensitization and CBD 
were found among workers who were typically exposed to low time-
weighted average airborne concentrations of beryllium. While jobs in 
the rod and wire area had the highest exposure levels in the plant, the 
median personal sample value was only 0.12 [mu]g/m\3\. However, workers 
may have occasionally been exposed to higher beryllium levels for short 
periods during specific tasks. A small fraction of personal samples 
recorded in rod and wire were above the OSHA PEL of 2.0 [mu]g/m\3\, and 
half of workers with sensitization or CBD reported that they had 
experienced a ``high-exposure incident'' at some point in their work 
history (Schuler et al., 2005). The only group of workers with no cases 
of sensitization or CBD, a group of 26 office administration workers, 
was the group with the lowest recorded exposures (median personal 
sample 0.01 [mu]g/m\3\, range <0.01-0.06 [mu]g/m\3\).
    After the BeLPT screening was conducted in 2000, the company began 
implementing new measures to further reduce workers' exposure to 
beryllium (Thomas et al., 2009). Requirements designed to minimize 
dermal contact with beryllium, including long-sleeve facility uniforms 
and polymer gloves, were instituted in production areas in 2000. In 
2001 the company installed LEV in die grinding and polishing. LP 
samples collected between June 2000 and December 2001 show reduced 
exposures plant-wide. Of 2,211 exposure samples collected, 98 percent 
were below 0.2 [mu]g/m\3\, and 59 percent below the limit of detection 
(LOD), which was either 0.02 [micro]g/m\3\ or 0.2 [micro]g/m\3\ 
depending on the method of sample analysis (Thomas et al., 2009). 
Median values below 0.03 [mu]g/m\3\ were reported for all processes 
except the wire annealing and pickling process. Samples for this 
process remained somewhat elevated, with a median of 0.1 [mu]g/m\3\. In 
January 2002, the plant enclosed the wire annealing and pickling 
process in a restricted access zone (RAZ), requiring respiratory PPE in 
the RAZ and implementing stringent measures to minimize the potential 
for skin contact and beryllium transfer out of the zone. While exposure 
samples collected by the facility were sparse following the enclosure, 
they suggest exposure levels comparable to the 2000-01 samples in areas 
other than the RAZ. Within the RAZ, required use of powered air-
purifying respirators indicates that respiratory exposure was 
negligible.
    To test the efficacy of the new measures in preventing 
sensitization and CBD, in June 2000 the facility began an intensive 
BeLPT screening program for all new workers. The company screened 
workers at the time of hire; at intervals of 3, 6, 12, 24, and 48 
months; and at 3-year intervals thereafter. Among 82 workers hired 
after 1999, three (3.7 percent) cases of sensitization were found. Two 
(5.4 percent) of 37 workers hired prior to enclosure of the wire 
annealing and pickling process were found to be sensitized within 3 and 
6 months of beginning work at the plant. One (2.2 percent) of 45 
workers hired after the enclosure was confirmed as sensitized.
    Thomas et al. calculated a sensitization IR of 1.9 per 1,000 
person-months for the workers hired after the exposure control program 
was initiated in 2000 (``program workers''), using the sum of 
sensitization-free months of employment among all 82 workers as the 
denominator (Thomas et al., 2009). They calculated an estimated IR of 
3.8 per 1,000 person-months for 43 workers hired between 1993 and 2000 
who had participated in the 2000 BeLPT screening (``legacy workers''). 
This estimated IR was based on one BeLPT screening, rather than BeLPTs 
conducted throughout the legacy workers' employment. The denominator in 
this case is the total months of employment until the 2000 screening. 
Because sensitized workers may have been sensitized prior to the 
screening, the denominator may overestimate sensitization-free time in 
the legacy group, and the actual sensitization IR for legacy workers 
may be somewhat higher than 3.8 per 1,000 person-months. Based on 
comparison of the IRs and the prevalence rates discussed previously, 
the authors concluded that the combination of dermal protection, 
respiratory protection, housekeeping improvements and engineering 
controls implemented beginning in 2000 appeared to have reduced the 
risk of sensitization among workers at the plant. However, they noted 
that the small size of the study population and the short follow-up 
time for the program workers suggested that further research is needed 
to confirm the program's efficacy (Thomas et al., 2009).
    Stanton et al. (2006) conducted a study of workers in three 
different copper-beryllium alloy distribution centers in the United 
States. The distribution centers, including one bulk products center 
established in 1963 and strip metal centers established in 1968 and 
1972, sell products received from beryllium production and finishing 
facilities and small quantities of copper-beryllium, aluminum-
beryllium, and nickel-beryllium alloy materials. Work at distribution 
centers does not require large-scale heat treatment or manipulation of 
material typical of beryllium processing and machining plants, but 
involves final processing steps that can generate airborne beryllium. 
Slitting, the main production activity at the two strip product 
distribution centers, generates low levels of airborne beryllium 
particles, while operations such as tensioning and welding used more 
frequently at the bulk products center can generate somewhat higher 
levels. Non-production jobs at all three centers included shipping and 
receiving, palletizing and wrapping, production-area administrative 
work, and office-area administrative work.
    The authors estimated workers' beryllium exposures using IH data 
from company records and job history information collected through 
interviews conducted by a company occupational health nurse. Stanton et 
al. evaluated airborne beryllium levels in various jobs based on 393 
full-shift LP samples collected from 1996 to 2004. Airborne beryllium 
levels at the plant were generally very low, with 54 percent of all 
samples at or below the LOD, which ranged from 0.02 to 0.1 [mu]g/m\3\. 
The authors reported a median of 0.03 [mu]g/m\3\ and an arithmetic mean 
of 0.05 [mu]g/m\3\ for the 393 full-shift LP samples, where samples 
below the LOD were assigned a value of half the applicable LOD. Median 
and geometric mean values for specific jobs ranged from 0.01-0.07 and 
0.02-0.07 [micro]g/m\3\, respectively. All measurements were

[[Page 47603]]

below the OSHA PEL of 2.0 [mu]g/m\3\ and 97 percent were below the DOE 
action level of 0.2 [mu]g/m\3\. The paper does not report use of 
respiratory or skin protection. Exposure conditions may have changed 
somewhat over the history of the plant due to changes in exposure 
control measures, including improvements to product and container 
cleaning practices instituted during the 1990s.
    Eighty-eight of the 100 workers (88 percent) employed at the three 
centers at the time of the study participated in screening for 
beryllium sensitization. Blood samples were collected between November 
2000 and March 2001 by the company's medical staff. Samples collected 
from employees of the strip metal centers were split and evaluated at 
two laboratories, while samples from the bulk product center workers 
were evaluated at a single laboratory. Participants were considered to 
be ``sensitized'' to beryllium if two or more BeLPT results, from two 
laboratories or from repeat testing at the same laboratory, were found 
to be abnormal. One individual was found to be sensitized and was 
offered clinical evaluation, including BAL and fiberoptic bronchoscopy. 
He was found to have lung granulomas and was diagnosed with CBD.
    The worker diagnosed with CBD had been employed at a strip metal 
distribution center from 1978 to 2000 as a shipper and receiver, 
loading and unloading trucks delivering materials from a beryllium 
production facility and to the distribution center's customers. 
Although the LP samples collected for his job between 1996 and 2000 
were generally low (n = 35, median 0.01, range < 0.02-0.13 [micro]g/
m\3\), it is not clear whether these samples adequately characterize 
his exposure conditions over the course of his work history. He 
reported that early in his work history, containers of beryllium oxide 
powder were transported on the trucks he entered. While he did not 
recall seeing any breaks or leaks in the beryllium oxide containers, 
some containers were known to have been punctured by forklifts on 
trailers used by the company during the period of his employment, and 
could have contaminated trucks he entered. With 22 years of employment 
at the facility, this worker had begun beryllium-related work earlier 
and performed it longer than about 90 percent of the study population 
(Stanton et al., 2006).
h. Nuclear Weapons Production Facilities & Cleanup of Former Facilities
    Primary exposure from nuclear weapons production facilities comes 
from beryllium metal and beryllium alloys. A study conducted by Kreiss 
et al. (1989) documented sensitization and CBD among beryllium-exposed 
workers in the nuclear industry. A company medical department 
identified 58 workers with beryllium exposure among a work force of 
500, of whom 51 (88 percent) participated in the study. Twenty-four 
workers were involved in research and development (R&D), while the 
remaining 27 were production workers. The R&D workers had a longer 
tenure with a mean time from first exposure of 21.2 years, compared to 
a mean time since first exposure of 5 years among the production 
workers. The number of workers with abnormal BeLPT readings was 6, with 
4 being diagnosed with CBD. This resulted in an estimated 11.8 percent 
prevalence of sensitization.
    Kreiss et al. (1993) expanded the work of Kreiss et al. (1989) by 
performing a cross-sectional study of 895 (current and former) 
beryllium workers in the same nuclear weapons plant. Participants were 
placed in qualitative exposure groups (``no exposure,'' ``minimal 
exposure,'' ``intermittent exposure,'' and ``consistent exposure'') 
based on questionnaire responses. The number of workers with abnormal 
BeLPT totaled 18 with 12 being diagnosed with CBD. Three additional 
workers with sensitization developed CBD over the next 2 years. 
Sensitization occurred in all of the qualitatively defined exposure 
groups. Individuals who had worked as machinists were statistically 
overrepresented among beryllium-sensitized cases, compared with non-
cases. Cases were more likely than non-cases to report having had a 
measured overexposure to beryllium (p = 0.009), a factor which proved 
to be a significant predictor of sensitization in logistic regression 
analyses, as was exposure to beryllium prior to 1970. Beryllium 
sensitized cases were also significantly more likely to report having 
had cuts that were delayed in healing (p = 0.02). The authors concluded 
that individual variability and susceptibility along with exposure 
circumstances are important factors in developing beryllium 
sensitization and CBD.
    In 1991, the Beryllium Health Surveillance Program (BHSP) was 
established at the Rocky Flats Nuclear Weapons Facility to offer BLPT 
screening to current and former employees who may have been exposed to 
beryllium (Stange et al., 1996). Participants received an initial BeLPT 
and follow-ups at one and three years. Based on histologic evidence of 
pulmonary granulomas and a positive BAL-BeLPT, Stange et al. published 
a study of 4,397 BHSP participants tested from June 1991 to March 1995, 
including current employees (42.8 percent) and former employees (57.2 
percent). Twenty-nine cases of CBD and 76 cases of sensitization were 
identified. The sensitization rate for the population was 2.43 percent. 
Available exposure data included fixed airhead (FAH) exposure samples 
collected between 1970 and 1988 (mean concentration 0.016 [micro]g/
m\3\) and personal samples collected between 1984 and 1987 (mean 
concentration 1.04 [micro]g/m\3\). Cases of CBD and sensitization were 
noted in individuals in all jobs classifications, including those 
believed to involve minimal exposure to beryllium. The authors 
recommended ongoing surveillance for workers in all jobs with potential 
for beryllium exposure.
    Stange et al. (2001) extended the previous study, evaluating 5,173 
participants in the Rocky Flats BHSP who were tested between June 1991 
and December 1997. Three-year serial testing was offered to employees 
who had not been tested for three years or more and did not show 
beryllium sensitization during the previous study. This resulted in 
2,891 employees being tested. Of the 5,173 workers participating in the 
study, 172 were found to have abnormal BeLPT. Ninety-eight (3.33 
percent) of the workers were found to be sensitized (confirmed abnormal 
BeLPT results) in the initial screening, conducted in 1991. Of these 
workers 74 were diagnosed with CBD (history of beryllium exposure, 
evidence of non-caseating granulomas or mononuclear cell infiltrates on 
lung biopsy, and a positive BeLPT or BAL-BeLPT). A follow-up survey of 
2,891 workers three years later identified an additional 56 sensitized 
workers and an additional seven cases of CBD. Sensitization and CBD 
rates were analyzed with respect to gender, building work locations, 
and length of employment. Historical employee data included hire date, 
termination date, leave of absences, and job title changes. Exposure to 
beryllium was determined by job categories and building or work area 
codes. Personal beryllium air monitoring results were used, when 
available, from employees with the same job title or similar job. 
However, no quantitative information was presented in the study. The 
authors conclude that for some individuals, exposure to beryllium at 
levels less that the OSHA PEL could cause sensitization and CBD.
    Viet et al. (2001) conducted a case-control study of the Rocky 
Flats worker population studied by Stange et al. (1996 and 2001) to 
examine the relationship between estimated

[[Page 47604]]

beryllium exposure level and risk of sensitization or CBD. The worker 
population included 74 beryllium-sensitized workers and 50 workers 
diagnosed with CBD. Beryllium exposure levels were estimated based on 
FAH airhead samples from one building, the beryllium machine shop. 
These were collected away from the BZ of the machine operator and 
likely underestimated exposure. To estimate levels in other locations, 
these air sample concentrations were used to construct a job exposure 
matrix that included the determination of the Building 444 exposure 
estimates for a 30-year period; each subject's work history by job 
location, task, and time period; and assignment of exposure estimates 
to each combination of job location, task, and time period as compared 
to Building 444 machinists. The authors adjusted the levels observed in 
the machine shop by factors based on interviews with former workers. 
Workers' estimated mean exposure concentrations ranged from 0.083 
[micro]g/m\3\ to 0.622 [micro]g/m\3\. Estimated maximum air 
concentrations ranged from 0.54 [micro]g/m\3\ to 36.8 [micro]g/m\3\. 
Cases were matched to controls of the same age, race, gender, and 
smoking status (Viet et al., 2001).
    Estimated mean and cumulative exposure levels and duration of 
employment were found to be significantly higher for CBD cases than for 
controls. Estimated mean exposure levels were significantly higher for 
sensitization cases than for controls. No significant difference was 
observed for estimated cumulative exposure or duration of exposure. 
Similar results were found using logistic regression analysis, which 
identified statistically significant relationships between CBD and both 
cumulative and mean estimated exposure, but did not find significant 
relationships between estimated exposure levels and sensitization 
without CBD. Comparing CBD with sensitization cases, Viet et al. found 
that workers with CBD had significantly higher estimated cumulative and 
mean beryllium exposure levels than workers who were sensitized, but 
did not have CBD.
    Johnson et al. (2001) conducted a review of personal sampling 
records and medical surveillance reports at an atomic weapons 
establishment in Cardiff, United Kingdom. The study evaluated airborne 
samples collected over the 36-year period of operation for the plant. 
Data included 367,757 area samples and 217,681 personal lapel samples 
from 194 workers over the time period from 1981-1997. Data was 
available prior to this time period but was not analyzed since this 
data was not available electronically. The authors estimated that over 
the 17 years of measurement data analyzed, airborne beryllium 
concentrations did exceed 2.0 [micro]g/m\3\, however, due to the 
limitations with regard to collection times it is difficult to assess 
the full reliability of this estimate. The authors noted that in the 
entire plant's history, only one case of CBD had been diagnosed. It was 
also noted that BeLPT has not been routinely conducted among any of the 
workers at this facility.
    Armojandi et al. (2010) conducted a cross-sectional study of 
workers at a nuclear weapons research and development (R&D) facility to 
determine the risk of developing CBD in sensitized workers at 
facilities with exposures much lower than production plants. Of the 
1875 current or former workers at the R&D facility, 59 were determined 
to be sensitized based on at least two positive BeLPTs (i.e., samples 
drawn on two separate occasions or on split samples tested in two 
separate DOE-approved laboratories) for a sensitization rate of 3.1 
percent. Workers found to have positive BeLPTs were further evaluated 
in an Occupational Medicine Clinic between 1999 through 2005. Armojandi 
et al. (2010) evaluated 50 of the sensitized workers who also had 
medical and occupational histories, physical examination, chest imaging 
with high-resolution computed tomography (HRCT) (N = 49), and pulmonary 
function testing (nine of the 59 workers refused physical examinations 
so were not included in this study). Forty of the 50 workers chosen for 
this study underwent bronchoscopy for bronchoalveolar lavage and 
transbronchial biopsies in additional to the other testing. Five of the 
49 workers had CBD at the time of evaluation (based on histology or 
high-resolution computed tomography); three others had evidence of 
probable CBD; however, none of these cases were classified as severe at 
the time of evaluation. The rate of CBD at the time of study among 
sensitized individuals was 12.5 percent (5/40) for those using 
pathologic review of lung tissue, and 10.2 percent (5/49) for those 
using HRCT as a criteria for diagnosis. The rate of CBD among the 
entire population (5/1875) was 0.3 percent.
    The mean duration of employment at the facility was 18 years, and 
the mean latency period (from first possible exposure) to time of 
evaluation and diagnosis was 32 years. There was no available exposure 
monitoring in the breathing zone of workers at the facility but the 
beryllium levels were believed to be relatively low (possibly less than 
0.1 [mu]g/m\3\ for most jobs). There was not an apparent exposure-
response relationship for sensitization or CBD. The sensitization 
prevalence was similar and the CBD prevalence higher among workers with 
the lower-exposure jobs. The authors concluded that these sensitized 
workers, who were subjected to an extended duration of low potential 
beryllium exposures over a long latency period, had a low prevalence of 
CBD (Armojandi et al., 2010).
i. Aluminum Smelting
    Bauxite ore, the primary source of aluminum, contains naturally 
occurring beryllium. Worker exposure to beryllium can occur at aluminum 
smelting facilities where aluminum extraction occurs via electrolytic 
reduction of aluminum oxide into aluminum metal. Characterization of 
beryllium exposures and sensitization prevalence rates were examined by 
Taiwo et al. (2010) in a study of nine aluminum smelting facilities 
from four different companies in the U.S., Canada, Italy and Norway.
    Of the 3,185 workers determined to be potentially exposed to 
beryllium, 1,932 agreed to participate in a medical surveillance 
program between 2000 and 2006 (60 percent participation rate). The 
medical surveillance program included serum BeLPT analysis, 
confirmation of an abnormal BeLPT with a second BeLPT, and follow-up of 
all confirmed positive responses by a pulmonary physician to evaluate 
for progression to CBD.
    Eight-hour TWAs were assessed utilizing 1,345 personal samples 
collected from the 9 smelters. The personal beryllium samples obtained 
showed a range of 0.01-13.00 [mu]g/m\3\ time-weighted average with an 
arithmetic mean of 0.25 [mu]g/m\3\ and geometric mean of 0.06 [mu]g/
m\3\. Exposure levels to beryllium observed in aluminum smelters are 
similar to those seen in other industries that utilize beryllium. Of 
the 1,932 workers surveyed by BeLPT, nine workers were diagnosed with 
sensitization (prevalence rate of 0.47 percent, 95% confidence interval 
= 0.21-0.88 percent) with 2 of these workers diagnosed with probable 
CBD after additional medical evaluations.
    The authors concluded that compared with beryllium-exposed workers 
in other industries, the rate of sensitization among aluminum smelter 
workers appears lower. The authors speculated that this lower observed 
rate could be related to a more soluble form of beryllium found in the 
aluminum smelting work environment as well as

[[Page 47605]]

the consistent use of respiratory protection. However, the authors also 
speculated that the 60 percent participation rate may have 
underestimated the sensitization rate in this worker population.
    A study by Nilsen et al. (2010) also found a low rate of 
sensitization among aluminum workers in Norway. Three-hundred sixty-two 
workers and thirty-one control individuals were tested for beryllium 
sensitization based on the BeLPT. The results found that one (0.28%) of 
the smelter workers had been sensitized. No borderline results were 
reported. The exposure estimated in this plant was 0.1 [micro]g/m\3\ to 
0.31 [micro]g/m\3\ (Nilsen et al., 2010).
6. Animal Models of CBD
    This section reviews the relevant animal studies supporting the 
mechanisms outlined above. Researchers have attempted to identify 
animal models with which to further investigate the mechanisms 
underlying the development of CBD. A suitable animal model should 
exhibit major characteristics of CBD, including the demonstration of a 
beryllium-specific immune response, the formation of immune granulomas 
following inhalation exposure to beryllium, and mimicking the 
progressive nature of the human disease. While exposure to beryllium 
has been shown to cause chronic granulomatous inflammation of the lung 
in animal studies using a variety of species, most of the granulomatous 
lesions were formed by foreign-body reactions, which result from 
persistent irritation and consist predominantly of macrophages and 
monocytes, and small numbers of lymphocytes. Foreign-body granulomas 
are distinct from the immune granulomas of CBD, which are caused by 
antigenic stimulation of the immune system and contain large numbers of 
lymphocytes. Animal studies have been useful in providing biological 
plausibility for the role of immunological alterations and lung 
inflammation and in clarifying certain specific mechanistic aspects of 
beryllium disease. However, the lack of a dependable animal model that 
mimics all facets of the human response combined with study limitations 
in terms of single dose experiments, few animals, or abbreviated 
observation periods have limited the utility of the data. Currently, no 
single model has completely mimicked the disease process as it 
progresses in humans. The following is a discussion of the most 
relevant animal studies regarding the mechanisms of sensitization and 
CBD development in humans. Table A.2 in the Appendix summarizes 
species, route, chemical form of beryllium, dose levels, and 
pathological findings of the key studies.
    Harmsen et al. performed a study to assess whether the beagle dog 
could provide an adequate model for the study of beryllium-induced lung 
diseases (Harmsen et al., 1986). One group of dogs served as a control 
group (air inhalation only) and four other groups received high 
(approximately 50 [mu]g/kg) and low (approximately 20 [mu]g/kg) doses 
of beryllium oxide calcined at 500 [deg]C or 1,000[deg] C, administered 
as aerosols in a single exposure. As discussed above, calcining 
temperature controls the solubility and SSA of beryllium particles. 
Those particles calcined at higher temperatures (e.g., 1,000[deg] C) 
are less soluble and have lower SSA than particles calcined at lower 
temperatures (e.g., 500 [deg]C). Solubility and SSA are factors in 
determining the toxic potential of beryllium compounds or materials.
    Cells were collected from the dogs by BAL at 30, 60, 90, 180, and 
210 days after exposure, and the percentages of neutrophils and 
lymphocytes were determined. In addition, the mitogenic responses of 
blood lymphocytes and lavage cells collected at 210 days were 
determined with either phytohemagglutinin or beryllium sulfate as 
mitogen. The percentage of neutrophils in the lavage fluid was 
significantly elevated only at 30 days with exposure to either dose of 
500 [deg]C beryllium oxide. The percentage of lymphocytes in the fluid 
was significantly elevated in samples across all times with exposure to 
the high dose of this beryllium oxide form. Beryllium oxide calcined at 
1,000[deg] C elevated lavage lymphocytes only in high dose at 30 days. 
No significant effect of 1,000[deg] C beryllium oxide exposure on 
mitogenic response of any lymphocytes was seen. In contrast, peripheral 
blood lymphocytes from the 500 [deg]C beryllium oxide exposed groups 
were significantly stimulated by beryllium sulfate compared with the 
phytohemagglutinin exposed cells. The investigators in this study were 
able to replicate some of the same findings as those observed in human 
studies--specifically, that beryllium in soluble and insoluble forms 
can be mitogenic to immune cells, an important finding for progression 
of sensitization and proliferation of immune cells to developing full-
blown CBD.
    In another beagle study Haley et al. also found that the beagle dog 
appears to model some aspects of human CBD (Haley et al., 1989). The 
authors monitored lung pathologic effects, particle clearance, and 
immune sensitization of peripheral blood leukocytes following a single 
exposure to beryllium oxide aerosol generated from beryllium oxide 
calcined at 500 [deg]C or 1,000[deg] C. The aerosol was administered to 
the dogs perinasally to attain initial lung burdens of 6 or 18 [mu]g 
beryllium/kg body weight. Granulomatous lesions and lung lymphocyte 
responses consistent with those observed in humans with CBD were 
observed, including perivascular and peribronchiolar infiltrates of 
lymphocytes and macrophages, progressing to microgranulomas with areas 
of granulomatous pneumonia and interstitial fibrosis. Beryllium 
specificity of the immune response was demonstrated by positive results 
in the BeLPT, although there was considerable inter-animal variation. 
The lesions declined in severity after 64 days post-exposure. Thus, 
while this model was able to mimic the formation of Be-specific immune 
granulomas, it was not able to mimic the progressive nature of disease.
    This study also provided an opportunity to compare the effects of 
beryllium oxide calcination temperature on granulomatous disease in the 
beagle respiratory system. Haley et al. found an increase in the 
percentage and numbers of lymphocytes in BAL fluid at 3 months post-
exposure in dogs exposed to either dose of beryllium oxide calcined at 
500 [deg]C, but not in dogs exposed to the material calcined at the 
higher temperature. Although there was considerable inter-animal 
variation, lesions were generally more severe in the dogs exposed to 
material calcined at 500 [deg]C. Positive BeLPT results were observed 
with BAL lymphocytes only in the group with a high initial lung burden 
of the material calcined at 500 [deg]C, but positive results with 
peripheral blood lymphocytes were observed at both doses with material 
calcined at both temperatures.
    The histologic and immunologic responses of canine lungs to 
aerosolized beryllium oxide were investigated in another Haley et al. 
(1989) study. Beagle-dogs were exposed in a single exposure to high 
dose (50 [micro]g/kg of body weight) or low dose (l7 [micro]g/kg) 
levels of beryllium oxide calcined at either 500[deg] or 1000[deg] C. 
One group of dogs was examined up to 365 days after exposure for lung 
histology and biochemical assay to determine the fate of inhaled 
beryllium oxide. A second group underwent BAL for lung lymphocyte 
analysis for up to 22 months after exposure. Histopathologic 
examination revealed peribronchiolar and perivascular lymphocytic 
histiocytic

[[Page 47606]]

inflammation, peaking at 64 days after beryllium oxide exposure. 
Lymphocytes were initially well differentiated, but progressed to 
lymphoblastic cells and aggregated in lymphofollicular nodules or 
microgranulomas over time. Alveolar macrophages were large, and filled 
with intracytoplasmic material. Cortical and paracortical lymphoid 
hyperplasia of the tracheobronchial nodes was found. Lung lymphocyte 
concentrations were increased at 3 months and returned to normal in 
both dose groups given 500 [deg]C treated beryllium chloride. No 
significant elevations in lymphocyte concentrations were found in dogs 
given 1,000[deg] C treated beryllium oxide. Lung retention was higher 
in the 500 [deg]C treated beryllium oxide group. The lesions found in 
dog lungs closely resembled those found in humans with CBD: severe 
granulomas, lymphoblast transformation, increased pulmonary lymphocyte 
concentrations and variation in beryllium sensitivity. It was concluded 
that the canine model for berylliosis may provide insight into this 
disease.
    In a follow-up experiment, control dogs and those exposed to 
beryllium oxide calcined at 500 [deg]C were allowed to rest for 2.5 
years, and then re-exposed to filtered air (controls) or beryllium 
oxide calcined at 500 [deg]C for an initial lung burden (ILB) target of 
50 [mu]g beryllium oxide/kg body weight (Haley et al., 1992). Immune 
responses of blood and BAL lymphocytes, and lung lesions in dogs 
sacrificed 210 days post-exposure, were compared with results following 
the initial exposure. The severity of lung lesions was comparable under 
both conditions, suggesting that a 2.5-year interval was sufficient to 
prevent cumulative pathologic effects. Conradi et al. (1971) found no 
exposure-related histological alterations in the lungs of six beagle 
dogs exposed to a range of 3,300-4,380 [mu]g Be/m\3\ as beryllium oxide 
calcined at 1,400[deg] C for 30 min, once per month for 3 months. 
Because the dogs were sacrificed 2 years post-exposure, the long time 
period between exposure and response may have allowed for the reversal 
of any beryllium-induced changes (EPA, 1998).
    A 1994 study by Haley et al. showed that intra-bronchiolar 
instillation of beryllium induced immune granulomas and sensitization 
in monkeys. Haley et al. (1994) exposed male cynomolgus monkeys to 
either beryllium metal or beryllium oxide calcined at 500 [deg]C by 
intrabronchiolar instillation as a saline suspension. Lymphocyte counts 
in BAL fluid were observed, and were found to be significantly 
increased in monkeys exposed to beryllium metal on post-exposure days 
14 to 90, and on post-exposure day 60 in monkeys exposed to beryllium 
oxide. The lungs of monkeys exposed to beryllium metal had lesions 
characterized by interstitial fibrosis, Type II cell hyperplasia, and 
lymphocyte infiltration. Some monkeys also exhibited immune granulomas. 
Similar lesions were observed in monkeys exposed to beryllium oxide, 
but the incidence and severity were much less. BAL lymphocytes from 
monkeys exposed to beryllium metal, but not from monkeys exposed to 
beryllium oxide, proliferated in response to beryllium sulfate in the 
BeLPT (EPA, 1998).
    In an experiment similar to the one conducted with dogs, Conradi et 
al. (1971) found no effect in monkeys (Macaca irus) exposed via whole-
body inhalation for three 30-minute monthly exposures to a range of 
3,300-4,380 [mu]g Be/m\3\ as beryllium oxide calcined at 1,400[deg] C. 
The lack of effect may have been related to the long period (2 years) 
between exposure and sacrifice, or to low toxicity of beryllium oxide 
calcined at such a high temperature.
    As discussed earlier in this Health Effects section, at the 
cellular level, beryllium dissolution must occur for either a dendritic 
cell or a macrophage to present beryllium as an antigen to induce the 
cell-mediated CBD immune reactions (Stefaniak et al., 2006). Several 
studies have shown that low-fired beryllium oxide, which is 
predominantly made up of poorly crystallized small particles, is more 
immunologically reactive than beryllium oxide calcined at higher firing 
temperatures that result in less reactivity due to increasing crystal 
size. As discussed previously, Haley et al. (1989a) found more severe 
lung lesions and a stronger immune response in beagle dogs receiving a 
single inhalation exposure to beryllium oxide calcined at 500 [deg]C 
than in dogs receiving an equivalent initial lung burden of beryllium 
oxide calcined at 1,000[deg] C. Haley et al. found that beryllium oxide 
calcined at 1,000[deg] C elicited little local pulmonary immune 
response, whereas the much more soluble beryllium oxide calcined at 500 
[deg]C produced a beryllium-specific, cell-mediated immune response in 
dogs (Haley et al., 1991).
    In a later study, beryllium metal appeared to induce a greater 
toxic response than beryllium oxide following intrabronchiolar 
instillation in cynomolgus monkeys, as evidenced by more severe lung 
lesions, a larger effect on BAL lymphocyte counts, and a positive 
response in the BeLPT with BAL lymphocytes only after exposure to 
beryllium metal (Haley et al., 1994). Because an oxide layer may form 
on beryllium-metal surfaces after exposure to air (Mueller and 
Adolphson, 1979; Harmsen et al., 1986) dissolution of small amounts of 
poorly soluble beryllium compounds in the lungs might be sufficient to 
allow persistent low-level beryllium presentation to the immune system 
(NAS, 2008).
    Genetic studies in humans led to the creation of an animal model 
containing different human HLA-DP alleles inserted into FVB/N mice for 
mechanistic studies of CBD. Three strains of genetically engineered 
mice (transgenic mice) were created that conferred different risks for 
developing CBD based on human studies (Weston et al., 2005; Snyder et 
al., 2008): (1) the HLDPB1*401 transgenic strain, where the transgene 
codes for lysine residue at the 69th position of the B-chain conferred 
low risk of CBD; (2) the HLA-DPB1*201 mice, where the transgene codes 
for glutamic acid residue at the 69th position of the B-chain and 
glycine residues at positions 84 and 85 conferred medium risk of CBD; 
and (3) the HLA-DPB1*1701 mice, where the transgene codes for glutamic 
acid at the 69th position of the B-chain and aspartic acid and glutamic 
acid residues at positions 84 and 85, respectively, conferred high risk 
of CBD (Tarantino-Hutchinson et al., 2009).
    In order to validate the transgenic model, Tarantino-Hutchison et 
al. challenged the transgenic mice along with seven different inbred 
mouse strains to determine the susceptibility and sensitivity to 
beryllium exposure. Mice were dermally exposed with either saline or 
beryllium, then challenged with either saline or beryllium (as 
beryllium sulfate) using the MEST protocol (mouse ear-swelling test). 
The authors determined that the high risk HLA-DPB1*1701 transgenic 
strain responded 4 times greater (as measured via ear swelling) than 
control mice and at least 2 times greater than other strains of mice. 
The findings correspond to epidemiological study results reporting an 
enhanced CBD odds ratio for the HLA-DPB1*1701 in humans (Weston et al., 
2005; Snyder et al., 2008). Transgenic mice with the genes 
corresponding to the low and medium odds ratio study did not respond 
significantly over the control group. The authors concluded that while 
HLA-DPB1*1701 is important to beryllium sensitization and progression 
to CBD, other genetic and environmental factors contribute to the 
disease process as well.

[[Page 47607]]

7. Preliminary Beryllium Sensitization and CBD Conclusions
    It is well-established that skin and inhalation exposure to 
beryllium may lead to sensitization and that inhalation exposure, or 
skin exposure coupled with inhalation exposure, may lead to the onset 
and progression of CBD. This is supported by extensive human studies. 
While all facets of the biological mechanism for this complex disease 
have yet to be fully elucidated, many of the key events in the disease 
sequence have been identified and described in the previous sections. 
Sensitization is a necessary first step to the onset of CBD (NAS, 
2008). Sensitization is the process by which the immune system 
recognizes beryllium as a foreign substance and responds in a manner 
that may lead to development of CBD. It has been documented that a 
substantial proportion of sensitized workers exposed to airborne 
beryllium progress to CBD (Rosenman et al., 2005; NAS, 2008; Mroz et 
al., 2009). Animal studies, particularly in dogs and monkeys, have 
provided supporting evidence for T-cell lymphocyte proliferation in the 
development of granulomatous lung lesions after exposure to beryllium 
(Harmsen et al., 1986; Haley et al., 1989, 1992, 1994). The animal 
studies have also provided important insights into the roles of 
chemical form, genetic susceptibility, and residual lung burden in the 
development of beryllium lung disease (Harmsen et al., 1986; Haley et 
al., 1992; Tarantino-Hutchison et al., 2009). OSHA has made a 
preliminary determination to consider sensitization and CBD to be 
adverse events along the pathological continuum in the disease process, 
with sensitization being the necessary first step in the progression to 
CBD.
    The epidemiological evidence presented in this section demonstrates 
that sensitization and CBD are continuing to occur from present-day 
exposures below OSHA's PEL (Rosenman, 2005 with erratum published 
2006). The available literature discussed above shows that disease 
prevalence can be reduced by reducing inhalation exposure (Thomas et 
al., 2009). However, the available epidemiological studies also 
indicate that it may be necessary to minimize skin exposure to further 
reduce the incidence of sensitization (Bailey et al., 2010). The 
preliminary risk assessment further discusses the effectiveness of 
interventions to reduce beryllium exposures and the risk of 
sensitization and CBD (see section VI, Preliminary Risk Assessment).
    Studies have demonstrated there remains a prevalence of 
sensitization and CBD in facilities with exposure levels below the 
current OSHA PEL (Rosenman et al., 2005; Thomas et al., 2009), that 
risk of sensitization and CBD appears to vary across industries and 
processes (Deubner et al., 2001; Kreiss et al., 1997; Newman et al., 
2001; Henneberger et al., 2001; Schuler et al., 2005; Stange et al., 
2001; Taiwo et al., 2010), and that efforts to reduce exposure have 
succeeded in reducing the frequency of beryllium sensitization and CBD 
(Bailey et al., 2010) (See Table A-1 in the Appendix).
    Of workers who were found to be sensitized and underwent clinical 
evaluation, 20-49 percent were diagnosed with CBD (Kreiss et al., 1993; 
Newman, 1996, 2005 and 2007; Stange et al., 2001). Overall prevalence 
of CBD in cross-sectional screenings ranges from 0.6 to 8 percent 
(Kreiss et al., 2007). A study by Newman (2005) estimated from ongoing 
surveillance of sensitized individuals, with an average follow-up time 
of 6 years, that 31 percent of beryllium-exposed employees progressed 
to CBD (Newman, 2005). However, Newman (2005) went on to suggest that 
if follow-up times were increased the rate of progression from 
sensitization to CBD could be much higher. A study of nuclear weapons 
facility employees enrolled in an ongoing medical surveillance program 
found that only about 20 percent of sensitized individuals employed 
less than five years eventually were diagnosed with CBD, while 40 
percent of sensitized employees employed ten years or more developed 
CBD (Stange et al., 2001) indicating length of exposure may play a role 
in further development of the disease. In addition, Mroz et al. (2009) 
conducted a longitudinal study of individuals clinically evaluated at 
National Jewish Health (between 1982 and 2002) who were identified as 
having sensitization and CBD through workforce medical surveillance. 
The authors identified 171 cases of CBD and 229 cases of sensitization; 
all individuals were identified through workplace screening using the 
BeLPT (Mroz et al., 2009). Over the 20-year study period, 8.8 percent 
(i.e., 22 cases out 251 sensitized) of individuals with sensitization 
went on to develop CBD. The findings from this study indicated that on 
the average span of time from initial beryllium exposure to CBD 
diagnosis was 24 years (Mroz et al., 2009).

E. Beryllium Lung Cancer Section

    Beryllium exposure has been associated with a variety of adverse 
health effects including lung cancer. The potential for beryllium and 
its compounds to cause cancer has been previously assessed by various 
other agencies (EPA, ATSDR, NAS, NIEHS, and NIOSH) with each agency 
identifying beryllium as a potential carcinogen. In addition, the 
International Agency for Research on Cancer (IARC) did an extensive 
evaluation in 1993 and reevaluation in April 2009 (IARC, 2012). In 
brief, IARC determined beryllium and its compounds to be carcinogenic 
to humans (Group 1 category), while EPA considers beryllium to be a 
probable human carcinogen (EPA, 1998), and the National Toxicology 
Program (NTP) has determined beryllium and its compounds to be known 
carcinogens (NTP, 2014). OSHA has conducted an independent evaluation 
of the carcinogenic potential of beryllium and these compounds as well. 
The following is a summary of the studies used to support the Agency 
findings that beryllium and its compounds are human carcinogens.
1. Genotoxicity Studies
    Genotoxicity can be an important indicator for screening the 
potential of a material to induce cancer and an important mechanism 
leading to tumor formation and carcinogenesis. In a review conducted by 
the National Academy of Science, beryllium and its compounds have 
tested positively in nearly 50 percent of the genotoxicity studies 
conducted without exogenous metabolic activity. However, they were 
found to be non-genotoxic in most bacterial assays (NAS, 2008).
    Gene mutations have been observed in mammalian cells cultured with 
beryllium chloride in a limited number of studies (EPA, 1998; ATSDR, 
2002; Gordon and Bowser, 2003). Culturing mammalian cells with 
beryllium chloride, beryllium sulfate, or beryllium nitrate has 
resulted in clastogenic alterations. However, most studies have found 
that beryllium chloride, beryllium nitrate, beryllium sulfate, and 
beryllium oxide did not induce gene mutations in bacterial assays with 
or without metabolic activation. In the case of beryllium sulfate, all 
mutagenicity studies (Ames (Simmon, 1979; Dunkel et al., 1984; 
Arlauskas et al., 1985; Ashby et al., 1990); E. coli pol A (Rosenkranz 
and Poirer, 1979); E. coli WP2 uvr A (Dunkel et al., 1984) and 
Saccharomyces cerevisiae (Simmon, 1979)) were negative with the 
exception of results reported for Bacillus subtilis rec assay (Kada et 
al., 1980; Kanematsu et al., 1980; EPA, 1998). Beryllium sulfate did 
not induce unscheduled

[[Page 47608]]

DNA synthesis in primary rat hepatocytes and was not mutagenic when 
injected intraperitoneally in adult mice in a host-mediated assay using 
Salmonella typhimurium (Williams et al., 1982).
    Beryllium nitrate was negative in the Ames assay (Tso and Fung, 
1981; Kuroda et al., 1991) but positive in a Bacillus subtilis rec 
assay (Kuroda et al., 1991). Beryllium chloride was negative in a 
variety of studies (Ames (Ogawa et al., 1987; Kuroda et al., 1991); E. 
coli WP2 uvr A (Rossman and Molina, 1984); and Bacillus subtilis rec 
assay (Nishioka, 1975)). In addition, beryllium chloride failed to 
induce SOS DNA repair in E. coli (Rossman et al., 1984). However, 
positive results were reported for Bacillus subtilis rec assay using 
spores (Kuroda et al., 1991), E. coli KMBL 3835; lacI gene (Zakour and 
Glickman, 1984), and hprt locus in Chinese hamster lung V79 cells 
(Miyaki et al., 1979). Beryllium oxide was negative in the Ames assay 
and Bacillus subtilis rec assays (Kuroda et al., 1991; EPA, 1998).
    Gene mutations have been observed in mammalian cells (V79 and CHO) 
cultured with beryllium chloride (Miyaki et al., 1979; Hsie et al., 
1979a, b), and culturing of mammalian cells with beryllium chloride 
(Vegni-Talluri and Guiggiani, 1967), and beryllium sulfate (Brooks et 
al., 1989; Larramendy et al., 1981) has resulted in clastogenic 
alterations--producing breakage or disrupting chromosomes (EPA, 1998). 
Beryllium chloride evaluated in a mouse model indicated increased DNA 
strand breaks and the formation of micronuclei in bone marrow (Attia et 
al., 2013).
    Data on the in vivo genotoxicity of beryllium are limited to a 
single study that found beryllium sulfate (1.4 and 2.3 g/kg, 50 percent 
and 80 percent of median lethal dose) administered by gavage did not 
induce micronuclei in the bone marrow of CBA mice. However, a marked 
depression of erythropoiesis (red blood cell production) was suggestive 
of bone marrow toxicity which was evident 24 hours after dosing. No 
mutations were seen in p53 or c-raf-1 and only weak mutations were 
detected in K-ras in lung carcinomas from F344/N rats given a single 
nose-only exposure to beryllium metal (Nickell-Brady et al., 1994). The 
authors concluded that the mechanisms for the development of lung 
carcinomas from inhaled beryllium in the rat do not involve gene 
dysfunctions commonly associated with human non-small-cell lung cancer 
(EPA, 1998).
2. Human Epidemiological Studies
    This section reviews in greater detail the studies used to support 
the mechanistic findings for beryllium-induced cancer. Table A.3 in the 
Appendix summarizes the important features and characteristics of each 
study.
    a. Beryllium Case Registry (BCR).
    Two studies evaluated participants in the BCR (Infante et al., 
1980; Steenland and Ward, 1991). Infante et al. (1980) evaluated the 
mortality patterns of white male participants in the BCR diagnosed with 
non-neoplastic respiratory symptoms of beryllium disease. Of the 421 
cases evaluated, 7 of the participants had died of lung cancer. Six of 
the deaths occurred more than 15 years after initial beryllium 
exposure. The duration of exposure for 5 of the 7 participants with 
lung cancer was less than 1 year, with the time since initial exposure 
ranging from 12 to 29 years. One of the participants was exposed for 4 
years with a 26-year interval since the initial exposure. Exposure 
duration for one participant diagnosed with pulmonary fibrosis could 
not be determined; however, it had been 32 years since the initial 
exposure. Based on BCR records, the participants were classified as 
being in the acute respiratory group (i.e., those diagnosed with acute 
respiratory illness at the time of entry in the registry) or the 
chronic respiratory group (i.e., those diagnosed with pulmonary 
fibrosis or some other chronic lung condition at the time of entry into 
the BCR). The 7 participants with lung cancer were in the BCR because 
of diagnoses of acute respiratory illness. For only one of those 
individuals was initial beryllium exposure less than 15 years prior. 
Only 1 of the 6 (with greater than 15 years since initial exposure to 
beryllium) had been diagnosed with chronic respiratory disease. The 
study did not report exposure concentrations or smoking habits. The 
authors concluded that the results of this cohort agreed with previous 
animal studies and with epidemiological studies demonstrating an 
increased risk of lung cancer in workers exposed to beryllium.
    Steenland and Ward (1991) extended the work of Infante et al. 
(1980) to include females and to include 13 additional years of follow-
up. At the time of entry in the BCR, 93 percent of the women in the 
study, but only 50 percent of the men, had been diagnosed with CBD. In 
addition, 61 percent of the women had worked in the fluorescent tube 
industry and 50 percent of the men had worked in the basic 
manufacturing industry. A total of 22 males and 6 females died of lung 
cancer. Of the 28 total deaths from lung cancer, 17 had been exposed to 
beryllium for less than 4 years and 11 had been exposed for greater 
than 4 years. The study did not report exposure concentrations. Survey 
data collected in 1965 provided information on smoking habits for 223 
cohort members (32 percent), on the basis of which the authors 
suggested that the rate of smoking among workers in the cohort may have 
been lower than U.S. rates. The authors concluded that there was 
evidence of increased risk of lung cancer in workers exposed to 
beryllium and diagnosed with beryllium disease.
b. Beryllium Manufacturing and/or Processing Plants (Extraction, 
Fabrication, and Processing)
    Several epidemiological cohort studies have reported excess lung 
cancer mortality among workers employed in U.S. beryllium production 
and processing plants during the 1930s to 1960s. The largest and most 
comprehensive study investigated the mortality experience of 9,225 
workers employed in seven different beryllium processing plants over a 
30-year period (Ward et al., 1992). The workers at the two oldest 
facilities (i.e., Lorain, OH, and Reading, PA) were found to have 
significant excess lung cancer mortality relative to the U.S. 
population. Of the seven plants in the study, these two plants were 
believed to have the highest exposure levels to beryllium. A different 
analysis of the lung cancer mortality in this cohort using various 
local reference populations and alternate adjustments for smoking 
generally found smaller, non-significant rates of excess mortality 
among the beryllium employees (Levy et al., 2002). Both cohort studies 
are limited by a lack of job history and air monitoring data that would 
allow investigation of mortality trends with beryllium exposure. The 
majority of employees at the Lorain, OH, and Reading, PA, facilities 
were employed for a relatively short period of less than one year.
    Bayliss et al. (1971) performed a nested cohort study of more than 
7,000 former workers from the beryllium processing industry employed 
from 1942-1967. Information for the workers was collected from the 
personnel files of participating companies. Of the more than 7,000 
employees, a cause of death was known for 753 male workers. The number 
of observed lung cancer deaths was 36 compared to 34.06 expected for a 
standardized mortality ratio (SMR) of 1.06. When evaluated by the 
number of years of employment, 24 of the 36 men were employed for less 
than 1 year in

[[Page 47609]]

the industry (SMR = 1.24), 8 were employed for 1 to 5 years (SMR 1.40), 
and 4 were employed for more than 5 years (SMR = 0.54). Half of the 
workers who died from lung cancer began employment in the beryllium 
production industry prior to 1947. When grouped by job classification, 
over two thirds of the workers with lung cancer were in production-
related jobs while the rest were classified as office workers. The 
authors concluded that while the lung cancer mortality rates were the 
highest of all other mortality rates, the SMR for lung cancer was still 
within range of the expected based on death rates in the United States. 
The limitations of this study included the lack of information 
regarding exposure concentrations, smoking habits, and the age and race 
of the participants.
    Mancuso (1970, 1979, 1980) and Mancuso and El-Attar (1969) 
performed a series of occupational cohort studies on a group of over 
3,685 workers (primarily white males) employed in the beryllium 
manufacturing industry during 1937-1948.\3\ The beryllium production 
facilities were located in Ohio and Pennsylvania and the records for 
the employees, including periods of employment, were obtained from the 
Social Security Administration. These studies did not include analyses 
of mortality by job title or exposure category. In addition, there were 
no exposure concentrations estimated or adjustments for smoking. The 
estimated duration of employment ranged from less than 1 year to 
greater than 5 years. In the most recent study (Mancuso, 1980), 
employees from the viscose rayon industry served as a comparison 
population. There was a significant excess of lung cancer deaths based 
on the total number of 80 observed lung cancer mortalities at the end 
of 1976 compared to an expected number of 57.06 based on the comparison 
population resulting in an SMR of 1.40 (p < 0.01) (Mancuso, 1980). 
There was a statistically significant excess in lung cancer deaths for 
the shortest duration of employment (< 12 months, p < 0.05) and the 
longest duration of employment (> 49 months, p < 0.01). Based on the 
results of this study, the author concluded that the ability of 
beryllium to induce cancer in workers does not require continuous 
exposure and that it is reasonable to assume that the amount of 
exposure required to produce lung cancer can occur within a few months 
of exposure regardless of the length of employment.
---------------------------------------------------------------------------

    \3\ The third study (Mancuso et al., 1979) restricted the cohort 
to workers employed between 1942 and 1948.
---------------------------------------------------------------------------

    Wagoner et al. (1980) expanded the work of Mancuso (1970; 1979; 
1980) using a cohort of 3,055 white males from the beryllium 
extraction, processing, and fabrication facility located in Reading, 
Pennsylvania. The men included in the study worked at the facility 
sometime between 1942 and 1968, and were followed through 1976. The 
study accounted for length of employment. Other factors accounted for 
included age, smoking history, and regional lung cancer mortality. 
Forty-seven members of the cohort died of lung cancer compared to an 
expected 34.29 based on U.S. white male lung cancer mortality rates (p 
< .05). The results of this cohort showed an excess risk of lung cancer 
in beryllium-exposed workers at each duration of employment (< 5 years 
and >= 5 years), with a statistically significant excess noted at < 5 
years durations of employment and a >= 25-year interval since the 
beginning of employment (p < 0.05). The study was criticized by several 
epidemiologists (MacMahon, 1978, 1979; Roth, 1983), by a CDC Review 
Committee appointed to evaluate the study, and by one of the study's 
coauthors (Bayliss, 1980) for inadequate discussion of possible 
alternative explanations of excess lung cancer in the cohort. The 
specific issues identified include the use of 1965-1967 U.S. white male 
lung cancer mortality rates to generate expected numbers of lung 
cancers in the period 1968-1975 and inadequate adjustment for smoking.
    Ward et al. (1992) performed a retrospective mortality cohort study 
of 9,225 male workers employed at seven beryllium processing 
facilities, including the Ohio and Pennsylvania facilities studied by 
Mancuso and El-Attar (1969), Mancuso (1970; 1979; 1980), and Wagoner et 
al. (1980). The men were employed for no less than 2 days between 
January 1940 and December 1988. At the end of the study 61.1 percent of 
the cohort was known to be living and 35.1 percent was known to be 
deceased. The duration of employment ranged from 1 year or less to 
greater than 10 years with the largest percentage of the cohort (49.7 
percent) employed for less than one year, followed by 1 to 5 years of 
employment (23.4 percent), greater than 10 years (19.1 percent), and 5 
to 10 years (7.9 percent). Of the 3,240 deaths, 280 observed deaths 
were caused by lung cancer compared to 221.5 expected deaths, yielding 
a statistically significant SMR of 1.26 (p < 0.01). Information on the 
smoking habits of 15.9 percent of the cohort members, obtained from a 
1968 Public Health Service survey conducted at four of the plants, was 
used to calculate a smoking-adjusted SMR of 1.12, which was not 
statistically significant. The number of deaths from lung cancer was 
also examined by decade of hire. The authors reported a relationship 
between earlier decades of hire and increased lung cancer risk.
    The EPA Integrated Risk Information System (IRIS), IARC, and 
California EPA Office of Environmental Health Hazard Assessment (OEHHA) 
have all based their cancer assessment on the Ward et al. 1992 study, 
with supporting data concerning exposure concentrations from Eisenbud 
and Lisson (1983) and NIOSH (1972), who estimated that the lower-bound 
estimate of the median exposure concentration exceeded 100 [micro]g/
m\3\ and found that concentrations in excess of 1,000 [micro]g/m\3\ 
were common. The IRIS cancer risk assessment recalculated expected lung 
cancers based on U.S. white male lung cancer rates (including the 
period 1968-1975) and used an alternative adjustment for smoking. In 
addition, one individual with lung cancer, who had not worked at the 
plant, was removed from the cohort. After these adjustments were made, 
an elevated rate of lung cancer was still observed in the overall 
cohort (46 cases vs. 41.9 expected cases). However, based on duration 
of employment or interval since beginning of employment, neither the 
total cohort nor any of the subgroups had a statistically significant 
excess in lung cancer (EPA, 1987). Based on their evaluation of this 
and other epidemiological studies, the EPA characterized the human 
carcinogenicity data then available as ``limited'' but ``suggestive of 
a causal relationship between beryllium exposure and an increased risk 
of lung cancer'' (IRIS database). This report includes quantitative 
estimates of risk that were derived using the information presented in 
Wagoner et al. (1980), the expected lung cancers recalculated by the 
EPA, and bounds on presumed exposure levels.
    Levy et al. (2002) questioned the results of Ward et al. (1992) and 
performed a reanalysis of the Ward et al. data. The Levy et al. 
reanalysis differed from the Ward et al. analysis in the following 
significant ways. First, Levy et al. (2002) examined two alternative 
adjustments for smoking, which were based on (1) a different analysis 
of the American Cancer Society (ACS) data used by Ward et al. (1992) 
for their smoking adjustment, or (2) results from a smoking/lung cancer 
study of veterans (Levy and Marimont, 1998). Second, Levy et al. (2002) 
also examined the

[[Page 47610]]

impact of computing different reference rates derived from information 
about the lung cancer rates in the cities in which most of the workers 
at two of the plants lived. Finally, Levy et al. (2002) considered a 
meta-analytical approach to combining the results across beryllium 
facilities. For all of the alternatives Levy et al. (2002) considered, 
except the meta-analysis, the facility-specific and combined SMRs 
derived were lower than those reported by Ward et al. (1992). Only the 
SMR for the Lorain, OH, facility remained statistically significantly 
elevated in some reanalyses. The SMR obtained when combining over the 
plants was not statistically significant in eight of the nine 
approaches they examined, leading Levy et al. (2002) to conclude that 
there was little evidence of statistically significant elevated SMRs in 
those plants.
    One occupational nested case-control study evaluated lung cancer 
mortality in a cohort of 3,569 male workers employed at a beryllium 
alloy production plant in Reading, PA, from 1940 to 1969 and followed 
through 1992 (Sanderson et al., 2001). There were a total of 142 known 
lung cancer cases and 710 controls. For each lung cancer death, 5 age- 
and race-matched controls were selected by incidence density sampling. 
Confounding effects of smoking were evaluated. Job history and 
historical air measurements at the plant were used to estimate job-
specific beryllium exposures from the 1930s to 1990s. Calendar-time-
specific beryllium exposure estimates were made for every job and used 
to estimate workers' cumulative, average, and maximum exposure. Because 
of the long period of time required for the onset of lung cancer, an 
``exposure lag'' was employed to discount recent exposures less likely 
to contribute to the disease.
    The cumulative, average, and maximum beryllium exposure 
concentration estimates for the 142 known lung cancer cases were 46.06 
 9.3[micro]g/m\3\-days, 22.8  3.4 [micro]g/
m\3\, and 32.4  13.8 [micro]g/m\3\, respectively. The lung 
cancer mortality rate was 1.22 (95 percent CI = 1.03 - 1.43). Exposure 
estimates were lagged by 10 and 20 years in order to account for 
exposures that did not contribute to lung cancer because they occurred 
after the induction of cancer. In the 10- and 20-year lagged exposures 
the geometric mean tenures and cumulative exposures of the lung cancer 
mortality cases were higher than the controls. In addition, the 
geometric mean and maximum exposures of the workers were significantly 
higher than controls when the exposure estimates were lagged 10 and 20 
years (p < 0.01).
    Results of a conditional logistic regression analysis indicated 
that there was an increased risk of lung cancer in workers with higher 
exposures when dose estimates were lagged by 10 and 20 years. There was 
also a lack of evidence that confounding factors such as smoking 
affected the results of the regression analysis. The authors noted that 
there was considerable uncertainty in the estimation of exposure in the 
1940's and 1950's and the shape of the dose-response curve for lung 
cancer. Another analysis of the study data using a different 
statistical method did not find a significantly greater relative risk 
of lung cancer with increasing beryllium exposures (Levy et al., 2007). 
The average beryllium air levels for the lung cancer cases were 
estimated to be an order of magnitude above the current 8-hour OSHA TWA 
PEL (2 [mu]g/m\3\) and roughly two orders of magnitude higher than the 
typical air levels in workplaces where beryllium sensitization and 
pathological evidence of CBD have been observed. IARC evaluated this 
reanalysis in 2012 and found the study introduced a downward bias into 
risk estimates (IARC, 2012).
    Schubauer-Berigan et al. reanalyzed data from the nested case-
control study of 142 lung cancer cases in the Reading, PA, beryllium 
processing plant (Schubauer-Berigan et al., 2008). This dataset was 
reanalyzed using conditional (stratified by case age) logistic 
regression. Independent adjustments were made for potential confounders 
of birth year and hire age. Average and cumulative exposures were 
analyzed using the values reported in the original study. The objective 
of the reanalysis was to correct for the known differences in smoking 
rates by birth year. In addition, the authors evaluated the effects of 
age at hire to determine differences observed by Sanderson et al. in 
2001. The effect of birth cohort adjustment on lung cancer rates in 
beryllium-exposed workers was evaluated by adjusting in a multivariable 
model for indicator variables for the birth cohort quartiles.
    Unadjusted analyses showed little evidence of lung cancer risk 
associated with beryllium occupational exposure using cumulative 
exposure until a 20-year lag was used. Adjusting for either birth 
cohort or hire age attenuated the risk for lung cancer associated with 
cumulative exposure. Using a 10- or 20-year lag in workers born after 
1900 also showed little evidence of lung cancer risk, while those born 
prior to 1900 did show a slight elevation in risk. Unlagged and lagged 
analysis for average exposure showed an increase in lung cancer risk 
associated with occupational exposure to beryllium. The finding was 
consistent for either workers adjusted or unadjusted for birth cohort 
or hire age. Using a 10-year lag for average exposure showed a 
significant effect by birth cohort.
    The authors stated that the reanalysis indicated that differences 
in the hire ages among cases and controls, first noted by Deubner et 
al. (2001) and Levy et al. (2007), were primarily due to the fact that 
birth years were earlier among controls than among cases, resulting 
from much lower baseline risk of lung cancer for men born prior to 1900 
(Schubauer-Berigan et al., 2008). The authors went on to state that the 
reanalysis of the previous NIOSH case-control study suggested the 
relationship observed previously between cumulative beryllium exposure 
and lung cancer was greatly attenuated by birth cohort adjustment.
    Hollins et al. (2009) re-examined the weight of evidence of 
beryllium as a lung carcinogen in a recent publication (Hollins et al., 
2009). Citing more than 50 relevant papers, the authors noted the 
methodological shortcomings examined above, including lack of well-
characterized historical occupational exposures and inadequacy of the 
availability of smoking history for workers. They concluded that the 
increase in potential risk of lung cancer was observed among those 
exposed to very high levels of beryllium and that beryllium's 
carcinogenic potential in humans at these very high exposure levels 
were not relevant to today's industrial settings. IARC performed a 
similar re-evaluation in 2009 (IARC, 2012) and found that the weight of 
evidence for beryllium lung carcinogenicity, including the animal 
studies described below, still warranted a Group I classification, and 
that beryllium should be considered carcinogenic to humans.
    Schubauer-Berigan et al. (2010) extended their analysis from a 
previous study estimating associations between mortality risk and 
beryllium exposure to include workers at 7 beryllium processing plants. 
The study (Schubauer-Berigan et al., 2010) followed the mortality 
incidences of 9,199 workers from 1940 through 2005 at the 7 beryllium 
plants. JEMs were developed for three plants in the cohort: The Reading 
plant, the Hazleton plant, and the Elmore plant. The last is described 
in Couch et al. 2010. Including these JEMs substantially improved the 
evidence base for evaluating the carcinogenicity of beryllium and, and 
this change

[[Page 47611]]

represents more than an update of the beryllium cohort. Standardized 
mortality ratios (SMRs) were estimated based on US population 
comparisons for lung, nervous system and urinary tract cancers, chronic 
obstructive pulmonary disease (COPD), chronic kidney disease, and 
categories containing chronic beryllium disease (CBD) and cor 
pulmonale. Associations with maximum and cumulative exposure were 
calculated for a subset of the workers.
    Overall mortality in the cohort compared with the US population was 
elevated for lung cancer (SMR 1.17; 95% CI 1.08 to 1.28), COPD (SMR 
1.23; 95% CI 1.13 to 1.32), and the categories containing CBD (SMR 
7.80; 95% CI 6.26 to 9.60) and cor pulmonale (SMR 1.17; 95% CI 1.08 to 
1.26). Mortality rates for most diseases of interest increased with 
time-since-hire. For the category including CBD, rates were 
substantially elevated compared to the US population across all 
exposure groups. Workers whose maximum beryllium exposure was >= 10 
[mu]g/m\3\ had higher rates of lung cancer, urinary tract cancer, COPD 
and the category containing cor pulmonale than workers with lower 
exposure. These studies showed strong associations for cumulative 
exposure (when short-term workers were excluded), maximum exposure or 
both. Significant positive trends with cumulative exposure were 
observed for nervous system cancers (p = 0.0006) and, when short-term 
workers were excluded, lung cancer (p = 0.01), urinary tract cancer (p 
= 0.003) and COPD (p < 0.0001).
    The authors concluded the findings from this reanalysis reaffirmed 
that lung cancer and CBD are related to beryllium exposure. The authors 
went on to suggest that beryllium exposures may be associated with 
nervous system and urinary tract cancers and that cigarette smoking and 
other lung carcinogens were unlikely to explain the increased 
incidences in these cancers. The study corrected an error that was 
discovered in the indirect smoking adjustment initially conducted by 
Ward et al., concluding that cigarette smoking rates did not differ 
between the cohort and the general U.S. population. No association was 
found between cigarette smoking and either cumulative or maximum 
beryllium exposure, making it very unlikely that smoking was a 
substantial confounder in this study (Schubauer-Berigan et al., 2010).
3. Animal Cancer Studies
    This section reviews the animal literature used to support the 
findings for beryllium-induced lung cancer. Lung tumors have been 
induced via inhalation and intratracheal administration of beryllium to 
rats and monkeys, and osteosarcomas have been induced via intravenous 
and intramedullary (inside the bone) injection of beryllium in rabbits 
and possibly in mice. The chronic oral studies did not report increased 
incidences of tumors in rodents, but these were conducted at doses 
below the maximum tolerated dose (MTD) (EPA, 1998).
    Early animal studies revealed that some beryllium compounds are 
carcinogenic when inhaled (ATSDR, 2002). Animal experiments have shown 
consistent increases in lung cancers in rats, mice and rabbits 
chronically exposed to beryllium and beryllium compounds by inhalation 
or intratracheal instillation. In addition to lung cancer, 
osteosarcomas have been produced in mice and rabbits exposed to various 
beryllium salts by intravenous injection or implantation into the bone 
(NTP, 1999).
    In an inhalation study assessing the potential tumorigenicity of 
beryllium, Schepers et al. (1957) exposed 115 albino Sherman and Wistar 
rats (male and female) via inhalation to 0.0357 mg beryllium/m\3\ (1 
[gamma] beryllium/ft\3\) \4\ as an aqueous aerosol of beryllium sulfate 
for 44 hours/week for 6 months, and observed the rats for 18 months 
after exposure. Three to four control rats were killed every two months 
for comparison purposes. Seventy-six lung neoplasms, \5\ including 
adenomas, squamous-cell carcinomas, acinous adenocarcinomas, papillary 
adenocarcinomas, and alveolar-cell adenocarcinomas, were observed in 52 
rats exposed to beryllium sulfate aerosol. Adenocarcinomata were the 
most numerous. Pulmonary metastases tended to localize in areas with 
foam cell clustering and granulomatosis. No neoplasia was observed in 
any of the control rats. The incidence of lung tumors in exposed rats 
is presented in the following Table 2:
---------------------------------------------------------------------------

    \4\ Schepers et al. (1957) reported concentrations in [gamma] 
Be/ft\3\; however, [gamma]/ft\3\ is no longer a common unit. 
Therefore, the concentration was converted to mg/m\3\.
    \5\ While a total of 89 tumors were observed or palpated at the 
time of autopsy in the BeSO4-exposed animals, only 76 
tumors are listed as histologically neoplastic. Only the new growths 
identified in single midcoronal sections of both lungs were 
recorded.

                       Table 2--Neoplasm Analysis
------------------------------------------------------------------------
                     Neoplasm                       Number    Metastases
------------------------------------------------------------------------
Adenoma..........................................        18
Squamous carcinoma...............................         5            1
Acinous adenocarcinoma...........................        24            2
Papillary adenocarcinoma.........................        11            1
Alveolar-cell adenocarcinoma.....................         7
Mucigenous tumor.................................         7            1
Endothelioma.....................................         1
Retesarcoma......................................         3            3
                                                  ----------------------
  Total..........................................        76            8
------------------------------------------------------------------------

    Schepers (1962) reviewed 38 existing beryllium studies that 
evaluated seven beryllium compounds and seven mammalian species. 
Beryllium sulfate, beryllium fluoride, beryllium phosphate, beryllium 
alloy (BeZnMnSiO4), and beryllium oxide were proven to be 
carcinogenic and have remarkable pleomorphic neoplasiogenic 
proclivities. Ten varieties of tumors were observed, with 
adenocarcinoma being the most common variety.
    In another study, Vorwald and Reeves (1959) exposed Sherman albino 
rats via the inhalation route to aerosols of 0.006 mg beryllium/m\3\ as 
beryllium oxide and 0.0547 mg beryllium/m\3\ as beryllium sulfate for 6 
hours/day, 5 days/week for an unspecified duration. Lung tumors (single 
or multifocal) were observed in the animals sacrificed following 9 
months of daily inhalation exposure. The histologic pattern of the 
cancer was primarily adenomatous; however, epidermoid and squamous cell 
cancers were also observed. Infiltrative, vascular, and lymphogenous 
extensions often developed with secondary metastatic growth in the 
tracheobronchial lymph nodes, the mediastinal connective tissue, the 
parietal pleura, and the diaphragm.
    In the first of two articles, Reeves et al. (1967a) investigated 
the carcinogenic process in lungs resulting from chronic (up to 72 
weeks) beryllium sulfate inhalation. One hundred fifty male and female 
Sprague Dawley C.D. strain rats were exposed to beryllium sulfate 
aerosol at a mean atmospheric concentration of 34.25 [mu]g beryllium/
m\3\ (with an average particle diameter of 0.12 [micro]m). Prior to 
initial exposure and again during the 67-68 and 75-76 weeks of life, 
the animals received prophylactic treatments of tetracycline-HCl to 
combat recurrent pulmonary infections.
    The animals entered the exposure chamber at 6 weeks of age and were

[[Page 47612]]

exposed 7 hours per day/5 days per week for up to 2,400 hours of total 
exposure time. An equal number of unexposed controls were held in a 
separate chamber. Three male and three female rats were sacrificed 
monthly during the 72-week exposure period. Mortality due to 
respiratory or other infections did not appear until 55 weeks of age, 
and 87 percent of all animals survived until their scheduled 
sacrifices.
    Average lung weight towards the end of exposure was 4.25 times 
normal with progressively increasing differences between control and 
exposed animals. The increase in lung weight was accompanied by notable 
changes in tissue texture with two distinct pathological processes--
inflammatory and proliferative. The inflammatory response was 
characterized by marked accumulation of histiocytic elements forming 
clusters of macrophages in the alveolar spaces. The proliferative 
response progressed from early epithelial hyperplasia of the alveolar 
surfaces, through metaplasia (after 20-22 weeks of exposure), anaplasia 
(cellular dedifferentiation) (after 32-40 weeks of exposure), and 
finally to lung tumors.
    Although the initial proliferative response occurred early in the 
exposure period, tumor development required considerable time. Tumors 
were first identified after nine months of beryllium sulfate exposure, 
with rapidly increasing rates of incidence until tumors were observed 
in 100 percent of exposed animals by 13 months. The 9-to-13-month 
interval is consistent with earlier studies. The tumors showed a high 
degree of local invasiveness. No tumors were observed in control rats. 
All 56 tumors studied appeared to be alveolar adenocarcinomas and 3 
``fast-growing'' tumors that reached a very large size comparatively 
early. About one-third of the tumors showed small foci where the 
histologic pattern differed. Most of the early tumor foci appeared to 
be alveolar rather than bronchiolar, which is consistent with the 
expected pathogenesis, since permanent deposition of beryllium was more 
likely on the alveolar epithelium rather than on the bronchiolar 
epithelium. Female rats appeared to have an increased susceptibility to 
beryllium exposure. Not only did they have a higher mortality (control 
males [n = 8], exposed males [n = 9] versus control females [n = 4], 
exposed females [n = 17]) and body weight loss than male rats, but the 
three ``fast-growing'' tumors only occurred in females.
    In the second article, Reeves et al. (1967b) described the rate of 
accumulation and clearance of beryllium sulfate aerosol from the same 
experiment (Reeves et al., 1967a). At the time of the monthly 
sacrifice, beryllium assays were performed on the lungs, 
tracheobronchial lymph nodes, and blood of the exposed rats. The 
pulmonary beryllium levels of rats showed a rate of accumulation which 
decreased during continuing exposure and reached a plateau (defined as 
equilibrium between deposition and clearance) of about 13.5 [mu]g 
beryllium for males and 9 [mu]g beryllium for females in whole lungs 
after approximately 36 weeks. Females were notably less efficient than 
males in utilizing the lymphatic route as a method of clearance, 
resulting in slower removal of pulmonary beryllium deposits, lower 
accumulation of the inhaled material in the tracheobronchial lymph 
nodes, and higher morbidity and mortality.
    There was no apparent correlation between the extent and severity 
of pulmonary pathology and total lung load. However, when the beryllium 
content of the excised tumors was compared with that of surrounding 
nonmalignant pulmonary tissues, the former showed a notable decrease 
(0.50  0.35 [mu]g beryllium/gram versus 1.50  
0.55 [mu]g beryllium/gram). This was believed to be largely a result of 
the dilution factor operating in the rapidly growing tumor tissue. 
However, other factors, such as lack of continued local deposition due 
to impaired respiratory function and enhanced clearance due to high 
vascularity of the tumor, may also have played a role. The portion of 
inhaled beryllium retained in the lungs for a longer duration, which is 
in the range of one-half of the original pulmonary load, may have 
significance for pulmonary carcinogenesis. This pulmonary beryllium 
burden becomes localized in the cell nuclei and may be an important 
factor in eliciting the carcinogenic response associated with beryllium 
inhalation.
    Groth et al. (1980) conducted a series of experiments to assess the 
carcinogenic effects of beryllium, beryllium hydroxide, and various 
beryllium alloys. For the beryllium metal/alloys experiment, 12 groups 
of 3-month-old female Wistar rats (35 rats/group) were used. All rats 
in each group received a single intratracheal injection of either 2.5 
or 0.5 mg of one of the beryllium metals or beryllium alloys as 
described in Table 3 below. These materials were suspended in 0.4 cc of 
isotonic saline followed by 0.2 cc of saline. Forty control rats were 
injected with 0.6 cc of saline. The geometric mean particle sizes 
varied from 1 to 2 [micro]m. Rats were sacrificed and autopsied at 
various intervals ranging from 1 to 18 months post-injection.

                           Table 3--Summary of Beryllium Dose From Groth et al. (1980)
----------------------------------------------------------------------------------------------------------------
                                                  Percent other   Total No. rats   Compound dose
          Form of Be              Percent Be        compounds        autopsied         (mg)        Be dose  (mg)
----------------------------------------------------------------------------------------------------------------
Be metal.....................  100.............  None...........              16             2.5             2.5
                                                                              21             0.5             0.5
Passivated Be metal..........  99..............  0.26% Chromium.              26             2.5             2.5
                                                                              20             0.5             0.5
BeAl alloy...................  62..............  38% Aluminum...              24             2.5            1.55
                                                                              21             0.5             0.3
BeCu alloy...................  4...............  96% Copper.....              28             2.5             0.1
                                                                              24             0.5            0.02
BeCuCo alloy.................  2.4.............  0.4% Cobalt....              33             2.5            0.06
                                                 96% Copper.....              30             0.5           0.012
BeNi alloy...................  2.2.............  97.8% Nickel...              28             2.5           0.056
                                                                              27             0.5           0.011
----------------------------------------------------------------------------------------------------------------

    Lung tumors were observed only in rats exposed to beryllium metal, 
passivated beryllium metal, and beryllium-aluminum alloy. Passivation 
refers to the process of removing iron contamination from the surface 
of

[[Page 47613]]

beryllium metal. As discussed, metal alloys may have a different 
toxicity than beryllium alone. Rats exposed to 100 percent beryllium 
exhibited relatively high mortality rates, especially in the groups 
where lung tumors were observed. Nodules varying from 1 to 10 mm in 
diameter were also observed in the lungs of rats exposed to beryllium 
metal, passivated beryllium metal, and beryllium-aluminum alloy. These 
nodules were suspected of being malignant.
    To test this hypothesis, transplantation experiments involving the 
suspicious nodules were conducted in nine rats. Seven of the nine 
suspected tumors grew upon transplantation. All transplanted tumor 
types metastasized to the lungs of their hosts. Lung tumors were 
observed in rats injected with both the high and low doses of beryllium 
metal, passivated beryllium metal, and beryllium-aluminum alloy. No 
lung tumors were observed in rats injected with the other compounds. 
From a total of 32 lung tumors detected, most were adenocarcinomas and 
adenomas; however, two epidermoid carcinomas and at least one poorly 
differentiated carcinoma were observed. Bronchiolar alveolar cell 
tumors were frequently observed in rats injected with beryllium metal, 
passivated beryllium metal, and beryllium-aluminum alloy. All stages of 
cuboidal, columnar, and squamous cell metaplasia were observed on the 
alveolar walls in the lungs of rats injected with beryllium metal, 
passivated beryllium metal, and beryllium-aluminum alloy. These lesions 
were generally reduced in size and number or absent from the lungs of 
animals injected with the other alloys (BeCu, BeCuCo, BeNi).
    The extent of alveolar metaplasia could be correlated with the 
incidence of lung cancer. The incidences of lung tumors in the rats 
that received 2.5 mg of beryllium metal, and 2.5 and 0.5 mg of 
passivated beryllium metal, were significantly different (p <= 0.008) 
from controls. When autopsies were performed at the 16-to-19-month 
interval, the incidence (2/6) of lung tumors in rats exposed to 2.5 mg 
of beryllium-aluminum alloy was statistically significant (p = 0.004) 
when compared to the lung tumor incidence (0/84) in rats exposed to 
BeCu, BeNi, and BeCuCo alloys, which contained much lower 
concentrations of Be (Groth et al., 1980).
    Finch et al. (1998b) investigated the carcinogenic effects of 
inhaled beryllium on heterozygous TSG-p53 knockout mice 
(p53+/-) and wild-type (p53+/+) mice. Knockout mice can be 
valuable tools in determining the role of specific genes on the 
toxicity of a material of interest, in this case, beryllium. Equal 
numbers of approximately 10-week-old male and female mice were used for 
this study. Two exposure groups were used to provide dose-response 
information on lung carcinogenicity. The maximum initial lung burden 
(ILB) target of 60 [mu]g beryllium was based on previous acute 
inhalation exposure studies in mice. The lower exposure target level of 
15 [mu]g was selected to provide a lung burden significantly less than 
the high-level group, but high enough to yield carcinogenic responses. 
Mice were exposed in groups to beryllium metal or to filtered air 
(controls) via nose-only inhalation. The specific exposure parameters 
are presented in Table 4 below. Mice were sacrificed 7 days post 
exposure for ILB analysis, and either at 6 months post exposure (n = 4-
5 mice per group per gender) or when 10 percent or less of the original 
population remained (19 months post exposure for p53+/- 
knockout and 22.5 months post exposure for p53+/+ wild-type mice). The 
sacrifice time was extended in the study because a significant number 
of lung tumors were not observed at 6 months post exposure.

                                                Table 4--Summary of Animal Data From Finch Et Al., 1998 b
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                        Number of mice
                                  Mean  exposure      Target be lung                        Mean daily  exposure                        with 1 or more
         Mouse strain              concentration      burden  ([mu]g)     Number of mice     duration  (minutes)   Mean ILB  ([mu]g)   lung tumors/total
                                   ([mu]g Be/L)                                                                                        number  examined
--------------------------------------------------------------------------------------------------------------------------------------------------------
Knockout (p53+/-).............  34                  15                  30                  112 (single)          NA                  0/29
                                36                  60                  30                  139[Dagger]           NA                  4/28
Wild-type (p53\+/+\)            34                  15                  6*                  112 (single)          12  4   NA
                                36                  60                  36[dagger]          139[Dagger]           54  6   0/28
Knockout (p53+/-).............  NA (air)            Control             30                  60-180 (single)       NA                  0/30
--------------------------------------------------------------------------------------------------------------------------------------------------------
ILB = initial lung burden; NA = not applicable
Median aerodynamic diameter of Be aerosol = 1.4 [mu]m ([sigma]g = 1.8)
* Wild-type mice in the low exposure group were not evaluated for carcinogenic effects; however ILB was analyzed in six wild-type mice.
[dagger] Thirty wild-type mice were analyzed for carcinogenic effects; six wild-type mice were analyzed for ILB.
[Dagger] Mice were exposed for 2.3 hours/day for three consecutive days.

    Lung burdens of beryllium measured in wild-type mice at 7 days post 
exposure were approximately 70-90 percent of target levels. No 
exposure-related effects on body weight were observed in mice; however, 
lung weights and lung-to-body-weight ratios were somewhat elevated in 
60 [mu]g target ILB p53+/- knockout mice compared to 
controls (0.05 < p < 0.10). In general, p53+/+ wild-type mice survived 
longer than p53+/- knockout mice and beryllium exposure 
tended to decrease survival time in both groups. The incidence of 
beryllium-induced lung tumors was marginally higher in the 60 [mu]g 
target ILB p53+/- knockout mice compared to 60 [mu]g target 
ILB p53+/+ wild-type mice (p = 0.056). The incidence of lung tumors in 
the 60 [mu]g target ILB p53+/- knockout mice was also 
significantly higher than controls (p = 0.048). No tumors developed in 
the control mice, 15 [mu]g target ILB p53+/- knockout mice, 
or 60 [mu]g target ILB p53+/+ wild-type mice throughout the length of 
the study. Most lung tumors in beryllium-exposed mice were squamous 
cell carcinomas, three of four of which were poorly circumscribed and 
all were associated with at least some degree of granulomatous 
pneumonia. The study results suggest that having an inactivated p53 
allele is associated with lung tumor progression in p53+/- 
knockout mice. This is based on the significant difference seen in the 
incidence of beryllium-induced lung neoplasms for the 
p53+/-knockout mice compared with the p53\+/+\ wild-type 
mice. The authors conclude that since there was a relatively late onset 
of tumors in the beryllium-exposed p53+/- knockout mice, a 
6-month bioassay in this mouse strain might not be an appropriate model 
for lung carcinogenesis (Finch et al., 1998b).

[[Page 47614]]

    Nickell-Brady et al. (1994) investigated the development of lung 
tumors in 12-week-old F344/N rats after a single nose-only inhalation 
exposure to beryllium aerosol, and evaluated whether beryllium lung 
tumor induction involves alterations in the K-ras, p53, and c-raf-1 
genes. Four groups of rats (30 males and 30 females per group) were 
exposed to different mass concentrations of beryllium (Group 1: 500 mg/
m\3\ for 8 min; Group 2: 410 mg/m\3\ for 30 min; Group 3: 830 mg/m\3\ 
for 48 min; Group 4: 980 mg/m\3\ for 39 min). The beryllium mass median 
aerodynamic diameter was 1.4 [mu]m ([sigma]g = 1.9). The 
mean beryllium lung burdens for each exposure group were 40, 110, 360, 
and 430 [mu]g, respectively.
    To examine genetic alterations, DNA isolation and sequencing 
techniques (PCR amplification and direct DNA sequence analysis) were 
performed on wild-type rat lung tissue (i.e., control samples) along 
with two mouse lung tumor cell lines containing known K-ras mutations, 
12 carcinomas induced by beryllium (i.e., experimental samples), and 12 
other formalin-fixed specimens. Tumors appeared in beryllium-exposed 
rats by 14 months, and 64 percent of exposed rats developed lung tumors 
during their lifetime. Lungs frequently contained multiple tumor sites, 
with some of the tumors greater than 1 cm. A total of 24 tumors were 
observed. Most of the tumors (n = 22) were adenocarcinomas exhibiting a 
papillary pattern characterized by cuboidal or columnar cells, although 
a few had a tubular or solid pattern. Fewer than 10 percent of the 
tumors were adenosquamous (n = 1) or squamous cell (n = 1) carcinomas.
    No transforming mutations of the K-ras gene (codons 12, 13, or 61) 
were detected by direct sequence analysis in any of the lung tumors 
induced by beryllium. However, using a more sensitive sequencing 
technique (PCR enrichment restriction fragment length polymorphism 
(RFLP) analysis) resulted in the detection of K-ras codon 12 GGT to GTT 
transversions in 2 of 12 beryllium-induced adenocarcinomas. No p53 and 
c-raf-1 alterations were observed in any of the tumors induced by 
beryllium exposure (i.e., no differences observed between beryllium-
exposed and control rat tissues). The authors note that the results 
suggest that activation of the K-ras proto-oncogene is both a rare and 
late event, possibly caused by genomic instability during the 
progression of beryllium-induced rat pulmonary adenocarcinomas. It is 
unlikely that the K-ras gene plays a role in the carcinogenicity of 
beryllium. The results also indicate that p53 mutation is unlikely to 
play a role in tumor development in rats exposed to beryllium.
    Belinsky et al. (1997) reviewed the findings by Nickell-Brady et 
al. (1994) to further examine the role of the K-ras and p53 genes in 
lung tumors induced in the F344 rat by non-mutagenic (non-genotoxic) 
exposures to beryllium. Their findings are discussed along with the 
results of other genomic studies that look at carcinogenic agents that 
are either similarly non-mutagenic or, in other cases, mutagenic. The 
authors conclude that the identification of non-ras transforming genes 
in rat lung tumors induced by non-mutagenic exposures, such as 
beryllium, as well as mutagenic exposures will help define some of the 
mechanisms underlying cancer induction by different types of DNA 
damage.
    The inactivation of the p16INK4a (p16) gene is a contributing 
factor in disrupting control of the normal cell cycle and may be an 
important mechanism of action in beryllium-induced lung tumors. 
Swafford et al. (1997) investigated the aberrant methylation and 
subsequent inactivation of the p16 gene in primary lung tumors induced 
in F344/N rats exposed to known carcinogens via inhalation. The 
research involved a total of 18 primary lung tumors that developed 
after exposing rats to five agents, one of which was beryllium. In this 
study, only one of the 18 lung tumors was induced by beryllium 
exposure; the majority of the other tumors were induced by radiation 
(x-rays or plutonium-239 oxide). The authors hypothesized that if p16 
inactivation plays a central role in development of non-small-cell lung 
cancer, then the frequency of gene inactivation in primary tumors 
should parallel that observed in the corresponding cell lines. To test 
the hypothesis, a rat model for lung cancer was used to determine the 
frequency and mechanism for inactivation of p16 in matched primary lung 
tumors and derived cell lines. The methylation-specific PCR (MSP) 
method was used to detect methylation of p16 alleles. The results 
showed that the presence of aberrant p16 methylation in cell lines was 
strongly correlated with absent or low expression of the gene. The 
findings also demonstrated that aberrant p16 CpG island methylation, an 
important mechanism in gene silencing leading to the loss of p16 
expression, originates in primary tumors.
    Building on the rat model for lung cancer and associated findings 
from Swafford et al. (1997), Belinsky et al. (2002) conducted 
experiments in 12-week-old F344/N rats (male and female) to determine 
whether beryllium-induced lung tumors involve inactivation of the p16 
gene and estrogen receptor [alpha] (ER) gene. Rats received a single 
nose-only inhalation exposure to beryllium aerosol at four different 
exposure levels. The mean lung burdens measured in each exposure group 
were 40, 110, 360, and 430 [mu]g. The methylation status of the p16 and 
ER genes was determined by MSP. A total of 20 tumors detected in 
beryllium-exposed rats were available for analysis of gene-specific 
promoter methylation. Three tumors were classified as squamous cell 
carcinomas and the others were determined to be adenocarcinomas. 
Methylated p16 was present in 80 percent (16/20), and methylated ER was 
present in one-half (10/20), of the lung tumors induced by exposure to 
beryllium. Additionally, both genes were methylated in 40 percent of 
the tumors. The authors noted that four tumors from beryllium-exposed 
rats appeared to be partially methylated at the p16 locus. Bisulfite 
sequencing of exon 1 of the ER gene was conducted on normal lung DNA 
and DNA from three methylated, beryllium-induced tumors to determine 
the density of methylation within amplified regions of exon 1 (referred 
to as CpG sites). Two of the three methylated, beryllium-induced lung 
tumors showed extensive methylation, with more than 80 percent of all 
CpG sites methylated.
    The overall findings of this study suggest that inactivation of the 
p16 and ER genes by promoter hypermethylation are likely to contribute 
to the development of lung tumors in beryllium-exposed rats. The 
results showed a correlation between changes in p16 methylation and 
loss of gene transcription. The authors hypothesize that the mechanism 
of action for beryllium-induced p16 gene inactivation in lung tumors 
may be inflammatory mediators that result in oxidative stress. The 
oxidative stress damages DNA directly through free radicals or 
indirectly through the formation of 8-hydroxyguanosine DNA adducts, 
resulting primarily in a single-strand DNA break.
    Wagner et al. (1969) studied the development of pulmonary tumors 
after intermittent daily chronic inhalation exposure to beryllium ores 
in three groups of male squirrel monkeys. One group was exposed to 
bertrandite ore, a second to beryl ore, and the third served as 
unexposed controls. Each of these three exposure groups contained 12 
monkeys. Monkeys from each group were sacrificed after 6, 12, or 23 
months of exposure. The 12-month sacrificed

[[Page 47615]]

monkeys (n = 4 for bertrandite and control groups; n = 2 for beryl 
group) were replaced by a separate replacement group to maintain a 
total animal population approximating the original numbers and to 
provide a source of confirming data for biologic responses that might 
arise following the ore exposures. Animals were exposed to bertrandite 
and beryl ore concentrations of 15 mg/m\3\, corresponding to 210 [mu]g 
beryllium/m\3\ and 620 [mu]g beryllium/m\3\ in each exposure chamber, 
respectively. The parent ores were reduced to particles with geometric 
mean diameters of 0.27 [mu]m ( 2.4) for bertrandite and 
0.64 [mu]m ( 2.5) for beryl. Animals were exposed for 
approximately 6 hours/day, 5 days/week. The histological changes in the 
lungs of monkeys exposed to bertrandite and beryl ore exhibited a 
similar pattern. The changes generally consisted of aggregates of dust-
laden macrophages, lymphocytes, and plasma cells near respiratory 
bronchioles and small blood vessels. There were, however, no consistent 
or significant pulmonary lesions or tumors observed in monkeys exposed 
to either of the beryllium ores. This is in contrast to the findings in 
rats exposed to beryl ore and to a lesser extent bertrandite, where 
atypical cell proliferation and tumors were frequently observed in the 
lungs. The authors hypothesized that the rats' greater susceptibility 
may be attributed to the spontaneous lung disease characteristic of 
rats, which might have interfered with lung clearance.
    As previously described, Conradi et al. (1971) investigated changes 
in the lungs of monkeys and dogs two years after intermittent 
inhalation exposure to beryllium oxide calcined at 1,400 [deg]C. Five 
adult male and female monkeys (Macaca irus) weighing between 3 and 5.75 
kg were used in the study. The study included two control monkeys. 
Beryllium concentrations in the atmosphere of whole-body exposed 
monkeys varied between 3.30 and 4.38 mg/m\3\. Thirty-minute exposures 
occurred once a month for three months, with beryllium oxide 
concentrations increasing at each exposure interval. Lung tissue was 
investigated using electron microscopy and morphometric methods. 
Beryllium content in portions of the lungs of five monkeys was measured 
two years following exposure by emission spectrography. The reported 
concentrations in monkeys (82.5, 143.0, and 112.7 [mu]g beryllium per 
100 gm of wet tissue in the upper lobe, lower lobe, and combined lobes, 
respectively) were higher than those in dogs. No neoplastic or 
granulomatous lesions were observed in the lungs of any exposed animals 
and there was no evidence of chronic proliferative lung changes after 
two years.
4. In vitro Studies
    The exact mechanism by which beryllium induces pulmonary neoplasms 
in animals remains unknown (NAS 2008). Keshava et al. (2001) performed 
studies to determine the carcinogenic potential of beryllium sulfate in 
cultured mammalian cells. Joseph et al. (2001) investigated 
differential gene expression to understand the possible mechanisms of 
beryllium-induced cell transformation and tumorigenesis. Both 
investigations used cell transformation assays to study the cellular/
molecular mechanisms of beryllium carcinogenesis and assess 
carcinogenicity. Cell lines were derived from tumors developed in nude 
mice injected subcutaneously with non-transformed BALB/c-3T3 cells that 
were morphologically transformed in vitro with 50-200 [mu]g beryllium 
sulfate/ml for 72 hours. The non-transformed cells were used as 
controls.
    Keshava et al. (2001) found that beryllium sulfate is capable of 
inducing morphological cell transformation in mammalian cells and that 
transformed cells are potentially tumorigenic. A dose-dependent 
increase (9-41 fold) in transformation frequency was noted. Using 
differential polymerase chain reaction (PCR), gene amplification was 
investigated in six proto-oncogenes (K-ras, c-myc, c-fos, c-jun, c-sis, 
erb-B2) and one tumor suppressor gene (p53). Gene amplification was 
found in c-jun and K-ras. None of the other genes tested showed 
amplification. Additionally, Western blot analysis showed no change in 
gene expression or protein level in any of the genes examined. Genomic 
instability in both the non-transformed and transformed cell lines was 
evaluated using random amplified polymorphic DNA fingerprinting (RAPD 
analysis). Using different primers, 5 of the 10 transformed cell lines 
showed genomic instability when compared to the non-transformed BALB/c-
3T3 cells. The results indicate that beryllium sulfate-induced cell 
transformation might, in part, involve gene amplification of K-ras and 
c-jun and that some transformed cells possess neoplastic potential 
resulting from genomic instability.
    Using the Atlas mouse 1.2 cDNA expression microarrays, Joseph et 
al. (2001) studied the expression profiles of 1,176 genes belonging to 
several different functional categories. Compared to the control cells, 
expression of 18 genes belonging to two functional groups (nine cancer-
related genes and nine DNA synthesis, repair, and recombination genes) 
was found to be consistently and reproducibly different (at least 2-
fold) in the tumor cells. Differential gene expression profile was 
confirmed using reverse transcription-PCR with primers specific to the 
differentially expressed genes. Two of the differentially expressed 
genes (c-fos and c-jun) were used as model genes to demonstrate that 
the beryllium-induced transcriptional activation of these genes was 
dependent on pathways of protein kinase C and mitogen-activated protein 
kinase and independent of reactive oxygen species in the control cells. 
These results indicate that beryllium-induced cell transformation and 
tumorigenesis are associated with up-regulated expression of the 
cancer-related genes (such as c-fos, c-jun, c-myc, and R-ras) and down-
regulated expression of genes involved in DNA synthesis, repair, and 
recombination (such as MCM4, MCM5, PMS2, Rad23, and DNA ligase I).
5. Preliminary Lung Cancer Conclusions
    OSHA has preliminarily determined that the weight of evidence 
indicates that beryllium compounds should be regarded as potential 
occupational lung carcinogens. Other scientific organizations, 
including the International Agency for Research on Cancer (IARC), the 
National Toxicology Program (NTP), the U.S. Environmental Protection 
Agency (EPA), the National Institute for Occupational Safety and Health 
(NIOSH), and the American Conference of Governmental Industrial 
Hygienists (ACGIH) have reached similar conclusions with respect to the 
carcinogenicity of beryllium.
    While some evidence exists for direct-acting genotoxicity as a 
possible mechanism for beryllium carcinogenesis, the weight of evidence 
suggests a possible indirect mechanism may be responsible for most 
tumorigenic activity of beryllium in animal models and possibly humans 
(EPA, 1998). Inflammation has been postulated to be a key contributor 
to many different forms of cancer (Jackson et al., 2006; Pikarsky et 
al., 2004; Greten et al., 2004; Leek, 2002). In fact, chronic 
inflammation may be a primary factor in the development of up to one-
third of all cancers (Ames et al., 1990; NCI, 2010).
    In addition to a T-cell mediated response beryllium has been 
demonstrated to produce an inflammatory response in animal models 
similar to other particles (Reeves et al., 1967; Swafford et al., 1997; 
Wagner et al., 1969) possibly

[[Page 47616]]

contributing to its carcinogenic potential. Animal studies, as 
summarized above, have demonstrated a consistent scenario of beryllium 
exposure resulting in chronic pulmonary inflammation. Studies conducted 
in rats have demonstrated that chronic inhalation of materials similar 
in solubility to beryllium result in increased pulmonary inflammation, 
fibrosis, epithelial hyperplasia, and, in some cases, pulmonary 
adenomas and carcinomas (Heinrich et al., 1995; Nikula et al., 1995; 
NTP, 1993; Lee et al., 1985; Warheit et al., 1996). This response is 
generally referred to as an ``overload'' response or threshold effect. 
Substantial data indicate that tumor formation in the rat after 
exposure to some sparingly soluble particles at doses causing marked, 
chronic inflammation is due to a secondary mechanism unrelated to the 
genotoxicity (or lack thereof) of the particle itself.
    It has been hypothesized that the recruitment of neutrophils during 
the inflammatory response and subsequent release of oxidants from these 
cells have been demonstrated to play an important role in the 
pathogenesis of rat lung tumors (Borm et al., 2004; Carter and 
Driscoll, 2001; Carter et al., 2006; Johnston et al., 2000; Knaapen et 
al., 2004; Mossman, 2000). Inflammatory mediators, as characterized in 
many of the studies summarized above, have been shown to play a 
significant role in the recruitment of cells responsible for the 
release of reactive oxygen and hydrogen species. These species have 
been determined to be highly mutagenic themselves as well as mitogenic, 
inducing a proliferative response (Feriola and Nettesheim, 1994; Jetten 
et al., 1990; Moss et al., 1994; Coussens and Werb, 2002). The 
resultant effect is an environment rich for neoplastic transformations 
and the progression of fibrosis and tumor formation. This finding does 
not imply no risk at levels below an inflammatory response; rather, the 
overall weight of evidence is suggestive of a mechanism of an indirect 
carcinogen at levels where inflammation is seen. While tumorigenesis 
secondary to inflammation is one reasonable mode of action, other 
plausible modes of action independent of inflammation (e.g., 
epigenetic, mitogenic, reactive oxygen mediated, indirect genotoxicity, 
etc.) may also contribute to the lung cancer associated with beryllium 
exposure.
    Epidemiological studies indicate excess risk of lung cancer 
mortality from occupational beryllium exposure levels at or below the 
current OSHA PEL (Schubauer-Berigan et al., 2010; Table 4).

F. Other Health Effects

    Past studies on other health effects have been thoroughly reviewed 
by several scientific organizations (NTP, 1999; EPA, 1998; ATSDR, 2002; 
WHO, 2001; HSDB, 2010). These studies include summaries of animal 
studies, in vitro studies, and human epidemiological studies associated 
with cardiovascular, hematological, hepatic, renal, endocrine, 
reproductive, ocular and mucosal, and developmental effects. High-dose 
exposures to beryllium have been shown to have an adverse effect upon a 
variety of organs and tissues in the body, particularly the liver. The 
adverse systemic effects from human exposures mostly occurred prior to 
the introduction of occupational and environmental standards set in 
1970-1972 (OSHA, 1971; ACGIH, 1971; ANSI, 1970) and 1974 (EPA, 1974) 
and therefore are less relevant today than in the past. The available 
data is fairly limited. The hepatic, cardiovascular, renal, and ocular 
and mucosal effects are briefly summarized below. Health effects in 
other organ systems listed above were only observed in animal studies 
at very high exposure levels and are, therefore, not discussed here.
 1. Hepatic Effects
    Beryllium has been shown to accumulate in the liver and a 
correlation has been demonstrated between beryllium content and hepatic 
damage. Different compounds have been shown to distribute differently 
within the hepatic tissues. For example, beryllium phosphate had 
accumulated almost exclusively within sinusoidal (Kupffer) cells of the 
liver, while the beryllium derived from beryllium sulfate was found 
mainly in parenchymal cells. Conversely, beryllium sulphosalicylic acid 
complexes were rapidly excreted (Skillteter and Paine, 1979).
    According to a few autopsies, beryllium-laden liver had central 
necrosis, mild focal necrosis as well as congestion, and occasionally 
beryllium granuloma.
    Residents near a beryllium plant may have been exposed by inhaling 
trace amounts of beryllium powder, and different beryllium compounds 
may have induced different toxicant reactions (Yian and Yin, 1982).
2. Cardiovascular Effects
    There is very limited evidence of cardiovascular effects of 
beryllium and its compounds in humans. Severe cases of chronic 
beryllium disease can result in cor pulmonale, which is hypertrophy of 
the right heart ventricle. In a case history study of 17 individuals 
exposed to beryllium in a plant that manufactured fluorescent lamps, 
autopsies revealed right atrial and ventricular hypertrophy (Hardy and 
Tabershaw, 1946). It is not likely that these cardiac effects were due 
to direct toxicity to the heart, but rather were a response to impaired 
lung function. However, an increase in deaths due to heart disease or 
ischemic heart disease was found in workers at a beryllium 
manufacturing facility (Ward et al., 1992).
    Animal studies performed in monkeys indicate heart enlargement 
after acute inhalation exposure to 13 mg beryllium/m\3\ as beryllium 
hydrogen phosphate, 0.184 mg beryllium/m\3\ as beryllium fluoride, or 
0.198 mg beryllium/m\3\ as beryllium sulfate (Schepers 1964). Decreased 
arterial oxygen tension was observed in dogs exposed to 30 mg 
beryllium/m\3\ as beryllium oxide for 15 days (HSDB, 2010), 3.6 mg 
beryllium/m\3\ as beryllium oxide for 40 days (Hall et al., 1950), or 
0.04 mg beryllium/m\3\ as beryllium sulfate for 100 days (Stokinger et 
al., 1950). These are expected to be indirect effects on the heart due 
to pulmonary fibrosis and toxicity which can increase arterial pressure 
and restrict blood flow.
3. Renal Effects
    Renal calculi (stones) were unusually prevalent in severe cases 
that resulted from high levels of beryllium exposure. Renal stones 
containing beryllium occurred in about 10 percent of patients affected 
by high exposures (Barnett, et al., 1961). Kidney stones were observed 
in 10 percent of the CBD cases collected by the BCR up to 1959 (Hall et 
al., 1959). In addition, an excess of calcium in the blood and urine 
has been seen frequently in patients with chronic beryllium disease 
(ATSDR, 2002).
4. Ocular and Mucosal Effects
    Both the soluble, sparingly soluble, and insoluble beryllium 
compounds have been shown to cause ocular irritation in humans (Van 
Orstrand et al., 1945; De Nardi et al., 1953; Nishimura, 1966; Epstein, 
1990; NIOSH, 1994). In addition, beryllium compounds (soluble, 
sparingly soluble, or insoluble) have been demonstrated to induce acute 
conjunctivitis with corneal maculae and diffuse erythema (HSDB, 2010).
    The mucosa (mucosal membrane) is the moist lining of certain 
tissues/organs including the eyes, nose, mouth, lungs, and the urinary 
and digestive tracts. Soluble beryllium salts have been

[[Page 47617]]

shown to be directly irritating to mucous membranes (HSDB, 2010).

G. Summary of Preliminary Conclusions Regarding Health Effects

    Through careful analysis of the current best available scientific 
information outlined in this Health Effects Section V, OSHA has 
preliminarily determined that beryllium and beryllium-containing 
compounds are able to cause sensitization, chronic beryllium disease 
(CBD) and lung cancer below the current OSHA PEL of 2 [mu]g/m\3\. The 
Agency has preliminarily determined through the studies outlined in 
section V.A.2 of this health effects section that skin and inhalation 
exposure to beryllium can lead to sensitization; and inhalation 
exposure, or skin exposure coupled with inhalation, can cause onset and 
progression of CBD. In addition, the Agency has preliminarily 
determined through studies outlined in section V.E. of this health 
effects section that inhalation exposure to beryllium and beryllium 
containing materials causes lung cancer.
1. Beryllium Causes Sensitization Below the Current PEL and 
Sensitization is a Precursor to CBD
    Through the biological and immunological processes outlined in 
section V.B. of the Health Effects, the Agency believes that the 
scientific evidence supports the following mechanism for the 
development of sensitization and CBD.
     Inhaled beryllium and beryllium-containing materials able 
to be retained and solubilized in the lungs initiate sensitization and 
facilitate CBD development (Section V.B.5).
     Beryllium compounds that dissolve in biological fluids, 
such as sweat, can penetrate intact skin and initiate sensitization 
(section V.A.2; V.B). Phagosomal fluid and lung fluid have been 
demonstrated to dissolve beryllium compounds in the lung (section 
V.A.2a).
     Sensitization occurs through a CD4+ T-cell mediated 
process with both soluble and insoluble beryllium and beryllium-
containing compounds through direct antigen presentation or through 
further antigen processing (section V.D.1) in the skin or lung. T-cell 
mediated responses, such as sensitization, are generally regarded as 
long-lasting (e.g., not transient or readily reversible) immune 
conditions.
     Beryllium sensitization and CBD are adverse events along a 
pathological continuum in the disease process with sensitization being 
the necessary first step in the progression to CBD (section V.D).
    [cir] Animal studies have provided supporting evidence for T-cell 
proliferation in the development of granulomatous lung lesions after 
beryllium exposure (section V.D.2; V.D.6).
    [cir] Since the pathogenesis of CBD involves a beryllium-specific, 
cell-mediated immune response, CBD cannot occur in the absence of 
beryllium sensitization (V.D.1). While no clinical symptoms are 
associated with sensitization, a sensitized worker is at risk of 
developing CBD upon subsequent inhalation exposure to beryllium.
    [cir] Epidemiological evidence that covers a wide variety of 
different beryllium compounds and industrial processes demonstrates 
that sensitization and CBD are continuing to occur at present-day 
exposures below OSHA's PEL (section V.D.4; V.D.5).
     OSHA considers CBD to be a progressive illness with a 
continuous spectrum of symptoms ranging from its earliest asymptomatic 
stage following sensitization through to full-blown CBD and death 
(section V.D.7).
     Genetic variabilities may enhance risk for developing 
sensitization and CBD in some groups (section V.D.3).
    In addition, epidemiological studies outlined in section V.D.5 have 
demonstrated that efforts to reduce exposures have succeeded in 
reducing the frequency of sensitization and CBD.
2. Evidence Indicates Beryllium is a Human Carcinogen
    OSHA has conducted an evaluation of the current available 
scientific information of the carcinogenic potential of beryllium and 
beryllium-containing compounds (section V.E). Based on weight of 
evidence and plausible mechanistic information obtained from in vitro 
and in vivo animal studies as well as clinical and epidemiological 
investigations, the Agency has preliminarily determined that beryllium 
and beryllium-containing materials should be regarded as human 
carcinogens. This information is in accordance with findings from IARC, 
NTP, EPA, NIOSH, and ACGIH (section V.E).
     Lung cancer is an irreversible and frequently fatal 
disease with an extremely poor 5-year survival rate (NCI, 2009).
     Epidemiological cohort studies have reported statistically 
significant excess lung cancer mortality among workers employed in U.S. 
beryllium production and processing plants during the 1930s to 1970s 
(Section V.E.2).
     Significant positive associations were found between lung 
cancer mortality and both average and cumulative beryllium exposures 
when appropriately adjusted for birth cohort and short-term work status 
(Section V.E.2).
     Studies in which large amounts of different beryllium 
compounds were inhaled or instilled in the respiratory tracts of 
experimental animals resulted in an increased incidence of lung tumors 
(Section V.E.3).
     Authoritative scientific organizations, such as the IARC, 
NTP, and EPA, have classified beryllium as a known or probable human 
carcinogen.
    While OSHA has preliminarily determined there is sufficient 
evidence of beryllium carcinogenicity, the exact tumorigenic mechanism 
for beryllium is unclear and a number of mechanisms are plausibly 
involved, including chronic inflammation, genotoxicity, mitogenicity 
oxidative stress, and epigenetic changes (section V.E.3).
     Studies of beryllium exposed animals have consistently 
demonstrated chronic pulmonary inflammation after exposure (section 
V.E.3).
    [cir] Substantial data indicate that tumor formation in certain 
animal models after inhalation exposure to sparingly soluble particles 
at doses causing marked, chronic inflammation is due to a secondary 
mechanism unrelated to the genotoxicty of the particle (section V.E.5).
     A review conducted by the NAS (2008) found that beryllium 
and beryllium-containing compounds tested positive for genotoxicity in 
nearly 50 percent of studies without exogenous metabolic activity, 
suggesting a possible direct-acting mechanism may exist (section V.E.1) 
as well as the potential for epigenetic changes (section V.E.4).
    Other health effects have been summarized in sections F of the 
Health Effects Section and include hepatic, cardiovascular, renal, 
ocular, and mucosal effects. The adverse systemic effects from human 
exposures mostly occurred prior to the introduction of occupational and 
environmental standards set in 1970-1972 (OSHA, 1971; ACGIH, 1971; 
ANSI, 1970) and 1974 (EPA, 1974) and therefore are less relevant today 
than in the past.

[[Page 47618]]

APPENDIX

                           Table A.1--Summary of Beryllium Sensitization and Chronic Beryllium Disease Epidemiological Studies
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                           (%) Prevalence                Range of         Exposure-
          Reference               Study type    ------------------------------------     exposure          response          Study          Additional
                                                   Sensitization          CBD          measurements      relationship     limitations        comments
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                            Studies Conducted Prior to BeLPT
--------------------------------------------------------------------------------------------------------------------------------------------------------
Hardy and Tabershaw, 1946....  Case-series.....  N/A.............  N/A.............  N/A.............  N/A............  Selection bias.  Small sample
                                                                                                                                          size.
Hardy, 1980..................  Case-series.....  N/A.............  N/A.............  N/A.............  N/A............  Selection bias.  Small sample
                                                                                                                                          size.
Machle et al., 1948..........  Case-series.....  N/A.............  N/A.............  Semi-             Yes............  Selection bias.  Small sample
                                                                                      quantitative.                                       size;
                                                                                                                                          unreliable
                                                                                                                                          exposure data.
Eisenbud et al., 1949........  Case-series.....  N/A.............  N/A.............  Average           ...............  ...............  Non-
                                                                                      concentration:                                      occupational;
                                                                                      350-750 ft from                                     ambient air
                                                                                      plant--0.05-0.1                                     sampling.
                                                                                      5 [mu]g/m\3\;.
                                                                                     <350 ft from
                                                                                      plant--2.1
                                                                                      [mu]g/m\3\.
Lieben and Metzner, 1959.....  ................  N/A.............  ................  N/A.............  ...............  No quantitative  Family member
                                                                                                                         exposure data.   contact with
                                                                                                                                          contaminated
                                                                                                                                          clothes.
Hardy et al., 1967...........  Case Registry     N/A.............  N/A.............  N/A.............  N/A............  Incomplete       ...............
                                Review.                                                                                  exposure
                                                                                                                         concentration
                                                                                                                         data.
Hasan and Kazemi, 1974.......  ................  N/A.............  ................  ................  ...............  ...............  ...............
Eisenbud and Lisson, 1983....  ................  N/A.............  1-10............  ................  ...............  ...............  ...............
Stoeckle et al., 1969........  Case-series (60   N/A.............  ................  ................  No.............  Selection bias.  Provided
                                cases).                                                                                                   information
                                                                                                                                          regarding
                                                                                                                                          progression
                                                                                                                                          and
                                                                                                                                          identifying
                                                                                                                                          sarcoidosis
                                                                                                                                          from CBD.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                Studies Conducted Following the Development of the BeLPT
--------------------------------------------------------------------------------------------------------------------------------------------------------
 
                                                             Beryllium Mining and Extraction
--------------------------------------------------------------------------------------------------------------------------------------------------------
Deubner et al., 2001b........  Cross-sectional   4.0 (3 cases)...  1.3 (1 case)....  Mining, milling-- No.............  Small sample     Personal
                                (75 workers).                                         range 0.05-0.8                     size.            sampling.
                                                                                      [mu]g/m\3\;
                                                                                     Annual maximum
                                                                                      0.04-165.7
                                                                                      [mu]g/m\3\.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                     Beryllium Metal Processing and Alloy Production
--------------------------------------------------------------------------------------------------------------------------------------------------------
Kreiss et al., 1997..........  Cross-sectional   6.9 (43 cases)..  4.6 (29 cases)..  Median--1.4       No.............  Inconsistent     Short-term
                                study of 627                                          [mu]g/m\3\.                        BeLPT results    Breathing Zone
                                workers.                                                                                 between labs.    sampling.
Rosenman et al., 2005........  Cross-sectional   14.5 (83 cases).  5.5 (32 cases)..  Mean average      No.............  ...............  Daily weighted
                                study of 577                                          range--7.1-8.7                                      average:
                                workers.                                              [mu]g/m\3\;.                                       High exposures
                                                                                     Mean peak range--                                    compared to
                                                                                      53-87 [mu]g/                                        other studies.
                                                                                      m\3\;.
                                                                                     Mean cumulative
                                                                                      range--100-209
                                                                                      [mu]g/m\3\.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                             Beryllium Machining Operations
--------------------------------------------------------------------------------------------------------------------------------------------------------
Newman et al., 2001..........  Longitudinal      9.4 (22 cases)..  8.5 (20 cases)..  ................  No.............  ...............  Engineering and
                                study of 235                                                                                              administrative
                                workers.                                                                                                  controls
                                                                                                                                          primarily used
                                                                                                                                          to control
                                                                                                                                          exposures.

[[Page 47619]]

 
Kelleher et al., 2001........  Case-control      11.5              11.5              0.08-0.6 [mu]g/   Yes............  ...............  Identified 20
                                study of 20       (machinists).     (machinists).     m\3\--lifetime                                      workers with
                                cases and 206    2.9 (non-         2.9 (non-          weighted                                            Sensitization
                                controls.         machinists).      machinists).      exposures.                                          or CBD.
Madl et al., 2007............  Longitudinal      ................  ................  Machining.......  Yes............  ...............  Personal
                                study of 27                                          1980-1995 median                                     sampling:
                                cases.                                                -0.33 [mu]g/                                       Required
                                                                                      m\3\; 1996-1999                                     evidence of
                                                                                      median--0.16                                        granulomas for
                                                                                      [mu]g/m\3\;                                         CBD diagnosis.
                                                                                      2000-2005
                                                                                      median--0.09
                                                                                      [mu]g/m\3\;.
                                                                                     Non-machining
                                                                                      1980-1995
                                                                                      median--0.12
                                                                                      [mu]g/m\3\;
                                                                                      1996-1999
                                                                                      median--0.08
                                                                                      [mu]g/m\3\;
                                                                                      2000-2005
                                                                                      median--0.06
                                                                                      [mu]g/m\3\.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                Beryllium Oxide Ceramics
--------------------------------------------------------------------------------------------------------------------------------------------------------
Kreiss et al., 1993b.........  Cross-sectional   3.6 (18 cases)..  1.8 (9 cases)...  ................  No                                ...............
                                survey of 505
                                workers.
Kreiss et al., 1996..........  Cross-sectional   5.9 (8 cases)...  4.4 (6 cases)...  Machining         No.............  Small study      Breathing Zone
                                survey of 136                                         median--0.6                        population.      Sampling.
                                workers.                                              [mu]g/m\3\;.
                                                                                     Other Areas
                                                                                      median--<0.3
                                                                                      [mu]g/m\3\;.
Henneberger et al., 2001.....  Cross-sectional   9.9 (15 cases)..  5.3 (8 cases)...  6.4% samples >2   Yes............  Small study      Breathing zone
                                survey of 151                                         [mu]g/m\3\;                        population.      sampling.
                                workers.                                              2.4% samples >5
                                                                                      [mu]g/m\3\;.
                                                                                     0.3% samples >25
                                                                                      [mu]g/m\3\.
Cummings et al., 2007........  Longitudinal      0.7-5.6 (4        0.1--7.9 (3       Production......  Yes............  Small sample     Personal
                                study of 93       cases).           cases).          1994-1999                           size.            sampling was
                                workers.                                              median--0.1[mu]                                     effective in
                                                                                      g/m\3\; 2000-                                       reducing rates
                                                                                      2003 median--                                       of new cases
                                                                                      0.04[mu]g/m\3\;.                                    of
                                                                                     Administrative                                       sensitization.
                                                                                      1994-1999
                                                                                      median <0.2
                                                                                      [mu]g/m\3\;
                                                                                      2000-2003
                                                                                      median--0.02
                                                                                      [mu]g/m\3\.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                   Copper-Beryllium Alloy Processing and Distribution
--------------------------------------------------------------------------------------------------------------------------------------------------------
Schuler et al., 2005.........  Cross-sectional   7.0 (10 cases)..  4.0 (6 cases)...  Rod and Wire      ...............  Small study      Personal
                                survey of 153                                         Production                         population.      sampling.
                                workers.                                              median--0.12
                                                                                      [mu]g/m\3\;
                                                                                     Strip Metal
                                                                                      Production
                                                                                      median--0.02
                                                                                      [mu]g/m\3\;.
                                                                                     Production
                                                                                      Support median--
                                                                                      0.02 [mu]g/
                                                                                      m\3\;.
                                                                                     Administration
                                                                                      median--0.02
                                                                                      [mu]g/m\3\.

[[Page 47620]]

 
Thomas et al., 2009..........  Cross-sectional   3.8 (3 cases)...  1.9 (1 case)....  Used exposure     ...............  Authors noted    Instituted PPE
                                study of 82                                           profile from                       workers may      to reduce
                                workers.                                              Schuler study.                     have been        dermal
                                                                                                                         sensitized       exposures.
                                                                                                                         prior to
                                                                                                                         available
                                                                                                                         screening,
                                                                                                                         underestimatin
                                                                                                                         g
                                                                                                                         sensitization
                                                                                                                         rate in legacy
                                                                                                                         workers.
Stanton et al., 2006.........  Cross-sectional   1.1 (1 case)....  1.1 (1 case)....  Bulk Products     ...............  Study did not    Personal
                                study of 88                                           Production                         report use of    sampling.
                                workers.                                              median 0.04                        PPE or
                                                                                      [mu]g/m\3\;                        respirators.
                                                                                      Strip Metal
                                                                                      Production
                                                                                      median--0.03
                                                                                      [mu]g/m\3\;
                                                                                      Production
                                                                                      support.
                                                                                     median--0.01
                                                                                      [mu]g/m\3\;
                                                                                      Administration
                                                                                      median 0.01
                                                                                      [mu]g/m\3\.
Bailey et al., 2010..........  Cross-sectional   11.0............  14.5 total......  ................  ...............  Study reported   ...............
                                study of 660                                                                             prevalence
                                total workers                                                                            rates for pre
                                (258 partial                                                                             enhanced
                                program, 290                                                                             control-
                                full program).                                                                           program,
                                                                                                                         partial
                                                                                                                         enhanced
                                                                                                                         control
                                                                                                                         program, and
                                                                                                                         full enhanced
                                                                                                                         control
                                                                                                                         program.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                         Nuclear Weapons Production Facilities and Cleanup of Former Facilities
--------------------------------------------------------------------------------------------------------------------------------------------------------
Kreiss et al., 1989..........  Cross-sectional   11.8 (6 cases)..  7.8 (4 cases)...  ................  No.............  Small study      ...............
                                survey of 51                                                                             population
                                workers.
Kreiss et al., 1993a.........  Cross-sectional   1.9 (18 cases)..  1.7 (15 cases)..  ................  No.............  Study            ...............
                                survey of 895                                                                            population
                                workers.                                                                                 includes some
                                                                                                                         workers with
                                                                                                                         no reported Be
                                                                                                                         exposure.
Stange et al., 1996..........  Longitudinal      2.4 (76 cases)..  0.7 (29 cases)..  Annual mean       No.............  ...............  Personal
                                Study of 4,397                                        concentration.                                      sampling.
                                BHSP                                                 1970-1988 0.016
                                participants.                                         [mu]g/m\3\;
                                                                                      1984-1987 1.04
                                                                                      [mu]g/m\3\.
Stange et al., 2001..........  Longitudinal      4.5 (154 cases).  1.6 (81 cases)..  No quantitative   No.............  ...............  Personal
                                study of 5,173                                        information                                         sampling.
                                workers.                                              presented in
                                                                                      study.
Viet et al., 2000............  Case-control....  74 workers        50 workers CBD..  Mean exposure     Yes............  Likely           Fixed airhead
                                                  sensitized.                         range: 0.083-                      underestimated   sampling away
                                                                                      0.622 [mu]g/                       exposures.       from breathing
                                                                                      m\3\.                                               zone:
                                                                                     Maximum                                             Matched
                                                                                      exposures: 0.54-                                    controls for
                                                                                      36.8 [mu]g/                                         age, sex,
                                                                                      m.\3\.                                              smoking.
--------------------------------------------------------------------------------------------------------------------------------------------------------
N/A = Information not available from study reports.


[[Page 47621]]


                                       Table A.2--Summary of Mechanistic Animal Studies for Sensitization and CBD
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                  Dose or exposure       Type of                              Other
           Reference                 Species               Study length            concentration        beryllium       Study results      information
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                  Intratracheal (intrabroncheal) or Nasal Instillation
--------------------------------------------------------------------------------------------------------------------------------------------------------
Barna et al., 1981............  Guinea pig.......                       3 month  10 mg-5[mu]m       beryllium oxide.  Granulomas,
                                                                                  particle size.                       interstitial
                                                                                                                       infiltrate with
                                                                                                                       fibrosis with
                                                                                                                       thickening of
                                                                                                                       alveolar septae.
Barna et al., 1984............  Guinea pig.......                       3 month  5 mg.............  beryllium oxide.  Granulomatous
                                                                                                                       lesions in
                                                                                                                       strain 2 but
                                                                                                                       not strain 13
                                                                                                                       indicating a
                                                                                                                       genetic
                                                                                                                       component.
Benson et al., 2000...........  Mouse............  ............................  0, 12.5, 25,       beryllium copper  Acute pulmonary
                                                                                  100[mu]g; 0, 2,    alloy;            toxicity
                                                                                  8 [mu]g.           beryllium metal.  associated with
                                                                                                                       beryllium/
                                                                                                                       copper alloy
                                                                                                                       but not
                                                                                                                       beryllium metal.
Haley et al., 1994............  Cynomolgus monkey               14, 60, 90 days  0, 1, 50, 150      Beryllium metal,  Beryllium oxide
                                                                                  [mu]g.             beryllium oxide.  particles were
                                                                                 0, 2.5, 12.5,                         less toxic than
                                                                                  37.5 [mu]g.                          the beryllium
                                                                                                                       metal.
Huang et al., 1992............  Mouse............  ............................  5 [mu]g..........  Beryllium         Granulomas        ................
                                                                                 1-5 [mu]g........   sulfate           produced in A/J
                                                                                                     immunization;     strain but not
                                                                                                     beryllium metal   BALB/c or C57BL/
                                                                                                     challenge.        6.
Votto et al., 1987............  Rat..............                       3 month  2.4 mg...........  Beryllium         Granulomas,
                                                                                 8 mg/ml..........   sulfate           however, no
                                                                                                     immunization;     correlation
                                                                                                     beryllium         between T-cell
                                                                                                     sulfate           subsets in lung
                                                                                                     challenge.        and BAL fluid.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                               Inhalation--Single Exposure
--------------------------------------------------------------------------------------------------------------------------------------------------------
Haley et al., 1989a...........  Beagle dog.......             Chronic--one dose  0, 6 [mu]g/kg, 18  500 [deg]C; 1000  Positive BeLPT    Granulomas
                                                                                  [mu]g/kg.          [deg]C            results--develo   resolved with
                                                                                                     beryllium oxide.  ped granulomas;   time, no full-
                                                                                                                       low-calcined      blown CBD.
                                                                                                                       beryllium oxide
                                                                                                                       more toxic than
                                                                                                                       high-calcined.
Haley et al., 1989b...........  Beagle dog.......      Chronic--one dose/2 year  0, 17 [mu]g/kg,    500 [deg]C; 1000  Granulomas,       Granulomas
                                                                       recovery   50 [mu]g/kg.       [deg]C            sensitization,    resolved over
                                                                                                     beryllium oxide.  low-fired more    time.
                                                                                                                       toxic than high
                                                                                                                       fired.
Robinson et al., 1968.........  Dog..............                       Chronic  0. 115mg/m\3\....  Beryllium oxide,  Foreign body
                                                                                                     beryllium         reaction in
                                                                                                     fluoride,         lung.
                                                                                                     beryllium
                                                                                                     chloride.
Sendelbach et al., 1989.......  Rat..............                        2 week  0, 4.05 [mu]g/L..  Beryllium as      Interstial
                                                                                                     beryllium         pneumonitis.
                                                                                                     sulfate.
Sendelbach and Witschi, 1987..  Rat..............                        2 week  0, 3.3, 7 [mu]g/L  Beryllium as      Enzyme changes
                                                                                                     beryllium         in BAL fluid.
                                                                                                     sulfate.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                               Inhalation--Repeat Exposure
--------------------------------------------------------------------------------------------------------------------------------------------------------
Conradi et al., 1971..........  Beagle dog.......               Chronic--2 year  0. 3300 [mu]g/     1400 [deg]C       No changes        May have been
                                                                                  m\3\, 4380 [mu]g/  beryllium oxide.  detected.         due to short
                                                                                  m\3\ once/month                                        exposure time
                                                                                  for 3 months.                                          followed by
                                                                                                                                         long recovery.

[[Page 47622]]

 
                                Macaca irus                     Chronic--2 year  0. 3300 [mu]g/     1400 [deg]C       No changes        May have been
                                 Monkey.                                          m\3\, 4380 [mu]g/  beryllium oxide.  detected.         due to short
                                                                                  m\3\ once/month                                        exposure time
                                                                                  for 3 months.                                          followed by
                                                                                                                                         long recovery.
Haley et al., 1992............  Beagle dog.......     Chronic--repeat dose (2.5  17, 50 [mu]g/kg..  500 [deg]C; 1000  Granulomatous
                                                                year intervals)                      [deg]C            pneumonitis.
                                                                                                     beryllium oxide.
Harmsen et al., 1985..........  Beagle dog.......                       Chronic  0, 20 [mu]g/kg,    500[deg]C; 1000
                                5 dogs per group.                                 50 [mu]g/kg.       [deg]C
                                                                                                     beryllium oxide.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                  Dermal or Intradermal
--------------------------------------------------------------------------------------------------------------------------------------------------------
Kang et al., 1977.............  Rabbit...........  ............................  10mg.............  Beryllium         Skin
                                                                                                     sulfate.          sensitization
                                                                                                                       and skin
                                                                                                                       granulomas.
Tinkle et al., 2003...........  Mouse............                       3 month  25 [mu]L.........  Beryllium         Microgranulomas
                                                                                 70 [mu]g.........   sulfate.          with some
                                                                                                    Beryllium oxide.   resolution over
                                                                                                                       time of study.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                      Intramuscular
--------------------------------------------------------------------------------------------------------------------------------------------------------
Eskenasy, 1979................  Rabbit...........  35 days (injections at 7 day  10mg.ml..........  Beryllium         Sensitization,
                                                                     intervals)                      sulfate.          evidence of CBD.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                Intraperitoneal Injection
--------------------------------------------------------------------------------------------------------------------------------------------------------
Marx and Burrell, 1973........  Guinea pig.......            24 weeks (biweekly  2.6 mg + 10 [mu]g  Beryllium         Sensitization...
                                                                    injections)   dermal             sulfate.
                                                                                  injections.
--------------------------------------------------------------------------------------------------------------------------------------------------------


                                           Table A-3--Summary of Beryllium Lung Cancer Epidemiological Studies
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                         Confounding         Study          Additional
          Reference               Study type      Exposure range     Study number     Mortality ratio      factors        limitations        comments
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                 Beryllium Case Registry
--------------------------------------------------------------------------------------------------------------------------------------------------------
Infante et al., 1980.........  Cohort..........  N/D.............  421 cases from    SMR 2.12........  Not reported...  Exposure         ...............
                                                                    the BCR.         7 lung cancer                       concentration
                                                                                      deaths.                            data or
                                                                                                                         smoking habits
                                                                                                                         not reported.
Steenland and Ward, 1991.....  Cohort..........  N/D.............  689 cases from    SMR 2.00 (95% CI  ...............  ...............  Included women:
                                                                    the BCR.          1.33-2.89).                                         93% women
                                                                                     28 lung cancer                                       diagnosed with
                                                                                      deaths.                                             CBD; 50% men
                                                                                                                                          diagnosed with
                                                                                                                                          CBD;
                                                                                                                                         SMR 157 for
                                                                                                                                          those with CBD
                                                                                                                                          and SMR 232
                                                                                                                                          for those with
                                                                                                                                          ABD.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                               Beryllium Manufacturing and/or Processing Plants (Extraction, Fabrication, and Processing)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Ward et al., 1992............  Retrospective     N/D.............  9,225 males.....  SMR 1.26........  ...............  Lack of job      Employment
                                Mortality                                            (95% CI 1.12-                       history and      period 1940-
                                Cohort.                                               1.42).                             air monitoring   1969.
                                                                                     280 lung cancer                     data.
                                                                                      deaths.

[[Page 47623]]

 
Levy et al., 2002............  Cohort..........  N/D.............  9225 males......  Statistically     Adjusted for     Lack of job      Majority of
                                                                                      non-significant   smoking.         history and      workers
                                                                                      elevation in                       air monitoring   studied
                                                                                      lung cancer                        data.            employed for
                                                                                      deaths.                                             less than one
                                                                                                                                          year
Bayliss et al., 1971.........  Nested cohort...  ................  8,000 workers...  SMR 1.06........  ...............  ...............  Employed prior
                                                                                     36 lung cancer                                       to 1947 for
                                                                                      deaths.                                             almost half
                                                                                                                                          lung cancer
                                                                                                                                          deaths.
Mancuso, 1970................  Cohort..........  411-43,300 [mu]g/ 1,222 workers at  SMR 1.42........  Only partial     Partial smoking  Employment
                                                  m\3\ annual       OH plant; 2,044  (95% CI 1.1-1.8)   smoking          history; No      period from
                                                  exposure          workers at PA    80 lung cancer     history.         job analysis     1937-1948.
                                                  (reported from    plant.            deaths.                            by title or
                                                  Zielinsky,                                                             exposure
                                                  1961).                                                                 category.
Mancuso, 1980................  Cohort..........  N/D.............  Same OH and PA    SMR 1.40........  No smoking       No adjustment    Employment
                                                                    plant analysis.                     adjustment.      by job title     period from
                                                                                                                         or exposure.     1942-1948;
                                                                                                                                          Used workers
                                                                                                                                          at rayon plant
                                                                                                                                          for
                                                                                                                                          comparison.
Mancuso and El Attar, 1969...  Cohort..........  N/D.............  3,685 white       SMR 1.49........  Adjusted for     No job exposure  Employment
                                                                    males.                              age and local.   data or          history from
                                                                                                                         smoking          1937-1944.
                                                                                                                         adjustment.
Wagner et al., 1980..........  Cohort..........  N/D.............  3,055 white       SMR 1.25........  ...............  Inadequately     Reanalysis
                                                                    males PA plant.  (95% CI 0.9-1.7)                    adjusted for     using PA lung-
                                                                                     47 lung cancer                      smoking; Used    cancer rate
                                                                                      deaths.                            national lung-   revealed 19%
                                                                                                                         cancer risk      underestimatio
                                                                                                                         for cancer not   n of beryllium
                                                                                                                         PA.              lung cancer
                                                                                                                                          deaths.
Sanderson et al., 2001.......  Nested case-      -- Average        3,569 males PA    SMR 1.22........  Smoking was      May not have     Found
                                control.          exposure          plant.           (95% CI 1.03-      found not to     adjusted         association
                                                  22.8[mu]g/m\3\.                     1.43).            be a             properly for     with 20 year
                                                 -- Maximum                          142 lung cancer    confounding      birth-year or    latency.
                                                  exposure                            deaths.           factor.          age at hire.
                                                  32.4[mu]g/m\3\.
Levy et al., 2007............  Nested case-      Used log          Reanalysis of     SMR 1.04........  Different        ...............  Found no
                                control.          transformed       Sanderson et     (95% CI 0.92-      methodology                       association
                                                  exposure data.    al., 2001.        1.17).            for smoking                       between
                                                                                                        adjustment.                       beryllium
                                                                                                                                          exposure and
                                                                                                                                          increased risk
                                                                                                                                          of lung
                                                                                                                                          cancer.
Schubauer-Berigan et al.,      Nested case-      Used exposure     Reanalysis of     Used Odds ratio:  Adjusted for     ...............  -- Controlled
 2008.                          control.          data from         Sanderson et      1.91 (95% CI      smoking, birth                    for birth-year
                                                  Sanderson et      al., 2001.        1.06-3.44)        cohort, age.                      and age at
                                                  al., 2001, Chen                     unadjusted;.                                        hire;
                                                  2001, and Couch                    1.29 (95% CI                                        -- Found
                                                  et al., 2010.                       0.61-2.71)                                          similar
                                                                                      birth-year                                          results to
                                                                                      adjusted;.                                          Sanderson et
                                                                                     1.24 (95% CI                                         al., 2001;
                                                                                      0.58-2.65) age-                                    -- Found
                                                                                      hire adjusted.                                      association
                                                                                                                                          with 10 year
                                                                                                                                          latency
                                                                                                                                         -- ``0'' = used
                                                                                                                                          minuscule
                                                                                                                                          value at start
                                                                                                                                          to eliminate
                                                                                                                                          the use of 0
                                                                                                                                          in a
                                                                                                                                          logarithmic
                                                                                                                                          analysis
Schubauer-Berigan et al.,      Cohort..........  N/D.............  9199 workers      SMR 1.17 (95%CI   Adjusted for     ...............  Male workers
 2010a.                                                             from 7            1.08-1.28).       smoking.                          employed at
                                                                    processing       545 deaths......                                     least 2 days
                                                                    plants.                                                               between 1940
                                                                                                                                          and 1970.
Schubauer-Berigan et al.,      Cohort..........  Used exposure     5436 workers OH   Evaluated using   Adjusted for     ...............  -- Exposure
 2010b.                                           data from         and PA plants.    hazard ratios     age, birth                        response was
                                                  Sanderson et                        and excess        cohort,                           found between
                                                  al., 2001.                          absolute risk.    asbestos                          0-10[mu]g/m\3\
                                                                                     293 deaths......   exposure,                         mean DWA;
                                                                                                        short-term                       -- Increased
                                                                                                        work status.                      with
                                                                                                                                          statistical
                                                                                                                                          significance
                                                                                                                                          at 4[mu]g/
                                                                                                                                          m\3\;
                                                                                                                                         -- 1 in 1000
                                                                                                                                          risk at
                                                                                                                                          0.033[mu]g/
                                                                                                                                          m\3\ mean DWA.
--------------------------------------------------------------------------------------------------------------------------------------------------------

[[Page 47624]]

 
                                                           Re-evaluation of Published Studies
--------------------------------------------------------------------------------------------------------------------------------------------------------
Hollins et al., 2009.........  Review..........  Re-examination    ................  ................  ...............  ...............  Found lung
                                                  of weight-of-                                                                           cancer excess
                                                  evidence from                                                                           risk was
                                                  more than 50                                                                            associated
                                                  publications.                                                                           with higher
                                                                                                                                          levels of
                                                                                                                                          exposure not
                                                                                                                                          relevant in
                                                                                                                                          today's
                                                                                                                                          industrial
                                                                                                                                          settings.
IARC, 2012...................  Multiple........  Insufficient      ................  Sufficient        IARC concluded   ...............  -- Greater lung
                                                  exposure                            evidence for      beryllium lung                    cancer risk in
                                                  concentration.                      carcinogenicity   cancer risk                       the BCR cohort
                                                 Data............                     of beryllium.     was not                          -- Correlation
                                                                                                        associated                        between
                                                                                                        with smoking.                     highest lung
                                                                                                                                          cancer rates
                                                                                                                                          and highest
                                                                                                                                          amounts of ABD
                                                                                                                                          or other non-
                                                                                                                                          malignant lung
                                                                                                                                          diseases
                                                                                                                                         -- Increased
                                                                                                                                          risk with
                                                                                                                                          longer latency
                                                                                                                                         -- Greater
                                                                                                                                          excess lung
                                                                                                                                          cancers among
                                                                                                                                          those hired
                                                                                                                                          prior to 1950.
--------------------------------------------------------------------------------------------------------------------------------------------------------
N/D = information not determined for most studies
DWA--daily weighted average

VI. Preliminary Beryllium Risk Assessment

    The Occupational Safety and Health (OSH) Act and court cases 
arising under it have led OSHA to rely on risk assessment to support 
the risk determinations required to set a permissible exposure limit 
(PEL) for a toxic substance in standards under the OSH Act. Section 
6(b)(5) of the OSH Act states that ``The Secretary [of Labor], in 
promulgating standards dealing with toxic materials or harmful physical 
agents under this subsection, shall set the standard which most 
adequately assures, to the extent feasible, on the basis of the best 
available evidence, that no employee will suffer material impairment of 
health or functional capacity even if such employee has regular 
exposure to the hazard dealt with by such standard for the period of 
his working life'' (29 U.S.C. 655(b)(5)).
    In Industrial Union Department, AFL-CIO v. American Petroleum 
Institute, 448 U.S. 607 (1980) (Benzene), the United States Supreme 
Court ruled that the OSH Act requires that, prior to the issuance of a 
new standard, a determination must be made that there is a significant 
risk of material impairment of health at the existing PEL and that 
issuance of a new standard will significantly reduce or eliminate that 
risk. The Court stated that ``before [the Secretary] can promulgate any 
permanent health or safety standard, the Secretary is required to make 
a threshold finding that a place of employment is unsafe--in the sense 
that significant risks are present and can be eliminated or lessened by 
a change in practices'' (Id. at 642). The Court also stated ``that the 
Act does limit the Secretary's power to requiring the elimination of 
significant risks'' (488 U.S. at 644 n.49), and that ``OSHA is not 
required to support its finding that a significant risk exists with 
anything approaching scientific certainty'' (Id. at 656).
    OSHA's approach for the risk assessment incorporates both a review 
of the recent literature on populations of workers exposed to beryllium 
below the current Permissible Exposure Limit (PEL) of 2 [mu]g/m\3\ and 
a statistical exposure-response analysis. OSHA evaluated risk at 
several alternate PELs under consideration by the Agency: 2 [mu]g/m\3\, 
1 [mu]g/m\3\, 0.5 [mu]g/m\3\, 0.2 [mu]g/m\3\, and 0.1 [mu]g/m\3\. A 
number of recently published epidemiological studies evaluate the risk 
of sensitization and CBD for workers exposed at and below the current 
PEL and the effectiveness of exposure control programs in reducing 
risk. OSHA also conducted a statistical analysis of the exposure-
response relationship for sensitization and CBD at the current PEL and 
alternate PELs the Agency is considering. For this analysis, OSHA used 
data provided by National Jewish Medical and Research Center (NJMRC) on 
a population of workers employed at a beryllium machining plant in 
Cullman, AL. The review of the epidemiological studies and OSHA's own 
analysis show substantial risk of sensitization and CBD among workers 
exposed at and below the current PEL of 2 [mu]g/m\3\. They also show 
substantial reduction in risk where employers have implemented a 
combination of controls, including stringent control of airborne 
beryllium levels and additional measures such as respirators, dermal 
personal protective equipment (PPE), and strict housekeeping to protect 
workers against dermal and respiratory beryllium exposure. To evaluate 
lung cancer risk, OSHA relied primarily on a quantitative risk 
assessment published in 2011 by NIOSH. This risk assessment was based 
on an update of the Reading cohort analyzed by Sanderson et al., as 
well as workers from two smaller plants (Schubauer-Berigan et al., 
2011) where workers were exposed to lower levels of beryllium and 
worked for longer periods than at the Reading plant. The authors found 
that lung cancer risk was strongly and significantly related to mean, 
cumulative, and maximum measures of workers' exposure; they predicted 
substantial risk of lung cancer at the current PEL, and substantial 
reductions in risk at the alternate PELs OSHA considered for the 
proposed rule (Schubauer-Berigan et al., 2011).

[[Page 47625]]

A. Review of Epidemiological Literature on Sensitization and Chronic 
Beryllium Disease From Occupational Exposure

    As discussed in the Health Effects section, studies of beryllium-
exposed workers conducted using the beryllium lymphocyte proliferation 
test (BeLPT) have found high rates of beryllium sensitization and CBD 
among workers in many industries, including at some facilities where 
exposures were primarily below OSHA's PEL of 2 [mu]g/m\3\ (Kreiss et 
al., 1993; Henneberger et al., 2001; Schuler et al., 2005; Schuler et 
al., 2012). In the mid-1990s, some facilities using beryllium began to 
aggressively monitor and reduce workplace exposures. Four plants where 
several rounds of BeLPT screening were conducted before and after 
implementation of new exposure control methods provide the best 
currently available evidence on the effectiveness of various exposure 
control measures in reducing the risk of sensitization and CBD. The 
experiences of these plants--a copper-beryllium processing facility in 
Reading, PA, a beryllia ceramics facility in Tucson, AZ; a beryllium 
processing facility in Elmore, OH; and a machining facility in Cullman, 
AL--show that efforts to prevent sensitization and CBD by using 
engineering controls to reduce workers' beryllium exposures to median 
levels at or around 0.2 [mu]g/m\3\ and did not emphasize PPE and 
stringent housekeeping methods, had only limited impact on risk. 
However, exposure control programs implemented more recently, which 
drastically reduced respiratory exposure to beryllium via a combination 
of engineering controls and respiratory protection, controlled dermal 
contact with beryllium using PPE, and employed stringent housekeeping 
methods to keep work areas clean and prevent transfer of beryllium 
between work areas, sharply curtailed new cases of sensitization among 
newly-hired workers. There is additional, but more limited, information 
available on the occurrence of sensitization and CBD among aluminum 
smelter workers with low-level beryllium exposures (Taiwo et al., 2008; 
Taiwo et al., 2010; Nilsen et al., 2010). A discussion of the 
experiences at these plants follows.
    The Health Effects section also discussed the role of particle 
characteristics and beryllium compound solubility in the development of 
sensitization and CBD among beryllium-exposed workers. Respirable 
particles small enough to reach the deep lung are responsible for CBD. 
However, larger inhalable particles that deposit in the upper 
respiratory tract may lead to sensitization. The weight of evidence 
indicates that both soluble and insoluble forms of beryllium are able 
to induce sensitization and CBD. Insoluble forms of beryllium that 
persist in the lung for longer periods may pose greater risk of CBD 
while soluble forms may more easily trigger immune sensitization. 
Although these factors potentially influence the toxicity of beryllium, 
the available data are too limited to reliably account for solubility 
and particle size in the Agency estimates of risk. The qualitative 
impact on conclusions and uncertainties with regard to risk are 
discussed in a later section.
1. Reading, PA, Plant
    Schuler et al. conducted a study of workers at a copper-beryllium 
processing facility in Reading, PA, screening 152 workers with the 
BeLPT (Schuler et al., 2005). Exposures at this plant were believed to 
be low throughout its history due to the low percentage of beryllium in 
the metal alloys used, and the relatively low exposures found in 
general area samples collected starting in 1969 (sample median <= 0.1 
[mu]g/m\3\, 97% < 0.5 [mu]g/m\3\). The reported prevalences of 
sensitization (6.5 percent) and CBD (3.9 percent) showed substantial 
risk at this facility, even though airborne exposures were primarily 
below OSHA's current PEL of 2 [mu]g/m\3\.
    Personal lapel samples were collected in production and production 
support jobs between 1995 and May 2000. These samples showed primarily 
very low airborne beryllium levels, with a median of 0.073 [mu]g/
m\3\.\6\ The wire annealing and pickling process had the highest 
personal lapel sample values, with a median of 0.149 [mu]g/m\3\. 
Despite these low exposure levels, cases of sensitization continued to 
occur among workers whose first exposures to beryllium occurred in the 
1990s. Five (11.5 percent) workers of 43 hired after 1992 who had no 
prior beryllium exposure became sensitized, including four in 
production work and one in production support (Thomas et al., 2009; 
evaluation for CBD not reported). Two (13 percent) of these sensitized 
workers were among 15 workers in this group who had been hired less 
than a year before the screening.
---------------------------------------------------------------------------

    \6\ In their publication, Schuler et al. presented median values 
for plant-wide and work-category-specific exposure levels; they did 
not present arithmetic or geometric mean values for personal 
samples.
---------------------------------------------------------------------------

    After the BeLPT screening was conducted in 2000, the company began 
implementing new measures to further reduce workers' exposure to 
beryllium. Requirements designed to minimize dermal contact with 
beryllium, including long-sleeve facility uniforms and polymer gloves, 
were instituted in production areas in 2000. In 2001 the company 
installed local exhaust ventilation (LEV) in die grinding and 
polishing. Personal lapel samples collected between June 2000 and 
December 2001 show reduced exposures plant-wide. Of 2,211 exposure 
samples collected during this ``pre-enclosure program'' period, 98 
percent were below 0.2 [mu]g/m\3\ (Thomas et al., 2009, p. 124). 
Median, arithmetic mean, and geometric mean values <= 0.03 [mu]g/m\3\ 
were reported in this period for all processes except the wire 
annealing and pickling process. Samples for this process remained 
elevated, with a median of 0.1 [mu]g/m\3\ (arithmetic mean of 0.127 
[mu]g/m\3\, geometric mean of 0.083 [mu]g/m\3\). In January 2002, the 
plant enclosed the wire annealing and pickling process in a restricted 
access zone (RAZ), required respiratory PPE in the RAZ, and implemented 
stringent measures to minimize the potential for skin contact and 
beryllium transfer out of the zone. While exposure samples collected by 
the facility were sparse following the enclosure, they suggest exposure 
levels comparable to the 2000-01 samples in areas other than the RAZ. 
Within the RAZ, required use of powered air-purifying respirators 
(PAPRs) indicates that respiratory exposure was negligible. A 2009 
publication on the facility reported that outside the RAZ, ``the vast 
majority of employees do not wear any form of respiratory protection 
due to very low airborne beryllium concentrations'' (Thomas et al., 
2009, p. 122).
    To test the efficacy of the new measures in preventing 
sensitization and CBD, in June 2000 the facility began an intensive 
BeLPT screening program for all new workers. The company screened 
workers at the time of hire; at intervals of 3, 6, 12, 24, and 48 
months; and at 3-year intervals thereafter. Among 82 workers hired 
after 1999, three cases of sensitization were found (3.7 percent). Two 
(5.4 percent) of 37 workers hired prior to enclosure of the wire 
annealing and pickling process were found to be sensitized within 3 and 
6 months of beginning work at the plant. One (2.2 percent) of 45 
workers hired after the enclosure was confirmed as sensitized. Among 
these early results, it appears that the greatest reduction in 
sensitization risk was achieved after median exposures in all areas of 
the plant were reduced to below 0.1 [mu]g/m\3\

[[Page 47626]]

and PPE to prevent dermal contact was instituted.
2. Tucson, AZ, Plant
    Kreiss et al. conducted a study of workers at a beryllia ceramics 
plant, screening 136 workers with the BeLPT in 1992 (Kreiss et al., 
1996). Full-shift area samples collected between 1983 and 1992 showed 
primarily low airborne beryllium levels at this facility. Of 774 area 
samples, 76 percent were at or below 0.1 [mu]g/m\3\ and less than 1 
percent exceeded 2 [mu]g/m\3\. A small set (75) of personal lapel 
samples collected at the plant beginning in 1991 had a median of 0.2 
[mu]g/m\3\ and ranged from 0.1 to 1.8 [mu]g/m\3\ (arithmetic and 
geometric mean values not reported) (Kreiss et al., 1996, p. 19). 
However, area samples and short-term breathing zone samples also showed 
occasional instances of very high beryllium exposure levels, with 
extreme values of several hundred [mu]g/m\3\ and 3.6 percent of short-
term breathing zone samples in excess of 5 [mu]g/m\3\.
    Kreiss et al. reported that eight (5.9 percent) of 136 workers 
tested were sensitized, six (4.4 percent) of whom were diagnosed with 
CBD. Seven of the eight sensitized employees had worked in machining, 
where general area samples collected between October 1985 and March 
1988 had a median of 0.3 [mu]g/m\3\, in contrast to a median value of 
less than 0.1 [mu]g/m\3\ in other areas of the plant (Kreiss et al., 
1996, p. 20; mean values not reported). Short-term breathing zone 
measurements associated with machining had a median of 0.6 [mu]g/m\3\, 
double the median of 0.3 [mu]g/m\3\ for breathing zone measurements 
associated with other processes (id., p. 20; mean values not reported). 
One sensitized worker was one of 13 administrative workers screened, 
and was among those diagnosed with CBD. Exposures of administrative 
workers were not well-characterized, but were believed to be among the 
lowest in the plant. Of three personal lapel samples reported for 
administrative staff during the 1990s, all were below the then 
detection limit of 0.2 [mu]g/m\3\ (Cummings et al., 2007, p.138).
    Following the 1992 screening, the facility reduced exposures in 
machining areas by enclosing machines and installing HEPA filter 
exhaust systems. Personal samples collected between 1994 and 1999 had a 
median of 0.2 [mu]g/m\3\ in production jobs and 0.1 [mu]g/m\3\ in 
production support (geometric means 0.21 [mu]g/m\3\ and 0.11 [mu]g/
m\3\, respectively; arithmetic means not reported. Cummings et al., 
2007, p. 138). In 1998, a second screening found that 9 percent of 
tested workers hired after the 1992 screening were sensitized, of whom 
one was diagnosed with CBD. All of the sensitized workers had been 
employed at the plant for less than two years (Henneberger et al., 
2001).
    Following the 1998 screening, the company continued efforts to 
reduce exposures and risk of sensitization and CBD by implementing 
additional engineering and administrative controls and PPE. Respirator 
use was required in production areas beginning in 1999, and latex 
gloves were required beginning in 2000. The lapping area was enclosed 
in 2000, and enclosures were installed for all mechanical presses in 
2001. Between 2000 and 2003, water-resistant or water-proof garments, 
shoe covers, and taped gloves were incorporated to keep beryllium-
containing fluids from wet machining processes off the skin. The new 
engineering measures did not appear to substantially reduce airborne 
beryllium levels in the plant. Personal lapel samples collected in 
production processes between 2000 and 2003 had a median and geometric 
mean of 0.18 [mu]g/m\3\, similar to the 1994-1999 samples (Cummings et 
al., 2007, p. 138). However, respiratory protection requirements were 
instituted in 2000 to control workers' airborne beryllium exposures.
    To test the efficacy of the new measures instituted after 1998, in 
January 2000 the company began screening new workers for sensitization 
at the time of hire and at 3, 6, 12, 24, and 48 months of employment 
(Cummings et al., 2007). These more stringent measures appear to have 
substantially reduced the risk of sensitization among new employees. Of 
97 workers hired between 2000 and 2004, one case of sensitization was 
identified (1 percent). This worker had experienced a rash after an 
incident of dermal exposure to lapping fluid through a gap between the 
glove and uniform sleeve, indicating that sensitization may have 
occurred via skin exposure.
3. Elmore, OH, Plant
    Kreiss et al., Schuler et al., and Bailey et al. conducted studies 
of workers at a beryllium metal, alloy, and oxide production plant. 
Workers participated in BeLPT surveys in 1992 (Kreiss et al., 1997) and 
in 1997 and 1999 (Schuler et al., 2012). Exposure levels at the plant 
between 1984 and 1993 were characterized by a mixture of general area, 
short-term breathing zone, and personal lapel samples. Kreiss et al. 
reported that the median area samples for various work areas ranged 
from 0.1 to 0.7 [mu]g/m\3\, with the highest values in the alloy arc 
furnace and alloy melting-casting areas (other measures of central 
tendency not reported). Personal lapel samples were available from 
1990-1992, and showed high exposures overall (median value of 1.0 
[mu]g/m\3\) with very high exposures for some processes. The authors 
reported median sample values of 3.8 [mu]g/m\3\ for beryllium oxide 
production, 1.75 [mu]g/m\3\ for alloy melting and casting, and 1.75 
[mu]g/m\3\ for the arc furnace.
    Kreiss et al. reported that 43 (6.9 percent) of 627 workers tested 
in 1992 were sensitized, six of whom were diagnosed with CBD (4.4 
percent). Workers with less than one year tenure at the plant were not 
tested in this survey (Bailey et al., 2010, p. 511). The work processes 
that appeared to carry the highest risk for sensitization and CBD 
(e.g., ceramics) were not those with the highest reported exposure 
levels (e.g., arc furnace and melting-casting). The authors noted 
several possible reasons for this, including factors such as 
solubility, particle size/number, and particle surface area that could 
not be accounted for in their analysis (Kreiss et al., 1997).
    In 1996-1999, the company took steps to reduce workers' beryllium 
exposures: some high-exposure processes were enclosed, special 
restricted-access zones were set up, HEPA filters were installed in air 
handlers, and some ventilation systems were updated. In 1997 workers in 
the pebble plant restricted access zone were required to wear half-face 
air-purifying respirators, and beginning in 1999 all new employees were 
required to wear loose-fitting powered air-purifying respirators (PAPR) 
in manufacturing buildings (Bailey et al., 2010, p. 506). Skin 
protection became part of the protection program for new employees in 
2000, and glove use was required in production areas and for handling 
work boots beginning in 2001. Also beginning in 2001, either half-mask 
respirators or PAPRs were required in the production facility (type 
determined by airborne beryllium levels), and respiratory protection 
was required for roof work and during removal of work boots (Bailey et 
al., 2010, p. 506). Respirator use was reported to be used on about 
half or less of industrial hygiene sample records for most processes in 
1990-1992 (Kreiss et al., 1996).
    Beginning in 2000, workers were offered periodic BeLPT testing to 
evaluate the effectiveness of a new exposure control program 
implemented by the company. Bailey et al. (2010) reported on the 
results of this surveillance for 290 workers hired between February 21, 
2000 and December 18, 2006. They compared the

[[Page 47627]]

occurrence of beryllium sensitization and disease among 258 employees 
who began work at the Elmore plant between January 15, 1993 and August 
9, 1999 (the `pre-program group') and among 290 employees who were 
hired between February 21, 2000 and December 18, 2006 and were tested 
at least once after hire (the `program group'). They found that, as of 
1999, 23 (8.9 percent) of the pre-program group were sensitized to 
beryllium. Six (2.1 percent) of the program group had confirmed 
abnormal results on their final round of BeLPTs, which occurred in 
different years for different employees. In addition, another five 
employees had confirmed abnormal BeLPT results at some point during the 
testing period, followed by at least one instance of a normal test 
result. One of these employees had a confirmed abnormal baseline BeLPT 
at hire, and had two subsequent normal BeLPT results at 6 and 12 months 
after hire. Four others had confirmed abnormal BeLPT results at 3 or 6 
months after hire, later followed by a normal test. Including these 
four in the count of sensitized workers, there were a total of ten (3.5 
percent) workers sensitized after hire in the program group. It is not 
clear whether the occurrence of a normal result following an abnormal 
result reflects an error in one of the test results, a change in the 
presence or level of memory T-cells circulating in the worker's blood, 
or other possibilities. Because most of the workers in the study had 
been employed at the facility for less than two years, Bailey et al. 
did not report the incidence of CBD among the sensitized workers 
(Bailey et al., 2010, p. 511).
    In addition, Bailey et al. divided the program group into the 
`partial program subgroup' (206 employees hired between February 21, 
2000 and December 31, 2003) and the `full program subgroup' (84 
employees hired between January 1, 2004 and December 18, 2006) to 
account for the greater effectiveness of the exposure control program 
after the first three years of implementation (Bailey et al., pp 506-
507). Four (1.9 percent) of the partial program group were found to be 
sensitized on their final BeLPT (excluding one with a confirmed 
abnormal BeLPT from their baseline test at hire). Two (2.4 percent) of 
the full program group were found to be sensitized on their final BeLPT 
(Bailey et al., 2010, p. 509). An additional three employees in the 
partial program group and one in the full program group were confirmed 
sensitized at 3 or 6 months after hire, then later had a single normal 
BeLPT (Bailey et al., 2010, p. 509).
    Schuler et al. (2012) published a study examining beryllium 
sensitization and CBD among short-term workers at the Elmore, OH plant, 
using exposure estimates created by Virji et al. (2012). The study 
population included 264 workers employed in 1999 with up to six years 
tenure at the plant (91 percent of the 291 eligible workers). By 
including only short-term workers, Virji et al. were able to construct 
participants' exposures with more precision than was possible in 
studies involving workers exposed for longer durations and in time 
periods with less exposure sampling. Each participant completed a work 
history questionnaire and was tested for beryllium sensitization. The 
overall prevalence of sensitization was 9.8 percent (26/264). 
Sensitized workers were offered further evaluation for CBD. Twenty-two 
sensitized workers consented to clinical testing for CBD via 
transbronchial biopsy. Six of those sensitized were diagnosed with CBD 
(2.3 percent, 6/264).
    Exposure estimates were constructed using two exposure surveys 
conducted in 1999: a survey of total mass exposures (4022 full-shift 
personal samples) and a survey of size-separated impactor samples (198 
samples). The 1999 exposure surveys and work histories were used to 
estimate long-term lifetime weighted (LTW) average, cumulative, and 
highest-job-worked exposure for total, respirable, and submicron 
beryllium mass concentrations. Schuler et al. (2012) found no cases of 
sensitization among workers with total mass LTW average exposures below 
0.09 [mu]g/m\3\, among workers with total mass cumulative exposures 
below 0.08 [mu]g/m\3\-yr, or among workers with total mass highest job 
worked exposures below 0.12 [mu]g/m\3\. Twenty-four percent, 16 
percent, and 25 percent of the study population were exposed below 
those levels, respectively. Both total and respirable beryllium mass 
concentration estimates were positively associated with sensitization 
(average and highest job), and CBD (cumulative) in logistic regression 
models.
4. Cullman, AL, Plant
    Newman et al. conducted a series of BeLPT screenings of workers at 
a precision machining facility between 1995 and 1999 (Newman et al., 
2001). A small set of personal lapel samples collected in the early 
1980s and in 1995 suggests that exposures in the plant varied widely 
during this time period. In some processes, such as engineering, 
lapping, and electrical discharge machining (EDM), exposures were 
apparently low (<= 0.1 [mu]g/m\3\). Madl et al. reported that personal 
lapel samples from all machining processes combined had a median of 
0.33 [mu]g/m\3\, with a much higher arithmetic mean of 1.63 [mu]g/m\3\ 
(Madl et al., 2007, Table IV, p. 457). The majority of these samples 
were collected in the high-exposure processes of grinding (median of 
1.05 [mu]g/m\3\, mean of 8.48 [mu]g/m\3\), milling (median of 0.3 
[mu]g/m\3\, mean of 0.82 [mu]g/m\3\), and lathing (median of 0.35 
[mu]g/m\3\, mean of 0.88 [mu]g/m\3\) (Madl et al., 2007, Table IV, p. 
457). As discussed in greater detail in the background document,\7\ the 
data set of machining exposure measurements included a few extremely 
high values (41-73 [mu]g/m\3\) that a NIOSH researcher identified as 
probable errors, and that appear to be included in Madl et al.'s 
arithmetic mean calculations. Because high single-data point exposure 
errors influence the arithmetic mean far more than the median value of 
a data range, OSHA believes the median values reported by Madl et al. 
are more reliable than the arithmetic means they reported.
---------------------------------------------------------------------------

    \7\ When used throughout this section, ``background document'' 
refers to a more comprehensive, companion risk-assessment document 
that can be found at www.regulations.gov in OSHA Docket No. ___.
---------------------------------------------------------------------------

    After a sentinel case of CBD was diagnosed at the plant in 1995, 
the company began BeLPT screenings to identify workers at increased 
risk of CBD and implemented engineering and administrative controls and 
PPE designed to reduce workers' beryllium exposures in machining 
operations. Newman et al. reported 22 (9.4 percent) sensitized workers 
among 235 tested, 13 of whom were diagnosed with CBD within the study 
period. Between 1995 and 1997, the company built enclosures and 
installed or updated local exhaust ventilation (LEV) for several 
machining departments, removed pressurized air hoses, and required the 
use of company uniforms. Madl et al. reported that historically, 
engineering and work process controls, rather than personal protective 
equipment, were used to limit workers' exposure to beryllium; 
respirators were used only in cases of high exposure, such as during 
sandblasting (Madl et al., 2007, p. 450). In contrast to the Reading 
and Tucson plants, gloves were not required at this plant.
    Personal lapel samples collected extensively between 1996 and 1999 
in machining jobs have an overall median of 0.16 [mu]g/m\3\, showing 
that the new controls achieved a marked reduction in machinists' 
exposures during this

[[Page 47628]]

period. Nearly half of the samples were collected in milling (median = 
0.18 [mu]g/m\3\). Exposures in other machining processes were also 
reduced, including grinding (median of 0.18 [mu]g/m\3\) and lathing 
(median of 0.13 [mu]g/m\3\). However, cases of sensitization and CBD 
continued to occur.
    At the time that Newman et al. reviewed the results of BeLPT 
screenings conducted in 1995-1999, a subset of 60 workers had been 
employed at the plant for less than a year. Four (6.7 percent) of these 
workers were found to be sensitized, of whom two were diagnosed with 
CBD and one with probable CBD (Newman et al., 2001). All four had been 
hired in 1996. Two (one CBD case, one sensitized only) had worked only 
in milling, and had worked for approximately 3-4 months (0.3-0.4 yrs) 
at the time of diagnosis. One of those diagnosed with CBD worked only 
in EDM, where lapel samples collected between 1996 and 1999 had a 
median of 0.03 [mu]g/m\3\. This worker was diagnosed with CBD in the 
same year that he began work at the plant. The last CBD case worked as 
a shipper, where exposures in 1996-1999 were similarly low, with a 
median of 0.09 [mu]g/m\3\.
    Beginning in 2000, exposures in all jobs at the machining facility 
were reduced to extremely low levels. Personal lapel samples collected 
in machining processes between 2000 and 2005 had a median of 0.09 
[mu]g/m\3\, where more than a third of samples came from the milling 
process (n = 765, median of 0.09 [mu]g/m\3\). A later publication on 
this plant by Madl et al. reported that only one worker hired after 
1999 became sensitized. This worker had been employed for 2.7 years in 
chemical finishing, where exposures were roughly similar to other 
machining processes (n = 153, median of 0.12 [mu]g/m\3\). Madl et al. 
did not report whether this worker was evaluated for CBD.
5. Aluminum Smelting Plants
    Taiwo et al. (2008) studied a population of 734 employees at four 
aluminum smelters located in Canada (2), Italy (1), and the United 
States (1). In 2000, a beryllium exposure limit of 0.2 [mu]g/m\3\ 8-
hour TWA (action level 0.1 [mu]g/m\3\) and a short-term exposure limit 
(STEL) of 1.0 [mu]g/m\3\ (15-minute sample) were instituted at these 
plants. Sampling to determine compliance with the exposure limit began 
at all smelters in 2000. Table VI-1 below, adapted from Taiwo et al. 
(2008), shows summary information on samples collected from the start 
of sampling through 2005.

                             Table VI-1--Exposure Sampling Data by Plant--2000-2005
----------------------------------------------------------------------------------------------------------------
                                                                                    Arithmetic
                     Smelter                         Number of    Median  ([mu]g/  mean  ([mu]g/  Geometric mean
                                                      samples          m\3\)           m\3\)        ([mu]g/m\3\)
----------------------------------------------------------------------------------------------------------------
Canadian smelter 1..............................             246            0.03            0.09            0.03
Canadian smelter 2..............................             329            0.11            0.29            0.08
Italian smelter.................................              44            0.12            0.14            0.10
U.S. smelter....................................             346            0.03            0.26            0.04
----------------------------------------------------------------------------------------------------------------
Adapted from Taiwo et al., 2008, Table 1.

    All employees potentially exposed to beryllium levels at or above 
the action level for at least 12 days per year, or exposed at or above 
the STEL 12 or more times per year, were offered medical surveillance 
including the BeLPT (Taiwo et al., 2008, p. 158). Table VI-2 below, 
adapted from Taiwo et al. (2008), shows test results for each facility 
between 2001 and 2005.

                                  Table VI-2--BeLPT Results by Plant--2001-2005
----------------------------------------------------------------------------------------------------------------
                                                     Employees                    Abnormal BeLPT     Confirmed
                     Smelter                          tested          Normal       (unconfirmed)    Sensitized
----------------------------------------------------------------------------------------------------------------
Canadian smelter 1..............................             109             107               1               1
Canadian smelter 2..............................             291             290               1               0
Italian smelter.................................              64              63               0               1
U.S. smelter....................................             270             268               2               0
----------------------------------------------------------------------------------------------------------------
Adapted from Taiwo et al., 2008, Table 2.

    The two workers with confirmed beryllium sensitization were offered 
further evaluation for CBD. Both were diagnosed with CBD, based on 
broncho-alveolar lavage (BAL) results in one case and pulmony function 
tests, respiratory symptoms, and radiographic evidence in the other.
    In 2010, Taiwo et al. published a study of beryllium-exposed 
workers from smelters at four companies, including some of the workers 
from the 2008 publication. 3,185 workers were determined to be 
``significantly exposed'' to beryllium and invited to participate in 
BeLPT screening. Each company used different criteria to determine 
``significant'' exposure, which appeared to vary considerably (p. 570). 
About 60 percent of invited workers participated in the program between 
2000 and 2006, of whom nine were determined to be sensitized (see Table 
VI-3 below). The authors state that all nine workers were referred to a 
respiratory physician for further evaluation for CBD. Two were 
diagnosed with CBD, as described above (Taiwo et al., 2008). The 
authors do not report the details of other sensitized workers' 
evaluation for CBD.

[[Page 47629]]



                          Table VI-3--Medical Surveillance for BeS in ALUMINUM Smelters
----------------------------------------------------------------------------------------------------------------
                                                     Number of        At-risk        Employees
                     Company                         smelters        employees        tested            BeS
----------------------------------------------------------------------------------------------------------------
A...............................................               4            1278             734               4
B...............................................               3             423             328               0
C...............................................               1            1100             508               4
D...............................................               1             384             362               1
                                                 ---------------------------------------------------------------
    Total.......................................               9            3185            1932               9
----------------------------------------------------------------------------------------------------------------
Adapted from Taiwo et al., 2011, Table 1.

    In general, there appeared to be a low level of sensitization and 
CBD among employees at the aluminum smelters studied by Taiwo et al. 
This is striking in light of the fact that many of the employees tested 
had worked at the smelters long before the institution of exposure 
limits for beryllium at some smelters in 2000. However, the authors 
note that respiratory protection had long been used at these plants to 
protect workers from other hazards. The results are roughly consistent 
with the observed prevalence of sensitization following the institution 
of respiratory protection at the Tucson beryllium ceramics plant 
discussed previously. A study by Nilsen et al. (2010) also found a low 
rate of sensitization among aluminum workers in Norway. Three-hundred 
sixty-two workers and thirty-one control individuals received BeLPT 
testing for beryllium sensitization. The authors found one sensitized 
worker (0.28 percent). No borderline results were reported. The authors 
reported that current exposures in this plant ranged from 0.1 [micro]g/
m\3\ to 0.31 [micro]g/m\3\ (Nilsen et al., 2010) and that respiratory 
protection was in use, as is the case in the smelters studied by Taiwo 
et al. (2008, 2010).

B. Preliminary Conclusions

    The published literature on beryllium sensitization and CBD shows 
that risk of both can be substantial in workplaces in compliance with 
OSHA's current PEL (Kreiss et al., 1993; Schuler et al., 2005). The 
experiences of several facilities in developing effective industrial 
hygiene programs have shown that minimizing both airborne and dermal 
exposure, using a combination of engineering and administrative 
controls, respiratory protection, and dermal PPE, has substantially 
lowered workers' risk of beryllium sensitization. In contrast, risk-
reduction programs that relied primarily on engineering controls to 
reduce workers' exposures to median levels in the range of 0.1-0.2 
[micro]g/m\3\, such as those implemented in Tucson following the 1992 
survey and in Cullman during 1996-1999, had only limited impact on 
reducing workers' risk of sensitization. The prevalence of 
sensitization among workers hired after such controls were installed at 
the Cullman plant remained high (Newman et al. (6.7 percent) and 
Henneberger et al. (9 percent)). A similar prevalence of sensitization 
was found in the screening conducted in 2000 at the Reading plant, 
where the available sampling data show median exposure levels of less 
than 0.2 [micro]g/m\3\ (6.5 percent). The risk of sensitization was 
found to be particularly high among newly-hired workers (<=1 year of 
beryllium exposure) in the Reading 2000 screening (13 percent) and the 
Tucson 1998 screening (16 percent).
    Cases of CBD have also continued to develop among workers in 
facilities and jobs where exposures were below 0.2 [micro]g/m\3\. One 
case of CBD was found in the Tucson 1998 screening among nine 
sensitized workers hired less than two years previously (Henneberger et 
al., 2001). At the Cullman plant, at least two cases of CBD were found 
among four sensitized workers screened in 1995-1999 and hired less than 
a year previously (Newman et al., 2001). These results suggest a 
substantial risk of progression from sensitization to CBD among workers 
exposed at levels well below the current PEL, especially considering 
the extremely short time of exposure and follow-up for these workers. 
Six of 10 sensitized workers identified at Reading in the 2000 
screening were diagnosed with CBD. The four sensitized workers who did 
not have CBD at their last clinical evaluation had been hired between 
one and five years previously; therefore, the time may have been too 
short for CBD to develop.
    In contrast, more recent exposure control programs that have used a 
combination of engineering controls, PPE, and stringent housekeeping 
measures to reduce workers' airborne and dermal exposures have 
substantially lowered risk of sensitization among newly-hired workers. 
Of 97 workers hired between 2000 and 2004 in Tucson, where respiratory 
and skin protection was instituted for all workers in production areas, 
only one (1 percent) worker became sensitized, and in that case the 
worker's dermal protection had failed during wet-machining work (Thomas 
et al., 2009). In the aluminum smelters discussed by Taiwo et al., 
where available exposure samples indicated median beryllium levels of 
about 0.1 [mu]g/m\3\ or below (measured as an 8-hour TWA) and workers 
used respiratory and dermal protection, confirmed cases of 
sensitization were rare (zero or one case per location). Sensitization 
was also rare among workers at a Norwegian aluminum smelter (Nilsen et 
al., 2010), where estimated exposures in the plant ranged from 0.1 
[mu]g/m\3\ to 0.3 [mu]g/m\3\ and respiratory protection was regularly 
used. In Reading, where in 2000-2001 airborne exposures in all jobs 
were reduced to a median of 0.1 [mu]g/m\3\ or below (measured as an 8-
hour TWA) and dermal protection was required for production-area 
workers, two (5.4 percent) of 37 newly hired workers became sensitized 
(Thomas et al., 2009). After the process with the highest exposures 
(median of 0.1 [mu]g/m\3\) was enclosed in 2002 and workers in that 
process were required to use respiratory protection, the remaining jobs 
had very low exposures (medians ~ 0.03 [mu]g/m\3\). Among 45 workers 
hired after the enclosure, one was found to be sensitized (2.2 
percent). In Elmore, where all workers were required to wear 
respirators and skin PPE in production areas beginning in 2000-2001, 
the estimated prevalence of sensitization among workers hired after 
these measures were put in place was around 2-3 percent (Bailey et al., 
2010). In addition, Schuler et al. (2012) found no cases of 
sensitization among short-term Elmore workers employed in 1999 who had 
total mass LTW average exposures below 0.09 [mu]g/m\3\, among workers 
with total mass cumulative exposures below 0.08 [mu]g/m\3\-yr, or among 
workers with total mass highest job worked exposures below 0.12 [mu]g/
m\3\.
    Madl et al. reported one case of sensitization among workers at the 
Cullman plant hired after 2000. The median personal exposures were 
about

[[Page 47630]]

0.1 [mu]g/m\3\ or below for all jobs during this period. Several 
changes in the facility's exposure control methods were instituted in 
the late 1990s that were likely to have reduced dermal as well as 
respiratory exposure to beryllium. For example, the plant installed 
change/locker rooms for workers entering the production facility, 
instituted requirements for work uniforms and dedicated work shoes for 
production workers, implemented annual beryllium hazard awareness 
training that encouraged glove use, and purchased high efficiency 
particulate air (HEPA) filter vacuum cleaners for workplace cleanup and 
decontamination.
    The results of the Reading, Tucson, and Elmore studies show that 
reducing airborne exposures to below 0.1 [mu]g/m\3\ and protecting 
workers from dermal exposure, in combination, have achieved a 
substantial reduction in sensitization risk among newly-hired workers. 
Because respirator use, dermal protection, and engineering changes were 
often implemented concurrently at these plants, it is difficult to 
attribute the reduced risk to any single control measure. The reduction 
is particularly evident when comparing newly-hired workers in the most 
recent Reading screenings (2.2-5.4 percent), and the rate of 
sensitization found among workers hired within the year before the 2000 
screening (13 percent). There is a similarly striking difference 
between the rate of prevalence found among newly-hired workers in the 
most recent Tucson study (1 percent) and the rate found among workers 
hired within the year before the 1998 screening at that plant (16 
percent). These results are echoed in the Cullman facility, which 
combined engineering controls to reduce airborne exposures to below 0.1 
[mu]g/m\3\ with measures such as housekeeping improvements and worker 
training to reduce dermal exposure.
    The studies on recent programs to reduce workers' risk of 
sensitization and CBD were conducted on populations with very short 
exposure and follow-up time. Therefore, they could not address the 
question of how frequently workers who become sensitized in 
environments with extremely low airborne exposures (median <0.1 [mu]g/
m\3\) develop CBD. Clinical evaluation for CBD was not reported for 
sensitized workers identified in the most recent Tucson, Reading, and 
Elmore studies. In Cullman, however, two of the workers with CBD had 
been employed for less than a year and worked in jobs with very low 
exposures (median 8-hour personal sample values of 0.03-0.09 [mu]g/
m\3\). The body of scientific literature on occupational beryllium 
disease also includes case reports of workers with CBD who are known or 
believed to have experienced minimal beryllium exposure, such as a 
worker employed only in shipping at a copper-beryllium distribution 
center (Stanton et al., 2006), and workers employed only in 
administration at a beryllium ceramics facility (Kreiss et al., 1996).
    Arjomandi et al. published a study of 50 sensitized workers from a 
nuclear weapons research and development facility (Arjomandi et al., 
2010). Occupational and medical histories including physical 
examination and chest imaging were available for the great majority 
(49) of these individuals. Forty underwent testing for CBD via 
bronchoscopy and transbronchial biopsies. In contrast to the studies of 
low-exposure populations discussed previously, this group had much 
longer follow-up time (mean time since first exposure = 32 years) and 
length of employment at the facility (mean of 18 years). Quantitative 
exposure estimates for the workers were not presented; however, the 
authors characterized their probable exposures as ``low'' (13 workers), 
``moderate'' (28 workers), or ``high'' (nine workers) based on the jobs 
they performed at the facility.
    Five of the 50 sensitized workers (10 percent) were diagnosed with 
CBD based on histology or high-resolution computed tomography. An 
additional three (who had not undergone full clinical evaluation for 
CBD) were identified as probable CBD cases, bringing the total 
prevalence of CBD and probable CBD in this group to 16 percent. As 
discussed in the epidemiology section of the Health Effects chapter, 
the prevalence of CBD among worker populations regularly exposed at 
higher levels (e.g., median > 0.1 [mu]g/m\3\) is typically much 
greater, approaching 80-100% in several studies. The lower prevalence 
of CBD in this group of sensitized workers, who were believed to have 
primarily low exposure levels, suggests that controlling respiratory 
exposure to beryllium may reduce risk of CBD among sensitized workers 
as well as reducing risk of CBD via prevention of sensitization. 
However, it also demonstrates that some workers in low-exposure 
environments can become sensitized and go on to develop CBD. The next 
section discusses an additional source of information on low-level 
beryllium exposure and CBD: studies of community-acquired CBD in 
residential areas surrounding beryllium production facilities.

C. Review of Community-Acquired CBD Literature

    The literature on community-acquired chronic beryllium disease (CA-
CBD) documents cases of CBD among individuals exposed to airborne 
beryllium at concentrations below the proposed PEL. OSHA notes that 
these case studies do not provide information on how frequently 
individuals exposed to very low airborne levels develop CBD and that 
reconstructed exposure estimates for CA-CBD cases are less reliable 
than exposure estimates for working populations reviewed in the 
previous sections. In addition, the cumulative exposure that an 
occupationally exposed person would accrue at any given exposure 
concentration is far less than would typically accrue from long-term 
environmental exposure. The literature on CA-CBD thus has important 
limitations and is not used as a basis for quantitative risk assessment 
for CBD from low-level beryllium exposure. Nevertheless, these case 
reports and the broader CA-CBD literature indicate that individuals 
exposed to airborne beryllium below the proposed PEL can develop CBD.
    Cases of CA-CBD were first reported among residents of Lorain, OH, 
and Reading, PA, who lived in the vicinity of beryllium plants. More 
recently, BeLPT screening has been used to identify additional cases of 
CA-CBD in Reading.
1. Lorain, OH
    In 1948, the State of Ohio Department of Public Health conducted an 
X-ray program surveying more than 6,000 people who lived within 1.5 
miles of a Lorain beryllium plant (Eisenbud, 1949; Eisenbud, 1982; 
Eisenbud, 1998). This survey, together with a later review of all 
reported cases of CBD in the area, found 13 cases of CBD. All of the 
residents who developed CBD lived within 0.75 miles of the plant, and 
none had occupational exposure or lived with beryllium-exposed workers. 
Among the population of 500 people living within 0.25 miles of the 
plant, seven residents (1.4 percent) were diagnosed with CBD. Five 
cases were diagnosed among residents living between 0.25 and 0.5 miles 
from the plant, one case was diagnosed among residents living between 
0.5 and 0.75 miles from the plant, and no cases were found among those 
living farther than 0.75 miles from the plant (total populations not 
reported) (Eisenbud, 1998).
    Beginning in January 1948, air sampling was conducted using a 
mobile sampling station to measure

[[Page 47631]]

atmospheric beryllium downwind from the plant. An approximate 
concentration of 0.2 [mu]g/m\3\ was measured at 0.25 miles from the 
plant's exhaust stack, and concentrations decreased with greater 
distance from the plant, to 0.003 [mu]g/m\3\ at a distance of 5 miles 
(Eisenbud, 1982). A 10-week sampling program was conducted using three 
fixed monitoring stations within 700 feet of the plant and one station 
7,000 feet from the plant. Interpolating the measurements collected at 
these locations, Eisenbud and colleagues estimated an average airborne 
beryllium concentration of between 0.004 and 0.02 [mu]g/m\3\ at a 
distance of 0.75 miles from the plant. Accounting for the possibility 
that previous exposures may have been higher due to production level 
fluctuations and greater use of rooftop emissions, they concluded that 
the lowest airborne beryllium level associated with CA-CBD in this 
community was somewhere between 0.01 [mu]g/m\3\ and 0.1 [mu]g/m\3\ 
(Eisenbud, 1982).
2. Reading, PA
    Thirty-two cases of CA-CBD were reported in a series of papers 
published in 1959-1969 concerning a beryllium refinery in Reading 
(Lieben and Metzner, 1959; Metzner and Lieben, 1961; Dattoli et al., 
1964; Lieben and Williams, 1969). The plant, which opened in 1935, 
manufactured beryllium oxide, alloys and metal, and beryllium tools and 
metal products (Maier et al., 2008; Sanderson et al., 2001b). In a 
follow-up study, Maier et al. presented eight additional cases of CA-
CBD who had lived within 1.5 miles of the plant (Maier et al., 2008). 
Individuals with a history of occupational beryllium exposure and those 
who had resided with occupationally exposed workers were not classified 
as having CA-CBD.
    The Pennsylvania Department of Health conducted extensive 
environmental sampling in the area of the plant beginning in 1958. 
Based on samples collected in 1958, Maier et al. stated that most cases 
identified in their study would typically have been exposed to airborne 
beryllium at levels between 0.0155 and 0.028 [mu]g/m\3\ on average, 
with the potential for some excursions over 0.35 [mu]g/m\3\ (Maier et 
al 2008, p. 1015). To characterize exposures to cases identified in the 
earlier publications, Lieben and Williams cited a sampling program 
conducted by the Department of Health between January and July 1962, 
using nine sampling stations located between 0.2 and 4.8 miles from the 
plant. They reported that 72 percent of 24-hour samples collected were 
below 0.01 [mu]g/m\3\. Of samples that exceeded 0.01 [mu]g/m\3\, most 
were collected at close proximity to the plant (e.g., 0.2 miles from 
the plant).
    In the early series of publications, cases of CA-CBD were reported 
among people living both close to the plant (Maier et al., 2008; Dutra, 
1948) and up to several miles away. Of new cases identified in the 1968 
update, all lived between 3 and 7.5 miles from the plant. Lieben and 
Williams suggested that some cases of CA-CBD found among more distant 
residents might have resulted from working or visiting a graveyard 
closer to the plant (Lieben and Williams, 1969). For example, a milkman 
who developed CA-CBD had a route in the neighborhood of the plant. 
Another resident with CA-CBD had worked as a cleaning woman in the area 
of the plant, and a third worked within a half-mile of the plant.
    At the time of the final follow-up study (1968), 11 residents 
diagnosed with CA-CBD were alive and 21 were deceased. Among those who 
had died, berylliosis was listed as the cause of death for three, 
including a 10-year-old girl and two women in their sixties. Fibrosis, 
granuloma or granulomatosis, and chronic or fibrous pneumonitis were 
listed as the cause of death for eight more of those deceased. 
Histologic evidence of CBD was reported for nine of 12 deceased 
individuals who had been evaluated for it. In addition to showing 
radiologic abnormalities associated with CBD, all living cases were 
dyspneic.
    Following the 1969 publication by Liebman and Williams, no 
additional CA-CBD cases were reported in the Reading area until 1999, 
when a new case was diagnosed. The individual was a 72-year-old woman 
who had had abnormal chest x-rays for the previous six years (Maier et 
al., 2008). After the diagnosis of this case, Maier et al. reviewed 
medical records and/or performed medical evaluations, including BeLPT 
results for 16 community residents who were referred by family members 
or an attorney.
    Among those referred, eight cases of definite or probable CBD were 
identified between 1999 and 2002. All eight were women who lived 
between 0.1 and 1.05 miles from the plant, beginning between 1943-1953 
and ending between 1956-2001. Five of the women were considered 
definite cases of CA-CBD, based on an abnormal blood or lavage cell 
BeLPT and granulomatous inflammation on lung biopsy. Three probable 
cases of CA-CBD were identified. One had an abnormal BeLPT and 
radiography consistent with CBD, but granulomatous disease was not 
pathologically proven. Two met Beryllium Case Registry epidemiologic 
criteria for CBD based on radiography, pathology and a clinical course 
consistent with CBD, but both died before they could be tested for 
beryllium sensitization. One of the probable cases, who could not be 
definitively diagnosed with CBD because she died before she could be 
tested, was the mother of both a definite case and the probable case 
who had an abnormal BeLPT but did not show granulomatous disease.
    The individuals with CA-CBD identified in this study suffered 
significant health impacts from the disease, including obstructive, 
restrictive, and gas exchange pulmonary defects in the majority of 
cases. All but two had abnormal pulmonary physiology. Those two were 
evaluated at early stages of disease following their mother's 
diagnosis. Six of the eight women required treatment with prednisone, a 
step typically reserved for severe cases due to the adverse side 
effects of steroid treatment. Despite treatment, three had died of 
respiratory impairment from CBD as of 2002 (Maier et al., 2008). The 
authors concluded that ``low levels of exposures with significant 
disease latency can result in significant morbidity and mortality'' 
(id., p. 1017).
    OSHA notes that compared with the occupational studies discussed in 
the previous section, there is comparatively sparse information on 
exposure levels of Lorain and Reading residents. There remains the 
possibility that some individuals with CA-CBD may have had higher 
exposures than were known and reported in these studies, or have had 
unreported exposure to beryllium dust via contact with beryllium-
exposed workers. Nevertheless, the studies conducted in Lorain and 
Reading demonstrate that long-term exposure to the apparent low levels 
of airborne beryllium, with sufficient disease latency, can lead to 
serious or fatal CBD. Genetic susceptibility may play a role in cases 
of CBD among individuals with very low or infrequent exposures to 
beryllium. The role of genetic susceptibility in the CBD disease 
process is discussed in detail in section V.D.3.

D. Exposure-Response Literature on Beryllium Sensitization and CBD

    To further examine the relationship between exposure level and risk 
of both sensitization and disease, we next review exposure-response 
studies in the CBD literature. Many publications have reported that 
exposure levels correlate with risk, including a small number of

[[Page 47632]]

exposure-response analyses. Most of these studies examined the 
association between job-specific beryllium air measurements and 
prevalence of sensitization and CBD. This section focuses on studies at 
three facilities that included a more rigorous historical 
reconstruction of individual worker exposures in their exposure-
response analyses.
1. Rocky Flats, CO, Facility
    In 2000, Viet et al. published a case-control study of participants 
in the Rocky Flats Beryllium Health Surveillance Program (BHSP), which 
was established in 1991 to screen workers at the Department of Energy's 
Rocky Flats, CO, nuclear weapons facility for beryllium sensitization 
and evaluate sensitized workers for CBD (Viet et al., 2000). The 
program, which at the time of publication had tested over 5,000 current 
and former Rocky Flats employees, had identified a total of 127 
sensitized individuals as of 1994 when Viet et al. initiated their 
study.
    Workers were considered sensitized if two BeLPT results were 
positive, either from two blood draws or from a single blood draw 
analyzed by two different laboratories. All sensitized individuals were 
offered clinical evaluation, and 51 were diagnosed with CBD based on 
positive lung LPT and evidence of noncaseating granulomas upon lung 
biopsy. The number of sensitized individuals who declined clinical 
evaluation was not reported. Two cases, one with CBD and one who was 
sensitized but not diagnosed with CBD, were excluded from the case-
control analysis due to reported or potential prior beryllium exposure 
at a ceramics plant. Another sensitized individual who had not been 
diagnosed with CBD was excluded because she could not be matched by the 
study's criteria to a non-sensitized control within the BHSP database. 
Viet et al. matched a total of 50 CBD cases to 50 controls who were 
negative on the BeLPT and had the same age ( 3 years), 
gender, race and smoking status, and were otherwise randomly selected 
from the database. Using the same matching criteria, 74 sensitized 
workers who were not diagnosed with CBD were age-, gender-, race-, and 
smoking status-matched to 74 control individuals who tested negative by 
the BeLPT from the BHSP database.
    Viet et al. developed exposure estimates for the cases and controls 
based on daily beryllium air samples collected in one of 36 buildings 
where beryllium was used at Rocky Flats, the Building 444 Beryllium 
Machine Shop. Over half of the approximately 500,000 industrial hygiene 
samples collected at Rocky Flats were taken from this building. Air 
monitoring in other buildings was reported to be limited and 
inconsistent and, thus, not utilized in the exposure assessment. The 
sampling data used to develop worker exposure estimates were 
exclusively Building 444 fixed airhead (FAH) area samples collected at 
permanent fixtures placed around beryllium work areas and machinery.
    Exposure estimates for jobs in Building 444 were constructed for 
the years 1960-1988 from this database. Viet et al. worked with Rocky 
Flats industrial hygienists and staff to assign a ``building area 
factor'' (BAF) to each of the other buildings, indicating the likely 
level of exposure in a building relative to exposures in Building 444. 
Industrial hygienists and staff similarly assigned a job factor (JF) to 
all jobs, representing the likely level of beryllium exposure relative 
to the levels experienced by beryllium machinists. A JF of 1 indicated 
the lowest exposures, and a JF of 10 indicated the highest exposures. 
For example, administrative work and vehicle operation were assigned a 
JF of 1, while machining, mill operation, and metallurgical operation 
were each assigned a JF of 10. Estimated FAH values for each 
combination of job, building and year in the study subjects' work 
histories were generated by multiplying together the job and building 
factors and the mean annual FAH exposure level. Using data collected by 
questionnaire from each BHSP participant, Viet et al. reconstructed 
work histories for each case and control, including job title and 
building location in each year of their employment at Rocky Flats. 
These work histories and the estimated FAH values were used to generate 
a cumulative exposure estimate (CEE) for each case and control in the 
study. A long-term mean exposure estimate (MEE) was generated by 
dividing each CEE by the individual's number of years employed at Rocky 
Flats.
    Viet et al.'s statistical analysis of the resulting data set 
included conditional logistic regression analysis, modeling the 
relationship between risk of each health outcome and log-transformed 
CEE and MEE. They found highly statistically significant relationships 
between log-CEE and risk of CBD (coef = 0.837, p = 0.0006) and between 
log-MEE (coef = 0.855, p = 0.0012) and risk of CBD, indicating that 
risk of CBD increases with exposure level. These coefficients 
correspond to odds ratios of 6.9 and 7.2 per 10-fold increase in 
exposure, respectively. Risk of sensitization without CBD did not show 
a statistically significant relationship with log-CEE (coef = 0.111, p 
= 0.32), but showed a nearly-significant relationship with log-MEE 
(coef = 0.230, p = 0.097).
2. Cullman, AL, Facility
    The Cullman, AL, precision machining facility discussed previously 
was the subject of a case-control study published by Kelleher et al. in 
2001. After the diagnosis of an index case of CBD at the plant in 1995, 
NJMRC researchers worked with the plant to conduct a medical 
surveillance program using the BeLPT to screen workers biennially for 
beryllium sensitization and CBD. Of 235 employees screened between 1995 
and 1999, 22 (9.4 percent) were found to be sensitized, including 13 
diagnosed with CBD (Newman et al., 2001). Concurrently, research was 
underway by Martyny et al. to characterize the particle size 
distribution of beryllium exposures generated by processes at this 
plant (Martyny et al., 2000). The exposure research showed that the 
machining operations during this time period generated respirable 
particles (10 [mu]m or less) at the worker breathing zone that made up 
greater than 50 percent of the beryllium mass. Kelleher et al. used the 
dataset of 100 personal lapel samples collected by Martyny et al. and 
other NJMRC researchers in 1996, 1997, and 1999 to characterize 
exposures for each job in the plant. Following a statistical analysis 
comparing the samples collected by NJMRC with earlier samples collected 
at the plant, Kelleher et al. concluded that the 1996-1999 data could 
be used to represent job-specific exposures from earlier periods.
    Detailed work history information gathered from plant data and 
worker interviews was used in combination with job exposure estimates 
to characterize cumulative and LTW average beryllium exposures for 
workers in the surveillance program. In addition to cumulative and LTW 
exposure estimates based the total mass of beryllium reported in their 
exposure samples, Kelleher et al. calculated cumulative and LTW 
estimates based specifically on exposure to particles < 6 [mu]m and 
particles < 1 [mu]m in diameter.
    To analyze the relationship between exposure level and risk of 
sensitization and CBD, Kelleher et al. performed a case-control 
analysis using measures of both total beryllium exposure and particle 
size-fractionated exposure. The analysis included sensitization cases 
identified in the 1995-1999 surveillance and 206 controls from the 
group of 215 non-sensitized workers. For nine workers, the researchers 
could not

[[Page 47633]]

reconstruct complete job histories. Logistic regression models using 
categorical exposure variables showed positive associations between 
risk of sensitization and the six exposure measures tested: Total CEE, 
total MEE, and variations of CEE and MEE constructed based on particles 
< 6 [mu]m and < 1 [mu]m in diameter. None of the associations were 
statistically significant (p < 0.05); however, the authors noted that 
the dataset was relatively small, with limited power to detect a 
statistically significant exposure-response relationship.
    Although the Viet et al. and Kelleher et al. exposure-response 
analyses provide valuable insight into exposure-response for beryllium 
sensitization and CBD, both studies have limitations that affect their 
suitability as a basis for quantitative risk assessment. Their 
limitations primarily involve the exposure data used to estimate 
workers' exposures. Viet et al.'s exposure reconstruction was based on 
area samples from a single building within a large, multi-building 
facility. Where possible, OSHA prefers to base risk estimates on 
exposure data collected in the breathing zone of workers rather than 
area samples, because data collected in the breathing zone more 
accurately represent workers' exposures. Kelleher's analysis, on the 
other hand, was based on personal lapel samples. However, the samples 
Kelleher et al. used were collected between 1996 and 1999, after the 
facility had initiated new exposure control measures in response to the 
diagnosis of a case of CBD in 1995. OSHA believes that industrial 
hygiene samples collected at the Cullman plant prior to 1996 better 
characterize exposures prior to the new exposure controls. In addition, 
since the publication of the Kelleher study, the population has 
continued to be screened for sensitization and CBD. Data collected on 
workers hired in 2000 and later, after most exposure controls had been 
completed, can be used to characterize risk at lower levels of exposure 
than have been examined in many previous studies.
    To better characterize the relationship between exposure level and 
risk of sensitization and CBD, OSHA developed an independent exposure-
response analysis based on a dataset maintained by NJMRC on workers at 
the Cullman, AL, machining plant. The dataset includes exposure samples 
collected between 1980 and 2005, and has updated work history and 
screening information for several hundred workers through 2003. OSHA's 
analysis of the NJMRC data set is presented in the next section, E. 
OSHA's Exposure-Response Analysis.
3. Elmore, OH, Facility
    After OSHA completed its analysis of the NJMRC data set, Schuler et 
al. (2012) published a study examining beryllium sensitization and CBD 
among 264 short-term workers employed at the previously described 
Elmore, OH plant in 1999. The analysis used a high-quality exposure 
reconstruction by Virji et al. (2012) and presented a regression 
analysis of the relationship between beryllium exposure levels and 
beryllium sensitization and CBD in the short-term worker population. By 
including only short-term workers, Virji et al. were able to construct 
participants' exposures with more precision than was possible in 
studies involving workers exposed for longer durations and in time 
periods with less exposure sampling. In addition, the focus on short-
term workers allowed more precise knowledge of when sensitization and 
CBD occurred than had been the case for previously published cross-
sectional studies of long-term workers. Each participant completed a 
work history questionnaire and was tested for beryllium sensitization, 
and sensitized workers were offered further evaluation for CBD. The 
overall prevalence of sensitization was 9.8 percent (26/264). Twenty-
two sensitized workers consented to clinical testing for CBD via 
transbronchial biopsy. Six of those sensitized were diagnosed with CBD 
(2.3 percent, 6/264).
    Schuler et al. (2012) used logistic regression to explore the 
relationship between estimated beryllium exposure and sensitization and 
CBD, using estimates of total, respirable, and submicron mass 
concentrations. Exposure estimates were constructed using two exposure 
surveys conducted in 1999: a survey of total mass exposures (4,022 
full-shift personal samples) and a survey of size-separated impactor 
samples (198 samples). The 1999 exposure surveys and work histories 
were used to estimate long-term lifetime weighted (LTW) average, 
cumulative, and highest-job-worked exposure for total, respirable, and 
submicron beryllium mass concentrations.
    For beryllium sensitization, logistic models showed elevated odds 
ratios for average (OR 1.48) and highest job (OR 1.37) exposure for 
total mass exposure; the OR for cumulative exposure was smaller (OR 
1.23) and borderline statistically significant (95 percent CI barely 
included unity). Relationships between sensitization and respirable 
exposure estimates were similarly elevated for average (OR 1.37) and 
highest job (OR 1.32). Among the submicron exposure estimates, only 
highest job (OR 1.24) had a 95 percent CI that just included unity for 
sensitization. For CBD, elevated odds ratios were observed only for the 
cumulative exposure estimates and were similar for total mass and 
respirable exposure (total mass OR 1.66, respirable (OR 1.68). 
Cumulative submicron exposure showed an elevated, borderline 
significant odds ratio (OR 1.58). The odds ratios for average exposure 
and highest-exposed job were not statistically significantly elevated. 
Schuler et al. concluded that both total and respirable mass 
concentrations of beryllium exposure were relevant predictors of risk 
for beryllium sensitization and CBD.

 E. OSHA's Exposure-Response Analysis

    OSHA evaluated exposure and health outcome data on a population of 
workers employed at the Cullman machining facility. NJMRC researchers, 
with consent and information provided by the facility, compiled a 
dataset containing employee work histories, medical diagnoses, and air 
sampling results and provided it to OSHA for analysis. OSHA's 
contractors from Eastern Research Group (ERG) gathered additional 
information from (1) two surveys of the Cullman plant conducted by 
OSHA's contractor (ERG, 2003 and ERG, 2004a), (2) published articles of 
investigations conducted at the plant by researchers from NJMRC 
(Kelleher et al., 2001; Madl et al., 2007; Martyny et al., 2000; and 
Newman et al., 2001), (3) a case file from a 1980 OSHA complaint 
inspection at the plant, (4) comments submitted to the OSHA docket 
office in 1976 and 1977 by representatives of the metal machining plant 
regarding their beryllium control program, and (5) personal 
communications with the plant's current industrial hygienist (ERG, 
2009b) and an industrial hygiene researcher at NJMRC (ERG, 2009a).
1. Plant Operations
    The Cullman plant is a leading fabricator of precision-machined and 
processed materials including beryllium and its alloys, titanium, 
aluminum, quartz, and glass (ERG, 2009b). The plant has approximately 
210 machines, primarily mills and lathes, and processes large 
quantities of beryllium on an annual basis. The plant provides complete 
fabrication services including ultra-precision machining; ancillary 
processing (brazing, ion milling, photo etching, precision cleaning, 
heat treating, stress relief, thermal cycling, mechanical assembly, and 
chemical

[[Page 47634]]

milling/etching); and coatings (plasma spray, anodizing, chromate 
conversion coating, nickel sulfamate plate, nickel plate, gold plate, 
black nickel plate, copper plate/strike, passivation, and painting). 
Most of the plant's beryllium operations involve machining beryllium 
metal and high beryllium content composite materials (beryllium metal/
beryllium oxide metal composites called E-Metal or E-Material), with 
occasional machining of beryllium oxide/metal matrix (such as AlBeMet, 
aluminum beryllium matrix) and beryllium-containing alloys. E-Materials 
such as E-20 and E-60 are currently processed in the E-Cell department.
    The 120,000 square-foot plant has two main work areas: a front 
office area and a large, open production shop. Operations in the 
production shop include inspection of materials, machining, polishing, 
and quality assurance. The front office is physically separated from 
the production shop. Office workers enter through the front of the 
facility and have access to the production shop through a change room 
where they must don laboratory coats and shoe covers to enter the 
production area. Production workers enter the shop area at the rear of 
the facility where a change/locker room is available to change into 
company uniforms and work shoes. Support operations are located in 
separate areas adjacent to the production shop and include management 
and administration, sales, engineering, shipping and receiving, and 
maintenance. Management and administrative personnel include two 
groups: those primarily working in the front offices (front office 
management) and those primarily working on the shop floor (shop 
management).
    In 1974, the company moved its precision machining operations to 
the plant's current location in Cullman. Workplace exposure controls 
reportedly did not change much until the diagnosis of an index case of 
CBD in 1995. Prior to 1995, exposure controls for machining operations 
primarily included a low volume/high velocity (LVHV) central exhaust 
system with operator-adjusted exhaust pickups and wet machining 
methods. Protective clothing, gloves, and respiratory protection were 
not required. After the diagnosis, the facility established an in-house 
target exposure level of 0.2 [mu]g/m\3\, installed change/locker rooms 
for workers entering the production facility, eliminated pressurized 
air hoses, discouraged the use of dry sweeping, initiated biennial 
medical surveillance using the BeLPT, and implemented annual beryllium 
hazard awareness training.
    In 1996, the company instituted requirements for work uniforms and 
dedicated work shoes for production workers, eliminated dry sweeping in 
all departments, and purchased high-efficiency particulate air (HEPA) 
filter vacuum cleaners for workplace cleanup and decontamination. Major 
engineering changes were also initiated in 1996, including the purchase 
of a new local exhaust ventilation (LEV) system to exhaust machining 
operations producing finer aerosols (e.g., dust and fume versus metal 
chips). The facility also began installing mist eliminators for each 
machine. Departments affected by these changes included cutter grind 
(tool and die), E-cell, electrical discharge machining (EDM), flow 
lines, grind, lapping, and optics. Dry machining operations producing 
chips were exhausted using the existing LVHV exhaust system (ERG, 
2004a). In the course of making the ventilation system changes, old 
ductwork and baghouses were dismantled and new ductwork and air 
cleaning devices were installed. The company also installed Plexiglas 
enclosures on machining operations in 1996-1997, including the lapping, 
deburring, grinding, EDM, and tool and die operations. In 1998, LEV was 
installed in EDM and modified in the lap, deburr, and grind 
departments.
    Most exposure controls were reportedly in place by 2000 (ERG, 
2009a). In 2004, the plant industrial hygienist reported that all 
machines had LEV and about 65 percent were also enclosed with either 
partial or full enclosures to control the escape of machining coolant 
(ERG, 2004b). Over time, the facility has built enclosures for 
operations that consistently produce exposures greater than 0.2 [mu]g/
m\3\. The company has never required workers to use gloves or other 
PPE.
2. Air Sampling Database and Job Exposure Matrix (JEM)
    The NJMRC dataset includes industrial hygiene sampling results 
collected by the plant (1980-1984 and 1995-2005) and NJMRC researchers 
(June 1996 to February 1997 and September 1999), including 4,370 
breathing zone (personal lapel) samples and 712 area samples (ERG, 
2004b). Limited air sampling data is available before 1980 and no 
exposure data appears to be available for the 10-year time period 1985 
through 1994. A review of the NJMRC air sampling database from 1995 
through 2005 shows a significant increase in the number of air samples 
collected beginning in 2000, which the plant industrial hygienist 
attributes to an increase in the number of air sampling pumps (from 5 
to 23) and the purchase of an automated atomic absorption 
spectrophotometer.
    ERG used the personal breathing zone sampling results contained in 
the sample database to quantify exposure levels for each year and for 
several-year periods. Separate exposure statistics were calculated for 
each job included in the job history database. For each job included in 
the job history database, ERG estimated the arithmetic mean, geometric 
mean, median, minimum, maximum, and 95th percentile value for the 
available exposure samples. Prior to generating these statistics ERG 
made several adjustments. After consultation with researchers at NJMRC, 
four particularly high exposures were identified as probably erroneous 
and excluded from calculations. In addition, a 1996 sample for the HS 
(Health and Safety) process was removed from the sample calculations 
after ERG determined it was for a non-employee researcher visiting the 
facility.
    Most samples in the sample database for which sampling times were 
recorded were long-term samples: 2,503 of the 2,557 (97.9 percent) 
breathing zone samples with sampling time recorded had times greater 
than or equal to 400 minutes. No adjustments were made for sampling 
time, except in the case of four samples for the ``maintenance'' 
process for 1995. These results show relatively high values and 
exceptionally short sampling times consistent with the nature of much 
maintenance work, marked by short-term exposures and periods of no 
exposure. The four 1995 maintenance samples were adjusted for an eight-
hour sampling time assuming that the maintenance workers received no 
further beryllium exposure over the rest of their work shift.
    OSHA examined the database for trends in exposure by reviewing 
sample statistics for individual years and grouping years into four 
time periods that correspond to stages in the plant's approach to 
beryllium exposure control. These were: 1980-1995, a period of 
relatively minimal control prior to the 1995 discovery of a case of CBD 
among the plant's workers; 1996-1997, a period during which some major 
engineering controls were in the process of being installed on 
machining equipment; 1998-1999, a period during which most engineering 
controls on the machining equipment had been installed; and 2000-2003, 
a period when installation of all exposure controls on machining 
equipment was complete and exposures very low throughout the plant. 
Table VI-4 below summarized the available data for each time period. As 
the four probable sampling errors identified in

[[Page 47635]]

the original data set are excluded here, arithmetic mean values are 
presented.

                 Table VI-4--Exposure Values for Machining Job Titles, Excluding Probable Sampling Errors ([mu]g/m\3\) in NJMRC Data Set
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                        1980-1995             1996-1997             1998-1999             2000-2003
                            Job title                            ---------------------------------------------------------------------------------------
                                                                   Samples      Mean     Samples      Mean     Samples      Mean     Samples      Mean
--------------------------------------------------------------------------------------------------------------------------------------------------------
Deburring.......................................................         27       1.17         19       1.29          0         NA         67        0.1
Electrical Discharge Machining..................................          2       0.06          2       1.32         16       0.08         63        0.1
Grinding........................................................         12       3.07          6       0.49         15       0.24         68        0.1
Lapping.........................................................          9       0.15         16       0.24         42       0.21        103        0.1
Lathe...........................................................         18       0.88          8       1.13         40       0.17        200        0.1
Milling.........................................................         43       0.64         15       0.23         95       0.17        434        0.1
--------------------------------------------------------------------------------------------------------------------------------------------------------

    Reviewing the revised statistics for individual years for different 
groupings, OSHA noted that exposures in the 1996-1997 period were for 
some machining jobs equivalent to, or even higher than, exposure levels 
recording during the 1980-1995 period. During 1996-1997, major 
engineering controls were being installed, but exposure levels were not 
yet consistently reduced.
    Table VI-5 below summarizes exposures for the four time periods in 
jobs other than beryllium machining. These include jobs such as 
administrative work, health and safety, inspection, toolmaking (`Tool' 
and `Cgrind'), and others. A description of jobs by title is available 
in the risk assessment background document.

                                 Table VI-5--Exposure Values for Non-Machining Job Titles ([mu]g/m\3\) in NJMRC Data Set
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                         1980-1995                      1996-1997                      1998-1999                      2000-2003
          Job title           --------------------------------------------------------------------------------------------------------------------------
                                 Samples          mean          Samples          mean          Samples          mean          Samples          mean
--------------------------------------------------------------------------------------------------------------------------------------------------------
Administration...............            0  NA..............            0  NA..............           39  0.052...........           74  0.061
Assembly.....................            0  NA..............            0  NA..............            8  0.136...........            2  0.051
Cathode......................            0  NA..............            0  NA..............            0  NA..............            9  0.156
Cgrind.......................            1  0.120...........            0  NA..............           14  0.105...........           76  0.112
Chem.........................            0  NA..............            1  0.529...........           21  0.277...........           91  0.152
Ecell........................            0  NA..............           13  1.873...........            0  NA..............           26  0.239
Engineering..................            1  0.065...........            0  NA..............           49  0.069...........          125  0.062
Flow Lines...................            0  NA..............            0  NA..............            0  NA..............          113  0.083
Gas..........................            0  NA..............            0  NA..............            0  NA..............          121  0.058
Glass........................            0  NA..............            0  NA..............            0  NA..............           38  0.068
Health and Safety \8\........            0  NA..............            0  NA..............            0  NA..............            5  0.076
Inspection...................            0  NA..............            0  NA..............           32  0.101...........          150  0.066
Maintenance..................            4  1.257...........            1  0.160...........           16  0.200...........           70  0.126
Msupp........................            0  NA..............            0  NA..............           47  0.094...........           68  0.081
Optics.......................            0  NA..............            0  NA..............            0  NA..............           41  0.090
PCIC.........................            1  0.040...........            0  NA..............           13  0.071...........           42  0.083
Qroom........................            1  0.280...........            0  NA..............            0  NA..............            2  0.130
Shop.........................            0  NA..............            0  NA..............            4  0.060...........            0  NA
Spec.........................            3  0.247...........            0  NA..............           24  0.083...........           19  0.087
Tool.........................            0  NA..............            0  NA..............            0  NA..............            1  0.070
--------------------------------------------------------------------------------------------------------------------------------------------------------

    From Table VI-5, it is evident that exposure samples are not 
available for many non-machining jobs prior to 2000. Where samples are 
available before 2000, sample numbers are small, particularly prior to 
1998. In jobs for which exposure values are available in 1998-1999 and 
2000-2003, exposures appear either to decline from 1998-1999 to 2000-
2003 (Assembly, Chem, Inspection, Maintenance) or to be roughly 
equivalent (Administration, Cgrind, Engineering, Msupp, PCIC, and 
Spec). Among the jobs with exposure samples prior to 1998, most had 
very few (1-5) samples, with the exception of Ecell (13 samples in 
1996-1997). Based on this limited information, it appears that 
exposures declined from the period before the first dentification of a 
CBD case to the period in which exposure controls were introduced.
---------------------------------------------------------------------------

    \8\ An exceptionally high result (0.845 [mu]g/m\3\, not shown in 
Table 5) for a 1996 sample for the HS (Health and Safety) process 
was removed from the sample calculations. OSHA's contractor 
determined this sample to be associated with a non-employee 
researcher visiting the facility.
---------------------------------------------------------------------------

    Because exposure results from 1996-1997 were not found to be 
consistently reduced in comparison to the 1985-1995 period in primary 
machining jobs, these two periods were grouped together in the JEM. 
Exposure monitoring for jobs other than the primary machining 
operations were represented by a single mean exposure value for 1980-
2003. As respiratory protection was not routinely used at the plant, 
there was no adjustment for respiratory protection in workers' exposure 
estimates. The job exposure matrix is presented in full in the 
background document for the quantitative risk assessment.
3. Worker Exposure Reconstruction
    The work history database contains job history records for 348 
workers, including start years, duration of employment, and percentage 
of worktime spent in each job. One hundred ninety-eight of the workers 
had been employed at some point in primary machining jobs, including 
deburring,

[[Page 47636]]

EDM, grinding, lapping, lathing, and milling. The remainder worked only 
in non-primary machining jobs, such as administration, engineering, 
quality control, and shop management. The total number of years worked 
at each job are presented as integers, leaving some uncertainty 
regarding the worker's exact start and end date at the job.
    Based on these records and the JEM described previously, ERG 
calculated cumulative and average exposure estimates for each worker in 
the database. Cumulative exposure was calculated as, [Sigma]i ei t i, 
where e(i) is the exposure level for job (i), and t(i) is the time 
spent in job (i). Cumulative exposure was divided by total exposure 
time to estimate each worker's long-term average exposure. These 
exposures were computed in a time-dependent manner for the statistical 
modeling. For workers with beryllium sensitization or CBD, exposure 
estimates excluded exposures following diagnosis.
    Workers who were employed for long time periods in jobs with low-
level exposures tend to have low average and cumulative exposures due 
to the way these measures are constructed, incorporating the worker's 
entire work history. As discussed in the Health Effects chapter, 
higher-level exposures or short-term peak exposures such as those 
encountered in machining jobs may be highly relevant to risk of 
sensitization. Unfortunately, because it is not possible to 
continuously monitor individuals' beryllium exposure levels and 
sensitization status, it is not known exactly when workers became 
sensitized or what their ``true'' peak exposures leading up to 
sensitization were. Only a rough approximation of the upper levels of 
exposure a worker experienced is possible. ERG constructed a third type 
of exposure estimate reflecting the exposure level associated with the 
highest-exposure job (HEJ) and time period experienced by each worker. 
This exposure estimate (HEJ), the cumulative exposure estimate, and the 
average exposure were used in the quartile analysis and statistical 
analyses.
4. Prevalence of Sensitization and CBD
    In the database provided to OSHA, seven workers were reported as 
sensitized only. Sixteen workers were listed as sensitized and 
diagnosed with CBD upon initial clinical evaluation. Three workers, 
first shown to be sensitized only, were later diagnosed with CBD. 
Tables VI-6, VI-7, and VI-8 below present the prevalence of 
sensitization and CBD cases across several categories of lifetime-
weighted (LTW) average, cumulative, and highest-exposed job (HEJ) 
exposure. Exposure values were grouped by quartile. Note that all 
workers with CBD are also sensitized. Thus, the columns ``Total 
Sensitized'' and ``Total %'' refer to all sensitized workers in the 
dataset, including workers with and without a diagnosis of CBD.

                           Table VI-6--Prevalence of Sensitization and CBD by LTW Average Exposure Quartile in NJMRC Data Set
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                            Sensitized                         Total
              Average exposure ([mu]g/m\3\)                 Group size         only             CBD         sensitized        Total %          CBD %
--------------------------------------------------------------------------------------------------------------------------------------------------------
0.0-0.080...............................................              91               1               1               2             2.2             1.0
0.081-0.18..............................................              73               2               4               6             8.2             5.5
0.19-0.51...............................................              77               0               6               6             7.8             7.8
0.51-2.15...............................................              78               4               8              12            15.4            10.3
                                                         -----------------------------------------------------------------------------------------------
    Total...............................................             319               7              19              26             8.2             6.0
--------------------------------------------------------------------------------------------------------------------------------------------------------


                            Table VI-7--Prevalence of Sensitization and CBD by Cumulative Exposure Quartile in NJMRC Data Set
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                            Sensitized                         Total
          Cumulative exposure ([mu]g/m\3\-yrs)              Group size         only             CBD         sensitized        Total %          CBD %
--------------------------------------------------------------------------------------------------------------------------------------------------------
0.0-0.147...............................................              81               2               2               4             4.9             2.5
0.148-1.467.............................................              79               0               2               2             2.5             2.5
1.468-7.008.............................................              79               3               8              11            13.9             8.0
7.009-61.86.............................................              80               2               7               9            11.3             8.8
                                                         -----------------------------------------------------------------------------------------------
    Total...............................................             319               7              19              26             8.2             6.0
--------------------------------------------------------------------------------------------------------------------------------------------------------


                       Table VI-8--Prevalence of Sensitization and CBD by Highest-Exposed Job Exposure Quartile in NJMRC Data Set
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                            Sensitized                         Total
                HEJ exposure ([mu]g/m\3\)                   Group size         only             CBD         sensitized        Total %          CBD %
--------------------------------------------------------------------------------------------------------------------------------------------------------
0.0-0.086...............................................              86               1               0               1             1.2             0.0
0.091-0.214.............................................              81               1               6               7             8.6             7.4
0.387-0.691.............................................              76               2               9              11            14.5            11.8
0.954-2.213.............................................              76               3               4               7             9.2             5.3
                                                         -----------------------------------------------------------------------------------------------
    Total...............................................             319               7              19              26             8.2             6.0
--------------------------------------------------------------------------------------------------------------------------------------------------------

    Table VI-6 shows increasing prevalence of total sensitization and 
CBD with increasing LTW average exposure, measured both as average and 
cumulative exposure. The lowest prevalence of sensitization and CBD was 
observed among workers with average exposure levels less than or equal 
to 0.08 [mu]g/m\3\, where two sensitized workers (2.2 percent) 
including one case of CBD (1.0 percent) were found. The sensitized 
worker in this category without CBD had worked at the facility as an 
inspector since 1972, one of the lowest-exposed jobs at the plant.

[[Page 47637]]

Because the job was believed to have very low exposures, it was not 
sampled prior to 1998. Thus, estimates of exposures in this job are 
based on data from 1998-2003 only. It is possible that exposures 
earlier in this worker's employment history were somewhat higher than 
reflected in his estimated average exposure. The worker diagnosed with 
CBD in this group had been hired in 1996 in production control, and had 
an estimated average exposure of 0.08 [mu]g/m\3\. He was diagnosed with 
CBD in 1997.
    The second quartile of LTW average exposure (0.081--0.18 [mu]g/
m\3\) shows a marked rise in overall prevalence of beryllium-related 
health effects, with six workers sensitized (8.2 percent), of whom four 
(5.5 percent) were diagnosed with CBD. Among six sensitized workers in 
the third quartile (0.19--0.50 [mu]g/m\3\), all were diagnosed with CBD 
(7.8 percent). Another increase in prevalence is seen from the third to 
the fourth quartile, with 12 cases of sensitization (15.4 percent), 
including eight (10.3 percent) diagnosed with CBD.
    The quartile analysis of cumulative exposure also shows generally 
increasing prevalence of sensitization and CBD with increasing 
exposure. As shown in Table VI-7, the lowest prevalences of CBD and 
sensitization are in the first two quartiles of cumulative exposure 
(0.0-0.147 [mu]g/m\3\-yrs, 0.148-1.467 [mu]g/m\3\-yrs). The upper bound 
on this cumulative exposure range, 1.467 [mu]g/m\3\-yrs, is the 
cumulative exposure that a worker would have if exposed to beryllium at 
a level of 0.03 [mu]g/m\3\ for a working lifetime of 45 years; 0.15 
[mu]g/m\3\ for ten years; or 0.3 [mu]g/m\3\ for five years.
    A sharp increase in prevalence of sensitization and CBD and total 
sensitization occurs in the third quartile (1.468-7.008 [mu]g/m\3\-
yrs), with roughly similar levels of both in the highest group (7.009-
61.86 [mu]g/m\3\-yrs). Cumulative exposures in the third quartile would 
be experienced by a worker exposed for 45 years to levels between 0.03 
and 0.16 [mu]g/m\3\, for 10 years to levels between 0.15 and 0.7 [mu]g/
m\3\, or for five years to levels between 0.3 and 1.4 [mu]g/m\3\.
    When workers' exposures from their highest-exposed job are 
considered, the exposure-response pattern is similar to that for LTW 
average exposure in the lower quartiles (Table VI-8). The lowest 
prevalence is observed in the first quartile (0.0-0.86 [mu]g/m\3\), 
with sharply rising prevalence from first to second and second to third 
exposure quartiles. The prevalence of sensitization and CBD in the top 
quartile (0.954-2.213 [mu]g/m\3\) decreases relative to the third, with 
levels similar to the overall prevalence in the dataset. Many workers 
in the highest exposure quartiles are long-time employees, who were 
hired during the early years of the shop when exposures were highest. 
One possible explanation for the drop in prevalence in the highest 
exposure quartiles is that highly-exposed workers from early periods 
may have developed CBD and left the plant before sensitization testing 
began in 1995.
    It is of some value to compare the prevalence analysis of the 
Cullman (NJMRC) data set with the results of the Reading and Tucson 
studies discussed previously. An exact comparison is not possible, in 
part because the Reading and Tucson exposure values are associated with 
jobs and the NJMRC values are estimates of lifetime weighted average, 
cumulative, and highest-exposed job (HEJ) exposures for individuals in 
the data set. Nevertheless, OSHA believes it is possible to very 
roughly compare the results of the Reading and Tucson studies and the 
results of the NJMRC prevalence analysis presented above. As discussed 
in detail below, OSHA found a general consistency between the 
prevalence of sensitization and CBD in the quartiles of average 
exposure in the NJMRC data set and the prevalence of sensitization and 
CBD at the Reading and Tucson plants for similar exposure values.
    Personal lapel samples collected at the Reading plant between 1995 
and 2000 were relatively low overall (median of 0.073 [mu]g/m\3\), with 
higher exposures (median of 0.149 [mu]g/m\3\) concentrated in the wire 
annealing and pickling process (Schuler et al., 2005). Exposures in the 
Reading plant in this time period were similar to the second-quartile 
average (Table VI-6-0.081-0.18 [mu]g/m\3\). The prevalence of 
sensitization observed in the NJMRC second quartile was 8.2 percent and 
appears roughly consistent with the prevalence of sensitization among 
Reading workers in the mid-1990s (11.5 percent). The reported 
prevalence of CBD (3.9 percent) among the Reading workforce was also 
consistent with that observed in the second NJMRC quartile (5.5 
percent), After 2000, exposure controls reduced exposures in most 
Reading jobs to median levels below 0.03 [mu]g/m\3\, with a median 
value of 0.1 [mu]g/m\3\ for the wire annealing and pickling process. 
The wire annealing and pickling process was enclosed and stringent 
respirator and skin protection requirements were applied for workers in 
that area after 2002, essentially eliminating airborne and dermal 
exposures for those workers. Thomas et al. (2009) reported that one of 
45 workers (2.2 percent) hired after the enclosure in 2002 was 
confirmed as sensitized, a value in line with the sensitization 
prevalence observed in the lowest quartiles of average exposure (2.2 
percent, 0.0-0.08 [mu]g/m\3\).
    As with Reading, the prevalence of sensitization observed at Tucson 
and in the NJMRC data set are not exactly comparable due to the 
different natures of the exposure estimates. Nevertheless, in a rough 
sense the results of the Tucson study and the NJMRC prevalence analysis 
appear similar. In Tucson, a 1998 BeLPT screening showed that 9.5 
percent of workers hired after 1992 were sensitized (Henneberger et 
al., 2001). Personal full-shift exposure samples collected in 
production jobs between 1994 and 1999 had a median of 0.2 [mu]g/m\3\ 
(0.1 [mu]g/m\3\ for non-production jobs). In the NJMRC data set, a 
sensitization prevalence of 8.2 percent was seen among workers with 
average exposures between 0.081 and 0.18 [mu]g/m\3\. At the time of the 
1998 screening, workers hired after 1992 had a median one year since 
first beryllium exposure and, therefore, CBD prevalence was only 1.4 
percent. This prevalence is likely an underestimate since CBD often 
requires more than a year to develop. Longer-term workers at the Tucson 
plant with a median 14 years since first beryllium exposure had a 9.1 
percent prevalence of CBD. There was a 5.5 percent prevalence of CBD 
among the entire workforce (Henneberger et al., 2001). As with the 
Reading plant employees, this reported prevalence is reasonably 
consistent with the 5.5 percent CBD prevalence observed in the second 
NJMRC quartile.
    Beginning in 1999, the Tucson facility instituted strict 
requirements for respiratory protection and other PPE, essentially 
eliminating airborne and dermal exposure for most workers. After these 
requirements were put in place, Cummings et al. (2007) reported only 
one case of sensitization (1 percent; associated with a PPE failure) 
among 97 workers hired between 2000 and 2004. This appears roughly in 
line with the sensitization prevalence of 2.2 percent observed in the 
lowest quartiles of average exposure (0.0-0.08 [mu]g/m\3\) in the NJMRC 
data set.
    While the literature analysis presented here shows a clear 
reduction in risk with well-controlled airborne exposures (<= 0.1 
[mu]g/m\3\ on average) and protection from dermal exposure, the level 
of detail presented in the published studies limits the Agency's 
ability to characterize risk at all the alternate PELs OSHA is 
considering. To better understand these risks, OSHA

[[Page 47638]]

used the NJMRC dataset to characterize risk of sensitization and CBD 
among workers exposed to each of the alternate PELs under consideration 
in the proposed beryllium rule.

F. OSHA's Statistical Modeling

    OSHA's contractor performed a complementary log-log proportional 
hazards model using the NJMRC data set. The proportional hazards model 
is a generalization of logistic regression that allows for time-
dependent exposures and differential time at risk. The proportional 
hazards model accounts for the fact that individuals in the dataset are 
followed for different amounts of time, and that their exposures change 
over time. The proportional hazards model provides hazards ratios, 
which estimate the relative risk of disease at a specified time for 
someone with exposure level 1 compared to exposure level 2. To perform 
this analysis, OSHA's contractor constructed exposure files with time-
dependent cumulative and average exposures for each worker in the data 
set in each year that a case of sensitization or CBD was identified. 
Workers were included in only those years after they started working at 
the plant and continued to be followed. Sensitized cases were not 
included in analysis of sensitization after the year in which they were 
identified as being sensitized, and CBD cases were not included in 
analyses of CBD after the year in which they were diagnosed with CBD. 
Follow-up is censored after 2002 because work histories were deemed to 
be less reliable after that date.
    The results of the discrete proportional hazards analyses are 
summarized in Tables VI-9-12 below. All coefficients used in the models 
are displayed, including the exposure coefficient, the model constant 
for diagnosis in 1995, and additional exposure-independent coefficients 
for each succeeding year (1996-1999 for sensitization and 1996-2002 for 
CBD) of diagnosis that are fit in the discrete time proportional 
hazards modeling procedure. Model equations and variables are explained 
more fully in the companion risk assessment background document.
    Relative risk of sensitization increased with cumulative exposure 
(p = 0.05). A positive, but not statistically significant, association 
was observed with LTW average exposure (p = 0.09). The association was 
much weaker for exposure duration (p = 0.31), consistent with the 
expected biological action of an immune hypersensitivity response where 
onset is believed to be more dependent on the concentration of the 
sensitizing agent at the target site rather than the number of years of 
occupational exposure. The association was also much weaker for 
highest-exposed job (HEJ) exposure (p = 0.3).

                  Table VI-9--Proportional Hazards Model--Cumulative Exposure and Sensitization
----------------------------------------------------------------------------------------------------------------
                   Variable                       Coefficient        95% Confidence interval          P-value
----------------------------------------------------------------------------------------------------------------
Cumulative Exposure ([mu]g/m\3\-yrs)..........           0.031  0.00 to 0.063...................            0.05
constant......................................           -3.48  -4.27 to -2.69..................          <0.001
1996..........................................           -1.49  -3.04 to 0.06...................            0.06
1997..........................................           -0.29  -1.31 to 0.72...................            0.57
1998..........................................           -1.56  -3.11 to -0.01..................            0.05
1999..........................................           -1.57  -3.12 to -0.02..................            0.05
----------------------------------------------------------------------------------------------------------------


                 Table VI-10--Proportional Hazards Model--LTW Average Exposure and Sensitization
----------------------------------------------------------------------------------------------------------------
                   Variable                       Coefficient        95% Confidence interval          P-value
----------------------------------------------------------------------------------------------------------------
Average Exposure ([mu]g/m\3\).................            0.54  -0.09 to 1.17...................            0.09
constant......................................           -3.55  -4.42 to -2.69..................          <0.001
1996..........................................           -1.48  -3.03 to 0.07...................            0.06
1997..........................................           -0.29  -1.31 to 0.72...................            0.57
1998..........................................           -1.54  -3.09 to 0.01...................            0.05
1999..........................................           -1.53  -3.08 to 0.03...................            0.05
----------------------------------------------------------------------------------------------------------------


                  Table VI-11--Proportional Hazards Model--Exposure Duration and Sensitization
----------------------------------------------------------------------------------------------------------------
                   Variable                       Coefficient        95% Confidence interval          P-value
----------------------------------------------------------------------------------------------------------------
Exposure Duration (years).....................            0.03  -0.03 to 0.08...................            0.31
constant......................................           -3.55  -4.57 to -2.53..................          <0.001
1996..........................................           -1.48  -3.03 to 0.70...................            0.06
1997..........................................           -0.30  -1.31 to 0.72...................            0.57
1998..........................................           -1.59  -3.14 to -0.04..................            0.05
1999..........................................           -1.62  -3.17 to -0.72..................            0.04
----------------------------------------------------------------------------------------------------------------


                     Table VI-12--Proportional Hazards Model--HEJ Exposure and Sensitization
----------------------------------------------------------------------------------------------------------------
                   Variable                       Coefficient        95% Confidence interval          P-value
----------------------------------------------------------------------------------------------------------------
HEJ Exposure ([mu]g/m\3\).....................            0.31  -0.27 to 0.88...................            0.30
constant......................................           -3.42  -4.27 to -2.56..................          <0.001
1996..........................................           -1.49  -3.04 to 0.06...................            0.06
1997..........................................           -0.31  -1.33 to 0.70...................            0.55
1998..........................................           -1.59  -3.14 to -0.04..................            0.05
1999..........................................           -1.60  -3.15 to -0.05..................            0.04
----------------------------------------------------------------------------------------------------------------


[[Page 47639]]

    The proportional hazards models for the CBD endpoint (Tables VI-13 
through 16 below) showed positive relationships with cumulative 
exposure (p = 0.09) and duration of exposure (p = 0.10). However, the 
association with the cumulative exposure metric was not as strong as 
that for sensitization, probably due to the smaller number of CBD 
cases. LTW average exposure and HEJ exposure were not closely related 
to relative risk of CBD (p-values > 0.5).

                      Table VI-13--Proportional Hazards Model--Cumulative Exposure and CBD
----------------------------------------------------------------------------------------------------------------
                   Variable                       Coefficient        95% Confidence interval          P-value
----------------------------------------------------------------------------------------------------------------
Cumulative Exposure ([mu]g/m\3\-yrs)..........            0.03  .00 to 0.07.....................            0.09
constant......................................           -3.77  -4.67 to -2.86..................          <0.001
1997..........................................           -0.59  -1.86 to 0.68...................            0.36
1998..........................................           -2.01  -4.13 to 0.11...................            0.06
1999..........................................           -0.63  -1.90 to 0.64...................            0.33
2002..........................................           -2.13  -4.25 to -0.01..................            0.05
----------------------------------------------------------------------------------------------------------------


                      Table VI-14--Proportional Hazards Model--LTW Average Exposure and CBD
----------------------------------------------------------------------------------------------------------------
                   Variable                       Coefficient        95% Confidence interval          P-value
----------------------------------------------------------------------------------------------------------------
Average Exposure ([mu]g/m\3\).................            0.24  -0.59 to 1.06...................            0.58
constant......................................           -3.62  -4.60 to -2.64..................          <0.001
1997..........................................           -0.61  -1.87 to 0.66...................            0.35
1998..........................................           -2.02  -4.14 to 0.10...................            0.06
1999..........................................           -0.64  -1.92 to 0.63...................            0.32
2002..........................................           -2.15  -4.28 to -0.02..................            0.05
----------------------------------------------------------------------------------------------------------------


                       Table VI-15--Proportional Hazards Model--Exposure Duration and CBD
----------------------------------------------------------------------------------------------------------------
                   Variable                       Coefficient        95% Confidence interval          P-value
----------------------------------------------------------------------------------------------------------------
Exposure Duration (yrs).......................            0.05  -0.01 to 0.11...................            0.10
constant......................................           -4.18  -5.40 to -2.96..................          <0.001
1997..........................................           -0.53  1.84 to 0.69....................            0.38
1998..........................................           -2.01  -4.13 to 0.11...................            0.06
1999..........................................           -0.67  -1.94 to 0.60...................            0.30
2002..........................................           -2.22  -4.34 to -0.10..................            0.04
----------------------------------------------------------------------------------------------------------------


                          Table VI-16--Proportional Hazards Model--HEJ Exposure and CBD
----------------------------------------------------------------------------------------------------------------
                   Variable                       Coefficient        95% Confidence interval          P-value
----------------------------------------------------------------------------------------------------------------
HEJ Exposure ([mu]g/m\3\).....................            0.03  -0.70 to 0.77...................            0.93
constant......................................           -3.49  -4.45 to -2.53..................          <0.001
1997..........................................           -0.62  -1.88 to 0.65...................            0.34
1998..........................................           -2.05  -4.16 to 0.07...................            0.06
1999..........................................           -0.68  -1.94 to 0.59...................            0.30
2002..........................................           -2.21  -4.33 to -0.09..................            0.04
----------------------------------------------------------------------------------------------------------------

    In addition to the models reported above, comparable models were 
fit to the upper 95 percent confidence interval of the HEJ exposure; 
log-transformed cumulative exposure; log-transformed LTW average 
exposure; and log-transformed HEJ exposure. Each of these measures was 
positively but not significantly associated with sensitization.
    OSHA used the proportional hazards models based on cumulative 
exposure, shown in Tables VI-9 and VI-13, to derive quantitative risk 
estimates. Of the metrics related to exposure level, the cumulative 
exposure metric showed the most consistent association with 
sensitization and CBD in these models. Table VI-17 summarizes these 
risk estimates for sensitization and the corresponding 95 percent 
confidence intervals separately for 1995 and 1999, the years with the 
highest and lowest baseline rates, respectively. The estimated risks 
for CBD are presented in VI-18. The expected number of cases is based 
on the estimated conditional probability of being a case in the given 
year. The models provide time-specific point estimates of risk for a 
worker with any given exposure level, and the corresponding interval is 
based on the uncertainty in the exposure coefficient (i.e., the 
predicted values based on the 95 percent confidence limits for the 
exposure coefficient).
    Each estimate represents the number of sensitized workers the model 
predicts in a group of 1000 workers at risk during the given year with 
an exposure history at the specified level and duration. For example, 
in the exposure scenario where 1000 workers are occupationally exposed 
to 2 [mu]g/m\3\ for 10 years in 1995, the model predicts that about 56 
(55.7) workers would be sensitized that year. The model for CBD 
predicts that about 42 (41.9) workers would be diagnosed with CBD that 
year.

[[Page 47640]]



  Table VI-17a--Predicted Cases of Sensitization per 1000 Workers Exposed at Current and Alternate PELs Based on Proportional Hazards Model, Cumulative
                            Exposure Metric, With Corresponding Interval Based on the Uncertainty in the Exposure Coefficient
                                                                     [1995 Baseline]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                             Exposure duration
                                                 -------------------------------------------------------------------------------------------------------
                                                           5 years                  10 years                  20 years                  45 years
        1995 Exposure level  ([mu]g/m\3\)        -------------------------------------------------------------------------------------------------------
                                                   Cumulative
                                                  ([mu]g/m\3\- cases/ 1000  [mu]g/m\3\-  cases/ 1000  [mu]g/m\3\-  cases/ 1000  [mu]g/m\3\-  cases/ 1000
                                                      yrs)                      yrs                       yrs                       yrs
--------------------------------------------------------------------------------------------------------------------------------------------------------
2.0.............................................         10.0         41.1         20.0         55.7         40.0        101.0         90.0        394.4
                                                                 30.3-56.2                30.3-102.9                30.3-318.1                30.3-999.9
1.0.............................................          5.0         35.3         10.0         41.1         20.0         55.7         45.0        116.9
                                                                 30.3-41.3                 30.3-56.2                30.3-102.9                30.3-408.2
0.5.............................................          2.5         32.7          5.0         35.3         10.0         41.1         22.5         60.0
                                                                 30.3-35.4                 30.3-41.3                 30.3-56.2                30.3-119.4
0.2.............................................          1.0         31.3          2.0         32.2          4.0         34.3          9.0         39.9
                                                                 30.3-32.3                 30.3-34.3                 30.3-38.9                 30.3-52.9
0.1.............................................          0.5         30.8          1.0         31.3          2.0         32.2          4.5         34.8
                                                                 30.3-31.3                 30.3-32.3                 30.3-34.3                 30.3-40.1
--------------------------------------------------------------------------------------------------------------------------------------------------------


  Table VI-17b--Predicted Cases of Sensitization per 1000 Workers Exposed at Current and Alternate PELs Based on Proportional Hazards Model, Cumulative
                            Exposure Metric, With Corresponding Interval Based on the Uncertainty in the Exposure Coefficient
                                                                     [1999 Baseline]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                             Exposure duration
                                                 -------------------------------------------------------------------------------------------------------
                                                           5 years                  10 years                  20 years                  45 years
        1999 Exposure level  ([mu]g/m\3\)        -------------------------------------------------------------------------------------------------------
                                                   Cumulative
                                                  ([mu]g/m\3\- cases/ 1000  [mu]g/m\3\-  cases/ 1000  [mu]g/m\3\-  cases/ 1000  [mu]g/m\3\-  cases/ 1000
                                                      yrs)                      yrs                       yrs                       yrs
--------------------------------------------------------------------------------------------------------------------------------------------------------
2.0.............................................         10.0          8.4         20.0         11.5         40.0         21.3         90.0         96.3
                                                                  6.2-11.6                  6.2-21.7                  6.2-74.4                 6.2-835.4
1.0.............................................          5.0          7.2         10.0          8.4         20.0         11.5         45.0         24.8
                                                                   6.2-8.5                  6.2-11.6                  6.2-21.7                 6.2-100.5
0.5.............................................          2.5          6.7          5.0          7.2         10.0          8.4         22.5         12.4
                                                                   6.2-7.3                   6.2-8.5                  6.2-11.6                  6.2-25.3
0.2.............................................          1.0          6.4          2.0          6.6          4.0          7.0          9.0          8.2
                                                                   6.2-6.6                   6.2-7.0                   6.2-8.0                  6.2-10.9
0.1.............................................          0.5          6.3          1.0          6.4          2.0          6.6          4.5          7.1
                                                                   6.2-6.4                   6.2-6.6                   6.2-7.0                   6.2-8.2
--------------------------------------------------------------------------------------------------------------------------------------------------------


 Table VI-18a--Predicted Number of Cases of CBD per 1000 Workers Exposed at Current and Alternative PELs Based on Proportional Hazards Model, Cumulative
                            Exposure Metric, With Corresponding Interval Based on the Uncertainty in the Exposure Coefficient
                                                                     [1995 baseline]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                             Exposure duration
                                                 -------------------------------------------------------------------------------------------------------
                                                           5 years                  10 years                  20 years                  45 years
        1995 Exposure level  ([mu]g/m\3\)        -------------------------------------------------------------------------------------------------------
                                                   Cumulative   Estimated                 Estimated                 Estimated                 Estimated
                                                  ([mu]g/m\3\-  cases/1000  [mu]g/m\3\-   cases/1000  [mu]g/m\3\-   cases/1000  [mu]g/m\3\-   cases/1000
                                                      yrs)       95% c.i.       yrs        95% c.i.       yrs        95% c.i.       yrs        95% c.i.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                  ...........         30.9  ...........         41.9  ...........         76.6  ...........        312.9
2.0.............................................         10.0    22.8-44.0         20.0    22.8-84.3         40.0   22.8-285.5         90.0   22.8-999.9
                                                  ...........         26.6  ...........         30.9  ...........         41.9  ...........         88.8
1.0.............................................          5.0    22.8-31.7         10.0    22.8-44.0         20.0    22.8-84.3         45.0   22.8-375.0
                                                  ...........         24.6  ...........         26.6  ...........         30.9  ...........         45.2
0.5.............................................          2.5    22.8-26.9          5.0    22.8-31.7         10.0    22.8-44.0         22.5    22.8-98.9
                                                  ...........         23.5  ...........         24.2  ...........         25.8  ...........         30.0
0.2.............................................          1.0    22.8-24.3          2.0    22.8-26.0          4.0    22.8-29.7          9.0    22.8-41.3
                                                  ...........         23.1  ...........         23.5  ...........         24.2  ...........         26.2
0.1.............................................          0.5    22.8-23.6          1.0    22.8-24.3          2.0    22.8-26.0          4.5    22.8-30.7
--------------------------------------------------------------------------------------------------------------------------------------------------------


[[Page 47641]]


 Table VI-18b--Predicted Number of Cases of CBD per 1000 Workers Exposed at Current and Alternative PELs Based on Proportional Hazards Model, Cumulative
                            Exposure Metric, With Corresponding Interval Based on the Uncertainty in the Exposure Coefficient
                                                                     [2002 baseline]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                             Exposure duration
                                                 -------------------------------------------------------------------------------------------------------
                                                           5 years                  10 years                  20 years                  45 years
        2002 Exposure level  ([mu]g/m\3\)        -------------------------------------------------------------------------------------------------------
                                                   Cumulative   Estimated                 Estimated                 Estimated                 Estimated
                                                  ([mu]g/m\3\-  cases/1000  [mu]g/m\3\-   cases/1000  [mu]g/m\3\-   cases/1000  [mu]g/m\3\-   cases/1000
                                                      yrs)       95% c.i.       yrs        95% c.i.       yrs        95% c.i.       yrs        95% c.i.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                  ...........          3.7  ...........          5.1  ...........          9.4  ...........         43.6
2.0.............................................         10.0      2.7-5.3         20.0     2.7-10.4         40.0     2.7-39.2         90.0    2.7-679.8
                                                  ...........          3.2  ...........          3.7  ...........          5.1  ...........         11.0
1.0.............................................          5.0      2.7-3.8         10.0      2.7-5.3         20.0     2.7-10.4         45.0     2.7-54.3
                                                  ...........          3.0  ...........          3.2  ...........          3.7  ...........          5.5
0.5.............................................          2.5      2.7-3.2          5.0      2.7-3.8         10.0      2.7-5.3         22.5     2.7-12.3
                                                  ...........          2.8  ...........          2.9  ...........          3.1  ...........          3.6
0.2.............................................          1.0      2.7-2.9          2.0      2.7-3.1          4.0      2.7-3.6          9.0      2.7-5.0
                                                  ...........          2.8  ...........          2.8  ...........          2.9  ...........          3.1
0.1.............................................          0.5      2.7-2.8          1.0      2.7-2.9          2.0      2.7-3.1          4.5      2.7-3.7
--------------------------------------------------------------------------------------------------------------------------------------------------------

    The statistical modeling analysis predicts high risk of both 
sensitization (96-394 cases per 1000, or 9.6-39.4 percent) and CBD (44-
313 cases per 1000, or 4.4-31.3 percent) at the current PEL of 2 [mu]g/
m\3\ for an exposure duration of 45 years (90 [mu]g/m\3\-yr). The 
predicted risks of < 8.2-39.9 per 1000 (0.8-3.9 percent) cases of 
sensitization or 3.6 to 30.0 per 1000 (0.4-3 percent) cases of CBD are 
substantially less for a 45-year exposure at the proposed PEL, 0.2 
[mu]g/m\3\ (9 [mu]g/m\3\-yr).
    The model estimates are not directly comparable to prevalence 
values discussed in previous sections. They assume a group without 
turnover and are based on a comparison of unexposed and hypothetically 
exposed workers at specific points in time, whereas the prevalence 
analysis simply reports the percentage of workers at the Cullman plant 
with sensitization or CBD in each exposure category. Despite the 
difficulty of direct comparison, the level of risk seen in the 
prevalence analysis and predicted in the modeling analysis appear 
roughly similar at low exposures. In the second quartile of cumulative 
exposure (0.148-1.467 [mu]g/m\3\-yr), prevalence of sensitization and 
CBD was 2.5 percent. This is roughly congruent with the model 
predictions for workers with cumulative exposures between 0.5 and 1 
[mu]g/m\3\-yr: 6.3-31.3 cases of sensitization per 1000 workers (0.6-
3.1 percent) and 2.8 to 23.5 cases of CBD per 1000 workers (0.28-2.4 
percent). As discussed in the background document for this analysis, 
most workers in the data set had low cumulative exposures (roughly half 
below 1.5 [mu]g/m\3\-years). It is difficult to make any statement 
about the results at higher levels, because there were few workers with 
high exposure levels and the higher quartiles of cumulative exposure 
include an extremely wide range of exposures. For example, the highest 
quartile of cumulative exposure was 7.009-61.86 [mu]g/m\3\-yr. This 
quartile, which showed an 11.3 percent prevalence of sensitization and 
8.8 percent prevalence of CBD, includes the cumulative exposure that a 
worker exposed for 45 years at the proposed PEL would experience (9 
[mu]g/m\3\-yr) near its lower bound. Its upper bound approaches the 
cumulative exposure that a worker exposed for 45 years at the current 
PEL would experience (90 [mu]g/m\3\-yr).
    Due to limitations including the size of the dataset, relatively 
limited exposure data from the plant's early years, study size-related 
constraints on the statistical analysis of the dataset, and limited 
follow-up time on many workers, OSHA must interpret the model-based 
risk estimates presented in Tables VI-17 and VI-18 with caution. The 
Cullman study population is a relatively small group and can support 
only limited statistical analysis. For example, its size precludes 
inclusion of multiple covariates in the exposure-response models or a 
two-stage exposure-response analysis to model both sensitization and 
the subsequent development of CBD within the subpopulation of 
sensitized workers. The limited size of the Cullman dataset is 
characteristic of studies on beryllium-exposed workers in modern, low-
exposure environments, which are typically small-scale processing 
plants (up to several hundred workers, up to 20-30 cases). However, 
these recent studies also have important strengths: They include 
workers hired after the institution of stringent exposure controls, and 
have extensive exposure sampling using full-shift personal lapel 
samples. In contrast, older studies of larger populations tend to have 
higher exposures, less exposure data, and exposure data collected in 
short-term samples or outside of workers' breathing zones.
    Another limitation of the Cullman dataset, which is common to 
recent low-exposure studies, is the short follow-up time available for 
many of the workers. While in some cases CBD has been known to develop 
in short periods (< 2 years), it more typically develops over a longer 
time period. Sensitization occurs in a typically shorter time frame, 
but new cases of sensitization have been observed in workers exposed to 
beryllium for many years. Because the data set is limited to 
individuals then working at the plant, the Cullman data set cannot 
capture CBD occurring among workers who retire or leave the plant. OSHA 
expects that the dataset does not fully represent the risk of 
sensitization, and is likely to particularly under-represent CBD among 
workers exposed to beryllium at this facility. The Agency believes the 
short follow-up time to be a significant source of uncertainty in the 
statistical analysis, a factor likely to lead to underestimation of 
risk in this population.
    A common source of uncertainty in quantitative risk assessment is 
the series of choices made in the course of statistical analysis, such 
as model type, inclusion or exclusion of additional explanatory 
variables, and the assumption of linearity in exposure-response. 
Sensitivity analyses and statistical checks were conducted to test the 
validity of the choices and

[[Page 47642]]

assumptions in the exposure-response analysis and the impact of 
alternative choices on the end results. These analyses did not yield 
substantially different results, adding to OSHA's confidence in the 
conclusions of its preliminary risk assessment.
    OSHA's contractor examined whether smoking and age were confounders 
in the exposure-response analysis by adding them as variables in the 
discrete proportional hazards model. Neither smoking status nor age was 
a statistically significant predictor of sensitization or CBD. The 
model coefficients, 95 percent confidence intervals, and p values can 
be found in the background document. A sensitivity analysis was done 
using the standard Cox model that treats survival time as continuous 
rather than discrete. The model coefficients with the standard Cox 
using cumulative exposure were 0.025 and very similar to the 0.03 
reported in Tables VI-9 and VI-13 above. The interaction between 
exposure and follow-up time was not significant in these models, 
suggesting that the proportional hazard assumption should not be 
rejected. The proportional hazards model assumes a linear relationship 
between exposure level and relative risk. The linearity assumption was 
assessed using a fractional polynomial approach. For both sensitization 
and CBD, the best-fitting fractional polynomial model did not fit 
significantly better than the linear model. This result supports OSHA's 
use of the linear model to estimate risk. The details of these 
statistical analyses can be found in the background document.
    The possibility that the number of times a worker has been tested 
for sensitization might influence the probability of a positive test 
was examined (surveillance bias). Surveillance bias could occur if 
workers were tested because they showed some sign of disease, and not 
tested otherwise. It is also possible that the original analysis 
included erroneous assumptions about the dates of testing for 
sensitization and CBD. OSHA's contractor performed a sensitivity 
analysis, modifying the original analysis to gauge the effect of 
different assumptions about testing dates. In the sensitivity analysis, 
the exposure coefficients increased for all four indices of exposure 
when the sensitization analysis was restricted to times when cohort 
members were assumed to be tested. The exposure coefficient was 
statistically significant for duration of exposure but not for 
cumulative, LTW average, or HEJ exposure. The increase in exposure 
coefficients suggests that the original models may have underestimated 
the exposure-response relationship for sensitization and CBD.
    Errors in exposure measurement are a common source of uncertainty 
in quantitative risk assessments. Because errors in high exposures can 
heavily influence modeling results, OSHA's contractor performed 
sensitivity analyses excluding the highest 5 percent of cumulative 
exposures (those above 25.265 [mu]g/m\3\-yrs) and the highest 10 
percent of cumulative exposures (those above 18.723 [mu]g/m\3\-yrs). As 
discussed in more detail in the background document, exposure 
coefficients were not statistically significant when these exposures 
were dropped. This is not surprising, given that the exclusion of high 
exposure values reduced the size of the data set. Prior to excluding 
high exposure values, the data set was already relatively small and 
many of the exposure coefficients were non-significant or weakly 
significant in the original analyses. As a result, the sensitivity 
analyses did not provide much information about uncertainty due to 
exposure measurement error and its effects on the modeling analysis.
    Particle size, particle surface area, and beryllium compound 
solubility are believed to be important factors influencing the risk of 
sensitization and CBD among beryllium-exposed workers. The workers at 
the Cullman machining plant were primarily handling insoluble beryllium 
compounds, such as beryllium metal and beryllium metal/beryllium oxide 
composites. Particle size distributions from a limited number of 
airborne beryllium samples collected just after the 1996 installation 
of engineering controls indicate worker exposure to a substantial 
proportion of respirable particulates. There was no available particle 
size data for the 1980 to 1995 period prior to installation of 
engineering controls when total beryllium mass exposure levels were 
greatest. Particle size data was also lacking from 1998 to 2003 when 
additional control measures were in place and total beryllium mass 
exposures were lowest. For these reasons, OSHA was not able to 
quantitatively account for the influence of particle size and 
solubility in developing the risk estimates based on the Cullman data 
set. However, it is not unreasonable to expect the CBD experienced by 
this cohort to generally reflect the risk from exposure to beryllium 
that is relatively insoluble and enriched with respirable particles. As 
explained previously, the role of particle size and surface area on 
risk of sensitization is more difficult to predict.
    Additional uncertainty is introduced when extrapolating the 
quantitative estimates presented above to operations that process 
beryllium compounds that have different solubility and particle 
characteristics than those encountered at the Cullman machining plant. 
OSHA does not have sufficient information to quantitatively assess the 
degree to which risks of beryllium sensitization and CBD based on the 
NJMRC data may be impacted in workplaces where such beryllium forms and 
processes are used. However, OSHA does not expect this uncertainty to 
alter its qualitative conclusions with regard to the risk at the 
current PEL and at alternate PELs as low as 0.1 [mu]g/m\3\. The 
existing studies provide clear evidence of sensitization and CBD risk 
among workers exposed to a number of beryllium forms as a result of 
different processes such as beryllium machining, beryllium-copper alloy 
production, and beryllium ceramics production. The Agency believes all 
of these forms of beryllium exposure contribute to the overall risk of 
sensitization and CBD among beryllium-exposed workers.

G. Lung Cancer

    OSHA considers lung cancer to be an important health endpoint for 
beryllium-exposed workers. The International Agency for Research on 
Cancer (IARC), National Toxicology Program (NTP), and American 
Conference of Governmental Industrial Hygienists (ACGIH) have all 
classified beryllium as a known human carcinogen. The National Academy 
of Sciences (NAS), Environmental Protection Agency, the Agency for 
Toxic Substances and Disease Registry (ATSDR), the National Institute 
of Occupational Safety and Health (NIOSH), and other reputable 
scientific organizations have reviewed the scientific evidence 
demonstrating that beryllium is associated with an increased incidence 
of cancer. OSHA also has performed an extensive review of the 
scientific literature regarding beryllium and cancer. This includes an 
evaluation of human epidemiological, animal cancer, and mechanistic 
studies described in the Health Effects section of this preamble. Based 
on the weight of evidence, the Agency has preliminarily determined 
beryllium to be an occupational carcinogen.
    Although epidemiological and animal evidence supports a conclusion 
of beryllium carcinogenicity, there is considerable uncertainty 
surrounding the mechanism of carcinogenesis for beryllium. The evidence 
for direct genotoxicity of beryllium and its compounds has been limited 
and

[[Page 47643]]

inconsistent (NAS, 2008; IARC, 1993; EPA, 1998; NTP, 2002; ATSDR, 
2002). One plausible pathway for beryllium carcinogenicity described in 
the Health Effects section of this preamble includes a chronic, 
sustained neutrophilic inflammatory response that induces epigenetic 
alterations leading to the neoplastic changes necessary for 
carcinogenesis. The National Cancer Institute estimates that nearly 
one-third of all cancers are caused by chronic inflammation (NCI, 
2009). This mechanism of action has also been hypothesized for 
crystalline silica and other agents that are known to be human 
carcinogens but have limited evidence of genotoxicity.
    OSHA's review of epidemiological studies of lung cancer mortality 
among beryllium workers found that most did not characterize exposure 
levels sufficiently for exposure-response analysis. However, one NIOSH 
study evaluated the association between beryllium exposure and lung 
cancer mortality based on data from a beryllium processing plant in 
Reading, PA (Sanderson et al., 2001a). As discussed in the Health 
Effects section of this preamble, this case-control study evaluated 
lung cancer incidence in a cohort of workers employed at the plant from 
1940 to 1969 and followed through 1992. For each lung cancer victim, 5 
age- and race-matched controls were selected by incidence density 
sampling, for a total of 142 lung cancer cases and 710 controls.
    Between 1971 and 1992, the plant collected close to 7,000 high 
volume filter samples consisting of both general area and short-term, 
task-based breathing zone measurements for production jobs and 
exclusively area measurements for office, lunch, and laboratory areas 
(Sanderson et al., 2001b). In addition, a few (< 200) impinger and 
high-volume filter samples were collected by other organizations 
between 1947 and 1961, and about 200 6-to-8-hour personal samples were 
collected in 1972 and 1975. Daily-weighted-average (DWA) exposure 
calculations based on the impinger and high-volume samples collected 
prior to the 1960s showed that exposures in this period were extremely 
high. For example, about half of production jobs had estimated DWAs 
ranging between 49 and 131 [mu]g/m\3\ in the period 1935-1960, and many 
of the ``lower-exposed'' jobs had DWAs of approximately 20-30 [mu]g/
m\3\ (Table II, Sanderson et al., 2001b). Exposures were reported to 
have decreased between 1959 and 1962 with the installation of 
ventilation controls and improved housekeeping and following the 
passage of the OSH Act in 1970. While no exposure measurements were 
available from the period 1961-1970, measurements from the period 1971-
1980 showed a dramatic reduction in exposures plant-wide. Estimated 
DWAs for all jobs in this period ranged from 0.1 [mu]g/m\3\ to 1.9 
[mu]g/m\3\. Calendar-time-specific beryllium exposure estimates were 
made for every job based on the DWA calculations and were used to 
estimate workers' cumulative, average, and maximum exposures. Exposure 
estimates were lagged by 10 and 20 years in order to account for 
exposures that did not contribute to lung cancer because they occurred 
after the induction of cancer.
    Results of a conditional logistic regression analysis showed an 
increased risk of lung cancer in workers with higher exposures when 
dose estimates were lagged by 10 and 20 years (Sanderson et al., 
2001a). The authors noted that there was considerable uncertainty in 
the estimation of exposure in the 1940s and 1950s and the shape of the 
dose-response curve for lung cancer. NIOSH later reanalyzed the data, 
adjusting for potential confounders of hire age and birth year 
(Schubauer-Berigan et al., 2008). The study reported a significant 
increasing trend (p<0.05) in the odds ratio when increasing quartiles 
of average (log transformed) exposure were lagged by 10 years. However, 
it did not find a significant trend when quartiles of cumulative (log 
transformed) exposure were lagged by 0, 10, or 20 years.
    OSHA is interested in lung cancer risk estimates from a 45-year 
(i.e., working lifetime) exposure to beryllium levels between 0.1 
[mu]g/m\3\ and 2 [mu]g/m\3\. The majority of case and control workers 
in the Sanderson et al. case-control analysis were first hired during 
the 1940s when exposures were extremely high (estimated DWAs > 20 
[mu]g/m\3\ for most jobs). The cumulative, average, and maximum 
beryllium exposure concentration estimates for the 142 known lung 
cancer cases were: 46.06  9.3[mu]g/m\3\-days, 22.8  3.4 [mu]g/m\3\, and 32.4  13.8 [mu]g/m\3\, 
respectively. About two-thirds of cases and half of controls worked at 
the plant for less than a year. Thus, a risk assessment based on this 
exposure-response analysis would need to extrapolate from very high to 
very low exposures, based on a working population with extremely short 
tenure. While OSHA risk assessments must often make extrapolations to 
estimate risk within the range of exposures of interest, the Agency 
acknowledges that these issues of short tenure and extremely high 
exposures would create substantial uncertainty in a risk assessment 
based on this study population.
    In addition, the relatively high exposures of even the least-
exposed workers in the NIOSH study may create methodological issues for 
the lung cancer case-control study design. Mortality risk is expressed 
as an odds ratio that compares higher exposure quartiles to the lowest 
quartile. It is preferable that excess risks attributable to 
occupational beryllium be determined relative to an unexposed or 
minimally exposed reference population. However, in the NIOSH study 
workers in the lowest quartile were exposed well above the OSHA PEL 
(average exposure <11.2 [mu]g/m\3\) and may have had a significant lung 
cancer risk. This issue would introduce further uncertainty in lung 
cancer risks estimated from this epidemiological study.
    In 2010, researchers at NIOSH published a quantitative risk 
assessment based on an update of the Reading cohort analyzed by 
Sanderson et al., as well as workers from two smaller plants 
(Schubauer-Berigan et al., 2010b). This new risk assessment addresses 
several of OSHA's concerns regarding the Sanderson et al. analysis. The 
new cohort was exposed, on average, to lower levels of beryllium and 
had fewer short-term workers. Finally, the updated cohorts followed the 
populations through 2005, increasing the length of follow-up time 
overall by an additional 17 years of observation. For these reasons, 
OSHA considers the Schubauer-Berigan risk analysis more appropriate 
than the Sanderson et al. analysis for its preliminary risk assessment.
    The cohort studied by Schubauer-Berigan et al. included 5,436 male 
workers who had worked for at least two days at the Reading facility 
and beryllium processing plants at Hazleton PA and Elmore OH prior to 
1970. The authors developed job-exposure matrices (JEMs) for the three 
plants based on extensive historical exposure data, primarily short-
term general area and personal breathing zone samples, collected on a 
quarterly basis from a wide variety of operations. These samples were 
used to create daily weighted average (DWA) estimates of workers' full-
shift exposures, using records of the nature and duration of tasks 
performed by workers during a shift. Details on the JEM and DWA 
construction can be found in Sanderson et al. (2001a), Chen et al. 
(2001), and Couch et al. (2010).
    Workers' cumulative exposures ([mu]g/m\3\-days) were estimated by 
summing daily average exposures (assuming five

[[Page 47644]]

workdays per week). To estimate mean exposure ([mu]g/m\3\), cumulative 
exposure was divided by exposure time (in days). Maximum exposure 
([mu]g/m\3\) was estimated as the highest annual DWA on record for a 
worker prior to the study cutoff date of December 31, 2005 and 
accounting where appropriate for lag time. Exposure estimates were 
lagged by 5, 10, 15, and 20 years in order to account for exposures 
that may not have contributed to lung cancer because of the long 
latency required for manifestation of the disease. The authors also fit 
models with no lag time. As shown in Table VI-19 below, estimated 
exposure levels for workers from the Hazleton and Elmore plants were on 
average far lower than those for workers from the Reading plant. The 
median worker from Hazleton had a mean exposure across his tenure of 
less than 2 [micro]g/m\3\, while the median worker from Elmore had a 
mean exposure of less than 1 [micro]g/m\3\. The Elmore and Hazleton 
worker populations also had fewer short-term workers than the Reading 
population. This was particularly evident at Hazleton where the median 
value for cumulative exposure among cases was higher than at Reading 
despite the much lower mean and maximum exposure levels.

                   Table VI-19--Cohort Description and Distribution of Cases by Exposure Level
----------------------------------------------------------------------------------------------------------------
                                                    All plants     Reading plant  Hazleton plant   Elmore plant
----------------------------------------------------------------------------------------------------------------
Number of cases...............  ................             293             218              30              45
Number of non-cases...........  ................            5143            3337             583            1223
Median value for mean exposure  No lag..........           15.42              25           1.443           0.885
([micro]g/m\3\) among cases...  10-year lag.....           15.15              25           1.443           0.972
Median value for cumulative     No lag..........            2843            2895            3968            1654
 exposure.
([micro]g/m\3\-days) among      10-year lag.....            2583            2832            3648            1449
 cases.
Median value for maximum        No lag..........              25            25.1            3.15            2.17
 exposure.
([micro]g/m\3\) among cases...  10-year lag.....              25              25            3.15            2.17
Number of cases with potential  ................       100 (34%)        68 (31%)        16 (53%)        16 (36%)
 asbestos exposure.
Number of cases who were        ................         26 (9%)        21 (10%)         3 (10%)          2 (4%)
 professional workers.
----------------------------------------------------------------------------------------------------------------
Table adapted from Schubauer-Berigan et al. 2011, Table 1.

    Schubauer-Berigan et al. analyzed the data set using a variety of 
exposure-response modeling approaches, including categorical analyses 
and continuous-variable piecewise log-linear and power models, 
described in Schubauer-Berigan et al. (2011). All models adjusted for 
birth cohort and plant. As exposure values were log-transformed for the 
power model analyses, the authors added small values to exposures of 0 
in lagged analyses (0.05 [micro]g/m\3\ for mean and maximum exposure, 
0.05 [micro]g/m\3\-days for cumulative exposure). The authors used 
restricted cubic spline models to assess the shape of the exposure-
response curve and suggest appropriate parametric model forms. The 
Akaike Information Criterion (AIC) value was used to evaluate the fit 
of different model forms and lag times.
    Because smoking information was available for only about 25 percent 
of the cohort, smoking could not be controlled for directly in the 
models. The authors reported that within the subset with smoking 
information, there was little difference in smoking by cumulative or 
maximum exposure category (p. 6), suggesting that smoking was unlikely 
to act as a confounder in the cohort. In addition to models based on 
the full cohort, Schubauer-Berigan et al. also prepared risk estimates 
based on models excluding professional workers and workers believed to 
have asbestos exposure. These models were intended to mitigate the 
potential impact of smoking and asbestos as confounders. If 
professional workers had both lower beryllium exposures and lower 
smoking rates than production workers, smoking could be a confounder in 
the cohort comprising both production and professional workers. 
However, the authors reasoned that smoking was unlikely to be 
correlated with beryllium exposure among production workers, and would 
therefore probably not act as a confounder in a cohort excluding 
professional workers.
    The authors found that lung cancer risk was strongly and 
significantly related to mean, cumulative, and maximum measures of 
workers' exposure (all models reported in Schubauer-Berigan et al., 
2011). They selected the best-fitting categorical, power, and monotonic 
piecewise log-linear (PWL) models with a 10-year lag to generate hazard 
ratios for male workers with a mean exposure of 0.5 [micro]g/m\3\ (the 
current NIOSH Recommended Exposure Limit for beryllium).\9\ To estimate 
excess lifetime risk of cancer, they multiplied this hazard ratio by 
the 2004-2006 background lifetime lung cancer rate among U.S. males who 
had survived, cancer-free, to age 30. In addition, they estimated the 
mean exposure that would be associated with an excess lifetime risk of 
one in 1000, a value often used as a benchmark for significant risk in 
OSHA regulations. At OSHA's request, they also estimated excess 
lifetime risks for workers with mean exposures at the current PEL of 2 
[mu]g/m\3\ each of the other alternate PELs under consideration: 1 
[mu]g/m\3\, 0.2 [mu]g/m\3\, and 0.1 [mu]g/m\3\ (Schubauer-Berigan, 4/
22/11). The resulting risk estimates are presented in Table VI-20 
below.
---------------------------------------------------------------------------

    \9\ Here, ``monotonic PWL model'' means a model producing a 
monotonic exposure-response curve in the 0-2 ug/m\3\ region.

[[Page 47645]]



                         Table VI-20--Excess Lifetime Risk per 1000 [95% Confidence Interval] for Male Workers at Alternate PELs
                                                                     [NIOSH models]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                   Mean exposure
                 Exposure-response model                  ----------------------------------------------------------------------------------------------
                                                           0.1 [micro]g/m\3\  0.2 [micro]g/m\3\  0.5 [micro]g/m\3\   1 [micro]g/m\3\    2 [micro]g/m\3\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Best monotonic PWL--all workers..........................        7.3[2.0-13]         15[3.3-29]           45[9-98]        120[20-340]        200[29-370]
Best monotonic PWL--excluding professional and asbestos           3.1[<0-11]         6.4[<0-23]          17[<0-74]         39[39-230]         61[<0-280]
 workers.................................................
Best categorical--all workers............................         4.4[1.3-8]          9[2.7-17]           25[6-48]         59[13-130]        170[29-530]
Best categorical--excluding professional and asbestos            1.4[<0-6.0]         2.7[<0-12]         7.1[<0-35]          15[<0-87]         33[<0-290]
 workers.................................................
Power model--all workers.................................           12[6-19]         19[9.3-29]          30[15-48]          40[19-66]          52[23-88]
Power model--excluding professional and asbestos workers.         19[8.6-31]          30[13-50]          49[21-87]         68[27-130]         90[34-180]
--------------------------------------------------------------------------------------------------------------------------------------------------------

    Schubauer-Berigan et al. discuss several strengths, weaknesses, and 
uncertainties of their analysis. Strengths include long (> 30 years) 
follow-up time for members of the cohort and the extensive exposure and 
work history data available for the development of exposure estimates 
for workers in the cohort. Among the weaknesses and uncertainties of 
the study are the limited information available on workers' smoking 
habits: smoking information was available only for workers employed in 
1968, about 25 percent of the cohort. In addition, the JEMs used did 
not account for possible respirator use among workers in the cohort. 
The authors note that workers' exposures may therefore have been 
overestimated, and that overestimation may have been especially severe 
for workers with high estimated exposures. They suggest that 
overestimation of exposures for workers in highly exposed positions may 
have caused attenuation of the exposure-response curve in some models 
at higher exposures.
    The NIOSH publication did not discuss the reasons for basing risk 
estimates on mean exposure rather than cumulative exposure that is more 
commonly used for lung cancer risk analysis. OSHA believes the decision 
may involve the nonmonotonic relationship NIOSH observed between cancer 
risk and cumulative exposure level. As discussed previously, workers 
from the Reading plant frequently had very short tenures and high 
exposures yielding lower cumulative exposures compared to cohort 
workers from other plants with longer employment. Despite the low 
estimated cumulative exposures among the short-term Reading workers, 
they may be at high risk of lung cancer due to the tendency of 
beryllium to persist in the lung for long periods. This exposure 
misclassification could lead to the appearance of a nonmonotonic 
relationship between cumulative exposure and lung cancer risk. It is 
possible that a dose-rate effect may exist for beryllium, such that the 
risk from a cumulative exposure gained by long-term, low-level exposure 
is not equivalent to the risk from a cumulative exposure gained by very 
short-term, high-level exposure. In this case, mean exposure level may 
better correlate with the risk of lung cancer than cumulative exposure 
level. For these reasons OSHA considers the NIOSH choice of mean 
exposure metric to be appropriate and scientifically defensible for 
this particular dataset.

H. Preliminary Conclusions

    As described above, OSHA's risk assessment for beryllium 
sensitization and CBD relied on two approaches: (1) review of the 
literature and (2) analysis of a dataset provided by NJRMC. First, the 
Agency reviewed the scientific literature to ascertain whether there is 
substantial risk to workers exposed at and below the current PEL and to 
characterize the expected impact of more stringent controls on workers' 
risk of sensitization and CBD. This review focused on facilities where 
exposures were primarily below the current PEL, and where several 
rounds of BeLPT and CBD screening had been conducted to evaluate the 
effectiveness of various exposure control measures. Second, OSHA 
investigated the exposure-response relationship for beryllium 
sensitization and CBD by analyzing a dataset that NJMRC provided on 
workers at a prominent, long-established beryllium machining facility. 
Although exposure-response studies have been published on sensitization 
and CBD, OSHA believes the nature and quality of their exposure data 
significantly limits their value for the Agency's risk assessment. 
Therefore, OSHA developed an independent exposure-response analysis 
using the NJMRC dataset, which was recently updated, includes workers 
exposed at low levels, and includes extensive exposure data collected 
in workers' breathing zones, as is preferred by OSHA.
    OSHA's review of the scientific literature found substantial risk 
of both sensitization and CBD in workplaces in compliance with OSHA's 
current PEL (e.g., Kreiss et al., 1992; Schuler et al., 2000; Madl et 
al., 2007). At these plants, including a copper-beryllium processing 
facility, a beryllia ceramics facility, and a beryllium machining 
facility, exposure reduction programs that primarily used engineering 
controls to reduce airborne exposures to median levels at or around 0.2 
[mu]g/m\3\ had only limited impact on workers' risk. Cases of 
sensitization continued to occur frequently among newly hired workers, 
and some of these workers developed CBD within the short follow-up 
time.
    In contrast, industrial hygiene programs that minimized both 
airborne and dermal exposure substantially lowered workers' risk of 
sensitization in the first years of employment. Programs that 
drastically reduced respiratory exposure via a combination of 
engineering controls and respiratory protection, minimized the 
potential for skin exposure via dermal PPE, and employed stringent 
housekeeping methods to keep work areas clean and prevent transfer of 
beryllium between areas sharply curtailed new cases of sensitization 
among newly-hired workers. For example, studies conducted at copper-
beryllium processing, beryllium production, and beryllia ceramics 
facilities show that reduction of exposures to below 0.1 [mu]g/m\3\ and 
protection from dermal exposure, in combination, achieved a substantial 
reduction in sensitization risk among newly-hired workers. However, 
even these stringent measures did not protect all workers from 
sensitization.

[[Page 47646]]

    The most recent epidemiological literature on programs that have 
been successful in reducing workers' risk of sensitization have had 
very short follow-up time; therefore, they cannot address the question 
of how frequently workers sensitized in very low-exposure environments 
develop CBD. Clinical evaluation for CBD was not reported for workers 
at the copper-beryllium processing, beryllium production, and ceramics 
facilities. However, cases of CBD among workers exposed at low levels 
at a machining plant and cases of CA-CBD demonstrate that individuals 
exposed to low levels of airborne beryllium can develop CBD, and over 
time, can progress to severe disease. This conclusion is also supported 
by case reports within the literature of workers with CBD who may have 
been minimally exposed to beryllium, such as a worker employed only in 
administration at a beryllium ceramics facility (Kreiss et al., 1996).
    The Agency's analysis of the Cullman dataset provided by NJMRC 
showed strong exposure-response trends using multiple analytical 
approaches, including examination of sensitization and disease 
prevalence by exposure categories and a proportional hazards modeling 
approach. In the prevalence analysis, cases of sensitization and 
disease were evident at all levels of exposure. The lowest prevalence 
of sensitization (2.0 percent) and CBD (1.0 percent) was observed among 
workers with LTW average exposure levels below 0.1 [mu]g/m\3\, while 
those with LTW average exposure between 0.1-0.2 [mu]g/m\3\ showed a 
marked increase in overall prevalence of sensitization (9.8 percent) 
and CBD (7.3 percent). Prevalence of sensitization and CBD also 
increased with cumulative exposure.
    OSHA's proportional hazards analysis of the Cullman dataset found 
increasing risk of sensitization with both cumulative exposure and 
average exposure. OSHA also found a positive relationship between risk 
of CBD and cumulative exposure, but not between CBD and average 
exposure. The Agency used the cumulative exposure model results to 
estimate hazards ratios and risk of sensitization and CBD at the 
current PEL of 2 [mu]g/m\3\ and each of the alternate PELs under 
consideration: 1 [mu]g/m\3\, 0.5 [mu]g/m\3\, 0.2 [mu]g/m\3\, and 0.1 
[mu]g/m\3\. To estimate risk of CBD from a working lifetime of 
exposure, the Agency calculated the cumulative exposure associated with 
45 years of exposure at each level, for total cumulative exposures of 
90, 45, 22.5, 9, and 4.5 [mu]g/m\3\-years. The risk estimates for 
sensitization and CBD ranged from 100-403 and 40-290 cases, 
respectively, per 1000 workers exposed at the current PEL of 2 [mu]g/
m\3\. The risks are projected to be substantially lower for both 
sensitization and CBD at 0.1 [mu]g/m\3\ and range from 7.2-35 cases per 
1000 and 3.1-26 cases per 1000, respectively. In these ways, the 
modeling results are similar to results observed from published studies 
of the Reading, Tucson, and Cullman plants and the OSHA analysis of 
sensitization and CBD prevalence within the Cullman plant.
    OSHA has a high level of confidence in the finding of substantial 
risk of sensitization and CBD at the current PEL, and the Agency 
believes that a standard requiring a combination of more stringent 
controls on beryllium exposure will reduce workers' risk of both 
sensitization and CBD. Programs that have reduced median levels to 
below 0.1 [mu]g/m\3\, tightly controlled both respiratory and dermal 
exposure, and incorporated stringent housekeeping measures have 
substantially reduced risk of sensitization within the first years of 
exposure. These conclusions are supported by the results of several 
studies conducted in state-of-the-art facilities dealing with a variety 
of production activities and physical forms of beryllium. In addition, 
these conclusions are supported by OSHA's statistical analysis of a 
dataset with highly detailed exposure and work history information on 
several hundred beryllium workers. While there is uncertainty regarding 
the precision of model-derived risk estimates, they provide further 
evidence that there is substantial risk of sensitization and CBD 
associated with exposure at the current PEL, and that this risk can be 
substantially lessened by stringent measures to reduce workers' 
beryllium exposure levels.
    Furthermore, OSHA believes that beryllium-exposed workers' risk of 
lung cancer will be reduced by more stringent control of airborne 
beryllium exposures. The risk estimates from NIOSH's recent lung cancer 
study, described above, range from 33 to 140 excess lung cancers per 
1000 workers exposed at the current PEL of 2 [mu]g/m\3\. The NIOSH risk 
assessment's six best-fitting models each predict substantial 
reductions in risk with reduced exposure, ranging from 3 to 19 excess 
lung cancers per 1000 workers exposed at the proposed PEL of 0.1 [mu]g/
m\3\. The evidence of lung cancer risk from NIOSH's risk assessment 
provides additional support for OSHA's preliminary conclusions 
regarding the significance of risk to workers exposed to beryllium 
levels at and below the current PEL. However, the lung cancer risks 
require a sizable low dose extrapolation below beryllium exposure 
levels experienced by workers in the NIOSH study. As a result, there is 
a greater uncertainty in the lung cancer risk estimates and lesser 
confidence in their significance of risk below the current PEL than 
with beryllium sensitization and CBD. The preliminary conclusions with 
regard to significance of risk are presented and further discussed in 
section VIII of the preamble.

VII. Expert Peer Review of Health Effects and Preliminary Risk 
Assessment

    In 2010, Eastern Research Group, Inc. (ERG), under contract to the 
Occupational Safety and Health Administration (OSHA) ,\10\ conducted an 
independent, scientific peer review of (1) a draft Preliminary 
Beryllium Health Effects Evaluation (OSHA, 2010a), (2) a draft 
Preliminary Beryllium Risk Assessment (OSHA, 2010b), and (3) two NIOSH 
study manuscripts (Schubauer-Berigan et al., 2011 and 2011a). This 
section of the preamble describes the review process and summarizes 
peer reviewers' comments and OSHA's responses.
---------------------------------------------------------------------------

    \10\ Task Order No. DOLQ59622303, Contract No. GS10F0125P, with 
a period of performance from May, 2010 through December, 2010.
---------------------------------------------------------------------------

    ERG conducted a search for nationally recognized experts in the 
areas of occupational epidemiology, occupational medicine, toxicology, 
immunology, industrial hygiene/exposure assessment, and risk 
assessment/biostatistics as requested by OSHA. ERG sought experts 
familiar with beryllium health effects research and who had no conflict 
of interest (COI) or apparent bias in performing the review. Interested 
candidates submitted evidence of their qualifications and responded to 
detailed COI questions. ERG also searched the Internet to determine 
whether qualified candidates had made public statements or declared a 
particular bias regarding beryllium regulation.
    From the pool of qualified candidates, ERG selected five experts to 
conduct the review, based on:
    [cir] Their qualifications, including their degrees, years of 
relevant experience, number of related peer-reviewed publications, 
experience serving as a peer reviewer for OSHA or other government 
organizations, and committee and association memberships related to the 
review topic;
    [cir] Lack of any actual, potential, or perceived conflict of 
interest; and
    [cir] The need to ensure that the panel collectively was 
sufficiently broad and

[[Page 47647]]

diverse to fairly represent the relevant scientific and technical 
perspectives and fields of knowledge appropriate to the review.
    OSHA reviewed the qualifications of the candidates proposed by ERG 
to verify that they collectively represented the technical areas of 
interest. ERG then contracted the following experts to perform the 
review.

    (1) John Balmes, MD, Professor of Medicine, University of 
California-San Francisco
    Expertise: pulmonary and occupational medicine, CBD, 
occupational lung disease, epidemiology, occupational exposures, 
medical surveillance.
    (2) Patrick Breysse, Ph.D., Professor, Johns Hopkins University 
Bloomberg School of Public Health
    Expertise: industrial hygiene, occupational/environmental health 
engineering, exposure monitoring/analysis, biomarkers, beryllium 
exposure assessment
    (3) Terry Gordon, Ph.D., Professor, New York University School 
of Medicine.
    Expertise: inhalation toxicology, pulmonary disease, beryllium 
toxicity and carcinogenicity, CBD genetic susceptibility, mode of 
action, animal models.
    (4) Milton Rossman, MD, Professor of Medicine, Hospital of the 
University of Pennsylvania School of Medicine.
    Expertise: pulmonary and clinical medicine, immunology, 
beryllium sensitization, BeLPT, clinical diagnosis for CBD.
    (5) Kyle Steenland, Ph.D., Professor, Emory University, Rollins 
School of Public Health.
    Expertise: occupational epidemiology, biostatistics, risk and 
exposure assessment, lung cancer, CBD, exposure-response models.

    Reviewers were provided with the Technical Charge and Instructions 
(see ERG, 2010), a Request for Peer Review of NIOSH Manuscripts (see 
ERG, 2010), the draft Preliminary OSHA Health Effects Evaluation (OSHA, 
2010a), the draft Preliminary Beryllium Risk Assessment (OSHA, 2010b), 
and access to relevant references. Each reviewer independently provided 
comments on the Health Effects, Risk Assessment, and NIOSH documents. A 
briefing call was held early in the review to ensure that reviewers 
understood the peer review process. ERG organized the call and OSHA 
representatives were available to respond to technical questions of 
clarification. Reviewers were invited to submit any subsequent 
questions of clarification.
    The written comments from each reviewer were received and organized 
by ERG by charge questions. The unedited individual and reorganized 
comments were submitted to OSHA and the reviewers in preparation for a 
follow-up conference call. The conference call, organized and 
facilitated by ERG, provided an opportunity for OSHA to clarify 
individual reviewer's comments. After the call, reviewers were given 
the opportunity to revise their written comments to include the 
clarifications or additional information provided on the call. ERG 
submitted the revised comments to OSHA organized by both individual 
reviewer and by charge question. A final peer review report is 
available in the docket (ERG, 2010). Section VII.A of this preamble 
summarizes the comments received on the draft health effects document 
and OSHA's responses to those comments. Section VII.B summarizes 
comments received on the draft Preliminary Risk Assessment and the OSHA 
response.

A. Peer Review of Draft Health Effects Evaluation

    The Technical Charge to peer reviewers posed general questions on 
the draft health effects document as well as specific questions 
pertaining to particle/chemical properties, kinetics and metabolism, 
acute beryllium disease, development of beryllium sensitization and 
CBD, genetic susceptibility, epidemiological studies of sensitization 
and CBD, animal models of chronic beryllium disease, genotoxicity, lung 
cancer epidemiological studies, animal cancer studies, other health 
effects, and preliminary conclusions drawn by OSHA.
    OSHA asked the peer reviewers to generally comment on whether the 
draft health effects evaluation included the important studies, 
appropriately addressed their strengths and limitations, accurately 
described the results, and drew scientifically sound conclusions. 
Overall, the reviewers felt that the studies were described in 
sufficient detail, the interpretations accurate, and the conclusions 
reasonable. They agreed that the OSHA document covered the significant 
health endpoints related to occupational beryllium exposure. However, 
several reviewers requested that additional studies and other specific 
information be included in various sections of the document and these 
are discussed further below.
    The reviewers had similar suggestions to improve the section V.A of 
this preamble on physical/chemical properties and section V.B on 
kinetics/metabolism. Dr. Balmes requested that physical and chemical 
characteristics of beryllium more clearly relate to development of 
sensitization and progression to CBD. Dr. Gordon requested greater 
consistency in the terminology used to describe particle 
characteristics, sampling methodologies, and the particle deposition in 
the respiratory tract. Dr. Breysse agreed and requested that the 
respiratory deposition discussion be better related to the onset of 
sensitization and CBD. Dr. Rossman suggested that the discussion of 
particle/chemical characteristics might be better placed after section 
V.D on the immunobiology of sensitization and CBD.
    OSHA made a number of revisions to sections V.A and V.B to address 
the peer review comments above. Terminology used to describe particle 
characteristics in various studies was modified to be more consistent 
and better reflect the authors' intent in the published research 
articles. Section V.B.1 on respiratory kinetics of inhaled beryllium 
was modified to more clearly describe particle deposition in the 
different regions of the respiratory tract and their influence on CBD. 
At the recommendation of Dr. Gordon, a confusing figure was removed 
since it did not portray particle deposition in a clear manner. Rather 
than relocate the entire discussion of particle/chemical 
characteristics, a new section V.B.5 was added to specifically address 
the influence of beryllium particle characteristics and chemical form 
on the development of sensitization and CBD. Other section areas were 
shortened to remove information that was not necessarily relevant to 
the overall disease process. Statements were added on the effect of 
pre-existing diseases and smoking on beryllium clearance from the lung. 
It was made clear that the precise role of dermal exposure in beryllium 
sensitization is not completely understood. These smaller changes were 
made at the request of individual reviewers.
    There were a couple of comments from reviewers pertaining to acute 
beryllium disease (ABD). Dr. Rossman commented that ABD did not make 
the development of CBD more likely. He requested that the document 
include a reference to the Van Ordstrand et al. (1943) article that 
first reported ABD in the U.S. Dr. Balmes pointed out that 
pathologists, rather than clinicians, interpret ABD pathology from lung 
tissue biopsy. Dr. Gordon commented that ABD is of lesser importance 
than CBD to the risk assessment and suggested that discussion of ABD be 
moved later in the document.
    The Van Ordstrand reference was included in section V.C on acute 
beryllium diseases and statements were modified to address the peer 
review comments above. While OSHA agrees that ABD does not have a great 
impact on the Agency risk findings, the Agency believes the current 
organization does

[[Page 47648]]

not create confusion on this point and decided not to move the ABD 
section later in the document. A statement that ABD is only relevant at 
exposures higher than the current PEL has been added to section V.C. 
Other reviewers did not feel the ABD discussion needed to be moved to a 
later section.
    Most reviewers found the description of the development and 
pathogenesis of CBD in section V.D to be accurate and understandable. 
Dr. Breysse felt the section could better delineate the steps in 
disease development (e.g., development of beryllium sensitization, CBD 
progression) and recommended the 2008 National Academy of Sciences 
report as a model. He and Dr. Gordon felt the section overemphasized 
the role of apoptosis in CBD development. Dr. Breysse and Dr. Balmes 
recommended avoiding the phrase `subclinical' to describe sensitization 
and asymptomatic CBD, preferring the term `early stage' as a more 
appropriate description. Dr. Balmes requested clarification regarding 
accumulation of inflammatory cells in the bronchoalveolar lavage (BAL) 
fluid during CBD development. Dr. Rossman suggested some additional 
description of beryllium binding with the HLA-class II receptor and 
subsequent interaction with the na[iuml]ve CD4\+\ T cells in the 
development of sensitization.
    OSHA extensively reorganized section V.D to clearly delineate the 
disease process in a more linear fashion starting with the formation of 
beryllium antigen complex, its interaction with na[iuml]ve T-cells to 
trigger CD4\+\ T-cell proliferation, and development of beryllium 
sensitization. This is presented in section V.D.1. A figure has been 
added that schematically presents this process in its entirety and the 
steps at which dermal exposure and genetic factors are believed to 
influence disease development (Figure 2 in section V.D). Section V.D.2 
describes how subsequent inhalation and the persistent residual 
presence of beryllium in the lung leads to CD4\+\ T cell 
differentiation, cytokine production, accumulation of inflammatory 
cells in the alveolar region, granuloma formation, and progression of 
CBD. The section was modified to present apoptosis as only one of the 
plausible mechanisms for development/progression of CBD. The `early 
stage' terminology was adopted and the role of inflammatory cells in 
BAL was clarified.
    While peer reviewers felt genetic susceptibility was adequately 
characterized, Dr. Rossman, Dr. Gordon, and Dr. Breysse suggested that 
additional study data be discussed to provide more depth on the 
subject, particularly the role genetic polymorphisms in providing a 
negatively charged HLA protein binding site for the positively charged 
beryllium ion. Section V.D.3 on genetic susceptibility now includes 
more information on the importance of gene-environment interaction in 
the development of CBD in low-exposed workers. The section expands on 
HLA-DPB1 alleles that influence beryllium-hapten binding and its impact 
on CBD risk.
    All reviewers found the definition of CBD to be clear and 
understandable. However, several reviewers commented on the document 
discussion of the BeLPT which operationally defines beryllium 
sensitization. Drs. Balmes and Rossman requested a more clear statement 
that two abnormal blood BeLPT results were generally necessary to 
confirm sensitization. Dr. Balmes and Dr. Breysse requested more 
discussion of historical changes in the BeLPT method that have led to 
improvement in test performance and reductions in interlaboratory 
variability. These comments were addressed in an expanded document 
section V.D.5.b on criteria for sensitization and CBD case definition 
following development of the BeLPT.
    Reviewers made suggestions to improve presentation of the many 
epidemiological studies of sensitization and CBD in the draft health 
effects document. Dr. Breysse and Dr. Gordon recommended that common 
weaknesses that apply to multiple studies be more rigorously discussed. 
Dr. Gordon requested that the discussion of the Beryllium Case Registry 
be modified to clarify the case inclusion criteria. Most reviewers 
called for the addition of tables to assist in summarizing the 
epidemiological study information.
    A paragraph has been added near the beginning of section V.D.5 that 
identifies the common challenges to interpreting the epidemiological 
evidence that supports the occurrence of sensitization and CBD at 
occupational beryllium exposures below the current PEL. These include 
studies with small numbers of subjects and CBD cases, potential 
exposure misclassification resulting from lack of personal and short-
term exposure data prior to the late 1990s, and uncertain dermal 
contribution among other issues. Table A.1 summarizing the key 
sensitization and CBD epidemiological studies was added to this 
preamble in appendix A of section V. Subsection V.D.5.a on studies 
conducted prior to the BeLPT has been reorganized to more clearly 
present the need for the Registry prior to listing the inclusion 
criteria.
    Several reviewers requested that the draft health effects document 
discuss additional occupational studies on sensitization and CBD. Dr. 
Balmes suggested including Bailey et al. (2010) on reduction in 
sensitization at a beryllium production plant and Arjomandi et al. 
(2010) on CBD among workers in a nuclear weapons facility. Dr. Breysse 
recommended adding a brief discussion of Taiwo et al. (2008) on 
sensitization in aluminum smelter workers. Dr. Gordon and Dr. Rossman 
suggested mention of Curtis, (1951) on cutaneous hypersensitivity to 
beryllium as important for the role of dermal exposure. Dr. Rossman 
also provided a reference to a number of other sensitization and CBD 
articles of historical significance.
    The above studies have been incorporated in several subsections of 
V.D.5 on human epidemiological evidence. The 1951 Curtis study is 
mentioned in the introduction to section V.D.5 as evidence of 
sensitization from dermal exposure. The Bailey et al. (2010) study is 
discussed in subsection V.D.5.d on beryllium metal processing and alloy 
production. The Arjomandi et al. (2010) study is discussed subsection 
V.D.5.h on nuclear weapons facilities and cleanup of former facilities. 
The Taiwo et al. (2008) study is discussed in subsection V.D.5.i on 
aluminum smelting. The other historical studies of historical 
significance are referenced in subsection V.D.5.a on studies conducted 
prior to the BeLPT.
    Dr. Gordon suggested that the draft health effects document make 
clear that limitations in study design and lack of an appropriate model 
limited extrapolation of animal findings to the human immune-based 
respiratory disease. Dr. Rossman also remarked on the lack of a good 
animal model that consistently demonstrates a specific cell-mediated 
immune response to beryllium. Section V.D.6 was modified to include a 
statement that lack of a dependable animal model combined with studies 
that used single doses, few animals or abbreviated observation periods 
have limited the utility of the data. Table A.2 was added that 
summarizes important information on key animal studies of beryllium-
induced immune response and lung inflammation.
    In general, peer reviewers considered the preliminary conclusions 
with regard to sensitization and CBD to be reasonable and well 
presented in the draft health effects evaluation. All reviewers agreed 
that the scientific evidence supports sensitization as a necessary 
condition and an early endpoint in the development of CBD.

[[Page 47649]]

The peer reviewers did not consider the presented evidence to 
convincingly show lung burden to be an important dose metric. Dr. 
Gordon explained that some animal studies in dogs have indicated that 
lung dose does influence granuloma formation but the importance of dose 
relative to genetic susceptibility, and physical/chemical form is 
unclear. He suggested the document indicate that many factors, 
including lung burden, affect the pulmonary tissue response to 
beryllium particles in the workplace.
    There were other suggested improvements to the preliminary 
conclusion section of the draft document. Dr. Breysse felt that 
presenting the range of observed prevalence from occupational studies 
would help support the Agency findings. He also recommended that the 
preliminary conclusions make clear that CBD is a very complex disease 
and certain steps involved in the onset and progression are not yet 
clearly understood. Dr. Rossman pointed out that a report from Mroz et 
al. (2009) updated information on the rate at which beryllium 
sensitized individuals progress to CBD.
    A statement has been added to section V.D.7 on the preliminary 
sensitization and CBD conclusions to indicate that all facets of 
development and progression of sensitization and CBD are not fully 
understood. Study references and prevalence ranges were provided to 
support the conclusion that epidemiological evidence demonstrates that 
sensitization and CBD occur from present-day exposures below OSHA's 
PEL. Statements were modified to indicate animal studies provide 
important insights into the roles of chemical form, genetic 
susceptibility, and residual lung burden in the development of 
beryllium lung disease. Updated information on rate of progression from 
sensitization to CBD was also included.
    Reviewers made suggestions to improve presentation of the 
epidemiological studies of lung cancer that were similar to their 
comments on the CBD studies. Dr. Steenland requested that a table 
summarizing the lung cancer studies be added. He also recommended that 
more emphasis be placed on the SMR results from the Ward et al. (1992) 
study. Dr. Balmes felt that more detail was presented on the animal 
cancer studies than necessary to convey the relevant message. All 
reviewers thought that the Schubauer-Berigan et al. (2010) cohort 
mortality study that addressed some of the shortcomings of earlier lung 
cancer mortality studies should be discussed in the health effects 
document.
    The recent Schubauer-Berigan et al. (2010) study conducted by the 
NIOSH Division of Surveillance, Hazard Evaluations, and Field Studies 
is now described and discussed in section V.E.2 on human epidemiology 
studies. Table A.3 summarizing the range of exposure measurements, 
study strengths and limitations, and other key lung cancer 
epidemiological study information was added to the health effects 
preamble. Section V.E.3 on the animal cancer studies already contained 
several tables that present study data so OSHA decided a summary table 
was not needed in this section.
    Reviewers were asked two questions regarding the OSHA preliminary 
conclusions on beryllium-induced lung cancer: was the inflammation 
mechanism presented in the lung cancer section reasonable; and were 
there other mechanisms or modes of action to be considered? All 
reviewers agreed that inflammation was a reasonable mechanistic 
presentation as outlined in the document. Dr. Gordon requested OSHA 
clarify that inflammation may not be the sole mechanism for 
carcinogenicity. OSHA inserted statements in section V.E.5 on the 
preliminary lung cancer conclusions clarifying that tumorigenesis 
secondary to inflammation is a reasonable mechanism of action but other 
plausible mechanisms independent of inflammation may also contribute to 
the lung cancer associated with beryllium exposure.
    There were a few comments from reviewers on health effects other 
than sensitization/CBD and lung cancer in the draft document. Dr. 
Balmes requested that the term ``beryllium poisoning'' not be used when 
referring to the hepatic effects of beryllium. He also offered language 
to clarify that the cardiovascular mortality among beryllium production 
workers in the Ward study cohort was probably due to ischemic heart 
disease and not the result of impaired lung function. Dr. Gordon 
requested removal of references to hepatic studies from in vitro and 
intravenous administration done at very high dose levels of little 
relevance to the occupational exposures of interest to OSHA. These 
changes were made to section V.F on other health effects.

B. Peer Review of the Draft Preliminary Risk Assessment

    The Technical Charge to peer reviewers for review of the draft 
preliminary risk assessment was to ensure OSHA selected appropriate 
study data, assessed the data in a scientifically credible manner, and 
clearly explained its analysis. Specific charge questions were posed 
regarding choice of data sets, risk models, and exposure metrics; the 
role of dermal exposure and dermal protection; construction of the job 
exposure matrix; characterization of the risk estimates and their 
uncertainties; and whether a quantitative assessment of lung cancer 
risk, in addition to sensitization and CBD, was warranted.
    Overall, the peer reviewers were highly supportive of the Agency's 
approach and major conclusions. They offered valuable suggestions for 
revisions and additional analysis to improve the clarity and certain 
technical aspects of the risk assessment. These suggestions and the 
steps taken by OSHA to address them are summarized here. A final peer 
review report (ERG, 2010c) and a risk assessment background document 
(OSHA, 2014a) are available in the docket.
    OSHA asked peer reviewers a series of questions regarding its 
selection of surveys from a beryllium ceramics facility, a beryllium 
machining facility, and a beryllium alloy processing facility as the 
critical studies that form the basis of the preliminary risk 
assessment. Research showed that these workplaces had well 
characterized and relatively low beryllium exposures and underwent 
plant-wide screenings for sensitization and CBD before and after 
implementation of exposure controls. The reviewers were requested to 
comment on whether the study discussions were clearly presented, 
whether the role of dermal exposure and dermal protection were 
adequately addressed, and whether the preliminary conclusions regarding 
the observed exposure-related prevalence and reduction in risk were 
reasonable and scientifically credible. They were also asked to 
identify other studies that should be reviewed as part of the 
sensitization/CBD risk assessment.
    Every peer reviewer felt the key studies were appropriate and their 
selection clearly explained in the document. Every peer reviewer 
regarded the preliminary conclusions from the OSHA review of these 
studies to be reasonable and scientifically sound. This conclusion 
stated that substantial risk of sensitization and CBD were observed in 
facilities where the highest exposed processes had median full-shift 
beryllium exposures around 0.2 [mu]g/m\3\ or higher and that the 
greatest reduction in risk was achieved when exposures for all 
processes were lowered to 0.1 [mu]g/m\3\ or below.
    The reviewers suggested that three additional studies be added to 
the risk assessment review of the

[[Page 47650]]

epidemiological literature. Dr. Balmes felt the document would be 
strengthened by including the Bailey et al. (2010) investigation of 
sensitization in a population of workers at the beryllium metal, alloy, 
and oxide production plant in Elmore, OH and the Arjomandi et al. 
(2010) publication on a group of 50 sensitized workers from a nuclear 
plant. Dr. Breysse suggested the study by Taiwo et al. (2008) on 
sensitization among workers in four aluminum smelters be considered.
    A new subsection VI.A.3 was added to the preliminary risk 
assessment that describes the changes in beryllium exposure 
measurements, prevalence of sensitization and CBD, and implementation 
of exposure controls between 1992 and 2006 at the Elmore plant. This 
subsection includes a discussion of the Bailey et al. study. A summary 
of the Taiwo et al. (2008) study was added as subsection VI.A.5. A 
discussion of the Arjomandi et al. (2010) study was added in subsection 
VI.B as evidence that sensitized workers with primarily low beryllium 
exposure go on to develop CBD. However, the low rates of CBD among this 
group of sensitized workers also suggest that low beryllium exposure 
may reduce CBD risk when compared to worker populations with higher 
exposure levels.
    While the majority of reviewers stated that OSHA adequately 
addressed the role of dermal exposure in sensitization and the 
importance of dermal protection for workers, a few had additional 
suggestions for OSHA's discussion. Dr. Breysse and Dr. Gordon pointed 
out that because the beryllium exposure control programs featured steps 
to reduce both skin contact and inhalation, it was difficult to 
distinguish between the effects of reducing airborne and dermal 
exposure. A statement was added to subsection VI.B that concurrent 
implementation of respirator use, dermal protection and engineering 
changes made it difficult to attribute reduced risk to any single 
control measure. Since the Cullman plant did not require glove use, 
OSHA believes it to be the best data set available for evaluating the 
effects of airborne exposure control on risk of sensitization.
    Dr. Breysse requested additional discussion of the role of 
respiratory protection in achieving reduction in risk. Dr. Gordon 
suggested some additional clarification regarding mean and median 
exposure measures. Additional information on respiratory programs and 
exposure measures (e.g., median, arithmetic and geometric means), where 
available, were presented for each of the studies discussed in 
subsection VI.A.
    The peer reviewers generally agreed that it was reasonable to 
conclude that community-acquired CBD (CA-CBD) resulted from low 
beryllium exposures. Drs. Breysse, Balmes and others noted that higher 
short-term excursions could not be ruled out. Dr. Gordon suggested that 
genetic susceptibility may have a role in cases of CA-CBD. Dr. Rossman 
raised the possibility that some CA-CBD cases could occur from contact 
with beryllium workers. All these points were added to subsection VI.C.
    OSHA asked the peer reviewers to evaluate the choice of the 
National Jewish Medical and Research Center (NJMRC) data set on the 
Cullman, AL machinist population as a basis for exposure-response 
analysis and the reliance on cumulative exposure as the basis for the 
exposure-response analysis of sensitization and CBD. All peer reviewers 
indicated that the choice of the NJMRC data set for exposure-response 
analysis was clearly explained and reasonable and that they knew of no 
better data set for the analysis. Dr. Rossman commented that the NJMRC 
data set was an excellent source of exposures to different levels of 
beryllium and testing and evaluation of the workers. Dr. Steenland and 
Dr. Gordon suggested that the results from the OSHA analysis of the 
NJMRC data be compared with the available data from the studies of 
other beryllium facilities discussed in the epidemiological literature 
analysis. While a rigorous quantitative comparison (e.g., meta 
analysis) is difficult due to differences in the study designs and data 
types available for each study, subsection VI.E.4 compares the results 
of OSHA's prevalence analysis from the Cullman data with results from 
studies of the Tucson and Reading facilities.
    OSHA asked the peer reviewers to evaluate methods used to construct 
the job exposure matrix (JEM) and to estimate beryllium exposure for 
each worker in the NJMRC data set. The JEM procedure was briefly 
summarized in the review document and described in detail as part of a 
risk assessment technical background document made available to the 
reviewers (OSHA, 2014a). Dr. Balmes felt that a more thorough 
discussion of the JEM would strengthen the preamble document. Dr. 
Gordon requested information about values assigned exposures below the 
limit of detection. Dr. Steenland requested that both the preamble and 
technical background document contain additional information on aspects 
of the JEM construction such as the job categories, job-specific 
exposure values, how jobs were grouped, and how non-machining jobs were 
handled in the JEM. He suggested the entire JEM be included in the 
technical background document. OSHA greatly expanded subsection VI.E.2 
on air sampling and JEM to include more detailed discussion of the JEM 
construction. Exposure values for machining and non-machining job 
titles were provided in Tables VI-4 and VI-5. The procedures and 
rationale for grouping job-specific measurements into four time periods 
was explained. Jobs were not grouped in the JEM; rather, individual 
exposure estimates were created for each job in the work history data 
set. The technical background document further clarifies the JEM 
construction and the full JEM is included as an appendix to the revised 
background document (OSHA, 2014a). Subsection VI.E.3 on worker exposure 
reconstruction contains further detail about the work histories.
    Peer reviewers fully supported OSHA's choice of the cumulative 
exposure metric to estimate risk of CBD from the NJMRC data set. As 
explained by Dr. Steenland, ``cumulative exposure is often the choice 
for many chronic diseases as opposed to average or highest exposure.'' 
He pointed out that the cumulative exposure metric also fit the CBD 
data better than other metrics. The reviewers generally felt that 
short-term peak exposure was probably the measure of airborne exposure 
most relevant to risk of beryllium sensitization. However, peer 
reviewers agreed that data required to capture workers' short-term peak 
exposures and to relate the peak exposure levels to sensitization were 
not available. Dr. Breysse explained that ``short-term (hrs to minutes) 
peak exposures may be important to sensitization risk, while long term 
averages are more important for CBD risk. Unfortunately data for short-
term peak exposures may not exist.'' Dr. Steenland explained that of 
the available metrics ``cumulative exposure fits the sensitization data 
better than the two alternatives, and hence is the best metric.'' 
Statements were added to subsection VI.E.3 to indicate that while 
short-term exposures may be highly relevant to risk of sensitization, 
the individual peak exposures leading up to onset of sensitization was 
not able to be determined in the NJRMC Cullman study.
    Peer reviewers found the methods used in the statistical exposure-
response analysis to be clearly described. With the exception of Dr. 
Steenland, reviewers believed that a detailed critique of the 
statistical approach was

[[Page 47651]]

beyond their level of expertise. Dr. Steenland supported OSHA's overall 
approach to the risk modeling and recommended additional analyses to 
explore the sensitivity of OSHA's results to alternate choices and to 
test the validity of aspects of the analysis. Dr. Steenland recommended 
that the logistic regression used by OSHA as a preliminary first 
analysis be dropped as an inappropriate model for a situation where it 
is important to account for changing exposures and case onset over 
time. Instead, he suggested a sensitivity analysis in which exposure-
response coefficients generated using a traditional Cox proportionate 
hazards model be compared to the discrete time Cox model analog (i.e., 
complementary log-log Cox model) used by OSHA. The sensitivity analysis 
would facilitate examination of the proportional hazard assumption 
implied by the use of these models. Dr. Steenland advocated that OSHA 
include a table that displayed the mean number of BeLPT tests for the 
study population in order to address whether the number of 
sensitization tests introduced a potential bias. He inquired about the 
possibility of determining a sensitization incidence rate using 
cumulative or average exposure. Dr. Steenland suggested that the model 
control for additional potential confounders, such as age, smoking 
status, race and gender. He wanted a more complete explanation of the 
model constant for the year of diagnosis in Tables VI-9 through VI-12 
to be included in the preamble as it was in the technical background 
document. Dr. Steenland recommended a sensitivity analysis that 
excludes the highest 5 to 10 percent of cumulative exposures which 
might address potential model uncertainty at the high end exposures. He 
requested that the results of statistical tests for non-linearity be 
included and confidence intervals for the risk estimates in Tables VI-
17 and VI-18 be determined.
    Many of Dr. Steenland's comments were addressed in subsection VI.F 
on the statistical modeling. The logistic regression analysis was 
removed from the section. A sensitivity analysis using the standard Cox 
model that treats survival time as continuous rather than discrete was 
added to the risk assessment background document and results were 
described in subsection VI.F. The interaction between exposure and 
follow-up time was not significant in the models suggesting that the 
proportional hazard assumption should not be rejected. The model 
coefficients using the standard Cox model were similar to model 
coefficients for the discrete model. Given this, OSHA did not feel it 
necessary to further estimate risks using the continuous Cox model at 
specific exposure levels.
    A table of the mean number of BeLPT tests across the study 
population was added to the risk assessment background document. 
Subsection VI.F describes the table results and its impact on the 
statistical modeling. Smoking status and age were included in the 
discrete Cox proportional hazards model and not found to be significant 
predictors of beryllium sensitization. However, the available study 
population composition did not allow a confounder analysis of race and 
gender. OSHA chose not to include a detailed explanation of the model 
constant for the year of diagnosis in the preamble section. OSHA agrees 
with Dr. Steenland that the risk assessment background document 
adequately describes the model terms. For that reason, OSHA prefers 
that the risk assessment preamble focus on the results and major points 
of the analysis and refer the reader to the more technical background 
document for an explanation of model parameters. The linearity 
assumption was assessed using a fractional polynomial approach. The 
best fitting polynomials did not fit significantly better than the 
linear model. The details of the analysis were included in the risk 
assessment background document. Tables VI-17 and VI-18 now include the 
upper 95 percent confidence limits on the model-predicted cases of 
sensitization and CBD for the current and alternative PELs.
    Most peer reviewers felt the major uncertainties of the risk 
assessment were clearly and adequately discussed in the documents they 
reviewed. Dr. Breysse requested that the risk assessment cover 
potential underestimation of risk from exposure misclassification bias. 
He requested further discussion of the degree to which the risk 
estimates from the Cullman machining plant could be extrapolated to 
workplaces that use other physical (e.g., particle size) and chemical 
forms of beryllium. He went on to question the strength of evidence 
that insoluble forms of beryllium cause CBD. Dr. Breysse also suggested 
that the assumptions used in the risk modeling be consolidated and more 
clearly presented. Dr. Steenland felt that there was potential 
underestimation of CBD risk resulting from exclusion of former workers 
and case status of current workers after employment.
    Discussion of these uncertainties was added in the final paragraphs 
of section VI.F. The section was modified to more clearly identify 
assumptions with regard to the risk modeling such as an assumed 
linearity in exposure-response and cumulative dose equivalency when 
extrapolating risks over a 45-year working lifetime. Section VI.F 
recognizes the uncertainties in risk that can result from 
reconstructing individual exposures with very limited sampling data 
prior to 1994. The potential exposure misclassification can limit the 
strength of exposure-response relationships and result in the 
underestimation of risk. A more technical discussion of modeling 
assumptions and exposure measurement error are provided in the risk 
assessment background document. Section VI.F points out that the NJMRC 
data set does not capture CBD that occurred among workers who retired 
or left the Cullman plant. This and the short follow-up time is a 
source of uncertainty that likely leads to underestimation of risk. The 
section indicates that it is not unreasonable to expect the risk 
estimates to generally reflect onset of sensitization and CBD from 
exposure to beryllium forms that are relatively insoluble and enriched 
with respirable particles as encountered at the Cullman machining 
plant. Additional uncertainty is introduced when extrapolating the risk 
estimates to beryllium compounds of vastly different solubility and 
particle characteristics. OSHA does not agree with the comment 
suggesting that the association between CBD and insoluble forms of 
beryllium is weak. The principle sources of beryllium encountered at 
the Cullman machining plant, the Reading copper beryllium processing 
plant and the Tucson ceramics plant where excessive CBD was observed 
are insoluble forms of beryllium, such as beryllium metal, beryllium 
alloy, and beryllium oxide.
    Finally, OSHA asked the peer reviewers to evaluate its treatment of 
lung cancer in the earlier draft preliminary risk assessment (OSHA, 
2010b). When that document was prepared, OSHA had elected not to 
conduct a lung cancer risk assessment. The Agency believed that the 
exposure-response data available to conduct a lung cancer risk 
assessment from a Sanderson et al. study of a Reading, PA beryllium 
plant by was highly problematic. The Sanderson study primarily involved 
workers with extremely high and short-term exposures above airborne 
exposure levels of interest to OSHA (2 [mu]g/m\3\ and below).
    Just prior to arranging the peer review, a NIOSH study was 
published by Schubauer-Berigan et al. updating the Reading, PA cohort 
studied by Sanderson et al. and adding cohorts

[[Page 47652]]

from two additional plants in Elmore, OH and Hazleton, PA (Schubauer-
Berigan, 2011). At OSHA's request, the peer reviewers reviewed this 
study to determine whether it could provide a better basis for lung 
cancer risk analysis than the Sanderson et al. study. The reviewers 
found that the NIOSH update addressed the major concerns OSHA had 
expressed about the Sanderson study. In particular, they pointed out 
that workers in the Elmore and Hazleton cohorts had longer tenure at 
the plants and experienced lower exposures than those at the Reading, 
PA plant. Dr. Steenland recommended that ``OSHA consider the new NIOSH 
data and develop risk estimates for lung cancer as well as 
sensitization and CBD.'' Dr. Breysse believed that the NIOSH data 
``suggest that a risk assessment for lung cancer should be conducted by 
OSHA and the results be compared to the CBD/sensitization risk 
assessment before recommending an appropriate exposure concentration.'' 
While acknowledging the improvements in the quality of the data, other 
reviewers were more restrained in their support for quantitative 
estimates of lung cancer risk. Dr. Gordon stated that despite 
improvements, there was ``still uncertainty associated with the paucity 
of data below the current PEL of 2 [mu]g/m\3\.'' Dr. Rossman noted that 
the NIOSH study ``did not address the problem of the uncertainty of the 
mechanism of beryllium carcinogenicity.'' He felt that the updated 
NIOSH lung cancer mortality data ``should not change the Agency's 
rationale for choosing to establish its risk findings for the proposed 
rule on its analysis for beryllium sensitization and CBD.'' Dr. Balmes 
agreed that ``the agency will be on firmer ground by focusing on 
sensitization and CBD.''
    The preliminary risk assessment preamble subsection VI.G on lung 
cancer includes a discussion of the quantitative lung cancer risk 
assessment published by NIOSH researchers in 2010 (Schubauer-Berigan, 
2011). The discussion describes the lower exposure levels, longer 
tenure, fewer short-term workers and additional years of observation 
that make the data more suitable for risk assessment. NIOSH relied on 
several modeling approaches to show that lung cancer risk was 
significantly related to both mean and cumulative beryllium exposure. 
Subsection VI.G provides the excess lifetime lung cancer risks 
predicted from several best-fitting NIOSH models at beryllium exposures 
of interest to OSHA (Table VI-20). Using the piecewise log-linear 
proportional hazards model favored by NIOSH, there is a projected drop 
in excess lifetime lung cancer risks from approximately 61 cases per 
1000 exposed workers at the current PEL of 2.0 [mu]g/m\3\ to 
approximately 6 cases per 1000 at the proposed PEL of 0.2 [mu]g/m\3\. 
Subsection VI.H on preliminary conclusions indicates that these 
projections support a reduced risk of lung cancer from more stringent 
control of beryllium exposures but that the lung cancer risk estimates 
are more uncertain than those for sensitization and CBD.

VIII. Significance of Risk

    To promulgate a standard that regulates workplace exposure to toxic 
materials or harmful physical agents, OSHA must first determine that 
the standard reduces a ``significant risk'' of ``material impairment.'' 
The first part of this requirement, ``significant risk,'' refers to the 
likelihood of harm, whereas the second part, ``material impairment,'' 
refers to the severity of the consequences of exposure.
    The Agency's burden to establish significant risk is based on the 
requirements of the OSH Act (29 U.S.C. 651 et seq). Section 3(8) of the 
Act requires that workplace safety and health standards be ``reasonably 
necessary or appropriate to provide safe or healthful employment'' (29 
U.S.C. 652(8)). The Supreme Court, in the Benzene decision, interpreted 
section 3(8) to mean that ``before promulgating any standard, the 
Secretary must make a finding that the workplaces in question are not 
safe'' (Industrial Union Department, AFL-CIO v. American Petroleum 
Institute, 448 U.S. 607, 642 (1980) (plurality opinion)). Examining 
section 3(8) more closely, the Court described OSHA's obligation to 
demonstrate significant risk:

    ``[S]afe'' is not the equivalent of ``risk-free.'' A workplace 
can hardly be considered ``unsafe'' unless it threatens the workers 
with a significant risk of harm. Therefore, before the Secretary can 
promulgate any permanent health or safety standard, he must make a 
threshold finding that the place of employment is unsafe in the 
sense that significant risks are present and can be eliminated or 
lessened by a change in practices (Id).

    As the Court made clear, the Agency has considerable latitude in 
defining significant risk and in determining the significance of any 
particular risk. The Court did not specify a means to distinguish 
significant from insignificant risks, but rather instructed OSHA to 
develop a reasonable approach to making a significant risk 
determination. The Court stated that ``it is the Agency's 
responsibility to determine in the first instance what it considers to 
be a 'significant' risk,'' (448 U.S. at 655) and it did not express 
``any opinion on the . . . difficult question of what factual 
determinations would warrant a conclusion that significant risks are 
present which make promulgation of a new standard reasonably necessary 
or appropriate'' (448 U.S. at 659). The Court also stated that, while 
OSHA's significant risk determination must be supported by substantial 
evidence, the Agency ``is not required to support the finding that a 
significant risk exists with anything approaching scientific 
certainty'' (448 U.S. at 656). Furthermore:

    A reviewing court [is] to give OSHA some leeway where its 
findings must be made on the frontiers of scientific knowledge . . . 
. [T]he Agency is free to use conservative assumptions in 
interpreting the data with respect to carcinogens, risking error on 
the side of overprotection rather than underprotection [so long as 
such assumptions are based on] a body of reputable scientific 
thought (448 U.S. at 656).

Thus, to make the significance of risk determination for a new or 
proposed standard, OSHA uses the best available scientific evidence to 
identify material health impairments associated with potentially 
hazardous occupational exposures and to evaluate exposed workers' risk 
of these impairments.

    The OSH Act also requires that the Agency make a finding that the 
toxic material or harmful physical agent at issue causes material 
impairment to worker health. In that regard, the Act directs the 
Secretary of Labor to set standards based on the available evidence 
where no employee, over his/her working life time, will suffer from 
material impairment of health or functional capacity, even if such 
employee has regular exposure to the hazard, to the exent feasible (29 
U.S.C. 655(b)(5)).
    As with significant risk, what constitutes material impairment in 
any given case is a policy determination for which OSHA is given 
substantial leeway. ``OSHA is not required to state with scientific 
certainty or precision the exact point at which each type of [harm] 
becomes a material impairment'' (AFL-CIO v. OSHA, 965 F.2d 962, 975 
(11th Cir. 1992)). Courts have also noted that OSHA should consider all 
forms and degrees of material impairment--not just death or serious 
physical harm--and that OSHA may act with a ``pronounced bias towards 
worker safety'' (Id; Bldg & Constr. Trades Dep't v. Brock, 838 F.2d 
1258, 1266 (D.C. Cir. 1988)). OSHA's long-standing policy is to 
consider 45 years as a ``working life,''

[[Page 47653]]

over which it must evaluate material impairment and risk.
    In formulating this proposed beryllium standard, OSHA has reviewed 
the best available evidence pertaining to the adverse health effects of 
occupational beryllium exposure, including lung cancer and chronic 
beryllium disease (CBD), and has evaluated the risk of these effects 
from exposures allowed under the current standard as well as the 
expected impact of the proposed standard on risk. Based on its review 
of extensive epidemiological and experimental research, OSHA has 
preliminarily determined that long-term exposure at the current 
Permissible Exposure Limit (PEL) would pose a significant risk of 
material impairment to workers' health, and that adoption of the new 
PEL and other provisions of the proposed rule will substantially reduce 
this risk.

A. Material Impairment of Health

    In this preamble at section V, Health Effects, OSHA reviewed the 
scientific evidence linking occupational beryllium exposure to a 
variety of adverse health effects, including CBD and lung cancer. Based 
on this review, OSHA preliminarily concludes that beryllium exposure 
causes these effects. The Agency's preliminary conclusion was strongly 
supported by a panel of independent peer reviewers, as discussed in 
section VII.
    Here, OSHA discusses its preliminary conclusion that CBD and lung 
cancer constitute material impairments of health, and briefly reviews 
other adverse health effects that can result from beryllium exposure. 
Based on this preliminary conclusion and on the scientific evidence 
linking beryllium exposure to both CBD and lung cancer, OSHA concludes 
that occupational exposure to beryllium causes ``material impairment of 
health or functional capacity'' within the meaning of the OSH Act.
1. Chronic Beryllium Disease
    CBD is a respiratory disease in which the body's immune system 
reacts to the presence of beryllium in the lung, causing a progression 
of pathological changes including chronic inflammation and tissue 
scarring. CBD can also impair other organs such as the liver, skin, 
spleen, and kidneys and cause adverse health effects such as granulomas 
of the skin and lymph nodes and cor pulmonale (i.e., enlargement of the 
heart) (Conradi et al., 1971; ACCP, 1965; Kriebel et al., 1988a and b). 
In early, asymptomatic stages of CBD, small granulomatous lesions and 
mild inflammation occur in the lungs. Early stage CBD among some 
workers has been observed to progress to more serious disease even 
after the worker is removed from exposure (Mroz, 2009), probably 
because common forms of beryllium have slow clearance rates and can 
remain in the lung for years after exposure. Sood et al. has reported 
that cessation of exposure can sometimes have beneficial effects on 
lung function (Sood et al., 2004). However, this was based on a small 
study of six patients with CBD, and more research is needed to better 
determine the relationship between exposure duration and disease 
progression. In general, progression of CBD from early to late stages 
is understood to vary widely, responding differently to exposure 
cessation and treatment for different individuals (Sood, 2009; Mroz, 
2009).
    Over time, the granulomas can spread and lead to lung fibrosis 
(scarring) and moderate to severe loss of pulmonary function, with 
symptoms including a persistent dry cough and shortness of breath 
(Saber and Dweik, 2000). Fatigue, night sweats, chest and joint pain, 
clubbing of fingers (due to impaired oxygen exchange), loss of 
appetite, and unexplained weight loss may occur as the disease 
progresses. Corticosteroid therapy, in workers whose beryllium exposure 
has ceased, has been shown to control inflammation, ease symptoms 
(e.g., difficulty breathing, fever, cough, and weight loss) and in some 
cases prevent the development of fibrosis (Marchand-Adam et al., 2008). 
Thus early treatment can lead to CBD regression in some patients, 
although there is no cure (Sood, 2004). Other patients have shown 
short-term improvements from corticosteroid treatment, but then 
developed serious fibrotic lesions (Marchand-Adam et al., 2008). Once 
fibrosis has developed in the lungs, corticosteroid treatment cannot 
reverse the damage (Sood, 2009). Persons with late-stage CBD experience 
severe respiratory insufficiency and may require supplemental oxygen 
(Rossman, 1991). Historically, late-stage CBD often ended in death 
(NAS, 2008).
    While the use of steroid therapy has mitigated CBD mortality, 
treatment with corticosteroids has side effects that need to be 
measured against the possibility of progression of disease 
(Trikudanathan and McMahon, 2008; Lipworth, 1999; Gibson et al., 1996; 
Zaki et al., 1987). Adverse effects associated with long-term 
corticosteroid use include, but are not limited to, increased risk of 
opportunistic infections (Lionakis and Kontoyiannis, 2003; 
Trikudanathan and McMahon, 2008); accelerated bone loss or osteoporosis 
leading to increased risk of fractures or breaks (Hamida et al., 2011; 
Lehouck et al., 2011; Silva et al., 2011; Sweiss et al., 2011; 
Langhammer et al., 2009); psychiatric effects including depression, 
sleep disturbances, and psychosis (Warrington and Bostwick, 2006; 
Brown, 2009); adrenal suppression (Lipworth, 1999; Frauman, 1996); 
ocular effects including cataracts, ocular hypertension, and glaucoma 
(Ballonzolli and Bourchier, 2010; Trikudanathan and McMahon, 2008; 
Lipworth, 1999); an increase in glucose intolerance (Trikudanathan and 
McMahon, 2008); excessive weight gain (McDonough et al., 2008; Torres 
and Nowson, 2007; Dallman et al., 2007; Wolf, 2002; Cheskin et al., 
1999); increased risk of atherosclerosis and other cardiovascular 
syndromes (Franchimont et al., 2002); skin fragility (Lipworth, 1999); 
and poor wound healing (de Silva and Fellows, 2010). Studies relating 
the long-term effect of corticosteroid use for the treatment of CBD 
need to be undertaken to evaluate the treatment's overall effectiveness 
against the risk of adverse side effects from continued usage.
    OSHA considers late-stage CBD to be a material impairment of 
health, as it involves permanent damage to the pulmonary system, causes 
additional serious adverse health effects, can have adverse 
occupational and social consequences, requires treatment associated 
with severe and lasting side effects, and may in some cases be life-
threatening. Furthermore, OSHA believes that material impairment begins 
prior to the development of symptoms of the disease.
    Although there are no symptoms associated with early-stage CBD, 
during which small lesions and inflammation appear in the lungs, the 
Agency has preliminarily concluded that the earliest stage of CBD is 
material impairment of health. OSHA bases this conclusion on evidence 
showing that early-stage CBD is a measurable change in the state of 
health which, with and sometimes without continued exposure, can 
progress to symptomatic disease. Thus, prevention of the earliest 
stages of CBD will prevent development of more serious disease. The 
OSHA Lead Standard established the Agency's position that a 
`subclinical' health effect may be regarded as a material impairment of 
health. In the preamble to that standard, the Agency said:

    OSHA believes that while incapacitating illness and death 
represent one extreme of a spectrum of responses, other biological 
effects such as metabolic or physiological changes are precursors or 
sentinels of disease which should be prevented . . . Rather than 
revealing beginnings of illness the standard must be selected to 
prevent an earlier point

[[Page 47654]]

of measurable change in the state of health which is the first 
significant indicator of possibly more severe ill health in the 
future. The basis for this decision is twofold--first, 
pathophysiologic changes are early stages in the disease process 
which would grow worse with continued exposure and which may include 
early effects which even at early stages are irreversible, and 
therefore represent material impairment themselves. Secondly, 
prevention of pathophysiologic changes will prevent the onset of the 
more serious, irreversible and debilitating manifestations of 
disease.\11\ (43 FR 52952, 52954, November 14, 1978)

    \11\ Even if asymptomatic CBD were not itself a material 
impairment of health, the D.C. Circuit upheld OSHA's authority to 
regulate to prevent subclinical health effects as precursors to 
disease in United Steelworkers of America, AFL-CIO v. Marshall, 647 
F.2d 1189, 1252 (D.C. Cir. 1980), which reviewed the Lead standard. 
Without deciding whether the early symptoms of disease were 
themselves a material impairment, the court concluded that OSHA may 
regulate subclinical effects if it can demonstrate on the basis of 
substantial evidence that preventing subclinical effects would help 
prevent the clinical phase of disease (Id.).

    Since the Lead rulemaking, OSHA has also found other non-
symptomatic health conditions to be material impairments of health. In 
the Bloodborne Pathogens (BP) rulemaking, OSHA maintained that material 
impairment includes not only workers with clinically ``active'' 
hepatitis from the hepatitis B virus (HBV) but also includes 
asymptomatic HBV ``carriers'' who remain infectious and are able to put 
others at risk of serious disease through contact with body fluids 
(e.g., blood, sexual contact) (56 FR 64004, December 6, 1991). OSHA 
stated: ``Becoming a carrier [of Hepatitis B] is a material impairment 
of health even though the carrier may have no symptoms. This is because 
the carrier will remain infectious, probably for the rest of his or her 
life, and any person who is not immune to HBV who comes in contact with 
the carrier's blood or certain other body fluids will be at risk of 
becoming infected'' (56 FR 64004, 64036).
    OSHA preliminarily finds that early-stage CBD is the type of 
asymptomatic health effect the Agency determined to be a material 
impairment of health in the lead standard. Early stage CBD involves 
lung tissue inflammation without symptomatology that can worsen with--
or without--continued exposure. The lung pathology progresses over time 
from a chronic inflammatory response to tissue scarring and fibrosis 
accompanied by moderate to severe loss in pulmonary function. Early 
stage CBD is clearly a precursor of advanced clinical disease, 
prevention of which will prevent symptomatic disease. OSHA argued in 
the Lead standard that such precursor effects should be considered 
material health impairments in their own right, and that the Agency 
should act to prevent them when it is feasible to do so. Therefore, 
OSHA preliminarily finds all stages of CBD to be material impairments 
of health.
2. Lung Cancer
    OSHA considers lung cancer, a frequently fatal disease, to be a 
material impairment of health. OSHA's finding that inhaled beryllium 
causes lung cancer is based on the best available epidemiological data, 
reflects evidence from animal and mechanistic research, and is 
consistent with the conclusions of other government and public health 
organizations (see this preamble at section V, Health Effects). For 
example, the International Agency for Research on Cancer (IARC), 
National Toxicology Program (NTP), and American Conference of 
Governmental Industrial Hygienists (ACGIH) have all classified 
beryllium as a known human carcinogen (IARC, 2009).
    The Agency's epidemiological evidence comes from multiple studies 
of U.S. beryllium workers (Sanderson et al., 2001a; Ward et al., 1992; 
Wagoner et al., 1980; Mancuso et al., 1979). Most recently, a NIOSH 
cohort study found significantly increased lung cancer mortality among 
workers at seven beryllium processing facilities (Schubauer-Berigan et 
al., 2011). The cohort was exposed, on average, to lower levels of 
beryllium than those in most previous studies, had fewer short-term 
workers, and had sufficient follow-up time to observe lung cancer in 
the population. OSHA considers the Schubauer-Berigan study to be the 
best available epidemiological evidence regarding the risk of lung 
cancer from beryllium at exposure levels near the PEL.\12\
---------------------------------------------------------------------------

    \12\ The scientific peer review panel for OSHA's Preliminary 
Risk Assessment agreed with the Agency that the Schubauer-Berigan 
analysis improves upon the previously available data for lung cancer 
risk assessment.
---------------------------------------------------------------------------

    Supporting evidence of beryllium carcinogenicity comes from various 
animal studies as well as in vitro genotoxicity and other studies (EPA, 
1998; ATSDR, 2002; Gordon and Bowser, 2003; NAS, 2008; Nickell-Brady et 
al., 1994; NTP, 1999 and 2005; IARC, 1993 and 2009). Multiple 
mechanisms may be involved in the carcinogenicity of beryllium, and 
factors such as epigenetics, mitogenicity, reactive oxygen-mediated 
indirect genotoxicity, and chronic inflammation may contribute to the 
lung cancer associated with beryllium exposure, although the results of 
studies testing the direct genotoxicity of beryllium are mixed (EPA 
summary, 1998). While there is uncertainty regarding the exact 
mechanism of carcinogenesis for beryllium, the overall weight of 
evidence for the carcinogenicity of beryllium is strong. Therefore, the 
Agency has preliminarily determined beryllium to be an occupational 
carcinogen.
3. Other Impairments
    While OSHA has relied primarily on the relationship between 
occupational beryllium exposure and CBD and lung cancer to demonstrate 
the necessity of the standard, the Agency has also determined that 
several other adverse health effects can result from exposure to 
beryllium. Inhalation of high airborne concentrations of beryllium 
(well above the 2 [mu]g/m\3\ OSHA PEL) can cause acute beryllium 
disease, a severe (sometimes fatal), rapid-onset inflammation of the 
lungs. Hepatic necrosis, damage to the heart and circulatory system, 
chronic renal disease, mucosal irritation and ulceration, and urinary 
tract cancer have also reportedly been associated with occupational 
exposures well above the current PEL (see this preamble at section V, 
Health Effects, subsection E, Epidemiological Studies, and subsection 
F, Other Health Effects). These adverse systemic effects and acute 
beryllium disease mostly occurred prior to the introduction of 
occupational and environmental standards set in 1970-1972 (OSHA, 1971; 
ACGIH, 1971; ANSI, 1970) and 1974 (EPA, 1974) and therefore are less 
relevant today than in the past. Because they occur only rarely in 
current-day occupational environments, they are not addressed in OSHA's 
risk analysis or significance of risk determination.
    The Agency has also determined that beryllium sensitization, a 
precursor which occurs before early stage CBD and is an essential step 
for worker development of the disease, can result from exposure to 
beryllium. The Agency takes no position at this time on whether 
sensitization constitutes a material impairment of health, because it 
was unnecessary to do so as part of this rulemaking. As discussed in 
Section V, Health Effects, only sensitized individuals can develop CBD 
(NAS, 2008). OSHA's risk assessment for sensitization informs the 
Agency's understanding of what exposure control measures have been 
successful in preventing sensitization, which in turn prevents 
development of CBD. Therefore sensitization is considered in the next 
section on significance of risk.

[[Page 47655]]

In AFL-CIO v. Marshall, 617 F.2d 636, 654 n.83 (D.C. Cir. 1979) (Cotton 
Dust), the D.C. Circuit upheld OSHA's authority to regulate to prevent 
precursors to a material impairment of health without deciding whether 
the precursors themselves constituted material impairment of health.

B. Significance of Risk and Risk Reduction

    To evaluate the significance of the health risks that result from 
exposure to hazardous chemical agents, OSHA relies on the best 
available epidemiological, toxicological, and experimental evidence. 
The Agency uses both qualitative and quantitative methods to 
characterize the risk of disease resulting from workers' exposure to a 
given hazard over a working lifetime at levels of exposure reflecting 
compliance with current standards and compliance with the new standards 
being proposed.
    As discussed above, the Agency's characterization of risk is guided 
in part by the Benzene decision. In Benzene, the Court broadly 
describes the range of risks OSHA might determine to be significant:

    It is the Agency's responsibility to determine in the first 
instance what it considers to be a ``significant'' risk. Some risks 
are plainly acceptable and others are plainly unacceptable. If, for 
example, the odds are one in a billion that a person will die from 
cancer by taking a drink of chlorinated water, the risk clearly 
could not be considered significant. On the other hand, if the odds 
are one in a thousand that regular inhalation of gasoline vapors 
that are 2 percent benzene will be fatal, a reasonable person might 
well consider the risk significant and take the appropriate steps to 
decrease or eliminate it (Benzene, 448 U.S. at 655).

The Court further stated, ``The requirement that a 'significant' risk 
be identified is not a mathematical straitjacket. . . . Although the 
Agency has no duty to calculate the exact probability of harm, it does 
have an obligation to find that a significant risk is present before it 
can characterize a place of employment as 'unsafe', ``and proceed to 
promulgate a regulation (Id.).

    In this preamble at section VI, Preliminary Risk Assessment, OSHA 
finds that the available epidemiological data are sufficient to 
evaluate risk for beryllium sensitization, CBD, and lung cancer among 
beryllium-exposed workers. The preliminary findings from this 
assessment are summarized below.
1. Risk of Beryllium Sensitization and CBD
    OSHA's preliminary risk assessment for CBD and beryllium 
sensitization relies on studies conducted at a Tucson, AZ beryllium 
ceramics plant (Kreiss et al., 1996; Henneberger et al., 2001; Cummings 
et al., 2006); a Reading, PA alloy processing plant (Schuler et al., 
2005; Thomas et al., 2009); a Cullman, AL beryllium machining plant 
(Kelleher et al., 2001; Madl et al., 2007); and an Elmore, OH metal, 
alloy, and oxide production plant (Kreiss et al., 1997; Bailey et al., 
2010; Schuler et al., 2012). The Agency uses these studies to 
demonstrate the significance of risk at the current PEL and the 
significant reduction in risk expected with reduction of the PEL. In 
addition to the effects OSHA anticipates from reduction of airborne 
beryllium exposure, the Agency expects that dermal protection 
provisions in the proposed rule will further reduce risk. Studies 
conducted in the 1950s by Curtis et al. showed that soluble beryllium 
particles could penetrate the skin and cause beryllium sensitization 
(Curtis 1951, NAS 2008). Tinkle et al. established that 0.5- and 1.0-
[mu]m particles can penetrate intact human skin surface and reach the 
epidermis, where beryllium particles would encounter antigen-presenting 
cells and initiate sensitization (Tinkle et al., 2003). Tinkle et al. 
further demonstrated that beryllium oxide and beryllium sulfate, 
applied to the skin of mice, generate a beryllium-specific, cell-
mediated immune response similar to human beryllium sensitization 
(Tinkle et al., 2003). In the epidemiological studies discussed below, 
the exposure control programs that most effectively reduced the risk of 
beryllium sensitization and CBD incorporated both respiratory and 
dermal protection. OSHA has preliminarily determined that an effective 
exposure control program should incorporate both airborne exposure 
reduction and dermal protection provisions.
    In the Tucson ceramics plant, 4,133 short-term breathing zone 
measurements collected between 1981 and 1992 had a median of 0.3 [mu]g/
m\3\. Kreiss et al. reported that eight (5.9 percent) of 136 workers 
tested for beryllium sensitization in 1992 were sensitized, six (4.4 
percent) of whom were diagnosed with CBD. Exposure control programs 
were initiated in 1992 to reduce workers' airborne beryllium exposure, 
but the programs did not address dermal exposure. Full-shift personal 
samples collected between 1994 and 1999 showed a median beryllium 
exposure of 0.2 [mu]g/m\3\ in production jobs and 0.1 [mu]g/m\3\ in 
production support (Cummings et al., 2007). In 1998, a second screening 
found that 6, (9 percent) of 69 tested workers hired after the 1992 
screening, were sensitized, of whom 1 was diagnosed with CBD. All of 
the sensitized workers had been employed at the plant for less than 2 
years (Henneberger et al., 2001), too short a time period for most 
people to develop CBD following sensitization. Of the 77 Tucson workers 
hired prior to 1992 who were tested in 1998, 8 (10.4 percent) were 
sensitized and all but 1 of these (9.7 percent) were diagnosed with CBD 
(Henneberger et al., 2001).
    Kreiss et al., studied workers at a beryllium metal, alloy, and 
oxide production plant in Elmore, OH. Workers participated in a BeLPT 
survey in 1992 (Kreiss et al., 1997). Personal lapel samples collected 
during 1990-1992 had a median value of 1.0 [mu]g/m\3\. Kreiss et al. 
reported that 43 (6.9 percent) of 627 workers tested in 1992 were 
sensitized, 6 of whom were diagnosed with CBD (4.4 percent).
    Newman et al. conducted a series of BeLPT screenings of workers at 
a Cullman, AL precision machining facility between 1995 and 1999 
(Newman et al., 2001). Personal lapel samples collected at this plant 
in the early 1980s and in 1995 from all machining processes combined 
had a median of 0.33 [mu]g/m\3\ (Madl et al., 2007). After a sentinel 
case of CBD was diagnosed at the plant in 1995, the company implemented 
engineering and administrative controls and PPE designed to reduce 
workers' beryllium exposures in machining operations. Personal lapel 
samples collected extensively between 1996 and 1999 in machining jobs 
have an overall median of 0.16 [mu]g/m\3\, showing that the new 
controls reduced machinists' exposures during this period. However, the 
results of BeLPT screenings conducted in 1995-1999 showed that the 
exposure control program initiated in 1995 did not sufficiently protect 
workers from beryllium sensitization and CBD. In a group of 60 workers 
who had been employed at the plant for less than a year, and thus would 
not have been working there prior to 1995, 4 (6.7 percent) were found 
to be sensitized. Two of these workers (3.35 percent) were diagnosed 
with CBD. (Newman et al., 2001).
    Sensitization and CBD were studied in a population of workers at a 
Reading, PA copper beryllium plant, where alloys containing a low level 
of beryllium were processed (Schuler et al., 2005). Personal lapel 
samples were collected in production and production support jobs 
between 1995 and May 2000. These samples showed primarily very low 
airborne beryllium levels, with a median of 0.073 [mu]g/m\3\. The wire

[[Page 47656]]

annealing and pickling process had the highest personal lapel sample 
values, with a median of 0.149 [mu]g/m\3\. Despite these low exposure 
levels, a BeLPT screening conducted in 2000 showed that 5, (11.5 
percent) workers of 43 hired after 1992 were sensitized (evaluation for 
CBD not reported). Two of the sensitized workers had been hired less 
than a year before the screening (Thomas et al., 2009).
    In summary, the epidemiological literature on beryllium 
sensitization and CBD that OSHA's risk assessment relied on show 
sensitization prevalences ranging from 6.5 percent to 11.5 percent and 
CBD prevalences ranging from 1.3 percent to 9.7 percent among workers 
who had full-shift exposures well below the current PEL and median 
full-shift exposures at or below the proposed PEL, and whose follow-up 
time was less than 45 years. As referenced earlier, OSHA is interested 
in the risk associated with a 45-year (i.e., working lifetime) 
exposure. Because CBD often develops over the course of years following 
sensitization, the risk of CBD that would result from 45 years' 
occupational exposure to airborne beryllium is likely to be higher than 
the prevalence of CBD observed among these workers.\13\ In either case, 
based on these studies, the risks to workers appear to be significant.
---------------------------------------------------------------------------

    \13\ This point was emphasized by members of the scientific peer 
review panel for OSHA's Preliminary Risk Assessment (see this 
preamble at section VII).
---------------------------------------------------------------------------

    The available epidemiological evidence shows that reducing workers' 
levels of airborne beryllium exposure can substantially reduce risk of 
beryllium sensitization and CBD. The best available evidence on 
effective exposure control programs comes partly from studies of 
programs introduced around 2000 at Reading, Tucson, and Elmore that 
used a combination of engineering controls, dermal and respiratory PPE, 
and stringent housekeeping measures to reduce workers' dermal exposures 
and airborne exposures to levels well below the proposed PEL of 0.2 
[mu]g/m\3\. These programs have substantially lowered the risk of 
sensitization among new workers. As discussed earlier, prevention of 
beryllium sensitization prevents subsequent development of CBD.
    In the Reading, PA copper beryllium plant, full-shift airborne 
exposures in all jobs were reduced to a median of 0.1 [mu]g/m\3\ or 
below and dermal protection was required for production-area workers 
beginning in 2000-2001 (Thomas et al., 2009). After these adjustments 
were made, 2 (5.4 percent) of 37 newly hired workers became sensitized. 
Thereafter, in 2002, the process with the highest exposures (median 0.1 
[mu]g/m\3\) was enclosed and workers involved in that process were 
required to use respiratory protection. As a result, the remaining jobs 
had very low exposures (medians ~ 0.03 [mu]g/m\3\). Among 45 workers 
hired after the enclosure was built and respiratory protection 
instituted, 1 was found to be sensitized (2.2 percent). This is a sharp 
reduction in sensitization from the 11.5 percent of 43 workers, 
discussed above, who were hired after 1992 and had been sensitized by 
the time of testing in 2000.
    In the Tucson beryllium ceramics plant, respiratory and skin 
protection was instituted for all workers in production areas in 2000. 
BeLPT testing done in 2000-2004 showed that only 1 (1 percent) worker 
had been sensitized out of 97 workers hired during that time period 
(Cummings et al., 2007; testing for CBD not reported). This contrasts 
with the prevalence of sensitization in the 1998 Tucson BeLPT 
screening, which found that 6 (9 percent) of 69 workers hired after 
1992 were sensitized (Cummings et al., 2007).
    The modern Elmore facility provides further evidence that combined 
reductions in respiratory exposure (via respirator use) and dermal 
exposure are effective in reducing risk of beryllium sensitization. In 
Elmore, historical beryllium exposures were higher than in Tucson, 
Reading, and Cullman. Personal lapel samples collected at Elmore in 
1990-1992 had a median of 1.0 [micro]g/m\3\. In 1996-1999, the company 
took steps to reduce workers' beryllium exposures, including 
engineering and process controls (Bailey et al., 2010; exposure levels 
not reported). Skin protection was not included in the program until 
after 1999. Beginning in 1999 all new employees were required to wear 
loose-fitting powered air-purifying respirators (PAPR) in manufacturing 
buildings (Bailey et al., 2010). Skin protection became part of the 
protection program for new employees in 2000, and glove use was 
required in production areas and for handling work boots beginning in 
2001. Bailey et al., (2010) compared the occurrence of beryllium 
sensitization and CBD in 2 groups of workers: 1) 258 employees who 
began work at the Elmore plant between January 15, 1993 and August 9, 
1999 (the ``pre-program group'') and were tested in 1997 and 1999, and 
2) 290 employees who were hired between February 21, 2000 and December 
18, 2006 and underwent BeLPT testing in at least one of frequent rounds 
of testing conducted after 2000 (the ``program group''). They found 
that, as of 1999, 23 (8.9 percent) of the pre-program group were 
sensitized to beryllium. The prevalence of sensitization among the 
``program group'' workers, who were hired after the respiratory 
protection and PPE measures were put in place, was around 2-3 percent. 
Respiratory protection and skin protection substantially reduced, but 
did not eliminate, risk of sensitization. Evaluation of sensitized 
workers for CBD was not reported.
    OSHA's preliminary risk assessment also includes analysis of a data 
set provided to OSHA by the National Jewish Research and Medical Center 
(NJMRC). The data set describes a population of 319 beryllium-exposed 
workers at a Cullman, AL machining facility. It includes exposure 
samples collected between 1980 and 2005, and has updated work history 
and screening information for over three hundred workers through 2003. 
Seven (2.2 percent) workers in the data set were reported as sensitized 
only. Sixteen (5.0 percent) workers were listed as sensitized and 
diagnosed with CBD upon initial clinical evaluation. Three (1.0 
percent) workers, first shown to be sensitized only, were later 
diagnosed with CBD. The data set includes workers exposed at airborne 
beryllium levels near the proposed PEL, and extensive exposure data 
collected in workers' breathing zones, as is preferred by OSHA. Unlike 
the Tucson, Reading, and Elmore facilities, respirator use was not 
generally required for workers at the Cullman facility. Thus, analysis 
of this data set shows the risk associated with varying levels of 
airborne exposure, rather than the virtual elimination of airborne 
exposure via respiratory PPE. Also unlike the Tucson, Elmore, and 
Reading facilities, glove use was not reported to be mandatory in the 
Cullman facility. Thus, OSHA believes reductions in risk at the Cullman 
facility to be the result of airborne exposure control, rather than the 
combination of airborne and dermal exposure controls at the Tucson, 
Elmore, and Reading facilities.
    OSHA analyzed the prevalence of beryllium sensitization and CBD 
among workers at the Cullman facility who were exposed to airborne 
beryllium levels at and below the current PEL of 2 [micro]g/m\3\. In 
addition, a statistical modeling analysis of the NJMRC Cullman data set 
was conducted under contract with Dr. Roslyn Stone of the University of 
Pittsburgh Graduate School of Public Heath, Department of 
Biostatistics. OSHA summarizes these analyses briefly below, and in 
more detail in this preamble at section VI, Preliminary Risk 
Assessment.

[[Page 47657]]

    Tables 1 and 2 below present the prevalence of sensitization and 
CBD cases across several categories of lifetime-weighted (LTW) average 
and highest-exposed job (HEJ) exposure at the Cullman facility. The HEJ 
exposure is the exposure level associated with the highest-exposure job 
and time period experienced by each worker. The columns ``Total'' and 
``Total percent'' refer to all sensitized workers in the dataset, 
including workers with and without a diagnosis of CBD.

               Table 1--Prevalence of Sensitization and CBD by Lifetime Weighted Average Exposure Quartile, Cullman, AL Machining Facility
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                            Sensitized
            LTW Average exposure ([mu]g/m\3\)               Group size         only             CBD            Total          Total %          CBD %
--------------------------------------------------------------------------------------------------------------------------------------------------------
0.0-0.080...............................................              91               1               1               2             2.2             1.0
0.081-0.18..............................................              73               2               4               6             8.2             5.5
0.19-0.51...............................................              77               0               6               6             7.8             7.8
0.51-2.15...............................................              78               4               8              12            15.4            10.3
                                                         -----------------------------------------------------------------------------------------------
    Total...............................................             319               7              19              26             8.2             6.0
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: Section VI, Preliminary Risk Assessment.


                  Table 2--Prevalence of Sensitization and CBD by Highest-Exposed Job Exposure Quartile, Cullman, AL Machining Facility
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                            Sensitized
                HEJ Exposure ([mu]g/m\3\)                   Group size         only             CBD            Total          Total %          CBD %
--------------------------------------------------------------------------------------------------------------------------------------------------------
0.0-0.086...............................................              86               1               0               1             1.2             0.0
0.091-0.214.............................................              81               1               6               7             8.6             7.4
0.387-0.691.............................................              76               2               9              11            14.5            11.8
0.954-2.213.............................................              76               3               4               7             9.2             5.3
                                                         -----------------------------------------------------------------------------------------------
    Total...............................................             319               7              19              26             8.2             6.0
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: Section VI, Preliminary Risk Assessment.

    The current PEL of 2 [mu]g/m\3\ is close to the upper bound of the 
highest quartile of LTW average (0.51-2.15 [mu]g/m\3\) and HEJ (0.954-
2.213) exposure levels. In the highest quartile of LTW average 
exposure, there were 12 cases of sensitization (15.4 percent), 
including 8 (10.3 percent) diagnosed with CBD. Notably, the Cullman 
workers had been exposed to beryllium dust for considerably less than 
45 years at the time of testing. A high prevalence of sensitization 
(9.2 percent) and CBD (5.3 percent) is seen in the top quartile of HEJ 
exposure as well, with even higher prevalences in the third quartile 
(0.387-0.691 [mu]g/m\3\).\14\
---------------------------------------------------------------------------

    \14\ This exposure-response pattern is sometimes attributed to a 
``healthy worker effect'' or to exposure misclassification, as 
discussed in this preamble at section VI, Preliminary Risk 
Assessment.
---------------------------------------------------------------------------

    The proposed PEL of 0.2 [mu]g/m\3\ is close to the upper bound of 
the second quartile of LTW average (0.81-0.18 [mu]g/m\3\) and HEJ 
(0.091-0.214 [mu]g/m\3\) exposure levels and to the lower bound of the 
third quartile of LTW average (0.19-0.50 [mu]g/m\3\) exposures. The 
second quartile of LTW average exposure shows a high prevalence of 
beryllium-related health effects, with six workers sensitized (8.2 
percent), of whom four (5.5 percent) were diagnosed with CBD. The 
second quartile of HEJ exposure also shows a high prevalence of 
beryllium-related health effects, with seven workers sensitized (8.6 
percent), of whom 6 (7.4 percent) were diagnosed with CBD. Among six 
sensitized workers in the third quartile of LTW average exposures, all 
were diagnosed with CBD (7.8 percent). The prevalence of CBD among 
workers in these quartiles was approximately 5-8 percent, and overall 
sensitization (including workers with and without CBD) was about 8 
percent. OSHA considers these rates as evidence that the risk of 
developing CBD is significant among workers exposed at and below the 
current PEL, even down to the proposed PEL. Much lower prevalences of 
sensitization and CBD were found among workers with exposure levels 
less than or equal to about 0.08 [mu]g/m\3\. Two sensitized workers 
(2.2 percent), including 1 case of CBD (1.0 percent), were found among 
workers with LTW average exposure levels and HEJ exposure levels less 
than or equal to 0.08 [mu]g/m\3\ and 0.086 [mu]g/m\3\, respectively. 
Strict control of airborne exposure to levels below 0.1 [mu]g/m\3\ can, 
therefore, significantly reduce risk of sensitization and CBD. Although 
OSHA recognizes that maintaining exposure levels below 0.1 [mu]g/m\3\ 
may not be feasible in some operations (see this preamble at section 
IX, Summary of the Preliminary Economic Analysis and Initial Regulatory 
Flexibility Analysis), the Agency believes that workers in facilities 
that meet the proposed action level of 0.1 [mu]g/m\3\ will be at less 
risk of sensitization and CBD than workers in facilities that cannot 
meet the action level.
    Table 3 below presents the prevalence of sensitization and CBD 
cases across cumulative exposure quartiles, based on the same Cullman 
data used to derive Tables 1 and 2. Cumulative exposure is the sum of a 
worker's exposure across the duration of his employment.

[[Page 47658]]



                       Table 3--Prevalence of Sensitization and CBD by Cumulative Exposure Quartile Cullman, AL Machining Facility
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                            Sensitized
          Cumulative exposure ([mu]g/m\3\ yrs)              Group size         only             CBD            Total          Total %          CBD %
--------------------------------------------------------------------------------------------------------------------------------------------------------
0.0-0.147...............................................              81               2               2               4             4.9             2.5
0.148-1.467.............................................              79               0               2               2             2.5             2.5
1.468-7.008.............................................              79               3               8              11            13.9             8.0
7.009-61.86.............................................              80               2               7               9            11.3             8.8
                                                         -----------------------------------------------------------------------------------------------
    Total...............................................             319               7              19              26             8.2             6.0
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: Section VI, Preliminary Risk Assessment.

    A 45-year working lifetime of occupational exposure at the current 
PEL would result in 90 [mu]g/m \3\-years, a value far higher than the 
cumulative exposures of workers in this data set, who worked for 
periods of time less than 45 years and whose exposure levels were 
mostly well below the PEL. Workers with 45 years of exposure to the 
proposed PEL would have a cumulative exposure (9 [mu]g/m \3\-years) in 
the highest quartile for this worker population. As with the average 
and HEJ exposures, the greatest risk of sensitization and CBD appears 
at high exposure levels (> 1.468 [mu]g/m \3\-years). The third 
cumulative quartile, at which a sharp increase in sensitization and CBD 
appears, is bounded by 1.468 and 7.008 [mu]g/m \3\-years. This is 
equivalent to 0.73-3.50 years of exposure at the current PEL of 2 
[mu]g/m \3\, or 7.34-35.04 years of exposure at the proposed PEL of 0.2 
[mu]g/m \3\. Prevalence of both sensitization and CBD is substantially 
lower in the second cumulative quartile (0.148-1.467 [mu]g/m \3\-
years). This is equivalent to approximately 0.7 to 7 years at the 
proposed PEL of 0.2 [mu]g/m \3\, or 1.5 to 15 years at the proposed 
action level of 0.1 [mu]g/m \3\. This supports that maintaining 
exposure levels below the proposed PEL, where feasible, will help to 
protect long-term workers against risk of beryllium sensitization and 
early stage CBD.
    As discussed in the Health Effects section (V.D), CBD often worsens 
with increased time and level of exposure. In a longitudinal study, 
workers initially identified as beryllium sensitized through workplace 
surveillance developed early stage CBD defined by granulomatous 
inflammation but no apparent physiological abnormalities (Newman et 
al., 2005). A study of workers with this early stage CBD showed 
significant declines in breathing capacity and gas exchange over the 30 
years from first exposure (Mroz et al., 2009). Many of the workers went 
on to develop more severe disease that required immunosuppressive 
therapy despite being removed from exposure. While precise beryllium 
exposure levels were not available on the individuals in these studies, 
most started work in the 1980s and 1990s and were likely exposed to 
average levels below the current 2 [mu]g/m \3\ PEL. The evidence for 
time-dependent disease progression indicates that the CBD risk 
estimates for a 45-year lifetime exposure at the current PEL will 
include a higher proportion of individuals with advanced clinical CBD 
than found among the workers in the NJMRC data set.
    Studies of community-acquired (CA) CBD support the occurrence of 
advanced clinical CBD from long-term exposure to airborne beryllium 
(Eisenbud, 1998; Maier et al., 2008). A discussion of the study 
findings can be found in this preamble at section VI.C, Preliminary 
Risk Assessment. For example, one study evaluated 16 potential cases of 
CA-CBD in individuals that resided near a beryllium production facility 
in the years between 1943 and 2001 (Maier et al., 2008). Five cases of 
definite CBD and three cases of probable CBD were found. Two of the 
subjects with probable cases died before they could be confirmed with 
the BeLPT; the third had an abnormal BeLPT and radiography consistent 
with CBD, but granulomatous disease was not pathologically proven. The 
individuals with CA-CBD identified in this study suffered significant 
health impacts from the disease, including obstructive, restrictive, 
and gas exchange pulmonary defects. Six of the eight cases required 
treatment with prednisone, a step typically reserved for severe cases 
due to the adverse side effects of steroid treatment. Despite 
treatment, three had died of respiratory impairment as of 2002. There 
was insufficient information to estimate exposure to the individuals, 
but the limited amount of ambient air sampling in the 1950s suggested 
that average beryllium levels in the area where the cases resided were 
below 2 [mu]g/m \3\. The authors concluded that ``low levels of 
exposures with significant disease latency can result in significant 
morbidity and mortality'' (Maier et al., 2008, p. 1017).
    OSHA believes that the literature review, prevalence analysis, and 
the evidence for time-dependent progression of CBD described above 
provide sufficient information to draw preliminary conclusions about 
significance of risk, and that further quantitative analysis of the 
NJMRC data set is not necessary to support the proposed rule. The 
studies OSHA used to support its preliminary conclusions regarding risk 
of beryllium sensitization and CBD were conducted at modern industrial 
facilities with exposure levels in the range of interest for this 
rulemaking, so a model is not needed to extrapolate risk estimates from 
high to low exposures, as has often been the case in previous rules. 
Nevertheless, the Agency felt further quantitative analysis might 
provide additional insight into the exposure-response relationship for 
sensitization and CBD.
    Using the NJMRC data set, Dr. Stone ran a complementary log-log 
proportional hazards model, an extension of logistic regression that 
allows for time-dependent exposures and differential time at risk. 
Relative risk of sensitization increased with cumulative exposure (p = 
0.05). A positive, but not statistically significant association was 
observed with LTW average exposure (p = 0.09). There was little 
association with highest-exposed job (HEJ) exposure (p = 0.3). 
Similarly, the proportional hazards models for the CBD endpoint showed 
positive relationships with cumulative exposure (p = 0.09), but LTW 
average exposure and HEJ exposure were not closely related to relative 
risk of CBD (p-values > 0.5). Dr. Stone used the cumulative exposure 
models to generate risk estimates for sensitization and CBD.
    Tables 4 and 5 below present risk estimates from these models, 
assuming 5, 10, 20, and 45 years of beryllium exposure. The tables 
present sensitization and CBD risk estimates based on year-specific 
intercepts, as

[[Page 47659]]

explained in the section on Risk Assessment and the accompanying 
background document. Each estimate represents the number of sensitized 
workers the model predicts in a group of 1000 workers at risk during 
the given year with an exposure history at the specified level and 
duration. For example, in the exposure scenario for 1995, if 1000 
workers were occupationally exposed to 2 [mu]g/m \3\ for 10 years, the 
model predicts that about 56 (55.7) workers would be identified as 
sensitized. The model for CBD predicts that about 42 (41.9) workers 
would be diagnosed with CBD that year. The year 1995 shows the highest 
risk estimates generated by the model for both sensitization and CBD, 
while 1999 and 2002 show the lowest risk estimates generated by the 
model for sensitization and CBD, respectively. The corresponding 95 
percent confidence intervals are based on the uncertainty in the 
exposure coefficient.

    Table 4a--Predicted Cases of Sensitization per 1000 Workers Exposed at Current and Alternate PELs Based on Proportional Hazards Model, Cumulative
                    Exposure Metric, With Corresponding Interval Based on the Uncertainty in the Exposure Coefficient. 1995 Baseline.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                      1995                                                                   Exposure duration
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                           5 years                  10 years                  20 years                  45 years
                                                 -------------------------------------------------------------------------------------------------------
          Exposure level  ([mu]g/m\3\)             Cumulative
                                                  ([mu]g/m\3\-  cases/1000  [mu]g/m\3\-   cases/1000  [mu]g/m\3\-   cases/1000  [mu]g/m\3\-   cases/1000
                                                      yrs)                      yrs                       yrs                       yrs
--------------------------------------------------------------------------------------------------------------------------------------------------------
2.0.............................................         10.0         41.1         20.0         55.7         40.0        101.0         90.0        394.4
                                                                 30.3-56.2                30.3-102.9                30.3-318.1                30.3-999.9
1.0.............................................          5.0         35.3         10.0         41.1         20.0         55.7         45.0        116.9
                                                                 30.3-41.3                 30.3-56.2                30.3-102.9                30.3-408.2
0.5.............................................          2.5         32.7          5.0         35.3         10.0         41.1         22.5         60.0
                                                                 30.3-35.4                 30.3-41.3                 30.3-56.2                30.3-119.4
0.2.............................................          1.0         31.3          2.0         32.2          4.0         34.3          9.0         39.9
                                                                 30.3-32.3                 30.3-34.3                 30.3-38.9                 30.3-52.9
0.1.............................................          0.5         30.8          1.0         31.3          2.0         32.2          4.5         34.8
                                                                 30.3-31.3                 30.3-32.3                 30.3-34.3                 30.3-40.1
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: Section VI, Preliminary Risk Assessment.


    Table 4b--Predicted Cases of Sensitization per 1000 Workers Exposed at Current and Alternate PELs Based on Proportional Hazards Model, Cumulative
                    Exposure Metric, With Corresponding Interval Based on the Uncertainty in the Exposure Coefficient. 1999 Baseline.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                      1999                                                                   Exposure duration
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                           5 years                  10 years                  20 years                  45 years
                                                 -------------------------------------------------------------------------------------------------------
           Exposure level ([mu]g/m\3\)             Cumulative
                                                  ([mu]g/m\3\-  cases/1000  [mu]g/m\3\-   cases/1000  [mu]g/m\3\-   cases/1000  [mu]g/m\3\-   cases/1000
                                                      yrs)                      yrs                       yrs                       yrs
--------------------------------------------------------------------------------------------------------------------------------------------------------
2.0.............................................         10.0          8.4         20.0         11.5         40.0         21.3         90.0         96.3
                                                                  6.2-11.6                  6.2-21.7                  6.2-74.4                 6.2-835.4
1.0.............................................          5.0          7.2         10.0          8.4         20.0         11.5         45.0         24.8
                                                                   6.2-8.5                  6.2-11.6                  6.2-21.7                 6.2-100.5
0.5.............................................          2.5          6.7          5.0          7.2         10.0          8.4         22.5         12.4
                                                                   6.2-7.3                   6.2-8.5                  6.2-11.6                  6.2-25.3
0.2.............................................          1.0          6.4          2.0          6.6          4.0          7.0          9.0          8.2
                                                                   6.2-6.6                   6.2-7.0                   6.2-8.0                  6.2-10.9
0.1.............................................          0.5          6.3          1.0          6.4          2.0          6.6          4.5          7.1
                                                                   6.2-6.4                   6.2-6.6                   6.2-7.0                   6.2-8.2
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: Section VI, Preliminary Risk Assessment.


   Table 5a--Predicted Number of Cases of CBD per 1000 Workers Exposed at Current and Alternative PELs Based on Proportional Hazards Model, Cumulative
                    Exposure Metric, With Corresponding Interval Based on the Uncertainty in the Exposure Coefficient. 1995 Baseline.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                      1995                                                                   Exposure duration
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                           5 years                  10 years                  20 years                  45 years
                                                 -------------------------------------------------------------------------------------------------------
           Exposure level ([mu]g/m\3\)             Cumulative    Estimated                Estimated                  Estimated                Estimated
                                                  ([mu]g/m\3\-  cases/1000  [mu]g/m\3\-   cases/1000  [mu]g/m\3\-   cases/1000  [mu]g/m\3\-   cases/1000
                                                      yrs)      (95% c.i.)      yrs       (95% c.i.)      yrs       (95% c.i.)      yrs       (95% c.i.)
--------------------------------------------------------------------------------------------------------------------------------------------------------
2.0.............................................         10.0         30.9         20.0         41.9         40.0         76.6         90.0        312.9
                                                                 22.8-44.0                 22.8-84.3                22.8-285.5                22.8-999.9
1.0.............................................          5.0         26.6         10.0         30.9         20.0         41.9         45.0         88.8
                                                                 22.8-31.7                 22.8-44.0                 22.8-84.3                22.8-375.0

[[Page 47660]]

 
0.5.............................................          2.5         24.6          5.0         26.6         10.0         30.9         22.5         45.2
                                                                 22.8-26.9                 22.8-31.7                 22.8-44.0                 22.8-98.9
0.2.............................................          1.0         23.5          2.0         24.2          4.0         25.8          9.0         30.0
                                                                 22.8-24.3                 22.8-26.0                 22.8-29.7                 22.8-41.3
0.1.............................................          0.5         23.1          1.0         23.5          2.0         24.2          4.5         26.2
                                                                 22.8-23.6                 22.8-24.3                 22.8-26.0                 22.8-30.7
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: Section VI, Preliminary Risk Assessment.


   Table 5b--Predicted Number of Cases of CBD per 1000 Workers Exposed at Current and Alternative PELs Based on Proportional Hazards Model, Cumulative
                    Exposure Metric, With Corresponding Interval Based on the Uncertainty in the Exposure Coefficient. 2002 Baseline.
--------------------------------------------------------------------------------------------------------------------------------------------------------
                      2002                                                                   Exposure duration
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                           5 years                  10 years                  20 years                  45 years
                                                 -------------------------------------------------------------------------------------------------------
           Exposure level ([mu]g/m\3\)             Cumulative    Estimated                Estimated                  Estimated                Estimated
                                                  ([mu]g/m\3\-  cases/1000  [mu]g/m\3\-   cases/1000  [mu]g/m\3\-   cases/1000  [mu]g/m\3\-   cases/1000
                                                      yrs)      (95% c.i.)      yrs       (95% c.i.)      yrs       (95% c.i.)      yrs       (95% c.i.)
--------------------------------------------------------------------------------------------------------------------------------------------------------
2.0.............................................         10.0          3.7         20.0          5.1         40.0          9.4         90.0         43.6
                                                                   2.7-5.3                  2.7-10.4                  2.7-39.2                 2.7-679.8
1.0.............................................          5.0          3.2         10.0          3.7         20.0          5.1         45.0         11.0
                                                                   2.7-3.8                   2.7-5.3                  2.7-10.4                  2.7-54.3
0.5.............................................          2.5          3.0          5.0          3.2         10.0          3.7         22.5          5.5
                                                                   2.7-3.2                   2.7-3.8                   2.7-5.3                  2.7-12.3
0.2.............................................          1.0          2.8          2.0          2.9          4.0          3.1          9.0          3.6
                                                                   2.7-2.9                   2.7-3.1                   2.7-3.6                   2.7-5.0
0.1.............................................          0.5          2.8          1.0          2.8          2.0          2.9          4.5          3.1
                                                                   2.7-2.8                   2.7-2.9                   2.7-3.1                   2.7-3.7
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: Section VI, Preliminary Risk Assessment.

    As shown in Tables 4 and 5, the exposure-response models Dr. Stone 
developed based on the Cullman data set predict a high risk of both 
sensitization (about 96-394 cases per 1000 exposed workers) and CBD 
(about 44-313 cases per 1000) at the current PEL of 2 [mu]g/m\3\ for an 
exposure duration of 45 years (90 [mu]g/m\3\-yr). For a 45-year 
exposure at the proposed PEL of 0.2 [mu]g/m\3\, risk estimates for 
sensitization (about 8-40 cases per 1000 exposed workers) and CBD 
(about 4-30 per 1000 exposed workers) are substantially reduced. Thus, 
the model predicts that the risk of sensitization and CBD at a PEL of 
0.2 [mu]g/m\3\ will be about 10 percent of the risk at the current PEL 
of 2 [mu]g/m\3\.
    OSHA does not believe the risk estimates generated by these 
exposure-response models to be highly accurate. Limitations of the 
analysis include the size of the dataset, relatively sparse exposure 
data from the plant's early years, study size-related constraints on 
the statistical analysis of the dataset, and limited follow-up time on 
many workers. The Cullman study population is a relatively small group 
and can support only limited statistical analysis. For example, its 
size precludes inclusion of multiple covariates in the exposure-
response models or a two-stage exposure-response analysis to model both 
sensitization and the subsequent development of CBD within the 
subpopulation of sensitized workers. The limited size of the Cullman 
dataset is characteristic of studies on beryllium-exposed workers in 
modern, low-exposure environments, which are typically small-scale 
processing plants (up to several hundred workers, up to 20-30 cases).
    Despite these issues with the statistical analysis, OSHA believes 
its main policy determinations are well supported by the best available 
evidence, including the literature review and careful examination of 
the prevalence of sensitization and CBD among workers with exposure 
levels comparable to the current and proposed PELs in the NJMRC data 
set. The previously described literature analysis and prevalence 
analysis demonstrate that workers with occupational exposure to 
airborne beryllium at the current PEL face a risk of becoming 
sensitized to beryllium and progressing to both early and advanced 
stages of CBD that far exceeds the value of 1 in 1000 used by OSHA as a 
benchmark of clearly significant risk. Furthermore, OSHA's preliminary 
risk assessment indicates that risk of beryllium sensitization and CBD 
can be significantly reduced by reduction of airborne exposure levels, 
along with respiratory and dermal protection measures, as demonstrated 
in facilities such as the Tucson ceramics plant, the Elmore beryllium 
production facility, and the Reading copper beryllium facility 
described in the literature review.

[[Page 47661]]

    OSHA's preliminary risk assessment also indicates that despite the 
reduction in risk expected with the proposed PEL, the risk to workers 
with average exposure levels of 0.2 [mu]g/m\3\ is still clearly 
significant (see this preamble at section VI). In the prevalence 
analysis, workers with LTW average or HEJ exposures close to 0.2 [mu]g/
m\3\ experienced high levels of sensitization and CBD. This finding is 
corroborated by the literature analysis, which showed that workers 
exposed to mean plant-wide airborne exposures between 0.1 and 0.5 
[mu]g/m\3\ had a similarly high prevalence of sensitization and CBD. 
Given the significant risk at these levels of exposure, the Agency 
believes that the proposed action level of 0.1 [mu]g/m\3\, dermal 
protection requirements, and other ancillary provisions of the proposed 
rule are key to reducing the risk of beryllium sensitization and CBD 
among exposed workers. OSHA preliminarily concludes that the proposed 
standard, including the PEL of 0.2 [mu]g/m\3\, the action level of 0.1 
[mu]g/m\3\, and provisions to limit dermal exposure to beryllium, 
together will significantly reduce workers' risk of beryllium 
sensitization and CBD from occupational beryllium exposure.
2. Risk of Lung Cancer
    OSHA's review of epidemiological studies of lung cancer mortality 
among beryllium workers found that most did not characterize exposure 
levels sufficiently to characterize risk of lung cancer at the current 
and proposed PELs. However, as discussed in this preamble at section V, 
Health Effects and section VI, Preliminary Risk Assessment, NIOSH 
recently published a quantitative risk assessment based on beryllium 
exposure and lung cancer mortality among 5436 male workers employed at 
beryllium processing plants in Reading, PA; Elmore, OH; and Hazleton, 
PA, prior to 1970 (Schubauer-Berigan et al., 2010b). This new risk 
assessment addresses important sources of uncertainty for previous lung 
cancer analyses, including the sole prior exposure-response analysis 
for beryllium and lung cancer, conducted by Sanderson et al. (2001) on 
workers from the Reading plant alone. Workers from the Elmore and 
Hazleton plants who were added to the analysis by Schubauer-Berigan et 
al. were, in general, exposed to lower levels of beryllium than those 
at the Reading plant. The median worker from Hazleton had a mean 
exposure across his tenure of less than 2 [mu]g/m\3\, while the median 
worker from Elmore had a mean exposure of less than 1 [mu]g/m\3\. The 
Elmore and Hazleton worker populations also had fewer short-term 
workers than the Reading population. Finally, the updated cohorts 
followed the worker populations through 2005, increasing the length of 
follow-up time compared to the previous exposure-response analysis. For 
these reasons, OSHA based its preliminary risk assessment for lung 
cancer on the Schubauer-Berigan risk analysis.
    Schubauer-Berigan et al. (2011) analyzed the data set using a 
variety of exposure-response modeling approaches, described in this 
preamble at section VI, Preliminary Risk Assessment. The authors found 
that lung cancer mortality risk was strongly and significantly related 
to mean, cumulative, and maximum measures of workers' exposure to 
beryllium (all models reported in Schubauer-Berigan et al., 2011). They 
selected the best-fitting models to generate risk estimates for male 
workers with a mean exposure of 0.5 [mu]g/m\3\ (the current NIOSH 
Recommended Exposure Limit for beryllium). In addition, they estimated 
the mean exposure that would be associated with an excess lung cancer 
mortality risk of one in one thousand. At OSHA's request, the authors 
also estimated excess risks for workers with mean exposures at each of 
the other alternate PELs under consideration: 1 [mu]g/m\3\, 0.2 [mu]g/
m\3\, and 0.1 [mu]g/m\3\. Table 6 presents the estimated excess risk of 
lung cancer mortality associated with various levels of beryllium 
exposure allowed under the current rule, based on the final models 
presented in Schubauer-Berigan et al's risk assessment.

      Table 6--Excess Risk of Lung Cancer Mortality per 1000 Male Workers at Alternate PELs (NIOSH Models)
----------------------------------------------------------------------------------------------------------------
                                                                   Mean exposure
                                 -------------------------------------------------------------------------------
     Exposure-response model       0.1 [micro]g/   0.2 [micro]g/   0.5 [micro]g/    1 [micro]g/     2 [micro]g/
                                       m\3\            m\3\            m\3\            m\3\            m\3\
----------------------------------------------------------------------------------------------------------------
Best monotonic PWL--all workers.             7.3              15              45             120             200
Best monotonic PWL--excluding                3.1             6.4              17              39              61
 professional and asbestos
 workers........................
Best categorical--all workers...             4.4               9              25              59             170
Best categorical--excluding                  1.4             2.7             7.1              15              33
 professional and asbestos
 workers........................
Power model--all workers........              12              19              30              40              52
Power model--excluding                        19              30              49              68              90
 professional and asbestos
 workers........................
----------------------------------------------------------------------------------------------------------------
Source: Section VI, Preliminary Risk Assessment.

    The lowest estimate of excess lung cancer deaths from the six final 
models presented by Schubauer-Berigan et al. is 33 per 1000 workers 
exposed at a mean level of 2 [mu]g/m\3\, the current PEL. Risk 
estimates as high as 200 lung cancer deaths per 1000 result from the 
other five models presented. Regardless of the model chosen, the excess 
risk of about 33 to 200 per 1000 workers is clearly significant, 
falling well above the level of risk the Supreme Court indicated a 
reasonable person might consider acceptable (See Benzene, 448 U.S. at 
655). The proposed PEL of 0.2 [mu]g/m\3\ is expected to reduce these 
risks significantly, to somewhere between 2.7-30 excess lung cancer 
deaths per 1000 workers. These risk estimates still fall above the 
threshold of 1 in 1000 that OSHA considers clearly significant. 
However, the Agency believes the lung cancer risks should be regarded 
with a greater degree of uncertainty than the risk estimates for CBD 
discussed previously. While the risk estimates for CBD at the proposed 
PEL were determined from exposure levels observed in occupational 
studies, the lung cancer risks are extrapolated from much higher 
exposure levels.

C. Conclusions

    As discussed above, OSHA used the best available scientific 
evidence to identify adverse health effects of

[[Page 47662]]

occupational beryllium exposure, and to evaluate exposed workers' risk 
of these impairments. The Agency reviewed extensive epidemiological and 
experimental research pertaining to adverse health effects of 
occupational beryllium exposure, including lung cancer, immunological 
sensitization to beryllium, and CBD, and has evaluated the risk of 
these effects from exposures allowed under the current and proposed 
standards. The Agency has, additionally, reviewed previous policy 
determinations and case law regarding material impairment of health, 
and has preliminarily determined that CBD, in all stages, and lung 
cancer constitute material health impairments. Furthermore, OSHA has 
preliminarily determined that long-term exposure to beryllium at the 
current PEL would pose a risk of CBD and lung cancer greater than the 
risk of 1 per 1000 exposed workers the Agency considers clearly 
significant. OSHA's risk assessment for beryllium indicates that 
adoption of the new PEL, action level, and dermal protection provisions 
of the proposed rule will significantly reduce this risk. OSHA 
therefore believes it has met the statutory requirements pertaining to 
significance of risk, consistent with the OSH Act, Supreme Court 
precedent, and the Agency's previous policy decisions.

IX. Summary of the Preliminary Economic Analysis and Initial Regulatory 
Flexibility Analysis

A. Introduction and Summary

    OSHA's Preliminary Economic Analysis and Initial Regulatory 
Flexibility Analysis (PEA) addresses issues related to the costs, 
benefits, technological and economic feasibility, and the economic 
impacts (including impacts on small entities) of this proposed 
respirable beryllium rule and evaluates regulatory alternatives to the 
proposed rule. Executive Orders 13563 and 12866 direct agencies to 
assess all costs and benefits of available regulatory alternatives and, 
if regulation is necessary, to select regulatory approaches that 
maximize net benefits (including potential economic, environmental, and 
public health and safety effects; distributive impacts; and equity), 
unless a statute requires another regulatory approach. Executive Order 
13563 emphasized the importance of quantifying both costs and benefits, 
of reducing costs, of harmonizing rules, and of promoting flexibility. 
The full PEA has been placed in OSHA rulemaking docket OSHA-H005C-2006-
0870. This rule is an economically significant regulatory action under 
Sec. 3(f)(1) of Executive Order 12866 and has been reviewed by the 
Office of Information and Regulatory Affairs in the Office of 
Management and Budget, as required by executive order.
    The purpose of the PEA is to:
     Identify the establishments and industries potentially 
affected by the proposed rule;
     Estimate current exposures and the technologically 
feasible methods of controlling these exposures;
     Estimate the benefits resulting from employers coming into 
compliance with the proposed rule in terms of reductions in cases of 
lung cancer and chronic beryllium disease;
     Evaluate the costs and economic impacts that 
establishments in the regulated community will incur to achieve 
compliance with the proposed rule;
     Assess the economic feasibility of the proposed rule for 
affected industries; and
     Assess the impact of the proposed rule on small entities 
through an Initial Regulatory Flexibility Analysis (IRFA), to include 
an evaluation of significant regulatory alternatives to the proposed 
rule that OSHA has considered.
    The PEA contains the following chapters:

Chapter I. Introduction
Chapter II. Assessing the Need for Regulation
Chapter III. Profile of Affected Industries
Chapter IV. Technological Feasibility
Chapter V. Costs of Compliance
Chapter VI. Economic Feasibility Analysis and Regulatory Flexibility 
Determination
Chapter VII. Benefits and Net Benefits
Chapter VIII. Regulatory Alternatives
Chapter IX. Initial Regulatory Flexibility Analysis

    The PEA includes all of the economic analyses OSHA is required to 
perform, including the findings of technological and economic 
feasibility and their supporting materials required by the OSH Act as 
interpreted by the courts (in Chapters III, IV, V, and VI); those 
required by EO 12866 and EO 13563 (primarily in Chapters III, V, and 
VII, though these depend on material in other chapters); and those 
required by the Regulatory Flexibility Act (in Chapters VI, VIII, and 
IX, though these depend, in part, on materials presented in other 
chapters).
    Key findings of these chapters are summarized below and in sections 
IX.B through IX.I of this PEA summary.
Profile of Affected Industries
    This proposed rule would affect employers and employees in many 
different industries across the economy. As described in Section IX.C 
and reported in Table IX-2 of this preamble, OSHA estimates that a 
total of 35,051 employees in 4,088 establishments are potentially at 
risk from exposure to beryllium.
Technological Feasibility
    As described in more detail in Section IX.D of this preamble and in 
Chapter IV of the PEA, OSHA assessed, for all affected sectors, the 
current exposures and the technological feasibility of the proposed PEL 
of 0.2 [mu]g/m\3\.
    Tables IX-5 in section IX.D of this preamble summarizes all nine 
application groups (industry sectors and production processes) studied 
in the technological feasibility analysis. The technological 
feasibility analysis includes information on current exposures, 
descriptions of engineering controls and other measures to reduce 
exposures, and a preliminary assessment of the technological 
feasibility of compliance with the proposed PELs.
    The preliminary technological feasibility analysis shows that for 
the majority of the job groups evaluated, exposures are either already 
at or below the proposed PEL, or can be adequately controlled with 
additional engineering and work practice controls. Therefore, OSHA 
preliminarily concludes that the proposed PEL of 0.2 [mu]g/m\3\ is 
technologically feasible for most operations most of the time.
    Based on the currently available evidence, it is more difficult to 
determine whether an alternative PEL of 0.1 [mu]g/m\3\ would also be 
feasible in most operations. For some application groups, a PEL of 0.1 
[mu]g/m\3\ would almost certainly be feasible. In other application 
groups, a PEL of 0.1 [mu]g/m\3\ appears feasible, except for 
establishments working with high beryllium content alloys. For 
application groups with the highest exposure, the exposure monitoring 
data necessary to more fully evaluate the effectiveness of exposure 
controls adopted after 2000 are not currently available to OSHA, which 
makes it difficult to determine the feasibility of achieving exposure 
levels at or below 0.1 [mu]g/m\3\.
    OSHA also evaluated the feasibility of a STEL of 2.0 [mu]g/m\3\. 
The majority of the available short-term measurements are below 2.0 
[mu]g/m\3\; therefore OSHA preliminarily concludes that the proposed 
STEL of 2.0 [mu]g/m\3\ can be achieved for most operations most of the 
time. OSHA recognizes that for a small number of tasks, short-term 
exposures may exceed the proposed STEL, even after feasible control 
measures to reduce TWA exposure to below the proposed PEL have been 
implemented, and therefore assumes that the use of

[[Page 47663]]

respiratory protection will continue to be required for some short-term 
tasks. It is more difficult based on the currently available evidence 
to determine whether the alternative STEL of 1.0 [mu]g/m\3\ would also 
be feasible in most operations based on lack of detail in the 
activities of the workers presented in the data. OSHA expects 
additional use of respiratory protection would be required for tasks in 
which peak exposures can be reduced to less than 2.0 [mu]g/m\3\ but not 
less than 1.0 [mu]g/m\3\. Due to limitations in the available sampling 
data and the higher detection limits for short term measurements, OSHA 
could not determine the percentage of the STEL measurements that are 
less than or equal to 0.5 [mu]g/m\3\.
Costs of Compliance
    As described in more detail in Section IX.E and reported, by 
application group and NAICS code, in Table IX-7 of this preamble, the 
total annualized cost of compliance with the proposed standard is 
estimated to be about $37.6 million. The major cost elements associated 
with the revisions to the standard are housekeeping ($12.6 million), 
engineering controls ($9.5 million), training ($5.8 million), and 
medical surveillance ($2.9 million).
    The compliance costs are expressed as annualized costs in order to 
evaluate economic impacts against annual revenue and annual profits, to 
be able to compare the economic impact of the rulemaking with other 
OSHA regulatory actions, and to be able to add and track Federal 
regulatory compliance costs and economic impacts in a consistent 
manner. Annualized costs also represent a better measure for assessing 
the longer-term potential impacts of the rulemaking. The annualized 
costs were calculated by annualizing the one-time costs over a period 
of 10 years and applying a discount rate of 3 percent (and an 
alternative discount rate of 7 percent).
    The estimated costs for the proposed beryllium standard represent 
the additional costs necessary for employers to achieve full 
compliance. They do not include costs associated with current 
compliance that has already been achieved with regard to the new 
requirements or costs necessary to achieve compliance with existing 
beryllium requirements, to the extent that some employers may currently 
not be fully complying with applicable regulatory requirements.
Economic Impacts
    To assess the nature and magnitude of the economic impacts 
associated with compliance with the proposed rule, OSHA developed 
quantitative estimates of the potential economic impact of the new 
requirements on entities in each of the affected industry sectors. The 
estimated compliance costs were compared with industry revenues and 
profits to provide an assessment of the economic feasibility of 
complying with the revised standard and an evaluation of the potential 
economic impacts.
    As described in greater detail in Section IX.F of this preamble and 
in Chapter VI of the PEA, the costs of compliance with the proposed 
rulemaking are not large in relation to the corresponding annual 
financial flows associated with each of the affected industry sectors. 
The estimated annualized costs of compliance represent about 0.11 
percent of annual revenues and about 1.52 percent of annual profits, on 
average, across all affected firms. Compliance costs do not represent 
more than 1 percent of revenues or more than 16.25 percent of profits 
in any affected industry.
    Based on its analysis of the relative inelasticity of demand for 
beryllium-containing inputs and products and of possible international 
trade effects, OSHA concluded that most or all costs arising from this 
proposed beryllium rule would be passed on in higher prices rather than 
absorbed in lost profits and that any price increases would result in 
minimal loss of business to foreign competition.
    Given the minimal potential impact on prices or profits in the 
affected industries, OSHA has preliminarily concluded that compliance 
with the requirements of the proposed rulemaking would be economically 
feasible in every affected industry sector.
Benefits, Net Benefits, and Cost-Effectiveness
    As described in more detail in Section VIII.G of this preamble, 
OSHA estimated the benefits, net benefits, and incremental benefits of 
the proposed beryllium rule. That section also contains a sensitivity 
analysis to show how robust the estimates of net benefits are to 
changes in various cost and benefit parameters. A full explanation of 
the derivation of the estimates presented there is provided in Chapter 
VII of the PEA for the proposed rule.
    OSHA estimated the benefits associated with the proposed beryllium 
PEL of 0.2 [mu]g/m\3\ and, for analytical purposes to comply with OMB 
Circular A-4, with alternative beryllium PELs of .1 [mu]g/m\3\ and .5 
[mu]g/m\3\ by applying the dose-response relationship developed in the 
Agency's preliminary risk assessment--summarized in Section VI of this 
preamble--to current exposure levels. OSHA determined current exposure 
levels by first developing an exposure profile for industries with 
workers exposed to beryllium, using OSHA inspection and site-visit 
data, and then applying this exposure profile to the total current 
worker population. The industry-by-industry exposure profile is 
summarized in Table IX-3 in Section IX.C of this preamble.
    By applying the dose-response relationship to estimates of current 
exposure levels across industries, it is possible to project the number 
of cases of the following diseases expected to occur in the worker 
population given current exposure levels (the ``baseline''):
     fatal cases of lung cancer,
     fatal cases of chronic beryllium disease (CBD), and
     morbidity related to chronic beryllium disease.
    Table IX-1 provides a summary of OSHA's best estimate of the costs 
and benefits of the proposed rule. As shown, the proposed rule, once it 
is fully effective, is estimated to prevent 96 fatalities and 50 non-
fatal beryllium-related illnesses annually, and the monetized 
annualized benefits of the proposed rule are estimated to be $575.8 
million using a 3-percent discount rate and $255.3 million using a 7-
percent discount rate. Also as shown in Table IX-1, the estimated 
annualized cost of the rule is $37.6 million using a 3-percent discount 
rate and $39.1 million using a 7-percent discount rate. The proposed 
rule is estimated to generate net benefits of $538.2 million annually 
using a 3-percent discount rate and $216.2 million annually using a 7-
percent discount rate. The estimated costs and benefits of the proposed 
rule, disaggregated by industry sector, were previously presented in 
Table I-1 in this preamble.

 Table IX-1--Annualized Costs, Benefits and Net Benefits of OSHA's Proposed Beryllium Standard of 0.2 [mu]g/m\3\
----------------------------------------------------------------------------------------------------------------
 
----------------------------------------------------------------------------------------------------------------
Discount Rate................................................                              3%                 7%
                                                                           -------------------------------------

[[Page 47664]]

 
Annualized Costs
    Engineering Controls.....................................                      $9,540,189        $10,334,036
    Respirators..............................................                         249,684            252,281
    Exposure Assessment......................................                       2,208,950          2,411,851
    Regulated Areas and Beryllium Work Areas.................                         629,031            652,823
    Medical Surveillance.....................................                       2,882,076          2,959,448
    Medical Removal..........................................                         148,826            166,054
    Exposure Control Plan....................................                       1,769,506          1,828,766
    Protective Clothing and Equipment........................                       1,407,365          1,407,365
    Hygiene Areas and Practices..............................                         389,241            389,891
    Housekeeping.............................................                      12,574,921         12,917,944
    Training.................................................                       5,797,535          5,826,975
                                                                           -------------------------------------
Total Annualized Costs (Point Estimate)......................                      37,597,325         39,147,434
Annual Benefits: Number of Cases Prevented
    Fatal Lung Cancer........................................          4.0
    CBD-Related Mortality....................................         92.0
    Total Beryllium Related Mortality........................         96.0       $572,981,864       $253,743,368
    Morbidity................................................         49.5          2,844,770          1,590,927
Monetized Annual Benefits (midpoint estimate)................                     575,826,633        255,334,295
Net Benefits.................................................                     538,229,308        216,186,861
----------------------------------------------------------------------------------------------------------------
Source: OSHA, Directorate of Standards and Guidance, Office of Regulatory Analysis.

Initial Regulatory Flexibility Analysis
    OSHA has prepared an Initial Regulatory Flexibility Analysis (IRFA) 
in accordance with the requirements of the Regulatory Flexibility Act, 
as amended in 1996. Among the contents of the IRFA are an analysis of 
the potential impact of the proposed rule on small entities and a 
description and discussion of significant alternatives to the proposed 
rule that OSHA has considered. The IRFA is presented in its entirety 
both in Chapter IX of the PEA and in Section IX.I of this preamble.
    The remainder of this section (Section IX) of the preamble is 
organized as follows:

B. The Need for Regulation
C. Profile of Affected Industry
D. Technological Feasibility Analysis
E. Costs of Compliance
F. Economic Feasibility Analysis and Regulatory Flexibility 
Determination
G. Benefits and Net Benefits
H. Regulatory Alternatives
I. Initial Regulatory Flexibility Analysis.

B. Need for Regulation

    Employees in work environments addressed by the proposed beryllium 
rule are exposed to a variety of significant hazards that can and do 
cause serious injury and death. As described in Chapter II of the PEA 
in support of the proposed rule, the risks to employees are excessively 
large due to the existence of various types of market failure, and 
existing and alternative methods of overcoming these negative 
consequences--such as workers' compensation systems, tort liability 
options, and information dissemination programs--have been shown to 
provide insufficient worker protection.
    After carefully weighing the various potential advantages and 
disadvantages of using a regulatory approach to improve upon the 
current situation, OSHA preliminarily concludes that, in the case of 
beryllium exposure, the proposed mandatory standards represent the best 
choice for reducing the risks to employees. In addition, rulemaking is 
necessary in this case in order to replace older existing standards 
with updated, clear, and consistent health standards.

C. Profile of Affected Industries

1. Introduction
    Chapter III of the PEA presents a profile of industries that use 
beryllium, beryllium oxide, and/or beryllium alloys. The discussion 
below summarizes the findings in that chapter. For each industry sector 
identified, the Agency describes the uses of beryllium and estimates 
the number of establishments and employees that may be affected by this 
proposed rulemaking. Employee exposure to beryllium can also occur as a 
result of certain processes such as welding that are found in many 
industries. OSHA uses the umbrella term ``application group'' to refer 
either to an industrial sector or a cross-industry group with a common 
process. These groups are all mutually exclusive and are analyzed in 
separate sections in Chapter III of the PEA. These sections briefly 
describe each application group and then explain how OSHA estimated the 
number of establishments working with beryllium and the number of 
employees exposed to beryllium. Beryllium is rarely used by all 
establishments in any particular application group because its unique 
properties and relatively high cost typically result in only very 
specific and limited usage within a portion of a group.
    The information in Chapter III of the PEA is based on reports 
prepared under task order by Eastern Research Group (ERG), an OSHA 
contractor; information collected during OSHA's Small Business Advocacy 
Review Panel (OSHA 2008b); and Agency research and analysis. 
Technological feasibility reports (summarized in Chapter IV of the PEA) 
for each beryllium-using application group provide a detailed 
presentation of processes and occupations with beryllium exposure, 
including available sampling exposure measurements and estimates of how 
many employees are affected in each specific occupation.
    OSHA has identified nine application groups that would be 
potentially affected by the proposed beryllium standard:
    1. Beryllium Production
    2. Beryllium Oxide Ceramics and Composites
    3. Nonferrous Foundries
    4. Secondary Smelting, Refining, and Alloying
    5. Precision Turned Products
    6. Copper Rolling, Drawing, and Extruding
    7. Fabrication of Beryllium Alloy Products
    8. Welding
    9. Dental Laboratories
    These application groups are broadly defined, and some include 
establishments in several North

[[Page 47665]]

American Industrial Classification System (NAICS) codes. For example, 
the Copper Rolling and Drawing, and Extruding application group is made 
up both of NAICS 331421 Copper Rolling, Drawing, and Extruding and 
NAICS 331422 Copper Wire Drawing. While an application group may 
contain numerous NAICS six-digit industry codes, in most cases only a 
fraction of the establishments in any individual six-digit NAICS 
industry use beryllium and would be affected by the proposed rule. For 
example, not all companies in the above application group work with 
copper that contains beryllium.
    One application group, welding, reflects industrial activities or 
processes that take place in various industry sectors. All of the 
industries in which a given activity or process may result in worker 
exposure to beryllium are identified in the sections on the application 
group. The section on each application group describes the production 
processes where occupational contact with beryllium can occur and 
contains estimates of the total number of firms, employees, affected 
establishments, and affected employees.
    Chapter III of the PEA presents formulas in the text, usually in 
parentheses, to help explain the derivation of estimates. Because the 
values used in the formulas shown in the text are sometimes rounded, 
while the actual spreadsheet formulas used to create final costs are 
not, the calculation using the presented formula will sometimes differ 
slightly from the total presented in the text--which is the actual 
total as shown in the tables.
    At the end of Chapter III in the PEA, OSHA discusses other industry 
sectors that have reportedly used beryllium in the past or for which 
there are anecdotal or informal reports of beryllium use. The Agency 
was unable to verify beryllium use in these sectors that would be 
affected by the proposed standard, and seeks further information in 
this rulemaking on these or other industries where there may be 
significant beryllium use and employee exposure.
2. Summary of Affected Establishments and Employers
    As shown in Table IX-2, OSHA estimates that a total of 35,051 
workers in 4,088 establishments will be affected by the proposed 
beryllium standard. Also shown are the estimated annual revenues for 
these entities.

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3. Beryllium Exposure Profile of At-Risk Workers
    The technological feasibility analyses presented in Chapter IV of 
the PEA contain data and discussion of worker exposures to beryllium 
throughout industry. Exposure profiles, by job category, were developed 
from individual exposure measurements that were judged to be 
substantive and to contain sufficient accompanying description to allow 
interpretation of the circumstance of each measurement. The resulting 
exposure profiles show the job categories with current overexposures to 
beryllium and, thus, the workers for whom beryllium controls would be 
implemented under the proposed rule.
    Table IX-3 summarizes, from the exposure profiles, the number of 
workers at risk from beryllium exposure and the distribution of 8-hour 
TWA respirable beryllium exposures by affected job category and sector. 
Exposures are grouped into the following ranges: Less than 0.1 [mu]g/
m\3\; >= 0.1 [mu]g/m\3\ and <= 0.2 [mu]g/m\3\; > 0.2 [mu]g/m\3\ and <= 
0.5 [mu]g/m\3\; > 0.5 [mu]g/m\3\ and <= 1.0 [mu]g/m\3\; > 1.0 [mu]g/
m\3\ and <= 2.0 [mu]g/m\3\; and greater than 2.0 [mu]g/m\3\. These 
frequencies represent the percentages of production employees in each 
job category and sector currently exposed at levels within the 
indicated range.
    Table IX-4 presents data by NAICS code on the estimated number of 
workers currently at risk from beryllium exposure, as well as the 
estimated number of workers at risk of beryllium exposure above 0 
[mu]g/m\3\, at or above 0.1 [mu]g/m\3\, at or above 0.2 [mu]g/m\3\, at 
or above 0.5 [mu]g/m\3\, at or above 1.0 [mu]g/m\3\, and at or above 
2.0 [mu]g/m\3\. As shown, an estimated 12,101 workers currently have 
beryllium exposures at or above the proposed action level of 0.1 [mu]g/
m\3\; and an estimated 8,091 workers currently have beryllium exposures 
above the proposed PEL of 0.2 [mu]g/m\3\.

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D. Technological Feasibility Analysis of the Proposed Permissible 
Exposure Limit to Beryllium Exposures

    This section summarizes the technological feasibility analysis 
presented in Chapter IV of the PEA (OSHA, 2014). The technological 
feasibility analysis includes information on current exposures, 
descriptions of engineering controls and other measures to reduce 
exposures, and a preliminary assessment of the technological 
feasibility of compliance with the proposed standard, including a 
reduction in OSHA's permissible exposure limits (PELs) in nine affected 
application groups. The current PELs for beryllium are 2.0 [mu]g/m\3\ 
as an 8-hour time weighted average (TWA), and 5.0 [mu]g/m\3\ as an 
acceptable ceiling concentration. OSHA is proposing a PEL of 0.2 [mu]g/
m\3\ as an 8-hour TWA and is additionally considering alternative TWA 
PELs of 0.1 and 0.5 [mu]g/m\3\. OSHA is also proposing a 15-minute 
short-term exposure limit (STEL) of 2.0 [mu]g/m\3\, and is considering 
alternative STELs of 0.5, 1.0 and 2.5 [mu]g/m\3\.
    The technological feasibility analysis includes nine application 
groups that correspond to specific industries or production processes 
that OSHA has preliminarily determined fall within the scope of the 
proposed standard. Within each of these application groups, exposure 
profiles have been developed

[[Page 47673]]

that characterize the distribution of the available exposure 
measurements by job title or group of jobs. Descriptions of existing 
engineering controls for operations that create sources of beryllium 
exposure, and of additional engineering and work practice controls that 
can be used to reduce exposure are also provided. For each application 
group, a preliminary determination is made regarding the feasibility of 
achieving the proposed permissible exposure limits. For application 
groups in which the median exposures for some jobs exceed the proposed 
TWA PEL, a more detailed analysis is presented by job or group of jobs 
within the application group. The analysis is based on the best 
information currently available to the Agency, including a 
comprehensive review of the industrial hygiene literature, National 
Institute for Occupational Safety and Health (NIOSH) Health Hazard 
Evaluations and case studies of beryllium exposure, site visits 
conducted by an OSHA contractor (Eastern Research Group (ERG)), 
submissions to OSHA's rulemaking docket, and inspection data from 
OSHA's Integrated Management Information System (IMIS). OSHA also 
obtained information on production processes, worker exposures, and the 
effectiveness of existing control measures from the primary beryllium 
producer in the United States, Materion Corporation, and from 
interviews with industry experts.
    The nine application groups included in this analysis were 
identified based on information obtained during preliminary rulemaking 
activities that included a SBRFA panel, a comprehensive review of the 
published literature, stakeholder input, and an analysis of IMIS data 
collected during OSHA workplace inspections where detectable airborne 
beryllium was found. The nine application groups and their 
corresponding section numbers in Chapter IV of the PEA are:
     Section 3--Beryllium Production,
     Section 4--Beryllium Oxide Ceramics and Composites,
     Section 5--Nonferrous Foundries,
     Section 6--Secondary Smelting, Refining, and Alloying,
     Section 7--Precision Turned Products,
     Section 8--Copper Rolling, Drawing, and Extruding,
     Section 9--Fabrication of Beryllium Alloy Products,
     Section 10--Welding, and
     Section 11--Dental Laboratories.
    OSHA developed exposure profiles by job or group of jobs using 
exposure data at the application, operation or task level to the extent 
that such data were available. In those instances where there were 
insufficient exposure data to create a profile, OSHA used analogous 
operations to characterize the operations. The exposure profiles 
represent baseline conditions with existing controls for each operation 
with potential exposure. For job groups where exposures were above the 
proposed TWA PEL of 0.2 [mu]g/m\3\, OSHA identified additional controls 
that could be implemented to reduce employee exposures to beryllium. 
These included engineering controls, such as process containment, local 
exhaust ventilation and wet methods for dust suppression, and work 
practices, such as improved housekeeping and the prohibition of 
compressed air for cleaning beryllium-contaminated surfaces.
    For the purposes of this technological feasibility assessment, 
these nine application groups can be divided into three general 
categories based on current exposure levels:
    (1) application groups in which current exposures for most jobs are 
already below the proposed PEL of 0.2 [mu]g/m\3\;
    (2) application groups in which exposures for most jobs are below 
the current PEL, but exceed the proposed PEL of 0.2 [mu]g/m\3\, and 
therefore additional controls would be required; and
    (3) application groups in which exposures in one or more jobs 
routinely exceed the current PEL, and therefore substantial reductions 
in exposure would be required to achieve the proposed PEL.
    The majority of exposure measurements taken in the application 
groups in the first category are already at or below the proposed PEL 
of 0.2 [mu]g/m\3\, and most of the jobs with exposure to beryllium in 
these four application groups have median exposures below the 
alternative PEL of 0.1 [mu]g/m\3\ (See Table IX-5). These four 
application groups include rolling, drawing, and extruding; fabrication 
of beryllium alloy products; welding; and dental laboratories.
    The two application groups in the second category include: 
precision turned products and secondary smelting. For these two groups, 
the median exposures in most jobs are below the current PEL, but the 
median exposure levels for some job groups currently exceed the 
proposed PEL. Additional exposure controls and work practices could be 
implemented that the Agency has preliminarily concluded would reduce 
exposures to or below the proposed PEL for most jobs most of the time. 
One exception is furnace operations in secondary smelting, in which the 
median exposure exceeds the current PEL. Furnace operations involve 
high temperatures that produce significant amounts of fumes and 
particulate that can be difficult to contain. Therefore, the proposed 
PEL may not be feasible for most furnace operations involved with 
secondary smelting, and in some cases, respiratory protection would be 
required to adequately protect furnace workers when exposures exceed 
0.2 [mu]g/m\3\ despite the implementation of all feasible controls.
    Exposures in the third category of application groups routinely 
exceed the current PEL for several jobs. The three application groups 
in this category include: Beryllium production, beryllium oxide 
ceramics production, and nonferrous foundries. The individual job 
groups for which exposures exceed the current PEL are discussed in the 
application group specific sections later in this summary, and 
described in greater detail in the PEA. For the jobs that routinely 
exceed the current PEL, OSHA identified additional exposure controls 
and work practices that the Agency preliminarily concludes would reduce 
exposures to or below the proposed PEL most of the time, with three 
exceptions: Furnace operations in primary beryllium production and 
nonferrous foundries, and shakeout operations at nonferrous foundries. 
For these jobs, OSHA recognizes that even after installation of 
feasible controls, respiratory protection may be needed to adequately 
protect workers.
    In conclusion, the preliminary technological feasibility analysis 
shows that for the majority of the job groups evaluated, exposures are 
either already at or below the proposed PEL, or can be adequately 
controlled with additional engineering and work practice controls. 
Therefore, OSHA preliminarily concludes that the proposed PEL of 0.2 
[mu]g/m\3\ is feasible for most operations most of the time. The 
preliminary feasibility determination for the proposed PEL is also 
supported by Materion Corporation, the sole primary beryllium 
production company in the U.S., and by the United Steelworkers, who 
jointly submitted a draft proposed standard that specified an exposure 
limit of 0.2 [mu]g/m\3\ to OSHA (Materion and USW, 2012). The 
technological feasibility analysis conducted for each application group 
is briefly summarized below, and a more detailed discussion is 
presented in Sections 3 through 11 of Chapter IV of the PEA (OSHA, 
2014).
    Based on the currently available evidence, it is more difficult to 
determine whether an alternative PEL of

[[Page 47674]]

0.1 [mu]g/m\3\ would also be feasible in most operations. For some 
application groups, such as fabrication of beryllium alloy products, a 
PEL of 0.1 [mu]g/m\3\ would almost certainly be feasible. In other 
application groups, such as precision turned products, a PEL of 0.1 
[mu]g/m\3\ appears feasible, except for establishments working with 
high beryllium content alloys. For application groups with the highest 
exposure, the exposure monitoring data necessary to more fully evaluate 
the effectiveness of exposure controls adopted after 2000 are not 
currently available to OSHA, which makes it difficult to determine the 
feasibility of achieving exposure levels at or below 0.1 [mu]g/m\3\.
    OSHA also evaluated the feasibility of a STEL of 2.0 [mu]g/m\3\, 
and alternative STELs of 0.5 and 1.0 [mu]g/m\3\. An analysis of the 
available short-term exposure measurements indicates that elevated 
exposures can occur during short-term tasks such as those associated 
with the operation and maintenance of furnaces at primary beryllium 
production facilities, at nonferrous foundries, and at secondary 
smelting operations. Peak exposure can also occur during the transfer 
and handling of beryllium oxide powders. OSHA believes that in many 
cases, reducing short-term exposures will be necessary to reduce 
workers' TWA exposures to or below the proposed PEL. The majority of 
the available short-term measurements are below 2.0 [mu]g/m\3\, 
therefore OSHA preliminarily concludes that the proposed STEL of 2.0 
[mu]g/m\3\ can be achieved for most operations most of the time. OSHA 
recognizes that for a small number of tasks, short-term exposures may 
exceed the proposed STEL, even after feasible control measures to 
reduce TWA exposure to below the proposed PEL have been implemented, 
and therefore assumes that the use of respiratory protection will 
continue to be required for some short-term tasks. It is more difficult 
based on the currently available evidence to determine whether the 
alternative STEL of 1.0 [mu]g/m\3\ would also be feasible in most 
operations based on lack of detail in the activities of the workers 
presented in the data. OSHA expects additional use of respiratory 
protection would be required for tasks in which peak exposures can be 
reduced to less than 2.0 [mu]g/m\3\ but not less than 1.0 [mu]g/m\3\. 
Due to limitations in the available sampling data and the higher 
detection limits for short term measurements, OSHA could not determine 
the percentage of the STEL measurements that are less than or equal to 
0.5 [mu]g/m\3\. A detailed discussion of the STELs being considered by 
OSHA is presented in Section 12 of Chapter IV of the PEA (OSHA, 2014).
    OSHA requests available exposure monitoring data and comments 
regarding the effectiveness of currently implemented control measures 
and the feasibility of the PELs under consideration, particularly the 
proposed TWA PEL of 0.2 [mu]g/m\3\, the alternative TWA PEL of 0.1 
[mu]g/m\3\, the proposed STEL of 2.0 [mu]g/m\3\, and the alternative 
STEL of 1.0 [mu]g/m\3\ to inform the Agency's final feasibility 
determinations.
Application Group Summaries
    This section summarizes the technological feasibility analysis for 
each of the nine application groups affected by the proposed standard. 
Chapter IV of the PEA, Technological Feasibility Analysis, identifies 
specific jobs or job groups with potential exposure to beryllium, and 
presents exposure profiles for each of these job groups (OSHA, 2014). 
Control measures and work practices that OSHA believes can reduce 
exposures are described along with preliminary conclusions regarding 
the feasibility of the proposed PEL. Table IX-5, located at the end of 
this summary, presents summary statistics for the personal breathing 
zone samples taken to measure full-shift exposures to beryllium in each 
application group. For the five application groups in which the median 
exposure level for at least one job group exceeds the proposed PEL, the 
sampling results are presented by job group. Table IX-5 displays the 
number of measurements; the range, the mean and the median of the 
measurement results; and the percentage of measurements less than 0.1 
[mu]g/m\3\, less than or equal to the proposed PEL of 0.2 [mu]g/m\3\, 
and less than or equal to the current PEL of 2.0 [mu]g/m\3\. A more 
detailed discussion of exposure levels by job or job group for each 
application group is provided in Chapter IV of the PEA, sections 3 
through 11, along with a description of the available exposure 
measurement data, existing controls, and additional controls that would 
be required to achieve the proposed PEL.
Beryllium Production
    Only one primary beryllium production facility is currently in 
operation in the United States, a plant owned and operated by Materion 
Corporation,\15\ located in Elmore, Ohio. OSHA identified eight job 
groups at this facility in which workers are exposed to beryllium. 
These include: Chemical operations, powdering operations, production 
support, cold work, hot work, site support, furnace operations, and 
administrative work.
---------------------------------------------------------------------------

    \15\ Materion Corporation was previously named Brush Wellman. In 
2011, subsequent to the collection of the information presented in 
this chapter, the name changed. ``Brush Wellman'' is used whenever 
the data being discussed pre-dated the name change.
---------------------------------------------------------------------------

    The Agency developed an exposure profile for each of these eight 
job groups to analyze the distribution of exposure levels associated 
with primary beryllium production. The job exposure profiles are based 
primarily on full-shift personal breathing zone (PBZ) (lapel-type) 
sample results from air monitoring conducted by Brush Wellman's primary 
production facility in 1999 (Brush Wellman, 2004). Starting in 2000, 
the company developed the Materion Worker Protection Program (MWPP), a 
multi-faceted beryllium exposure control program designed to reduce 
airborne exposures for the vast majority of workers to less than an 
internally established exposure limit of 0.2 [mu]g/m\3\. According to 
information provided by Materion, a combination of engineering 
controls, work practices, and housekeeping were used together to reduce 
average exposure levels to below 0.2 [mu]g/m\3\ for the majority of 
workers (Materion Information Meeting, 2012). Also, two operations with 
historically high exposures, the wet plant and pebble plants, were 
decommissioned in 2000, thereby reducing average exposure levels. 
Therefore, the samples taken prior to 2000 may overestimate current 
exposures.
    Additional exposure samples were taken by NIOSH at the Elmore 
facility from 2007 through 2008 (NIOSH, 2011). This dataset, which was 
made available to OSHA by Materion, contains fewer samples than the 
1999 survey. OSHA did not incorporate these samples into the exposure 
profile due to the limited documentation associated with the sampling 
data. The lack of detailed information for individual samples has made 
it difficult for OSHA to correlate job classifications and identify the 
working conditions associated with the samples. Sampling data provided 
by Materion for 2007 and 2008 were not incorporated into the exposure 
profiles because the data lacked specific information on jobs and 
workplace conditions. In a meeting in May 2012 held between OSHA and 
Materion Corporation at the Elmore facility, the Agency was able to 
obtain some general information on the exposure control modifications 
that Materion Corporation made between 1999 and 2007, but has been 
unable to determine what specific

[[Page 47675]]

controls were in place at the time NIOSH conducted sampling (Materion 
Information Meeting, 2012).
    In five of the primary production job groups (i.e., hot work, cold 
work, production support, site support, and administrative work), the 
baseline exposure profile indicates that exposures are already lower 
than the proposed PEL of 0.2 [mu]g/m\3\. Median exposure values for 
these job groups range from nondetectable to 0.08 [mu]g/m\3\.
    For three of the job groups involved with primary beryllium 
production, (i.e., chemical operations, powdering, and furnace 
operations), the median exposure level exceeds the proposed PEL of 0.2 
[mu]g/m\3\. Median exposure values for these job groups are 0.47, 0.37, 
and 0.68 [mu]g/m\3\ respectively, and only 17 percent to 29 percent of 
the available measurements are less than or equal to 0.2 [mu]g/m\3\. 
Therefore, additional control measures for these job groups would be 
required to achieve compliance with the proposed PEL. OSHA has 
identified several engineering controls that the Agency preliminarily 
concludes can reduce exposures in chemical processes and powdering 
operations to less than or equal to 0.2 [mu]g/m\3\. In chemical 
processes, these include fail-safe drum-handling systems, full 
enclosure of drum-handling systems, ventilated enclosures around 
existing drum positions, automated systems to prevent drum overflow, 
and automated systems for container cleaning and disposal such as those 
designed for hazardous powders in the pharmaceutical industry. Similar 
engineering controls would reduce exposures in powdering operations. In 
addition, installing remote viewing equipment (or other equally 
effective engineering controls) to eliminate the need for workers to 
enter the die-loading hood during die filling will reduce exposures 
associated with this powdering task and reduce powder spills. Based on 
the availability of control methods to reduce exposures for each of the 
major sources of exposure in chemical operations, OSHA preliminarily 
concludes that exposures at or below the proposed 0.2 [mu]g/m\3\ PEL 
can be achieved in most chemical and powdering operations most of the 
time. OSHA believes furnace operators' exposures can be reduced using 
appropriate ventilation, including fume capture hoods, and other 
controls to reduce overall beryllium levels in foundries, but is not 
certain whether the exposures of furnace operators can be reduced to 
the proposed PEL with currently available technology. OSHA requests 
additional information on current exposure levels and the effectiveness 
of potential control measures for primary beryllium production 
operations to further refine this analysis.
Beryllium Oxide Ceramics Production
    OSHA identified seven job groups involved with beryllium oxide 
ceramics production. These include: Material preparation operator, 
forming operator, machining operator, kiln operator, production 
support, metallization, and administrative work. Four of these jobs 
(material preparation, forming operator, machining operator and kiln 
operator) work directly with beryllium oxides, and therefore these jobs 
have a high potential for exposure. The other three job groups 
(production support work, metallization, and administrative work) have 
primarily indirect exposure that occurs only when workers in these jobs 
groups enter production areas and are exposed to the same sources to 
which the material preparation, forming, machining and kiln operators 
are directly exposed. However, some production support and 
metallization activities do require workers to handle beryllium 
directly, and workers performing these tasks may at times be directly 
exposed to beryllium.
    The Agency developed exposure profiles for these jobs based on air 
sampling data from four sources: (1) Samples taken between 1994 and 
2003 at a large beryllium oxide ceramics facility, (2) air sampling 
data obtained during a site visit to a primary beryllium oxide ceramics 
producer, (3) a published report that provides information on beryllium 
oxide ceramics product manufacturing for a slightly earlier time 
period, and (4) exposure data from OSHA's Integrated Management 
Information System (OSHA, 2009). The exposure profile indicates that 
the three job groups with mostly indirect exposure (production support 
work, metallization, and administrative work) already achieve the 
proposed PEL of 0.2 [mu]g/m\3\. Median exposure sample values for these 
job groups did not exceed 0.06 [mu]g/m\3\.
    The four job groups with direct exposure had higher exposures. In 
forming operations and machining operations, the median exposure levels 
of 0.18 and 0.15 ug/m\3\, respectively, are below the proposed PEL, 
while the median exposure levels for material preparation and kiln 
operations of 0.41 [mu]g/m\3\ and 0.25 [mu]g/m\3\, respectively, exceed 
the proposed PEL.
    The profile for the directly exposed jobs may overestimate 
exposures due to the preponderance of data from the mid-1990s, a time 
period prior to the implementation of a variety of exposure control 
measures introduced after 2000. In forming operations, 44 percent of 
sample values in the exposure profile exceeded 0.2 ug/m\3\. However, 
the median exposure levels for some tasks, such as small-press and 
large-press operation, based on sampling conducted in 2003 were below 
0.1 [mu]g/m\3\. The exposure profile for kiln operation was based on 
three samples taken from a single facility in 1995, and are all above 
0.2 ug/m\3\. Since then, exposures at the facility have declined due to 
changes in operations that reduced the amount of time kiln operators 
spend in the immediate vicinity of the kilns, as well as the 
discontinuation of a nearby high-exposure process. More recent 
information communicated to OSHA suggests that current exposures for 
kiln operators at the facility are currently below 0.1 ug/m\3\. 
Exposures in machining operations, most of which were already below 0.2 
ug/m\3\ during the 1990s, may have been further reduced since then 
through improved work practices and exposure controls (PEA Chapter IV, 
Section 7). For forming, kiln, and machining operations, OSHA 
preliminarily concludes that the installation of additional controls 
such as machine interlocks (for forming) and improved enclosures and 
ventilation will reduce exposures to or below the proposed PEL most of 
the time. OSHA requests information on recent exposure levels and 
controls in beryllium oxide forming and kiln operations to help the 
Agency evaluate the effectiveness of available exposure controls for 
this application group.
    In the exposure profile for material preparation, 73 percent of 
sample values exceeded 0.2 ug/m\3\. As with other parts of the exposure 
profile, exposure values from the mid-1990s may overestimate airborne 
beryllium levels for current operations. During most material 
preparation tasks, such as material loading, transfer, and spray 
drying, OSHA preliminarily concludes that exposures can be reduced to 
or below 0.2 [mu]g/m\3\ with process enclosures, ventilation hoods, and 
improved housekeeping procedures. However, OSHA acknowledges that peak 
exposures from some short-term tasks such as servicing of the spray 
chamber might continue to drive the TWA exposures above 0.2 [mu]g/m\3\ 
on days when these material preparation tasks are performed. 
Respirators may be needed to protect workers from exposures above the 
proposed TWA PEL

[[Page 47676]]

during these tasks.\16\ OSHA notes that material preparation for 
production of beryllium oxide ceramics currently takes place at only 
two facilities in the United States.
---------------------------------------------------------------------------

    \16\ One facility visited by ERG has reportedly modified this 
process to reduce worker exposures, but OSHA has no data to quantify 
the reduction.
---------------------------------------------------------------------------

Nonferrous Foundries
    OSHA identified eight job groups in aluminum and copper foundries 
with beryllium exposure: Molding, material handling, furnace operation, 
pouring, shakeout operation, abrasive blasting, grinding/finishing, and 
maintenance. The Agency developed exposure profiles based on an air 
monitoring survey conducted by NIOSH in 2007, a Health Hazard 
Evaluation (HHE) conducted by NIOSH in 1975, a site visit by ERG in 
2003, a site visit report from 1999 by the California Cast Metals 
Association (CCMA); and two sets of data from air monitoring surveys 
obtained from Materion in 2004 and 2010.
    The exposure profile indicates that in foundries processing 
beryllium alloys, six of the eight job groups have median exposures 
that exceed the proposed PEL of 0.2 [mu]g/m\3\ with baseline working 
conditions. One exception is grinding/finishing operations, where the 
median value is 0.12 [mu]g/m\3\ and 73 percent of exposure samples are 
below 0.2 [mu]g/m\3\. The other exception is abrasive blasting. The 
samples for abrasive blasting used in the exposure profile were 
obtained during blasting operations using enclosed cabinets, and all 5 
samples were below 0.2 [mu]g/m\3\. Exposures for other job groups 
ranged from just below to well above the proposed PEL, including molder 
(all samples above 0.2 [mu]g/m\3\), material handler (1 sample total, 
above 0.2 [mu]g/m\3\), furnace operator (81.8 percent of samples above 
0.2 [mu]g/m\3\), pouring operator (60 percent of samples above 0.2 
[mu]g/m\3\), shakeout operator (1 sample total, above 0.2 [mu]g/m\3\), 
and maintenance worker (50 percent of samples above 0.2 [mu]g/m\3\).
    In some of the foundries at which the air samples included in the 
exposure profile were collected, there are indications that the 
ventilation systems were not properly used or maintained, and dry 
sweeping or brushing and the use of compressed air systems for cleaning 
may have contributed to high dust levels. OSHA believes that exposures 
in foundries can be substantially reduced by improving and properly 
using and maintaining the ventilation systems; switching from dry 
brushing, sweeping and compressed air to wet methods and use of HEPA-
filtered vacuums for cleaning molds and work areas; enclosing 
processes; automation of high-exposure tasks; and modification of 
processes (e.g., switching from sand-based to alternative casting 
methods). OSHA preliminarily concludes that these additional 
engineering controls and modified work practices can be implemented to 
achieve the proposed PEL most of the time for molding, material 
handling, maintenance, abrasive blasting, grinding/finishing, and 
pouring operations at foundries that produce aluminum and copper 
beryllium alloys.
    The Agency is less confident that exposure can be reliably reduced 
to the proposed PEL for furnace and shakeout operators. Beryllium 
concentrations in the proximity of the furnaces are typically higher 
than in other areas due to the fumes generated and the difficulty of 
controlling emissions during furnace operations. The exposure profile 
for furnace operations shows a median beryllium exposure level of 1.14 
[mu]g/m\3\. OSHA believes that furnace operators' exposures can be 
reduced using local exhaust ventilation and other controls to reduce 
overall beryllium levels in foundries, but it is not clear that they 
can be reduced to the proposed PEL with currently available technology. 
In foundries that use sand molds, the shakeout operation typically 
involves removing the freshly cast parts from the sand mold using a 
vibrating grate that shakes the sand from castings. The shakeout 
equipment generates substantial amounts of airborne dust that can be 
difficult to contain, and therefore shakeout operators are typically 
exposed to high dust levels. During casting of beryllium alloys, the 
dust may contain beryllium and beryllium oxide residues dislodged from 
the casting during the shakeout process. The exposure profile for the 
shakeout operations contains only one result of 1.3 [mu]g/m\3\. This 
suggests that a substantial reduction would be necessary to achieve 
compliance with a proposed PEL of 0.2 [mu]g/m\3\. OSHA requests 
additional information on recent employee exposure levels and the 
effectiveness of dust controls for shakeout operations for copper and 
aluminum alloy foundries.
Secondary Smelting, Refining, and Alloying
    OSHA identified two job groups in this application group with 
exposure to beryllium: Mechanical process operators and furnace 
operations workers. Mechanical operators handle and treat source 
material, and furnace operators run heating processes for refining, 
melting, and casting metal alloy. OSHA developed exposure profiles for 
these jobs based on exposure data from ERG site visits to a precious/
base metals recovery facility and a facility that melts and casts 
beryllium-containing alloys, both conducted in 2003. The available 
exposure data for this application group are limited, and therefore, 
the exposure profile is supplemented in part by summary data presented 
in secondary sources of information on beryllium exposures in this 
application group.
    The exposure profile for mechanical processing operators indicates 
low exposures (3 samples less than 0.2 [mu]g/m\3\), even though these 
samples were collected at a facility where the ventilation system was 
allowing visible emissions to escape exhaust hoods. Summary data from 
studies and reports published in 2005-2009 showed that mechanical 
processing operator exposures averaged between 0.01 and 0.04 [mu]g/m\3\ 
at facilities where mixed or electronic waste including beryllium alloy 
parts were refined. Based on these results, OSHA preliminarily 
concludes that the proposed PEL is already achieved for most mechanical 
processing operations most of the time, and exposures could be further 
reduced through improved ventilation system design and other measures, 
such as process enclosures.
    As with furnace operations examined in other application groups, 
the exposure profile indicates higher worker exposures for furnace 
operators in the secondary smelting, refining, and alloying application 
group (six samples with a median of 2.15 [mu]g/m\3\, and 83.3 percent 
above 0.2 [mu]g/m\3\). The two lowest samples in this job's exposure 
profile (0.03 and 0.5 [mu]g/m\3\) were collected at a facility engaged 
in recycling and recovery of precious metals where work with beryllium-
containing material is incidental. At this facility, the furnace is 
enclosed and fumes are ducted into a filtration system. The four higher 
samples, ranging from 1.92 to 14.08 [mu]g/m\3\, were collected at a 
facility engaged primarily in beryllium alloying operations, where 
beryllium content is significantly higher than in recycling and 
precious metal recovery activities, the furnace is not enclosed, and 
workers are positioned directly in the path of the exhaust ventilation 
over the furnace. OSHA believes these exposures could be reduced by 
enclosing the furnace and repositioning the worker, but is not certain 
whether the reduction achieved would be enough to bring exposures down 
to the proposed PEL. Based on the limited number of samples in the 
exposure profile and surrogate data from furnace operations, the 
proposed PEL

[[Page 47677]]

may not be feasible for furnace work in beryllium recovery and 
alloying, and respirators may be necessary to protect employees 
performing these tasks.
Precision Turned Products
    OSHA's preliminary feasibility analysis for precision turned 
products focuses on machinists who work with beryllium-containing 
alloys. The Agency also examined the available exposure data for non-
machinists and has preliminarily concluded that, in most cases, 
controlling the sources of exposures for machinists will also reduce 
exposures for other job groups with indirect exposure when working in 
the vicinity of machining operations.
    OSHA developed exposure profiles based on exposure data from four 
NIOSH surveys conducted between 1976 and 2008; ERG site visits to 
precision machining facilities in 2002, 2003, and 2004; case study 
reports from six facilities machining copper-beryllium alloys; and 
exposure data collected between 1987 and 2001 by the U.S. Navy 
Environmental Health Center (NEHC). Analysis of the exposure data 
showed a substantial difference between the median exposure level for 
workers machining pure beryllium and/or high-beryllium alloys compared 
to workers machining low-beryllium alloys. Most establishments in the 
precision turned products application group work only with low-
beryllium alloys, such as copper-beryllium. A relatively small number 
of establishments (estimated at 15) specialize in precision machining 
of pure beryllium and/or high-beryllium alloys.
    The exposure profile indicates that machinists working with low-
beryllium alloys have mostly low exposure to airborne beryllium. 
Approximately 85 percent of the 80 exposure results are less than or 
equal to 0.2 [mu]g/m\3\, and 74 percent are less than or equal to 0.1 
[mu]g/m\3\. Some of the results below 0.1 [mu]g/m\3\ were collected at 
a facility where machining operations were enclosed, and metal cutting 
fluids were used to control the release of airborne contaminants. 
Higher results (0.1 [mu]g/m\3\-1.07 [mu]g/m\3\) were found at a 
facility where cutting and grinding operations were conducted in 
partially enclosed booths equipped with LEV, but some LEV was not 
functioning properly. A few very high results (0.77 [mu]g/m\3\-24 
[mu]g/m\3\) were collected at a facility where exposure controls were 
reportedly inadequate and poor work practices were observed (e.g., 
improper use of downdraft tables, use of compressed air for cleaning). 
Based on these results, OSHA preliminarily concludes that exposures 
below 0.2 [mu]g/m\3\ can be achieved most of the time for most 
machinists at facilities dealing primarily with low-beryllium alloys. 
OSHA recognizes that higher exposures may sometimes occur during some 
tasks where exposures are difficult to control with engineering 
methods, such as cleaning, and that respiratory protection may be 
needed at these times.
    Machinists working with high-beryllium alloys have higher exposure 
than those working with low-beryllium alloys. This difference is 
reflected in the exposure profile for this job, where the median of 
exposure is 0.31 [mu]g/m\3\ and 75 percent of samples exceed the 
proposed PEL of 0.2 [mu]g/m\3\. The exposure profile was based on two 
machining facilities at which LEV was used and machining operations 
were performed under a liquid coolant flood. Like most facilities where 
pure beryllium and high-beryllium alloys are machined, these facilities 
also used some combination of full or partial enclosures, as well as 
work practices to minimize exposure such as prohibiting the use of 
compressed air and dry sweeping and implementing dust migration control 
practices to prevent the spread of beryllium contamination outside 
production areas. At one facility machining high-beryllium alloys, 
where all machining operations were fully enclosed and ventilated, 
exposures were mostly below 0.1 [mu]g/m\3\ (median 0.035 [mu]g/m\3\, 
range 0.02-0.11 [mu]g/m\3\). Exposures were initially higher at the 
second facility, where some machining operations were not enclosed, 
existing LEV system were in need of upgrades, and some exhaust systems 
were improperly positioned. Samples collected there in 2003 and 2004 
were mostly below the proposed PEL in 2003 (median 0.1 [mu]g/m\3\) but 
higher in 2004 (median 0.25 [mu]g/m\3\), and high exposure means in 
both years (1.65 and 0.68 [mu]g/m\3\ respectively) show the presence of 
high exposure spikes in the facility. However, the facility reported 
that measures to reduce exposure brought almost all machining exposures 
below 0.2 [mu]g/m\3\ in 2006. With the use of fully enclosed machines 
and LEV and work practices that minimize worker exposures, OSHA 
preliminarily concludes that the proposed PEL is feasible for the vast 
majority of machinists working with pure beryllium and high-beryllium 
alloys. OSHA recognizes that higher exposures may sometimes occur 
during some tasks where exposures are difficult to control with 
engineering methods, such as machine cleaning and maintenance, and that 
respiratory protection may be needed at these times.
Copper Rolling, Drawing, and Extruding
    OSHA's exposure profile for copper rolling, drawing, and extruding 
includes four job groups with beryllium exposure: strip metal 
production, rod and wire production, production support, and 
administrative work. Exposure profiles for these jobs are based on 
personal breathing zone lapel sampling conducted at the Brush Wellman 
Reading, Pennsylvania, rolling and drawing facility from 1977 to 2000.
    Prior to 2000, the Reading facility had limited engineering 
controls in place. Equipment in use included LEV in some operations, 
HEPA vacuums for general housekeeping, and wet methods to control loose 
dust in some rod and wire production operations. The exposure profile 
shows very low exposures for all four job groups. All had median 
exposure values below 0.1 [mu]g/m\3\, and in strip metal production, 
production support, and administrative work, over 90 percent of samples 
were below 0.1 [mu]g/m\3\. In rod and wire production, 70 percent of 
samples were below 0.1 [mu]g/m\3\.
    To characterize exposures in extrusion, OSHA examined the results 
of an industrial hygiene survey of a copper-beryllium extruding process 
conducted in 2000 at another facility. The survey reported eight PBZ 
samples, which were not included in the exposure profile because of 
their short duration (2 hours). Samples for three of the four jobs 
involved with the extrusion process (press operator, material handler, 
and billet assembler) were below the limit of detection (LOD) (level 
not reported). The two samples for the press operator assistant, taken 
when the assistant was buffing, sanding, and cleaning extrusion tools, 
were very high (1.6 and 1.9 [mu]g/m\3\). Investigators recommended a 
ventilated workstation to reduce exposure during these activities.
    In summary, exposures at or below 0.2 [mu]g/m\3\ have already been 
achieved for most jobs in rolling, drawing, and extruding operations, 
and OSHA preliminarily concludes that the proposed PEL of 0.2 [mu]g/
m\3\ is feasible for this application group. For jobs or tasks with 
higher exposures, such as tool refinishing, use of exposure controls 
such as local exhaust ventilation can help reduce workers' exposures. 
The Agency recognizes the limitations of the available data, which were 
drawn from two facilities and did not include full-shift PBZ samples 
for extrusion. OSHA requests additional exposure data from other 
facilities in this application group, especially data from facilities 
where extrusion is performed.

[[Page 47678]]

Fabrication of Beryllium Alloy Products
    This application group includes the fabrication of beryllium alloy 
springs, stampings, and connectors for use in electronics. The exposure 
profile is based on a study conducted at four precision stamping 
companies; a NIOSH report on a spring and stamping company; an ERG site 
visit to a precision stamping, forming, and plating establishment; and 
exposure monitoring results from a stamping facility presented at the 
American Industrial Hygiene Conference and Exposition in 2007. The 
exposure profiles for this application group include three jobs: 
chemical processing operators, deburring operators, and assembly 
operators. Other jobs for which all samples results were below 0.1 
[mu]g/m\3\ are not shown in the profile.
    For the three jobs in the profile, the majority of exposure samples 
were below 0.1 [mu]g/m\3\ (deburring operators, 79 percent; chemical 
processing operators, 81 percent; assembly operators, 93 percent). 
Based on these results, OSHA preliminarily concludes that the proposed 
PEL is feasible for this application group. The Agency notes that a few 
exposures above the proposed PEL were recorded for the chemical 
processing operator (in plating and bright cleaning) and for deburring 
(during corn cob deburring in an open tumbling mill). OSHA believes the 
use of LEV, improved housekeeping, and work practice modifications 
would reduce the frequency of excursions above the proposed PEL.
Welding
    Most of the samples in OSHA's exposure profile for welders in 
general industry were collected between 1994 and 2001 at two of Brush 
Wellman's alloy strip distribution centers, and in 1999 at Brush 
Wellman's Elmore facility. At these facilities, tungsten inert gas 
(TIG) welding was conducted on beryllium alloy strip. Seven samples in 
the exposure profile came from a case study conducted at a precision 
stamping facility, where airborne beryllium levels were very low (see 
previous summary, Fabrication of Beryllium Alloy Products). At this 
facility, resistance welding was performed on copper-beryllium parts, 
and welding processes were automated and enclosed.
    Most of the sample results in the welding exposure profile were 
below 0.2 [mu]g/m\3\. Of the 44 welding samples in the profile, 75 
percent were below 0.2 [mu]g/m\3\ and 64 percent were below 0.1 [mu]g/
m\3\, with most values between 0.01 and 0.05 [mu]g/m\3\. All but one of 
the 16 exposure samples above 0.1 [mu]g/m\3\ were collected in Brush 
Wellman's Elmore facility in 1999. According to company 
representatives, these higher exposure levels may have been due to 
beryllium oxide that can form on the surface of the material as a 
result of hot rolling. All seven samples from the precision stamping 
facility were below the limit of detection. Based on these results, 
OSHA preliminarily concludes that the proposed PEL of 0.2 [mu]g/m\3\ is 
feasible for most welding operations in general industry.
Dental Laboratories
    OSHA's exposure profile for dental technicians includes sampling 
results from a site visit conducted by ERG in 2003; a study of six 
dental laboratories published by Rom et al. in 1984; a data set of 
exposure samples collected between 1987 and 2001, on dental technicians 
working for the U.S. Navy; and a docket submission from CMP Industries 
including two samples from a large commercial dental laboratory using 
nickel-beryllium alloy. Information on exposure controls in these 
facilities suggests that controls in some cases may have been absent or 
improperly used.
    The exposure profile indicates that 52 percent of samples are less 
than or equal to 0.2 [mu]g/m\3\. However, the treatment of 
nondetectable samples in the feasibility analysis may overestimate many 
of the sample values in the exposure profile. Twelve of the samples in 
the profile are nondetectable for beryllium. In the exposure profile, 
these were assigned the highest possible value, the limit of detection 
(LOD). For eight of the nondetectable samples, the LOD was reported as 
0.2 [mu]g/m\3\. For the other four nondetectable samples, the LOD was 
between 0.23 and 0.71 [mu]g/m\3\. If the true values for these four 
nondetectable samples are actually less than or equal to the assigned 
value of 0.2 [mu]g/m\3\, then the true percentage of profile sample 
values less than or equal to 0.2 [mu]g/m\3\ is between 52 and 70 
percent. Of the sample results with detectable beryllium above 0.2 
[mu]g/m\3\, some were collected in 1984 at facilities studied by Rom et 
al., who reported that they occurred during grinding with LEV that was 
improperly used or, in one case, not used at all. Others were collected 
at facilities where little contextual information was available to 
determine what control equipment or work practices might have reduced 
exposures.
    Based on this information, OSHA preliminarily concludes that 
beryllium exposures for most dental technicians are already below 0.2 
[mu]g/m\3\ most of the time. OSHA furthermore believes that exposure 
levels can be reduced to or below 0.1 [mu]g/m\3\ most of the time via 
material substitution, engineering controls, and work practices. 
Beryllium-free alternatives for casting dental appliances are readily 
available from commercial sources, and some alloy suppliers have 
stopped carrying alloys that contain beryllium. For those dental 
laboratories that continue to use beryllium alloys, exposure control 
options include properly designed, installed, and maintained LEV 
systems (equipped with HEPA filters) and enclosures; work practices 
that optimize LEV system effectiveness; and housekeeping methods that 
minimize beryllium contamination in the workplace. In summary, OSHA 
preliminarily concludes that the proposed PEL is feasible for dental 
laboratories.

[[Page 47679]]



                                   Table IX-5--Beryllium Full-Shift PBZ Samples by Application/Job Group ([mu]g/m\3\)
--------------------------------------------------------------------------------------------------------------------------------------------------------
      Application/Job group               N                Range               Mean           Median           %<0.1          %<=0.2          %<=2.0
--------------------------------------------------------------------------------------------------------------------------------------------------------
Be Production Operations (Section
 3)
    Furnace Operations...........             172  0.05 to 254                      3.80            0.68               5              17              82
    Chemical Operations..........              20  0.05 to 9.6                      1.02            0.47               5              15              95
    Powdering Operations.........              72  0.06 to 11.5                     0.82            0.37              11              29              94
    Production Support...........             861  0.02 to 22.7                     0.51            0.08              56              71              94
    Cold Work....................             555  0.04 to 24.9                     0.31            0.08              61              80              98
    Hot Work.....................             297  0.01 to 2.21                     0.12            0.06              69              88              99
    Site Support.................             879  0.05 to 4.22                     0.11            0.05              81              92              99
    Administrative...............             981  0.05 to 4.54                     0.10            0.05              85              94              99
Be Oxide Ceramics (Section 4)
    Material Preparation Operator              77  0.02 to 10.6                     1.01            0.41              13              27              90
    Forming Operator.............             408  0.02 to 53.2                     0.48            0.18              27              56              99
    Machining Operator...........             355  0.01 to 5.0                      0.32            0.15              37              63              98
    Kiln Operator................               3  0.22 to 0.36                     0.28            0.25               0               0             100
    Production Support Worker....             119  0.02 to 7.7                      0.21            0.05              68              88              98
    Metallization Worker.........              36  0.02 to 0.62                     0.15            0.06              55              69             100
    Administrative...............             185  0.02 to 1.2                      0.06            0.05              93              98             100
Aluminum and Copper Foundries
 (Section 5)
    Furnace Operator.............              11  0.2 to 19.76                     4.41            1.14               0              18              64
    Pouring Operator.............               5  0.2 to 2.2                       1.21            1.40               0              40              60
    Shakeout Operator............               1  1.3                              1.30            1.30               0               0             100
    Material Handler.............               1  0.93                             0.93            0.93               0               0             100
    Molder.......................               8  0.24 to 2.29                     0.67            0.45               0               0              88
    Maintenance..................              78  0.05 to 22.71                    0.87            0.21              15              50              96
    Abrasive Blasting Operator...               5  0.05 to 0.15                     0.11            0.12              40             100             100
    Grinding/finishing Operator..              56  0.01 to 4.79                     0.31            0.05              59              73              95
Secondary Smelting (Section 6)
    Furnace operations worker....               6  0.03 to 14.1                     3.85            2.15              17              17              50
    Mechanical processing                       3  0.03 to 0.2                      0.14            0.20              33             100             100
     operator.
Precision Turned Products
 (Section 7)
    High Be Content Alloys.......              80  0.02 to 7.2                      0.72            0.31              14              25              92
    Low Be Content Alloys........              59  0.005 to 24                      0.45            0.01              74              85              96
Rolling, Drawing, and Extruding               650  0.006 to 7.8                     0.11           0.024              86              93              99
 (Section 8)
Alloy Fabrication (Section 9)                  71  0.004 to 0.42                   0.056           0.025              83              94             100
Welding: Beryllium Alloy (Section              44  0.005 to 2.21                    0.19            0.02              64              75              98
 10)
Dental Laboratories (Section 11)               23  0.02 to 4.4                      0.74             0.2              13              52              87
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: OSHA, Directorate of Standards and Guidance, Office of Regulatory Analysis.


[[Page 47680]]

E. Costs of Compliance

    Chapter V of the PEA in support of the proposed beryllium rule 
provides a detailed assessment of the costs to establishments in all 
affected application groups of reducing worker exposures to beryllium 
to an eight-hour time-weighted average (TWA) permissible exposure limit 
(PEL) of 0.2 [mu]g/m\3\ and to the proposed short-term exposure limit 
(STEL) of 2.0 [mu]g/m\3\, as well as of complying with the proposed 
standard's ancillary provisions. OSHA describes its methodology and 
sources in more detail in Chapter V. OSHA's preliminary cost assessment 
is based on the Agency's technological feasibility analysis presented 
in Chapter IV of the PEA; analyses of the costs of the proposed 
standard conducted by OSHA's contractor, Eastern Research Group (ERG); 
and the comments submitted to the docket in response to the request for 
information (RFI) and as part of the SBREFA process.
    As shown in Table IX-7 at the end of this section, OSHA estimates 
that the proposed standard would have an annualized cost of $37.6 
million. All cost estimates are expressed in 2010 dollars and were 
annualized using a discount rate of 3 percent, which--along with 7 
percent--is one of the discount rates recommended by OMB.\17\ 
Annualization periods for expenditures on equipment are based on 
equipment life, and one-time costs are annualized over a 10-year 
period.
---------------------------------------------------------------------------

    \17\ Appendix V-A of the PEA presents costs by NAICS industry 
and establishment size categories using, as alternatives, a 7 
percent discount rate--shown in Table V-A-1--and a 0 percent 
discount rate--shown in Table V-A-2.
---------------------------------------------------------------------------

    The estimated costs for the proposed beryllium rule represent the 
additional costs necessary for employers to achieve full compliance. 
They do not include costs associated with current compliance that may 
already have been achieved with regard to existing beryllium 
requirements or costs necessary to achieve compliance with existing 
beryllium requirements, to the extent that some employers may currently 
not be fully complying with applicable regulatory requirements.
    Throughout this section and in the PEA, OSHA presents cost formulas 
in the text, usually in parentheses, to help explain the derivation of 
cost estimates for individual provisions. Because the values used in 
the formulas shown in the text are shown only to the second decimal 
place, while the actual spreadsheet formulas used to create final costs 
are not limited to two decimal places, the calculation using the 
presented formula will sometimes differ slightly from the presented 
total in the text, which is the actual and mathematically correct total 
as shown in the tables.
1. Compliance With the Proposed PEL/STEL
    OSHA's estimate of the costs for affected employers to comply with 
the proposed PEL of 0.2 [mu]g/m\3\ and the proposed STEL of 2.0 [mu]g/
m\3\ consists of two parts. First, costs are estimated for the 
engineering controls, additional studies and custom design requirements 
to implement those controls, work practices, and specific training 
required for those work practices (as opposed to general training in 
compliance with the rule) needed for affected employers to meet the 
proposed PEL and STEL, as well as opportunity costs (lost productivity) 
that may result from working with some of the new controls. In most 
cases, the PEA breaks out these costs, but in other instances some or 
all of the costs are shortened simply to ``engineering controls'' in 
the text, for convenience. Second, for employers unable to meet the 
proposed PEL and STEL using engineering controls and work practices 
alone, costs are estimated for respiratory protection sufficient to 
reduce worker exposure to the proposed PEL and STEL or below.
    In the technological feasibility analysis presented in Chapter IV 
of the PEA, OSHA concluded that implementing all engineering controls 
and work practices necessary to reach the proposed PEL will, except for 
a small residual group (accounting for about 6 percent of all exposures 
above the STEL), also reduce exposures below the STEL. However, based 
on the nature of the processes this residual group is likely to be 
engaged in, the Agency expects that employees would already be using 
respirators to comply with the PEL under the proposed standard. 
Therefore, with the proposed STEL set at ten times the proposed PEL, 
the Agency has preliminarily determined that engineering controls, work 
practices, and (when needed) respiratory protection sufficient to meet 
the proposed PEL are also sufficient to meet the proposed STEL. For 
that reason, OSHA has taken no additional costs for affected employers 
to meet the proposed STEL. The Agency invites comment and requests that 
the public provide data on this issue.
a. Engineering Controls
    For this preliminary cost analysis, OSHA estimated the necessary 
engineering controls and work practices for each affected application 
group according to the exposure profile of current exposures by 
occupation presented in Chapter III of the PEA. Under the requirements 
of the proposed standard, employers would be required to implement 
engineering or work practice controls whenever beryllium exposures 
exceed the proposed PEL of 0.2 [mu]g/m\3\ or the proposed STEL of 2.0 
[mu]g/m\3\.
    In addition, even if employers are not exposed above the proposed 
PEL or proposed STEL, paragraph (f)(2) of the proposed standard would 
require employers at or above the action level to use at least one 
engineering or work practice control to minimize worker exposure. Based 
on the technological feasibility analysis presented in Chapter IV of 
the PEA, OSHA has determined that, for only two job categories in two 
application groups--chemical process operators in the Stamping, Spring 
and Connection Manufacture application group and machinists in the 
Machining application group--do the majority of facilities at or above 
the proposed action level, but below the proposed PEL, lack the 
baseline engineering or work controls required by paragraph (f)(2). 
Therefore, OSHA has estimated costs, where appropriate, for employers 
in these two application groups to comply with paragraph (f)(2).
    By assigning controls based on application group, the Agency is 
best able to identify those workers with exposures above the proposed 
PEL and to design a control strategy for, and attribute costs 
specifically to, these groups of workers. By using this approach, 
controls are targeting those specific processes, emission points, or 
procedures that create beryllium exposures. Moreover, this approach 
allows OSHA to assign costs for technologies that are demonstrated to 
be the most effective in reducing exposures resulting from a particular 
process.
    In developing cost estimates, OSHA took into account the wide 
variation in the size or scope of the engineering or work practice 
changes necessary to minimize beryllium exposures based on technical 
literature, judgments of knowledgeable consultants, industry observers, 
and other sources. The resulting cost estimates reflect the 
representative conditions for the affected workers in each application 
group and across all work settings. In all but a handful of cases (with 
the exceptions noted in the PEA), all wage costs come from the 2010 
Occupational Employment Statistics (OES) of the Bureau of Labor 
Statistics (BLS, 2010a) and utilize the median wage for the appropriate 
occupation. The wages used include a 30.35 percent markup for fringe 
benefits as a percentage of total

[[Page 47681]]

compensation, which is the average percentage markup for fringe 
benefits for all civilian workers from the 2010 Employer Costs for 
Employee Compensation of the BLS (BLS, 2010b). All descriptions of 
production processes are drawn from the relevant sections of Chapter IV 
of the PEA.
    The specific engineering costs for each of the applications groups, 
and the NAICS industries that contain those application groups, are 
discussed in Chapter V of the PEA. Like the industry profile and 
technological feasibility analysis presented in other PEA chapters, 
Chapter V of the PEA presents engineering control costs for the 
following application groups:

Beryllium Production
Beryllium Oxide, Ceramics & Composites Production
Nonferrous Foundries
Stamping, Spring and Connection Manufacture
Secondary Smelting, Refining, and Alloying
Copper Rolling, Drawing, and Extruding
Secondary Smelting, Refining, and Alloying
Precision Machining
Welding
    Dental Laboratories

    The costs within these application groups are estimated by 
occupation and/or operation. One application group could have multiple 
occupations, operations, or activities where workers are exposed to 
levels of beryllium above the proposed PEL, and each will need its own 
set of controls. The major types of engineering controls needed to 
achieve compliance with the proposed PEL include ventilation equipment, 
pharmaceutical-quality high-containment isolators, decontainment 
chambers, equipment with controlled water sprays, closed-circuit remote 
televisions, enclosed cabs, conveyor enclosures, exhaust hoods, and 
portable local-exhaust-ventilation (LEV) systems. Capital costs and 
annual operation and maintenance (O&M) costs, as well as any other 
annual costs, are estimated for the set of engineering controls 
estimated to be necessary for limiting beryllium exposures for each 
occupation or operation within each application group.
    Tables V-2 through V-10 in Chapter V of the PEA summarize capital, 
maintenance, and operating costs for each application group 
disaggregated by NAICS code. Table IX-7 at the end of this section 
breaks out the costs of engineering controls/work practices by 
application group and NAICS code.
    Some engineering control costs are estimated on a per-worker basis 
and then multiplied by the estimated number of affected workers--as 
identified in Chapter III: Profile of Affected Industries in the PEA--
to arrive at a total cost for a particular control within a particular 
application group. This worker-based method is necessary because--even 
though OSHA has data on the number of firms in each affected industry, 
the occupations and industrial activities that result in worker 
exposure to beryllium, and the exposure profile of at-risk 
occupations--the Agency does not have a way to match up these data at 
the firm level. Nor does the Agency have establishment-specific data on 
worker exposure to beryllium for all establishments, or even 
establishment-specific data on the level of activity involving worker 
exposure to beryllium. Thus, OSHA could not always directly estimate 
per-affected-establishment costs, but instead first had to estimate 
aggregate compliance costs (using an estimated per-worker cost 
multiplied by the number of affected workers) and then calculate the 
average per-affected-establishment costs by dividing those aggregate 
costs by the number of affected establishments. This method, while 
correct on average, may under- or over-state costs for certain firms. 
For other controls that are implemented on a fixed-cost basis per 
establishment (e.g., creating a training program, writing a control 
program), the costs are estimated on an establishment basis, and these 
costs were multiplied by the number of affected establishments in the 
given application group to obtain total control costs.
    In developing cost estimates, the Agency sometimes had to make 
case-specific judgments about the number of workers affected by each 
engineering control. Because work environments vary within occupations 
and across establishments, there are no definitive data on how many 
workers are likely to have their exposures reduced by a given set of 
controls. In the smallest establishments, especially those that might 
operate only one shift per day, some controls would limit exposures for 
only a single worker in one specific affected occupation. More 
commonly, however, several workers are likely to benefit from each 
enhanced engineering control. Many controls were judged to reduce 
exposure for employees in multi-shift work or where workstations are 
used by more than one worker per shift.
    In general, improving work practices involves operator training, 
actual work practice modifications, and better enforcement or 
supervision to minimize potential exposures. The costs of these process 
improvements consist of the supervisor and worker time involved and 
would include the time spent by supervisors to develop a training 
program.
    Unless otherwise specified, OSHA viewed the extent to which 
exposure controls are already in place to be reflected in the 
distribution of exposures at levels above the proposed PEL among 
affected workers. Thus, for example, if 50 percent of workers in a 
given occupation are found to be exposed to beryllium at levels above 
the proposed PEL, OSHA judged this equivalent to 50 percent of 
facilities lacking adequate exposure controls. The facilities may have, 
for example, the correct equipment installed but without adequate 
ventilation to provide protection to workers exposed to beryllium. In 
this example, the Agency would expect that the remaining 50 percent of 
facilities to either have installed the relevant controls to reduce 
beryllium exposures below the PEL or that they engage in activities 
that do not require that the exposure controls be in place (for 
example, they do not perform any work with beryllium-containing 
materials). To estimate the need for incremental controls on a per-
worker basis, OSHA used the exposure profile information as the best 
available data. OSHA recognizes that a very small percentage of 
facilities might have all the relevant controls in place but are still 
unable, for whatever reason, to achieve the proposed PEL through 
controls alone. ERG's review of the industrial hygiene literature and 
other source materials (ERG, 2007b), however, suggest that the large 
majority of workplaces where workers are exposed to high levels of 
beryllium lack at least some of the relevant controls. Thus, in 
estimating the costs associated with the proposed standard, OSHA has 
generally assumed that high levels of exposure to beryllium occur due 
to the absence of suitable controls. This assumption likely results in 
an overestimate of costs since, in some cases, employers may not need 
to install and maintain new controls in order to meet the proposed PEL 
but merely need to upgrade or better maintain existing controls, or to 
improve work practices.
b. Respiratory Protection Costs
    Based on the findings of the technological feasibility analysis, a 
small subset of employees working with a few processes in a handful of 
application groups will need to use respirators, in addition to 
required engineering controls and improved work practices, to reduce 
employee exposures to meet the proposed PEL. Specifically, furnace 
operators--both in non-ferrous foundries (both sand and non-sand) and 
in secondary smelting, refining, and alloying--as well as welders in a 
few other processes, will

[[Page 47682]]

need to wear half-mask respirators. In beryllium production, workers 
who rebuild or otherwise maintain furnaces and furnace tools will need 
to wear full-face powered air-purifying respirators. Finally, the 
Agency recognizes the possibility that, after all feasible engineering 
and other controls are in place, there may still be a residual group 
with potential exposure above the proposed PEL and/or STEL. To account 
for these residual cases, OSHA estimates that 10 percent of the 
workers, across all application groups and job categories, who are 
above the proposed PEL before the beryllium proposed standard is in 
place (according to the baseline exposure profile presented in Chapter 
III of the PEA), would still be above the PEL after all feasible 
controls are implemented and, hence, would need to use half-mask 
respirators to achieve compliance with the proposed PEL.
    There are five primary costs for respiratory protection. First, 
there is a cost per establishment to set up a written respirator 
program in accordance with the respiratory protection standard (29 CFR 
1910.134). The respiratory protection standard requires written 
procedures for the proper selection, use, cleaning, storage, and 
maintenance of respirators. As derived in the PEA, OSHA estimates that, 
when annualized over 10 years, the annualized per-establishment cost 
for a written respirator program is $207.
    For reasons unrelated to the proposed standard, certain 
establishments will already have a respirator program in place. Table 
V-11 in Chapter V of the PEA presents OSHA's estimates, by application 
group, of current levels of compliance with the respirator program 
provision of the proposed rule.
    The four other major costs of respiratory protection are the per-
employee costs for all aspects of respirator use: equipment, training, 
fit-testing, and cleaning. Table V-12 of Chapter V in the PEA breaks 
out OSHA's estimate of the unit costs for the two types of respirators 
needed: A half-mask respirator and a full-face powered air-purifying 
respirator. As derived in the PEA, the annualized per-employee cost for 
a half-mask respirator would be $524 and the annualized per-employee 
cost for a full-face powered air-purifying respirator would be $1,017.
    Table V-13 in Chapter V of the PEA presents the number of 
additional employees, by application group and NAICS code, that would 
need to wear respirators to comply with the proposed standard and the 
cost to industry to comply with the respirator protection provisions in 
the proposed rule. OSHA judges that only workers in Beryllium 
Production work with processes that would require a full-face 
respirator and estimates that there are 23 of those workers. Three 
hundred and eighteen workers in other assorted application groups are 
estimated to need half-mask respirators. A total of 341 employees would 
need to wear some type of respirator, resulting in a total annualized 
cost of $249,684 for affected industries to comply with the respiratory 
protection requirements of the proposed standard. Table IX-7 at the end 
of this section breaks out the costs of respiratory protection by 
application group and NAICS code.
2. Ancillary Provisions
    This section presents OSHA's estimated costs for ancillary 
beryllium control programs required under the proposed rule. Based on 
the program requirements contained in the proposed standard, OSHA 
considered the following cost elements in the following employer 
duties: (a) Assess employees' exposure to airborne beryllium, (b) 
establish regulated areas, (c) develop a written exposure control plan, 
(d) provide protective work clothing, (e) establish hygiene areas and 
practices, (f) implement housekeeping measures, (g) provide medical 
surveillance, (h) provide medical removal for employees who have 
developed CBD or been confirmed positive for beryllium sensitization, 
and (i) provide appropriate training.
    The worker population affected by each program element varies by 
several criteria discussed in detail in each subsection below. In 
general, some elements would apply to all workers exposed to beryllium 
at or above the action level. Other elements would apply to a smaller 
set of workers who are exposed above the PEL. The training requirements 
would apply to all employees who work in a beryllium work area (e.g., 
an area with any level of exposure to airborne beryllium). The 
regulated area program elements triggered by exposures exceeding the 
proposed PEL of 0.2 [mu]g/m\3\ would apply to those workers for whom 
feasible controls are not adequate. In the earlier discussion of 
respiratory protection, OSHA estimated that 10 percent of all affected 
workers with current exposures above the proposed PEL would fall in 
this category.
    Costs for each program requirement are aggregated by employment and 
by industry. For the most part, unit costs do not vary by industry, and 
any variations are specifically noted. The estimated compliance rate 
for each provision of the proposed standard by application group is 
presented in Table V-15 of the PEA.
a. Exposure Assessment
    Most establishments wishing to perform exposure monitoring would 
require the assistance of an outside consulting industrial hygienist 
(IH) to obtain accurate results. While some firms might already employ 
or train qualified staff, OSHA judged that the testing protocols are 
fairly challenging and that few firms have sufficiently skilled staff 
to eliminate the need for outside consultants.
    The proposed standard requires that, after receiving the results of 
any exposure monitoring where exposures exceed the TWA PEL or STEL, the 
employer notify each such affected employee in writing of suspected or 
known sources of exposure, and the corrective action(s) being taken to 
reduce exposure to or below the PEL. Those workers exposed at or above 
the action level and at or below the PEL must have their exposure 
levels monitored annually.
    For costing purposes, OSHA estimates that, on average, there are 
four workers per work area. OSHA interpreted the initial exposure 
assessment as requiring first-year testing of at least one worker in 
each distinct job classification and work area who is, or may 
reasonably be expected to be, exposed to airborne concentrations of 
beryllium at or above the action level.
    The proposed standard requires that whenever there is a change in 
the production, process, control equipment, personnel, or work 
practices that may result in new or additional exposures, or when the 
employer has any reason to suspect that a change may result in new or 
additional exposures, the employer must conduct additional monitoring. 
The Agency has estimated that this provision would require an annual 
sampling of 10 percent of the affected workers.
    OSHA estimates that an industrial hygienist (IH) would spend 1 day 
each year to sample 2 workers, for a per worker IH fee of $257. This 
exposure monitoring requires that three samples be taken per worker: 
One TWA and two STEL for an annual IH fee per sample of $86. Based on 
the 2000 EMSL Laboratory Testing Catalog (ERG, 2007b), OSHA estimated 
that analysis of each sample would cost $137 in lab fees. When combined 
with the IH fee, OSHA estimated the annual cost to obtain a TWA sample 
to be $223 per sampled worker and the annual cost to obtain the two 
STEL samples to be $445 per sampled worker. The direct exposure 
monitoring unit costs are

[[Page 47683]]

summarized in Table V-16 in Chapter V of the PEA.
    The cost of the sample also incorporates a productivity loss due to 
the additional time for the worker to participate in the sampling (30 
minutes per worker sampled) as well as for the associated recordkeeping 
time incurred by a manager (15 minutes per worker sampled). The STEL 
samples are assumed to be taken along with the TWA sample and, thus, 
labor costs were not added to both unit costs. Including the costs 
related to lost productivity, OSHA estimates the total annual cost of a 
TWA sample to be $251, and 2 STEL samples, $445. The total annual cost 
per worker for all sampling taken is then $696. OSHA estimates the 
total annualized cost of this provision to be $2,208,950 for all 
affected industries. The annualized cost of this provision for each 
affected NAICS industry is shown in Table IX-6.
b. Beryllium Work Areas and Regulated Areas
    The proposed beryllium standard requires the employer to establish 
and maintain a regulated area wherever employees are, or can reasonably 
expected to be, exposed to airborne beryllium at levels above the TWA 
PEL or STEL. Regulated areas require specific provisions that both 
limit employee exposure within its boundaries and curb the migration of 
beryllium outside the area. The Agency judged, based on the preliminary 
findings of the technological feasibility analysis, that companies can 
reduce establishment-wide exposure by ensuring that only authorized 
employees wearing proper protective equipment have access to areas of 
the establishment where such higher concentrations of beryllium exist, 
or can be reasonably expected to exist. Workers in other parts of the 
establishment are also likely to see a reduction in beryllium exposures 
due to these measures since fewer employees would be traveling through 
regulated areas and subsequently carrying beryllium residue to other 
work areas on their clothes and shoes.
    Requirements in the proposed rule for a regulated area include: 
Demarcating the boundaries of the regulated area as separate from the 
rest of the workplace, limiting access to the regulated area, providing 
an appropriate respirator to each person entering the regulated area 
and other protective clothing and equipment as required by paragraph 
(g) and paragraph (h), respectively.
    OSHA estimated that the total annualized cost per regulated area, 
including set-up costs ($76), respirators ($1,768) and protective 
clothing ($4,500), is $6,344.
    When establishments are in full compliance with the standard, 
regulated areas would be required only for those workers for whom 
controls could not feasibly reduce their exposures to or below the 0.2 
[mu]g/m\3\ TWA PEL and the 2 [mu]g/m\3\ STEL. Based on the findings of 
the technological feasibility analysis, OSHA estimated that 10 percent 
of the affected workers would be exposed above the TWA PEL or STEL 
after implementation of engineering controls and thus would require 
regulated areas (with one regulated area, on average, for every four 
workers exposed above the proposed TWA PEL or STEL).
    The proposed standard requires that all beryllium work areas are 
adequately established and demarcated. ERG estimated that one work area 
would need to be established for every 12 at-risk workers. OSHA 
estimates that the annualized cost would be $33 per work area.
    OSHA estimates the total annualized cost of the regulated areas and 
work areas is $629,031 for all affected industries. The cost for each 
affected application group and NAICS code is shown in Table IX-6.
c. Written Exposure Control Plan
    The proposed standard requires that employers must establish and 
maintain a written exposure control plan for beryllium work areas. The 
written program must contain:
    1. An inventory of operations and job titles reasonably expected to 
have exposure.
    2. An inventory of operations and job titles reasonably expected to 
have exposure at or above the action level.
    3. An inventory of operations and job titles reasonably expected to 
have exposure above the TWA PEL or STEL.
    4. Procedures for minimizing cross-contamination, including but not 
limited to preventing the transfer of beryllium between surfaces, 
equipment, clothing, materials and articles within beryllium work 
areas.
    5. Procedures for keeping surfaces in the beryllium work area free 
as practicable of beryllium.
    6. Procedures for minimizing the migration of beryllium from 
beryllium work areas to other locations within or outside the 
workplace.
    7. An inventory of engineering and work practice controls required 
by paragraph (f)(2) of this standard.
    8. Procedures for removal, laundering, storage, cleaning, 
repairing, and disposal of beryllium-contaminated personal protective 
clothing and equipment, including respirators.
    The unit cost estimates take into account the judgment that (1) 
most establishments have an awareness of beryllium risks and, thus, 
should be able to develop or modify existing safeguards in an 
expeditious fashion, and (2) many operations have limited beryllium 
activities and these establishments need to make only modest changes in 
procedures to create the necessary exposure control plan. ERG's experts 
estimated that managers would spend eight hours per establishment to 
develop and implement such a written exposure control plan, yielding a 
total cost per establishment to develop and implement the written 
control plan of $563.53 and an annualized cost of $66. In addition, 
because larger firms with more affected workers will need to develop 
more complicated written control plans, the development of a plan would 
require an extra thirty minutes of a manager's time per affected 
employee, for a cost of $35 per affected employee and an annualized 
cost of $4 per employee. Managers would also need 12 minutes (0.2 
hours) per affected employee per quarter, or 48 minutes per affected 
employee per year to review and update the plan, for a recurring cost 
of $56 per affected employee per year to maintain and update the plan. 
Five minutes of clerical time would also be needed per employee for 
providing each employee with a copy of the written exposure control 
plan--yielding an annualized cost of $2 per employee. The total annual 
per-employee cost for development, implementation, review, and update 
of a written exposure control plan is then $62. The Agency estimates 
the total annualized cost of this provision to be $1,769,506 for all 
affected establishments. The breakdown of these costs by application 
group and NAICS code is presented in Table IX-6.
d. Personal Protective Clothing and Equipment
    The proposed standard requires personal protective clothing and 
equipment for workers:
    1. Whose exposure can reasonably be expected to exceed the TWA PEL 
or STEL.
    2. When work clothing or skin may become visibly contaminated with 
beryllium, including during maintenance and repair activities or during 
non-routine tasks.
    3. Where employees' skin can reasonably be expected to be exposed 
to soluble beryllium compounds.
    OSHA has determined that it would be necessary for employers to 
provide reusable overalls and/or lab coats at a

[[Page 47684]]

cost of $284 and $86, respectively, for operations in the following 
application groups:

Beryllium Production
Beryllium Oxide, Ceramics & Composites
Nonferrous Foundries
Fabrication of Beryllium Alloy Products
Copper Rolling, Drawing & Extruding
Secondary Smelting, Refining and Alloying
Precision Turned Products
Dental Laboratories

    Chemical process operators in the spring and stamping application 
group would require chemical resistant protective clothing at an annual 
cost of $849. Gloves and/or shoe covers would be required when 
performing operations in several different application groups, 
depending on the process being performed, at an annual cost of $50 and 
$78, respectively.
    The proposed standard requires that all reusable protective 
clothing and equipment be cleaned, laundered, repaired, and replaced as 
needed to maintain their effectiveness. This includes such safeguards 
as transporting contaminated clothing in sealed and labeled impermeable 
bags and informing any third party businesses coming in contact with 
such materials of the risks associated with beryllium exposure. OSHA 
estimates that the lowest cost alternative to satisfy this provision is 
for an employer to rent and launder reusable protective clothing--at an 
estimated annual cost per employee of $49. Ten minutes of clerical time 
would also be needed per establishment with laundry needs to notify the 
cleaners in writing of the potentially harmful effects of beryllium 
exposure and how the protective clothing and equipment must be handled 
in accordance with this standard--at a per establishment cost of $3.
    The Agency estimates the total annualized cost of this provision to 
be $1,407,365 for all affected establishments. The breakdown of these 
costs by application group and NAICS code is shown in Table IX-6.
e. Hygiene Areas and Practices
    The proposed standard requires employers to provide readily 
accessible washing facilities to remove beryllium from the hands, face, 
and neck of each employee working in a beryllium work area and also to 
provide a designated change room in workplaces where employees would 
have to remove their personal clothing and don the employer-provided 
protective clothing. The proposed standard also requires that employees 
shower at the end of the work shift or work activity if the employee 
reasonably could have been exposed to beryllium at levels above the PEL 
or STEL, and if those exposures could reasonably be expected to have 
caused contamination of the employee's hair or body parts other than 
hands, face, and neck.
    In addition to other forms of PPE costed previously, for processes 
where hair may become contaminated, head coverings can be purchased at 
an annual cost of $28 per employee. This could satisfy the requirement 
to avoid contaminated hair. If workers are covered by protective 
clothing such that no body parts (including their hair where necessary, 
but not including their hands, face, and neck) could reasonably be 
expected to have been contaminated by beryllium, and they could not 
reasonably be expected to be exposed to beryllium while removing their 
protective clothing, they would not need to shower at the end of a work 
shift or work activity. OSHA notes that some facilities already have 
showers, and the Agency judges that all employers either already have 
showers where needed or will have sufficient measures in place to 
ensure that employees could not reasonably be expected to be exposed to 
beryllium while removing protective clothing. Therefore, OSHA has 
preliminarily determined that employers will not need to provide any 
new shower facilities to comply with the standard.
    The Agency estimated the costs for the addition of a change room 
and segregated lockers based on the costs for acquisition of portable 
structures. The change room is presumed to be used in providing a 
transition zone from general working areas into beryllium-using 
regulated areas. OSHA estimated that portable building, adequate for 10 
workers per establishment can be rented annually for $3,251, and that 
lockers could be procured for a capital cost of $407--or $48 
annualized--per establishment. This results in an annualized cost of 
$3,299 per facility to rent a portable change room with lockers. OSHA 
estimates that the 10 percent of affected establishments unable to meet 
the proposed TWA PEL would require change rooms. The Agency estimated 
that a worker using a change room would need 2 minutes per day to 
change clothes. Assuming 250 days per year, this annual time cost for 
changing clothes is $185 per employee.
    The Agency estimates the total annualized cost of the provision on 
hygiene areas and practices to be $389,241 for all affected 
establishments. The breakdown of these costs by application group and 
NAICS code can be seen in Table IX-6.
f. Housekeeping
    The proposed rule specifies requirements for cleaning and disposing 
of beryllium-contaminated wastes. The employer shall maintain all 
surfaces in beryllium work areas as free as practicable of 
accumulations of beryllium and shall ensure that all spills and 
emergency releases of beryllium are cleaned up promptly, in accordance 
with the employer's written exposure control plan and using a HEPA-
filtered vacuum or other methods that minimize the likelihood and level 
of exposure. The employer shall not allow dry sweeping or brushing for 
cleaning surfaces in beryllium work areas unless HEPA-filtered 
vacuuming or other methods that minimize the likelihood and level of 
exposure have been tried and were not effective.
    ERG's experts estimated that each facility would need to purchase a 
single vacuum at a cost of $2,900 for every five affected employees in 
order to successfully integrate housekeeping into their daily routine. 
The per-employee cost would be $580, resulting in an annualized cost of 
$68 per worker. ERG's experts also estimated that all affected workers 
would require an additional five minutes per work day (.083 hours) to 
complete vacuuming tasks and to label and dispose of beryllium-
contaminated waste. While this allotment is modest, OSHA judged that 
the steady application of this incremental additional cleaning, when 
combined with currently conducted cleaning, would be sufficient in 
average establishments to address dust or surface contamination 
hazards. Assuming that these affected workers would be working 250 days 
per year, OSHA estimates that the annual labor cost per employee for 
additional time spent cleaning in order to comply with this provision 
is $462.
    The proposed standard requires each disposal bag with contaminated 
materials to be properly labeled. ERG estimated a cost of 10 cents per 
label with one label needed per day for every five workers. With the 
disposal of one labeled bag each day and 250 working days, the per-
employee annual cost would be $5. The annualized cost of a HEPA-
filtered vacuum, combined with the additional time needed to perform 
housekeeping and the labeling of disposal bags, results in a total 
annualized cost of $535 per employee.
    The Agency estimates the total annualized cost of this provision to 
be $12,574,921 for all affected establishments. The breakdown of these 
costs by application group and NAICS code is shown in Table IX-6.

[[Page 47685]]

g. Medical Surveillance
    The proposed standard requires the employer to make medical 
surveillance available at no cost to the employee, and at a reasonable 
time and place, for the following employees:
    1. Employees who have worked in a regulated area for more than 30 
days in the last 12 months
    2. Employees showing signs or symptoms of chronic beryllium disease 
(CBD)
    3. Employees exposed to beryllium during an emergency; and
    4. Employees exposed to airborne beryllium above 0.2 [mu]g/m\3\ for 
more than 30 days in a 12-month period for 5 years or more.
    As discussed in the regulated areas section of this analysis of 
program costs, the Agency estimates that approximately 10 percent of 
affected employees would have exposure in excess of the PEL after the 
standard goes into effect and would therefore be placed in regulated 
areas. The Agency further estimates that a very small number of 
employees will be affected by emergencies in a given year, likely less 
than 0.1 percent of the affected population, representing a small 
additional cost. The number of workers who would suffer signs and 
symptoms of CBD after the rule takes effect is difficult to estimate, 
but would likely substantially exceed those with actual cases of CBD.
    While the symptoms of CBD vary greatly, the first to appear are 
usually chronic dry cough (generally defined as a nonproductive cough, 
without phlegm or sputum, lasting two months or more) and shortness of 
breath during exertion. Ideally, in developing these costs estimates, 
OSHA would first estimate the percent of affected workers who might be 
presenting with a chronic cough and/or experiencing shortness of 
breath.
    Studies have found the prevalence of a chronic cough ranging from 
10 to 38 percent across various community populations, with smoking 
accounting for up to 18 percent of cough prevalence (Irwin, 1990; 
Barbee, 1991). However, these studies are over 20 years old, and the 
number of smokers has decreased substantially since then. It's also not 
clear whether the various segments of the U.S. population studied are 
similar enough to the population of workers exposed to beryllium such 
that results of these studies could be generalized to the affected 
worker population.
    A more recent study from a plant in Cullman, Alabama that works 
with beryllium alloy found that about five percent of employees said 
they were current smokers, with roughly 52 percent saying they were 
previous smokers and approximately 43 percent stating they had never 
smoked (Newman et al., 2001). This study does not, however, report on 
the prevalence of chronic cough in this workplace.
    OSHA was unable to identify any studies on the general prevalence 
of the other common early symptom of CBD, shortness of breath. Lacking 
any better data to base an estimate on, the Agency used the studies 
cited above (Irwin, 1990; Barbee, 1991) showing the prevalence of 
chronic cough in the general population, adjusted to account for the 
long term decrease in smoking prevalence (and hence, the amount of 
overall cases of chronic cough), and estimated that 15 percent of the 
worker population with beryllium exposure would exhibit a chronic cough 
or other sign or symptom of CBD that would trigger medical 
surveillance. The Agency welcomes comment and further data on this 
question.
    According to the proposed rule, the initial (baseline) medical 
examination would consist of the following:
    1. A medical and work history, with emphasis on past and present 
exposure, smoking history and any history of respiratory system 
dysfunction;
    2. A physical examination with emphasis on the respiratory tract;
    3. A physical examination for skin breaks and wounds;
    4. A pulmonary function test;
    5. A standardized beryllium lymphocyte proliferation test (BeLPT) 
upon the first examination and within every two years from the date of 
the first examination until the employee is confirmed positive for 
beryllium sensitization;
    6. A CT scan, offered every two years for the duration of the 
employee's employment, if the employee was exposed to airborne 
beryllium at levels above 0.2 [mu]g/m\3\ for more than 30 days in a 12-
month period for at least 5 years. This obligation begins on the start-
up date of this standard, or on the 15th year after the employee's 
first exposure above for more than 30 days in a 12-month period, 
whichever is later; and
    7. Any other test deemed appropriate by the Physician or other 
Licensed Health Care Professional (PLHCP).
    Table V-17 in Chapter V of the PEA lists the direct unit costs for 
initial medical surveillance activities including: Work and medical 
history, physical examination, pulmonary function test, BeLPT, CT scan, 
and costs of additional tests. In OSHA's cost model, all of the 
activities will take place during an employee's initial visit and on an 
annual basis thereafter and involve a single set of travel costs, 
except that: (1) The BeLPT tests will only be performed at two-year 
intervals after the initial test, but will be conducted in conjunction 
with the annual general examination (no additional travel costs); and 
(2) the CT scans will typically involve different specialists and are 
therefore treated as separate visits not encompassed by the general 
exams (therefore requiring separate travel costs). Not all employees 
would require CT scans, and employers would only be required to offer 
them every other year.
    In addition to the fees for the annual medical exam, employers may 
also incur costs for lost work time when their employees are 
unavailable to perform their jobs. This includes time for traveling, a 
health history review, the physical exam, and the pulmonary function 
test. Each examination would require 15 minutes (or 0.25 hours) of a 
human resource manager's time for recording the results of the exam and 
tests and the PLHCP's written opinion for each employee and any 
necessary post-exam consultation with the employee. There is also a 
cost of 15 minutes of supervisor time to provide information to the 
physician, five minutes of supervisor time to process a licensed 
physician's written medical opinion, and five minutes for an employee 
to receive a licensed physician's written medical opinion. The total 
unit annual cost for the medical examinations and tests, excluding the 
BeLPT test, and the time required for both the employee and the 
supervisor is $297.
    The estimated fee for the BeLPT is $259. With the addition of the 
time incurred by the worker to undergo the test, the total cost for a 
BeLPT is $261. The standard requires a biennial BeLPT for each employee 
covered by the medical surveillance provision, so most workers would 
receive between two and five BeLPT tests over a ten year period 
(including the BeLPT performed during the initial examination), 
depending on whether the results of these tests were positive. OSHA 
therefore estimates a net present value (NPV) of $1,417 for all five 
tests. This NPV annualized over a ten year period is $166.
    Together, the annualized net present value of the BeLPT and the 
annualized cost of the remaining medical surveillance produce an annual 
cost of $436 per employee.
    The proposed standard requires that a helical tomography (CT scan) 
be offered to employees exposed to airborne beryllium above 0.2 [mu]g/
m\3\ for more than 30 days in a 12-month period, for a period of 5 
years or more. The five years

[[Page 47686]]

do not need to be consecutive, and the exposure does not need to occur 
after the effective date of the standard. The CT scan shall be offered 
every 2 years starting on the 15th year after the first year the 
employee was exposed above 0.2 [mu]g/m\3\ for more than 30 days in a 
12-month period, for the duration of their employment. The total yearly 
cost for biennial CT scans consists of medical costs totaling $1,020, 
comprised of a $770 fee for the scan and the cost of a specialist to 
review the results, which OSHA estimates would cost $250. The Agency 
estimates an additional cost of $110 for lost work time, for a total of 
$1,131. The annualized yearly cost for biennial CT scans is $574.
    Based on OSHA's estimates explained earlier in this section, all 
workers in regulated areas, workers exposed in emergencies, and an 
estimated 15 percent of workers not in regulated areas who exhibit 
signs and symptoms of CBD will be eligible for medical surveillance 
other than CT scans. The estimate for the number of workers eligible to 
receive CT scans is 25 percent of workers who are exposed above 0.2 in 
the exposure profile. The estimate of 25 percent is based on the facts 
that roughly this percentage of workers have 15-plus years of job 
tenure in the durable manufacturing sector and the estimate that all 
those with 15-plus years of job tenure and current exposure over 0.2 
would have had at least 5 years of such exposure in the past.
    The costs estimated for this provision are likely to be 
significantly overestimated, since not all affected employees offered 
medical surveillance would necessarily accept the offer. At Department 
of Energy facilities, only about 50 percent of eligible employees 
participate in the voluntary medical surveillance tests, and a report 
on an initial medical surveillance program at four aluminum manufacture 
facilities found participation rates to be around 57 percent (Taiwo et 
al., 2008). Where employers already offer equivalent health 
surveillance screening, no new costs are attributable to the proposed 
standard.
    Within 30 days after an employer learns that an employee has been 
confirmed positive for beryllium sensitization, the employer's 
designated licensed physician shall consult with the employee to 
discuss referral to a CBD diagnostic center that is mutually agreed 
upon by the employer and the employee. If, after this consultation, the 
employee wishes to obtain a clinical evaluation at a CBD diagnostic 
center, the employer must provide the evaluation at no cost to the 
employee. OSHA estimates this consultation will take 15 minutes, with 
an estimated total cost of $33.
    Table V-18 in Chapter V of the PEA lists the direct unit costs for 
a clinical evaluation with a specialist at a CBD diagnostic center. To 
estimate these costs, ERG contacted a healthcare provider who commonly 
treats patients with beryllium-related disease, and asked them to 
provide both the typical tests given and associated costs of an initial 
examination for a patient with a positive BeLPT test, presented in 
Table V-18 in Chapter V of the PEA. Their typical evaluation includes 
bronchoscopy with lung biopsy, a pulmonary stress test, and a chest CAT 
scan. The total cost for the entire suite of tests is $6,305.
    In addition, there are costs for lost productivity and travel. The 
Agency has estimated the clinical evaluation would take three days of 
paid time for the worker to travel to and from one of two locations: 
Penn Lung Center at the Cleveland Clinic Foundation in Cleveland, Ohio 
or National Jewish Medical Center in Denver, Colorado. OSHA estimates 
lost work time is 24 hours, yielding total cost for the 3 days of $532.
    OSHA estimates that roundtrip air-fare would be available for most 
facilities at $400, and the cost of a hotel room would be approximately 
$100 per night, for a total cost of $200 for the hotel room. OSHA 
estimates a per diem cost of $50 for three days, for a total of $150. 
The total cost per trip for traveling expenses is therefore $750.
    The total cost of a clinical evaluation with a specialist at a CBD 
diagnostic center is equal to the cost of the examination plus the cost 
of lost work-time and the cost for the employee to travel to the CBD 
diagnostic center, or $7,620.
    Based on the data from the exposure profile and the prevalence of 
beryllium sensitization observed at various levels of cumulative 
exposure,\18\ OSHA estimated the number of workers eligible for BeLPT 
testing (4,181) and the percentage of workers who will be confirmed 
positive for sensitization (two positive BeLPT tests, as specified in 
the proposed standard) and referred to a CBD diagnostic center. During 
the first year that the medical surveillance provisions are in effect, 
OSHA estimates that 9.4 percent of the workers who are tested for 
beryllium sensitization will be identified as sensitized. This 
percentage is an average based on: (1) The number of employees in the 
baseline exposure profile that are in a given cumulative exposure 
range; (2) the expected prevalence for a given cumulative exposure 
range (from Table VI-6 in Section VI of the preamble); and (3) an 
assumed even distribution of employees by cumulative years of exposure 
at a given level--20 percent having exposures at a given level for 5 
years, 20 percent for 15 years, 20 percent for 25 years, 20 percent for 
30 years, and 20 percent for 40 years.
---------------------------------------------------------------------------

    \18\ See Table VI-6 in Section VI of the preamble, Preliminary 
Risk Assessment.
---------------------------------------------------------------------------

    OSHA did not assume that all workers with confirmed sensitization 
would choose to undergo evaluation at a CBD diagnostic center, which 
may involve invasive procedures and/or travel. For purposes of this 
cost analysis, OSHA estimates that approximately two-thirds of workers 
who are confirmed positive for beryllium sensitization will choose to 
undergo evaluation for CBD. OSHA requests comment on the CBD evaluation 
participation rate. OSHA estimates that about 264 of all non-dental lab 
workers will go to a diagnostic center for CBD evaluation in the first 
year.
    The calculation method described above applies to all workers 
except dental technicians, who were analyzed with one modification. The 
rates for dental technicians are calculated differently due to the 
estimated 75 percent beryllium-substitution rate at dental labs, where 
the 75 percent of labs that eliminate all beryllium use are those at 
higher exposure levels. None of the remaining labs affected by this 
standard had exposures above 0.1 [mu]g/m\3\. For the dental labs, the 
same calculation was done as presented in the previous paragraph, but 
only the remaining 25 percent of employees (2,314) who would still face 
beryllium exposures were included in the baseline cumulative exposure 
profile. With that one change, and all other elements of the 
calculation the same, OSHA estimates that 9 percent of dental lab 
workers tested for beryllium sensitization will be identified as 
sensitized. The predicted prevalence of sensitization among those 
dental lab workers tested in the first year after the standard takes 
effect is slightly lower than the predicted prevalence among all other 
tested workers combined. This slightly lower rate is not surprising 
because only dental lab workers with exposures below 0.1 [mu]g/m\3\ are 
included (after adjusting for substitution), and OSHA's exposure 
profile indicates that the vast majority of non-dental workers exposed 
to beryllium are also exposed at 0.1 [mu]g/m\3\ or lower. OSHA 
estimates that 20 dental lab workers (out of 347 tested for 
sensitization) would go to a diagnostic center for CBD evaluation in 
the first year.

[[Page 47687]]

    In each year after the first year, OSHA relied on a 10 percent 
worker turnover rate in a steady state (as discussed in Chapter VII of 
the PEA) to estimate that the annual sensitization incidence rate is 10 
percent of the first year's incidence rate. Based on that rate and the 
number of workers in the medical surveillance program, the CBD 
evaluation rate for workers other than those in dental labs would drop 
to 0.63 percent (.063 x .10). The evaluation rate for dental labs 
technicians is similarly estimated to drop to 0.58 percent (.058 x 
.10).
    Based on these unit costs and the number of employees requiring 
medical surveillance estimated above, OSHA estimates that the medical 
surveillance and referral provisions would result in an annualized 
total cost of $2,882,706. These costs are presented by application 
group and NAICS code in Table IX-7.
h. Medical Removal Provision
    Once a licensed physician diagnoses an employee with CBD or the 
employee is confirmed positive for sensitization to beryllium, that 
employee is eligible for medical removal and has two choices:
    (a) Removal from current job, or
    (b) Remain in a job with exposure above the action level while 
wearing a respirator pursuant to 29 CFR 1910.134.
    To be eligible for removal, the employee must accept comparable 
work if such is available, but if not available the employer would be 
required to place the employee on paid leave for six months or until 
such time as comparable work becomes available, whichever comes first. 
During that six-month period, whether the employee is re-assigned or 
placed on paid leave, the employer must continue to maintain the 
employee's base earnings, seniority and other rights, and benefits that 
existed at the time of the first test.
    For purposes of this analysis, OSHA has conservatively estimated 
the costs as if all employees will choose removal, rather than 
remaining in the current job while wearing a respirator. In practice, 
many workers may prefer to continue working at their current job while 
wearing a respirator, and the employer would only incur the respirator 
costs identified earlier in this chapter. The removal costs are 
significantly higher over the same six-month period, so this analysis 
likely overestimates the total costs for this provision.
    OSHA estimated that the majority of firms would be able to reassign 
the worker to a job at least at the clerical level. The employer will 
often incur a cost for re-assigning the worker because this provision 
requires that, regardless of the comparable work the medically removed 
worker is performing, the employee must be paid the full base earnings 
for the previous position for six months. The cost per hour of 
reassigning a worker to a clerical job is based on the wage difference 
of a production worker of $22.16 and a clerical worker of $19.97, for a 
difference of $2.19. Over the six-month period, the incremental cost of 
reassigning a worker to a clerical position would be $2,190 per 
employee. This estimate is based on the employee remaining in a 
clerical position for the entire 6-month period, but the actual cost 
would be lower if there is turnover or if the employee is placed in any 
alternative position (for any part of the six-month period) that is 
compensated at a wage closer to the employee's previous wage.
    Some firms may not have the ability to place the worker in an 
alternate job. If the employee chooses not to remain in the current 
position, the additional cost to the employer would be at most the cost 
of equipping that employee with a respirator, which would be required 
if the employee would continue to face exposures at or above the action 
level. Based on the earlier discussion of respirator costs, that option 
would be significantly cheaper than the alternative of providing the 
employee with six months of paid leave. Therefore, in order to estimate 
the maximum potential economic cost of the remaining alternatives, the 
Agency has conservatively estimated the cost per worker based on the 
cost of 6 months paid leave.
    Using the wage rate of a production worker of $22.16 for 6 months 
(or 8 hours a day for 125 days), the total per-worker cost for this 
provision when a firm cannot place a worker in an alternate job is 
$22,161.
    OSHA has estimated an average medical removal cost per worker 
assuming 75 percent of firms are able to find the employee an alternate 
job, and the remaining 25 percent of firms would not. The weighted 
average of these costs is $7,183. Based on these unit costs, OSHA 
estimates that the medical removal provision would result in an 
annualized total cost of $148,826. The breakdown of these costs by 
application group and NAICS code is shown in Table IX-6.
i. Training
    As specified in the proposed standard and existing OSHA standard 29 
CFR 1910.1200 on hazard communication, training is required for all 
employees where there is potential exposure to beryllium. In addition, 
newly hired employees would require training before starting work.
    OSHA anticipates that training in accordance with the requirements 
of the proposed rule, which includes hazard communication training, 
would be conducted by in-house safety or supervisory staff with the use 
of training modules or videos. ERG estimated that this training would 
last, on average, eight hours. (Note that this estimate does not 
include the time taken for hazard communication training that is 
already required by 29 CFR 1910.1200.) The Agency judged that 
establishments could purchase sufficient training materials at an 
average cost of $2 per worker, encompassing the cost of handouts, video 
presentations, and training manuals and exercises. For initial and 
periodic training, ERG estimated an average class size of five workers 
with one instructor over an eight hour period. The per-worker cost of 
initial training totals to $239.
    Annual retraining of workers is also required by the standard. OSHA 
estimates the same unit costs as for initial training, so retraining 
would require the same per-worker cost of $239.
    Finally, to calculate training costs, the Agency needs the turnover 
rate of affected workers to know how many workers are receiving initial 
training versus retraining. Based on a 26.3 percent new hire rate in 
manufacturing, OSHA calculated a total net present value (NPV) of ten 
years of initial and annual retraining of $2,101 per employee. 
Annualizing this NPV gives a total annual cost for training of $246.
    Based on these unit costs, OSHA estimates that the training 
requirements in the standard would result in an annualized total cost 
of $5,797,535. The breakdown of these costs by application group and 
NAICS code is presented in Table IX-6.

[[Page 47688]]

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[[Page 47690]]


[GRAPHIC] [TIFF OMITTED] TP07AU15.011


[[Page 47691]]


Total Annualized Cost
    As shown in Table IX-7, the total annualized cost of the proposed 
rule is estimated to be about $37.6 million. As shown, at $27.8 
million, the program costs represent about 74 percent of the total 
annualized costs of the proposed rule. The annualized cost of complying 
with the PEL accounts for the remaining 26 percent, almost all of which 
is for engineering controls and work practices. Respiratory protection, 
at about $237,600, represents only 3 percent of the annualized cost of 
complying with the PEL and less than 1 percent of the annualized cost 
of the proposed rule.
[GRAPHIC] [TIFF OMITTED] TP07AU15.012


[[Page 47692]]


[GRAPHIC] [TIFF OMITTED] TP07AU15.013

F. Economic Feasibility Analysis and Regulatory Flexibility 
Determination

    Chapter VI of the PEA, summarized here, investigates the economic 
impacts of the proposed beryllium rule on affected employers. This 
impact investigation has two overriding objectives: (1) To establish 
whether the proposed rule is economically feasible for all affected 
application groups/industries, and (2) to determine if the Agency can 
certify that the proposed rule will not have a significant economic 
impact on a substantial number of small entities.
    In the discussion below, OSHA first presents its approach for 
achieving these objectives and next applies this approach to industries 
with affected employers. The Agency invites comment on any aspect of 
the methods, data, or preliminary findings presented here or in Chapter 
VI of the PEA.
1. Analytic Approach
a. Economic Feasibility
    Section 6(b)(5) of the OSH Act directs the Secretary of Labor to 
set standards based on the available evidence where no employee, over 
his/her working life time, will suffer from material impairment of 
health or functional capacity, even if such employee has regular 
exposure to the hazard, ``to the exent feasible'' (29 U.S.C. 
655(b)(5)). OSHA interpreted the phrase ``to the extent feasible'' to 
encompass economic feasibility and was supported in this view by the 
U.S. Court of Appeals for the D.C. Circuit, which has long held that 
OSHA standards would satisfy the economic feasibility criterion even if 
they imposed significant costs on regulated industries and forced some 
marginal firms out of business, so long as they did not cause massive 
economic dislocations within a particular industry or imperil the 
existence of that industry. Am. Iron and Steel Inst. v. OSHA, 939 F.2d 
975, 980 (D.C. Cir. 1991); United Steelworkers of Am., AFL-CIO-CLC v. 
Marshall, 647 F.2d 1189, 1265 (D.C. Cir. 1980); Indus. Union Dep't v. 
Hodgson, 499 F.2d 467 (D.C. Cir. 1974).
b. The Price Elasticity of Demand and Its Relationship to Economic 
Feasibility
    In practice, the economic burden of an OSHA standard on an 
industry--and whether the standard is economically feasible for that 
industry--depends on

[[Page 47693]]

the magnitude of compliance costs incurred by establishments in that 
industry and the extent to which they are able to pass those costs on 
to their customers. That, in turn, depends, to a significant degree, on 
the price elasticity of demand for the products sold by establishments 
in that industry.
    The price elasticity of demand refers to the relationship between 
the price charged for a product and the demand for that product: The 
more elastic the relationship, the less an establishment's compliance 
costs can be passed through to customers in the form of a price 
increase and the more the establishment has to absorb compliance costs 
in the form of reduced profits. When demand is inelastic, 
establishments can recover most of the costs of compliance by raising 
the prices they charge; under this scenario, profit rates are largely 
unchanged and the industry remains largely unaffected. Any impacts are 
primarily on those customers using the relevant product. On the other 
hand, when demand is elastic, establishments cannot recover all 
compliance costs simply by passing the cost increase through in the 
form of a price increase; instead, they must absorb some of the 
increase from their profits. Commonly, this will mean reductions both 
in the quantity of goods and services produced and in total profits, 
though the profit rate may remain unchanged. In general, ``[w]hen an 
industry is subjected to a higher cost, it does not simply swallow it; 
it raises its price and reduces its output, and in this way shifts a 
part of the cost to its consumers and a part to its suppliers,'' in the 
words of the court in Am. Dental Ass'n v. Sec'y of Labor (984 F.2d 823, 
829 (7th Cir. 1993)).
    The court's summary is in accord with microeconomic theory. In the 
long run, firms can remain in business only if their profits are 
adequate to provide a return on investment that ensures that investment 
in the industry will continue. Over time, because of rising real 
incomes and productivity increases, firms in most industries are able 
to ensure an adequate profit. As technology and costs change, however, 
the long-run demand for some products naturally increases and the long-
run demand for other products naturally decreases. In the face of 
additional compliance costs (or other external costs), firms that 
otherwise have a profitable line of business may have to increase 
prices to stay viable. Increases in prices typically result in reduced 
quantity demanded, but rarely eliminate all demand for the product. 
Whether this decrease in the total production of goods and services 
results in smaller output for each establishment within the industry or 
the closure of some plants within the industry, or a combination of the 
two, is dependent on the cost and profit structure of individual firms 
within the industry.
    If demand is perfectly inelastic (i.e., the price elasticity of 
demand is zero), then the impact of compliance costs that are one 
percent of revenues for each firm in the industry would be a one 
percent increase in the price of the product, with no decline in 
quantity demanded. Such a situation represents an extreme case, but 
might be observed in situations in which there were few, if any, 
substitutes for the product in question, or if the products of the 
affected sector account for only a very small portion of the revenue or 
income of its customers.
    If the demand is perfectly elastic (i.e., the price elasticity of 
demand is infinitely large), then no increase in price is possible and 
before-tax profits would be reduced by an amount equal to the costs of 
compliance (net of any cost savings--such as reduced workers' 
compensation insurance premiums--resulting from the proposed standard) 
if the industry attempted to maintain production at the same level as 
previously. Under this scenario, if the costs of compliance are such a 
large percentage of profits that some or all plants in the industry 
could no longer operate in the industry with hope of an adequate return 
on investment, then some or all of the firms in the industry would 
close. This scenario is highly unlikely to occur, however, because it 
can only arise when there are other products--unaffected by the 
proposed rule--that are, in the eyes of their customers, perfect 
substitutes for the products the affected establishments make.
    A commonly-discussed intermediate case would be a price elasticity 
of demand of one (in absolute terms). In this situation, if the costs 
of compliance amount to one percent of revenues, then production would 
decline by one percent and prices would rise by one percent. As a 
result, industry revenues would remain the same, with somewhat lower 
production, but with similar profit rates per unit of output (in most 
situations where the marginal costs of production net of regulatory 
costs would fall as well). Customers would, however, receive less of 
the product for their (same) expenditures, and firms would have lower 
total profits; this, as the court described in Am. Dental Ass'n v. 
Sec'y of Labor, is the more typical case.
c. Variable Costs Versus Fixed Costs
    A decline in output as a result of an increase in price may occur 
in a variety of ways: individual establishments could each reduce their 
levels of production; some marginal plants could close; or, in the case 
of an expanding industry, new entry may be delayed until demand equals 
supply. In some situations, there could be a combination of these three 
effects. Which possibility is most likely depends on the form that the 
costs of the regulation take. If the costs are variable costs (i.e., 
costs that vary with the level of production at a facility), then 
economic theory suggests that any reductions in overall output will be 
the result of reductions in output at each affected facility, with few, 
if any, plant closures. If, on the other hand, the costs of a 
regulation primarily take the form of fixed costs (i.e., costs that do 
not vary with the level of production at a facility), then reductions 
in overall output are more likely to take the form of plant closures or 
delays in new entry.
    Most of the costs of this regulation, as estimated in Chapter V of 
the PEA, are variable costs in the sense that they will tend to vary by 
production levels and/or employment levels. Almost all of the major 
costs of program elements, such as medical surveillance and training, 
will vary in proportion to the number of employees (which is a rough 
proxy for the amount of production). Exposure monitoring costs will 
vary with the number of employees, but do have some economies of scale 
to the extent that a larger firm need only conduct representative 
sampling rather than sample every employee. Finally, the costs of 
operating and maintaining engineering controls tend to vary by usage--
which typically closely tracks the level of production and are not 
fixed costs in the strictest sense.
    This leaves two kinds of costs that are, in some sense, fixed 
costs--capital costs of engineering controls and certain initial costs. 
The capital costs of engineering controls due to the standard--many of 
which are scaled to production and/or employment levels--constitute a 
relatively small share of the total costs, representing 10 percent of 
total annualized costs (or approximately $870 per year per affected 
establishment).
    Some ancillary provisions require initial costs that are fixed in 
the sense that they do not vary by production activity or the number of 
employees. Some examples are the costs to develop a training plan for 
general training not currently required and to develop a written 
exposure control plan.

[[Page 47694]]

    As a result of these considerations, OSHA expects it to be quite 
likely that any reductions in total industry output would be due to 
reductions in output at each affected facility rather than as a result 
of plant closures. However, closures of some marginal plants or poorly 
performing facilities are always possible.
d. Economic Feasibility Screening Analysis
    To determine whether a rule is economically feasible, OSHA begins 
with two screening tests to consider minimum threshold effects of the 
rule under two extreme cases: (1) All costs are passed through to 
customers in the form of higher prices (consistent with a price 
elasticity of demand of zero), and (2) all costs are absorbed by the 
firm in the form of reduced profits (consistent with an infinite price 
elasticity of demand).
    In the former case, the immediate impact of the rule would be 
observed in increased industry revenues. While there is no hard and 
fast rule, in the absence of evidence to the contrary, OSHA generally 
considers a standard to be economically feasible for an industry when 
the annualized costs of compliance are less than a threshold level of 
one percent of annual revenues. Retrospective studies of previous OSHA 
regulations have shown that potential impacts of such a small magnitude 
are unlikely to eliminate an industry or significantly alter its 
competitive structure,\19\ particularly since most industries have at 
least some ability to raise prices to reflect increased costs, and 
normal price variations for products typically exceed three percent a 
year.
---------------------------------------------------------------------------

    \19\ See OSHA's Web page, http://www.osha.gov/dea/lookback.html#Completed, for a link to all completed OSHA lookback 
reviews.
---------------------------------------------------------------------------

    In the latter case, the immediate impact of the rule would be 
observed in reduced industry profits. OSHA uses the ratio of annualized 
costs to annual profits as a second check on economic feasibility. 
Again, while there is no hard and fast rule, in the absence of evidence 
to the contrary, OSHA generally considers a standard to be economically 
feasible for an industry when the annualized costs of compliance are 
less than a threshold level of ten percent of annual profits. In the 
context of economic feasibility, the Agency believes this threshold 
level to be fairly modest, given that normal year-to-year variations in 
profit rates in an industry can exceed 40 percent or more. OSHA also 
considered whether this threshold would be adequate to assure that 
upfront costs would not create major credit problems for affected 
employers. To do this, OSHA examined a worst case scenario in which 
annualized costs were ten percent of profits and all of the annualized 
costs were the result of upfront costs. In this scenario, assuming a 
three percent discount rate and a ten year life of equipment, total 
costs would be 85 percent of profits \20\ in the year in which these 
upfront costs were incurred. Because upfront costs would be less than 
one year's profits in the year they were incurred, this means that an 
employer could pay for all of these costs from that year's profits and 
would not necessarily have to incur any new borrowing. As a result, it 
is unlikely that these costs would create a credit crunch or other 
major credit problems. It would be true, however, that paying 
regulatory costs from profits might reduce investment from profits in 
that year. OSHA's choice of a threshold level of ten percent of annual 
profits is low enough that even if, in a hypothetical worst case, all 
compliance costs were upfront costs, then upfront costs--assuming a 
three percent discount rate and a ten-year time period--would be no 
more than 85 percent of first-year profits and thus would be affordable 
from profits without resort to credit markets. If the threshold level 
were first-year costs of ten percent of annual profits, firms could 
even more easily expect to cover first-year costs at the threshold 
level out of current profits without having to access capital markets 
and otherwise being threatened with short-term insolvency.
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    \20\ At a discount rate of 3 percent over a life of investment 
of 10 years, the present value of that stream of annualized costs 
would be 8.53 times a single year's annualized costs. Hence, if 
yearly annualized costs are 10 percent of profits, upfront costs 
would be 85 percent of the profits in that first year. As a simple 
example, assume annualized costs are $1 for each of the 10 years. If 
annualized costs are 10 percent of profits, this translates to a 
yearly profit of $10. The present value of that stream of $1 for 
each year is $8.53. (The formula for this calculation is 
($1*(1.03[caret]10)-1)/((.03)x(1.03)[caret]10).
---------------------------------------------------------------------------

    In general, because it is usually the case that firms would be able 
to pass on to their customers some or all of the costs of the proposed 
rule in the form of higher prices, OSHA will tend to give much more 
weight to the ratio of industry costs to industry revenues than to the 
ratio of industry costs to industry profits. However, if costs exceed 
either the threshold percentage of revenue or the threshold percentage 
of profits for an industry, or if there is other evidence of a threat 
to the viability of an industry because of the proposed standard, OSHA 
will examine the effect of the rule on that industry more closely. Such 
an examination would include market factors specific to the industry, 
such as normal variations in prices and profits, and any special 
circumstances, such as close domestic substitutes of equal cost, which 
might make the industry particularly vulnerable to a regulatory cost 
increase.
    The preceding discussion focused on the economic viability of the 
affected industries in their entirety. However, even if OSHA found that 
a proposed standard did not threaten the survival of affected 
industries, there is still the question of whether the industries' 
competitive structure would be significantly altered. For example, if 
the annualized costs of an OSHA standard were equal to 10 percent of an 
industry's annual profits, and the price elasticity of demand for the 
products in that industry were equal to one, then OSHA would not expect 
the industry to go out of business. However, if the increase in costs 
were such that most or all small firms in that industry would have to 
close, it might reasonably be concluded that the competitive structure 
of the industry had been altered. For this reason, OSHA also calculates 
compliance costs by size of firm and conducts its economic feasibility 
screening analysis for small and very small entities.
e. Regulatory Flexibility Screening Analysis
    The Regulatory Flexibility Act (RFA), Public Law 96-354, 94 Stat. 
1164 (codified at 5 U.S.C. 601), requires Federal agencies to consider 
the economic impact that a proposed rulemaking will have on small 
entities. The RFA states that whenever a Federal agency is required to 
publish general notice of proposed rulemaking for any proposed rule, 
the agency must prepare and make available for public comment an 
initial regulatory flexibility analysis (IRFA). 5 U.S.C. 603(a). 
Pursuant to section 605(b), in lieu of an IRFA, the head of an agency 
may certify that the proposed rule will not have a significant economic 
impact on a substantial number of small entities. A certification must 
be supported by a factual basis. If the head of an agency makes a 
certification, the agency shall publish such certification in the 
Federal Register at the time of publication of general notice of 
proposed rulemaking or at the time of publication of the final rule. 5 
U.S.C. 605(b).
    To determine if the Assistant Secretary of Labor for OSHA can 
certify that the proposed beryllium rule will not have a significant 
economic impact on a substantial number of small entities, the Agency 
has developed screening tests to consider minimum threshold effects of 
the proposed rule on

[[Page 47695]]

small entities. These screening tests do not constitute hard and fast 
rules and are similar in concept to those OSHA developed above to 
identify minimum threshold effects for purposes of demonstrating 
economic feasibility.
    There are, however, two differences. First, for each affected 
industry, the screening tests are applied, not to all establishments, 
but to small entities (defined as ``small business concerns'' by SBA) 
and also to very small entities (as defined by OSHA as businesses with 
fewer than 20 employees). Second, although OSHA's regulatory 
flexibility screening test for revenues also uses a minimum threshold 
level of annualized costs equal to one percent of annual revenues, OSHA 
has established a minimum threshold level of annualized costs equal to 
five percent of annual profits for the average small entity or very 
small entity. The Agency has chosen a lower minimum threshold level for 
the profitability screening analysis and has applied its screening 
tests to both small entities and very small entities in order to ensure 
that certification will be made, and an IRFA will not be prepared, only 
if OSHA can be highly confident that a proposed rule will not have a 
significant economic impact on a substantial number of small entities 
or very small entities in any affected industry.
    Furthermore, certification will not be made, and an IRFA will be 
prepared, if OSHA believes the proposed rule might otherwise have a 
significant economic impact on a substantial number of small entities, 
even if the minimum threshold levels are not exceeded for revenues or 
profitability for small entities or very small entities in all affected 
industries.
2. Impacts on Affected Industries
    In this section, OSHA applies its screening criteria and other 
analytic methods, as needed, to determine (1) whether the proposed rule 
is economically feasible for all affected industries within the scope 
of this proposed rule, and (2) whether the Agency can certify that the 
proposed rule will not have a significant economic impact on a 
substantial number of small entities.
a. Economic Feasibility Screening Analysis: All Establishments
    To determine whether the proposed rule's projected costs of 
compliance would threaten the economic viability of affected 
industries, OSHA first compared, for each affected industry, annualized 
compliance costs to annual revenues and profits per (average) affected 
establishment. The results for all affected establishments in all 
affected industries are presented in Table IX-8. Shown in the table for 
each affected industry are the total number of establishments, the 
total number of affected establishments, annualized costs per affected 
establishment, annual revenues per establishment, the profit rate, 
annual profits per establishment, annualized compliance costs as a 
percentage of annual revenues, and annualized compliance costs as a 
percentage of annual profits.
    The annualized costs per affected establishment for each affected 
industry were calculated by distributing the industry-level 
(incremental) annualized compliance costs among all affected 
establishments in the industry, where annualized compliance costs 
reflect a 3 percent discount rate. The annualized cost of the proposed 
rule for the average affected establishment is estimated at $9,197 in 
2010 dollars. It is clear from Table IX-8 that the estimates of the 
annualized costs per affected establishment vary widely from industry 
to industry. These estimates range from $1,257,214 for NAICS 331419 
(Beryllium Production) and $120,372 for NAICS 327113a (Porcelain 
Electrical Supply Manufacturing (primary)) to $1,636 for NAICS 621210 
(Offices of Dentists) and $1,632 for NAICS 339116 (Dental 
Laboratories).

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[GRAPHIC] [TIFF OMITTED] TP07AU15.015

    As previously discussed, OSHA has established a minimum threshold 
level of annualized costs equal to one percent of annual revenues--and, 
secondarily, annualized costs equal to 10 percent of annual profits--
below which the

[[Page 47698]]

Agency has concluded that costs are unlikely to threaten the economic 
viability of an affected industry. The results of OSHA's threshold 
tests for all affected establishments are displayed in Table IX-8. For 
all affected establishments, the estimated annualized cost of the 
proposed rule is, on average, equal to 0.11 percent of annual revenue 
and 1.52 percent of annual profit.
    As Table IX-8 shows, there are no industries in which the 
annualized costs of the proposed rule exceed one percent of annual 
revenues. However there are three six-digit NAICS industries where 
annualized costs exceed ten percent of annual profits.
    NAICS 331525 (Copper foundries except die-casting) has the highest 
cost impact as a percentage of profits. NAICS 331525 is made up of two 
types of copper foundries: sand casting foundries and non-sand casting 
foundries, incurring an annualized cost as a percent of profit of 16.25 
percent and 14.92 percent, respectively. The other two six-digit NAICS 
industries where annualized costs exceed ten percent of annual profits 
are NAICS 331534: Aluminum foundries (except die-casting), 13.65 
percent; and NAICS 811310: Commercial and industrial machinery and 
equipment repair, 10.19 percent.
    OSHA believes that the beryllium-containing inputs used by these 
industries have a relatively inelastic demand for three reasons. First, 
beryllium has rare and unique characteristics, including low mass, high 
melting temperature, dimensional stability over a wide temperature 
range, strength, stiffness, light weight, and high elasticity 
(``springiness'') that can significantly improve the performance of 
various alloys. These characteristics cannot easily be replicated by 
other materials. In economic terms, this means that the elasticity of 
substitution between beryllium and non-beryllium inputs will be low. 
Second, products which contain beryllium or beryllium-alloy components 
typically have high-performance applications (whose performance depends 
on the use of higher-cost beryllium). The lack of available competing 
products with these performance characteristics suggests that the price 
elasticity of demand for products containing beryllium or beryllium-
alloy components will be low. Third, components made of beryllium or 
beryllium-containing alloys typically account for only a small portion 
of the overall cost of the finished goods that these parts are used to 
make. For example, the cost of brakes made of a beryllium-alloy used in 
the production of a jet airplane represents a trivial percentage of the 
overall cost to produce that airplane. As economic theory indicates, 
the elasticity of derived demand for a factor of production (such as 
beryllium) varies directly with the elasticity of substitution between 
the input in question and other inputs; the price elasticity of demand 
for the final product that the input is used to produce; and, in 
general, the share of the cost of the final product that the input 
accounts for. Applying these three conditions to beryllium points to 
the relative inelastic derived demand for this factor of production and 
the likelihood that cost increases resulting from the proposed rule 
would be passed on to the consumer in the form of higher prices.
    A secondary point is that the establishments in an industry that 
use beryllium may be more profitable than those that don't. This 
follows from the prior arguments about beryllium's rare and desirable 
characteristics and its valuable applications. For example, of the 208 
establishments that make up NAICS 331525, OSHA estimated that 45 
establishments (or 21 percent) work with beryllium. Of the 394 
establishments that make up NAICS 331524, OSHA estimated that only 7 
establishments (less than 2 percent) work with beryllium. Of the 21,960 
establishments that make up NAICS 811310, OSHA estimated that 143 (0.7 
percent) work with beryllium. However, when OSHA calculated the cost-
to-profit ratio, it used the average profit per firm for the entire 
NAICs industry, not the average profit per firm for firms working with 
beryllium.
(1) Normal Year-to-Year Variations in Prices and Profit Rates
    The United States has a dynamic and constantly changing economy in 
which an annual percentage increase in industry revenues or prices of 
one percent or more are common. Examples of year-to-year changes in an 
industry that could cause such an increase in revenues or prices 
include increases in fuel, material, real estate, or other costs; tax 
increases; and shifts in demand.
    To demonstrate the normal year-to-year variation in prices for all 
the manufacturers in general industry affected by the proposed rule, 
OSHA developed in the PEA year-to-year producer price indices and year-
to-year percentage changes in producer prices, by industry, for the 
years 1999-2010. For all of the industries estimated to be affected by 
this proposed standard over the 12-year period, the average change in 
producer prices was 4.4 percent a year--which is over 4 times as high 
as OSHA's 1 percent cost-to-revenue threshold. For the industries found 
to have the largest estimated potential annual cost impact as a 
percentage of revenue shown in Chapter VI of the PEA are--NAICS 331524: 
Aluminum Foundries (except Die-Casting), (0.71 percent); NAICS 331525(a 
and b): Copper Foundries (except Die-Casting) (average of 0.81 
percent); NAICS 332721a: Precision Turned Product Manufacturing of high 
content beryllium (0.49 percent); \21\ and NAICS 811310: Commercial and 
Industrial Machinery and Equipment (Except Automotive and Electronic) 
Repair and Maintenance (0.55 percent)--the average annual changes in 
producer prices in these industries over the 12-year period analyzed 
were 3.1 percent, 8.2 percent, 3.6 percent and 2.3 percent, 
respectively.
---------------------------------------------------------------------------

    \21\ By contrast, NAICS 332721b: Precision Turned Product 
Manufacturing of low content beryllium alloys has a cost to revenue 
ratio below 0.4 percent.
---------------------------------------------------------------------------

    Based on these data, it is clear that the potential price impacts 
of the proposed rule in affected industries are all well within normal 
year-to-year variations in prices in those industries. The maximum cost 
impact of the proposed rule as a percentage of revenue in any affected 
industry is 0.84 percent, while, as just noted, the average annual 
change in producer prices for affected industries was 4.4 percent for 
the period 1999-2010. In fact, Chapter VI of the PEA shows two of the 
industries within the secondary smelting, refining, and alloying group, 
for example, the prices rose over 60 percent in one year without 
imperiling the existence of those industries. Thus, OSHA preliminarily 
concludes that the potential price impacts of the proposal would not 
threaten the economic viability of any industries affected by this 
proposed standard.
    Profit rates are also subject to the dynamics of the U.S. economy. 
A recession, a downturn in a particular industry, foreign competition, 
or the increased competitiveness of producers of close domestic 
substitutes are all easily capable of causing a decline in profit rates 
in an industry of well in excess of ten percent in one year or for 
several years in succession.
    To demonstrate the normal year-to-year variation in profit rates 
for all the manufacturers affected by the proposed rule, OSHA presented 
data in the PEA on year-to-year profit rates and year-to-year 
percentage changes in profit rates, by industry, for the years 2002-
2009. For the industries that OSHA has estimated will be affected by 
this

[[Page 47699]]

proposed standard over the 8-year period, the average change in profit 
rates is calculated to be 39 percent per year. For the industries with 
the largest estimated potential annual cost impacts as a percentage of 
profit--NAICS 331524: Aluminum foundries (except die-casting), (14 
percent); NAICS 331525(a and b): Copper foundries (except die-casting) 
(16 percent); NAICS 332721a: Precision Turned Product Manufacturing of 
high content beryllium (8 percent); \22\ and NAICS 811310 Commercial 
and Industrial Machinery and Equipment (Except Automotive and 
Electronic) Repair and Maintenance (10 percent)--the average annual 
changes in profit rates in these industries over the eight-year period 
were 35 percent, 35 percent, 11 percent, and 5 percent, respectively.
---------------------------------------------------------------------------

    \22\ By contrast, NAICS 332721b: Precision Turned Product 
Manufacturing of low content beryllium alloys has a cost to profit 
ratio of 6 percent.
---------------------------------------------------------------------------

    A longer-term loss of profits in excess of 10 percent a year could 
be more problematic for some affected industries and might conceivably, 
under sufficiently adverse circumstances, threaten an industry's 
economic viability. However, as previously discussed, OSHA's analysis 
indicates that affected industries would generally not absorb the costs 
of the proposed rule in reduced profits but, instead, would be able to 
pass on most or all of those costs in the form of higher prices (due to 
the relative price inelasticity of demand for beryllium and beryllium-
containing inputs). It is possible that such price increases will 
result in some reduction in output, and the reduction in output might 
be met through the closure of a small percentage of the plants in the 
industry. The only realistic circumstance where an entire industry 
would be significantly affected by small potential price increases 
would be where there is a very close or perfect substitute product 
available not subject to OSHA regulation. In most cases where beryllium 
is used, there is no substitute product that could be used in place of 
beryllium and achieve the same level of performance. The main potential 
concern would be substitution by foreign competition, but the following 
discussion reveals why such competition is not likely.
(2) International Trade Effects
    World production of beryllium is a thin market, with only a handful 
of countries known to process beryllium ores and concentrates into 
beryllium products, and characterized by a high degree of variation and 
uncertainty. The United States accounts for approximately 65 percent of 
world beryllium deposits and 90 percent of world production, but there 
is also a significant stockpiling of beryllium materials in Kazakhstan, 
Russia, China, and possibly other countries (USGS, 2013a). For the 
individual years 2008-2012, the United States' net import reliance as a 
percentage of apparent consumption (that is, imports minus exports net 
of industry and government stock adjustments) ranged from 10 percent to 
61 percent (USGS, 2013b). To assure an adequate stockpile of beryllium 
materials to support national defense interests, the U.S. Department of 
Defense, in 2005, under the Defense Production Act, Title III, invested 
in a public-private partnership with the leading U.S. beryllium 
producer to build a new $90.4 million primary beryllium facility in 
Elmore, Ohio. Construction of that facility was completed in 2011 
(USGS, 2013b).
    One factor of importance to firms working with beryllium and 
beryllium alloys is to have a reliable supply of beryllium materials. 
U.S. manufacturers can have a relatively high confidence in the 
availability of beryllium materials relative to manufacturers in many 
foreign countries, particularly those that do not have economic or 
national security partnerships with the United States.
    Firms using beryllium in production must consider not just the cost 
of the chemical itself but also the various regulatory costs associated 
with the use, transport, and disposal of the material. For example, for 
marine transport, metallic beryllium powder and beryllium compounds are 
classified by the International Maritime Organization (IMO) as 
poisonous substances, presenting medical danger. Beryllium is also 
classified as flammable. The United Nations classification of beryllium 
and beryllium compounds for the transport of dangerous goods is 
``poisonous substance'' and, for packing, a ``substance presenting 
medium danger'' (WHO, 1990). Because of beryllium's toxicity, the 
material is subject to various workplace restrictions as well as 
international, national, and State requirements and guidelines 
regarding beryllium content in environmental media (USGS, 2013a).
    As the previous discussion indicates, the production and use of 
beryllium and beryllium alloys in the United States and foreign markets 
appears to depend on the availability of production facilities; 
beryllium stockpiles; national defense and political considerations; 
regulations limiting the shipping of beryllium and beryllium products; 
international, national, and State regulations and guidelines regarding 
beryllium content in environmental media; and, of course, the special 
performance properties of beryllium and beryllium alloys in various 
applications. Relatively small changes in the price of beryllium would 
seem to have a minor effect on the location of beryllium production and 
use. In particular, as a result of this proposed rule, OSHA would 
expect that, if all compliance costs were passed through in the form of 
higher prices, a price increase of 0.11 percent, on average, for firms 
manufacturing or using beryllium in the United States--and not 
exceeding 1 percent in any affected industry--would have a negligible 
effect on foreign competition and would therefore not threaten the 
economic viability of any affected domestic industries.
(b) Economic Feasibility Screening Analysis: Small and Very Small 
Businesses
    The preceding discussion focused on the economic viability of the 
affected industries in their entirety. Even though OSHA found that the 
proposed standard did not threaten the survival of these industries, 
there is still the possibility that the competitive structure of these 
industries could be significantly altered such as by small entities 
exiting from the industry as a result of the proposed standard.
    To address this possibility, OSHA examined the annualized costs of 
the proposed standard per affected small entity, and per affected very 
small entity, for each affected industry. Again, OSHA used a minimum 
threshold level of annualized compliance costs equal to one percent of 
annual revenues--and, secondarily, annualized compliance costs equal to 
ten percent of annual profits--below which the Agency has concluded 
that the costs are unlikely to threaten the survival of small entities 
or very small entities or, consequently, to alter the competitive 
structure of the affected industries.
    Based on the results presented in Table IX-9, the annualized cost 
of compliance with the proposed rule for the average affected small 
entity is estimated to be $8,108 in 2010 dollars. Based on the results 
presented in Table IX-10, the annualized cost of compliance with the 
proposed rule for the average affected very small entity is estimated 
to be $1,955 in 2010 dollars. These tables also show that there are no 
industries in which the annualized costs of the proposed rule for small 
entities or very small entities exceed one percent of annual revenues. 
NAICS 331525b: Sand Copper Foundries (except die-casting) has the 
highest estimated cost

[[Page 47700]]

impact as a percentage of revenues for small entities, 0.95 percent, 
and NAICS 336322b: Other motor vehicle electrical and electronic 
equipment has the highest estimated cost impact as a percentage of 
revenues for very small entities, 0.70 percent.
    Small entities in four industries--NAICS 331525: Sand and non-sand 
foundries (except die-casting); NAICS 331524(a and b): Aluminum 
foundries (except die-casting); NAICS 811310: Commercial and Industrial 
Machinery and Equipment; and NAICS 331522: Nonferrous (except aluminum) 
die-casting foundries--have annualized costs in excess of 10 percent of 
annual profits (17.45 percent, 16.12 percent, 11.68 percent, and 10.64 
percent, respectively). Very small entities in 7 industries are 
estimated to have annualized costs in excess of 10 percent of annual 
profit; NAICS 336322b: Other motor vehicle electrical and electronic 
equipment (38.49 percent); \23\ NAICS 336322a: Other motor vehicle 
electrical and electronic equipment, (18.18 percent); NAICS 327113: 
Porcelain electrical Supply Manufacturing (13.82 percent); NAICS 
811310: Commercial and Industrial Machinery and Equipment (Except 
Automotive and Electronic) Repair and Maintenance (12.76 percent); 
NAICS 332721a: Precision turned product manufacturing (10.50 percent); 
NAICS 336214: Travel trailer and camper manufacturing (10.75 percent); 
and NAICS 336399: All other motor vehicle parts manufacturing (10.38 
percent).
---------------------------------------------------------------------------

    \23\ NAICS 336322 contains entities that fall into three 
separate application groups. NAICS 336322b is in the Beryllium Oxide 
Ceramics and Composites application group. NAICS 336322a (which 
follows in the text) is in the Fabrication of Beryllium Alloy 
Products application group.
---------------------------------------------------------------------------

    In general, cost impacts for affected small entities or very small 
entities will tend to be somewhat higher, on average, than the cost 
impacts for the average business in those affected industries. That is 
to be expected. After all, smaller businesses typically suffer from 
diseconomies of scale in many aspects of their business, leading to 
less revenue per dollar of cost and higher unit costs. Small businesses 
are able to overcome these obstacles by providing specialized products 
and services, offering local service and better service, or otherwise 
creating a market niche for themselves. The higher cost impacts for 
smaller businesses estimated for this rule--other than very small 
entities in NAICS 336322b: Other motor vehicle electrical and 
electronic equipment--generally fall within the range observed in other 
OSHA regulations and, as verified by OSHA's lookback reviews, have not 
been of such a magnitude to lead to the economic failure of regulated 
small businesses.
    The ratio of annualized costs to annual profit is a sizable 38.49 
percent in NAICS 336322b: Other motor vehicle electrical and electronic 
equipment. However, OSHA believes that the actual ratio is 
significantly lower. There are 386 very small entities in NAICS 336322, 
of which only 6, or 1.5 percent, are affected entities using beryllium. 
When OSHA calculated the cost-to-profit ratio, it used the average 
profit per firm for the entire NAICs industry, not the average profit 
rate for firms working with beryllium. The profit rate for all 
establishments in NAICS 336322b was estimated at 1.83 percent. If, for 
example, the average profit rate for a very small entity in NAICS 
336322b were equal to 5.95 percent, the average profit rate for its 
application group, Beryllium Oxide Ceramics and Composites, then the 
ratio of the very small entity's annualized cost of the proposed rule 
to its annual profit would actually be 11.77 percent. OSHA tentatively 
concludes the 6 establishments in the NAICS specializing in beryllium 
production will have a higher than average profit rate and will be able 
to pass much of the cost onto the consumer for three main reasons: (1) 
The absence of substitutes containing the rare performance 
characteristics of beryllium; (2) the relative price insensitivity of 
(other) motor vehicles containing the special performance 
characteristics of beryllium and beryllium alloys; and (3) the fact 
that electrical and electronic components made of beryllium or 
beryllium-containing alloys typically account for only a small portion 
of the overall cost of the finished (other) motor vehicles. The 
annualized compliance cost to annual revenue ratio for NAICS 336332b is 
0.70 percent, 0.30 percent below the 1 percent threshold. Based on 
OSHA's experience, price increases of this magnitude have not 
historically been associated with the economic failure of small 
businesses.

[[Page 47701]]

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[[Page 47707]]


(c) Regulatory Flexibility Screening Analysis
    To determine if the Assistant Secretary of Labor for OSHA can 
certify that the proposed beryllium standard will not have a 
significant economic impact on a substantial number of small entities, 
the Agency has developed screening tests to consider minimum threshold 
effects of the proposed standard on small entities. The minimum 
threshold effects for this purpose are annualized costs equal to one 
percent of annual revenues, and annualized costs equal to five percent 
of annual profits, applied to each affected industry. OSHA has applied 
these screening tests both to small entities and to very small 
entities. For purposes of certification, the threshold level cannot be 
exceeded for affected small entities or very small entities in any 
affected industry.
    Tables IX-9 and Table IX-10, presented above, show that the 
annualized costs of the proposed standard do not exceed one percent of 
annual revenues for affected small entities or affected very small 
entities in any affected industry. These tables also show that the 
annualized costs of the proposed standard exceed five percent of annual 
profits for affected small entities in 12 industries and for affected 
very small entities in 30 industries. OSHA is therefore unable to 
certify that the proposed standard will not have a significant economic 
impact on a substantial number of small entities and must prepare an 
Initial Regulatory Flexibility Analysis (IRFA). The IRFA is presented 
in Chapter IX of the PEA and is reproduced in Section IX.I of this 
preamble.

G. Benefits and Net Benefits

    In this section, OSHA presents a summary of the estimated benefits 
and net benefits of the proposed beryllium rule. This section proceeds 
in five steps. The first step estimates the numbers of diseases and 
deaths prevented by comparing the current (baseline) situation to a 
world in which the proposed PEL is adopted in a final standard to a 
world in which employees are exposed at the level of the proposed PEL 
throughout their working lives. The second step also assumes that the 
proposed PEL is adopted, but uses the results from the first step to 
estimate what would happen under a more realistic scenario in which 
employees have been exposed for varying periods of time to the baseline 
situation and will thereafter be exposed to the new PEL.
    The third step covers the monetization of benefits. Then, in the 
fourth step, OSHA estimates the net benefits and incremental benefits 
of the proposed rule by comparing the monetized benefits to the costs 
presented in Chapter V of the PEA. The models underlying each step 
inevitably need to make a variety of assumptions based on limited data. 
In the fifth step, OSHA provides a sensitivity analysis to explore the 
robustness of the estimates of net benefits with respect to many of the 
assumptions made in developing and applying the underlying models. A 
full explanation of the derivation of the estimates presented here is 
provided in Chapter VII of the PEA for the proposed rule. OSHA invites 
comments on any aspect of the data and methods used to estimate the 
benefits and net benefits of this proposed rule. Because dental labs 
constitute a significant source of both costs and benefits to the rule 
(over 40 percent), OSHA is particularly interested in comments 
regarding the appropriateness of the model, assumptions, and data to 
estimating the benefits to workers in that industry.
    OSHA has added to the docket the spreadsheets used to calculate the 
estimates of benefits outlined below (OSHA, 2015a). Those interested in 
exploring the details and methodology of OSHA's benefits analysis, such 
as how the life table referred to below was developed and applied, 
should consult those spreadsheets.
Step 1--Estimation of the Steady-State Number of Beryllium-Related 
Diseases Avoided
Methods of Estimation
    The first step in OSHA's development of the benefits analysis 
compares the situation in which employees continue to be at baseline 
exposure levels for their entire working lives to the situation in 
which all employees have been exposed at a given PEL for their entire 
working lives. This is a comparison of two steady-state situations. To 
do this, OSHA must estimate both the risk associated with the baseline 
exposure levels and the risk following the promulgation of a new 
beryllium standard. OSHA's approach assumes for inputs such as the 
turnover rate and the exposure response function that they are similar 
across all workers exposed to beryllium, regardless of industry.
    An exposure-response model, discussed below, is used to estimate a 
worker's risk of beryllium-related disease based on the worker's 
cumulative beryllium exposure. The Agency used a lifetime risk model to 
estimate the baseline risk and the associated number of cases for the 
various disease endpoints. A lifetime risk model explicitly follows a 
worker each year, from work commencement onwards, accumulating the 
worker's beryllium exposure in the workplace and estimating outcomes 
each year for the competing risks that can occur. To go from exposure 
to number of cases, the Agency needs to estimate an exposure-response 
relationship, and this is discussed below. The possible outcomes are no 
change, or the various health endpoints OSHA has considered (beryllium 
sensitization, CBD, lung cancer, and the mortality associated with 
these endpoints). As part of the estimation discussion, OSHA will 
mention specific parameters used in some of the estimation methods, but 
will further discuss how these parameters were derived later in this 
section.
    The baseline lifetime risk model is the most complicated part of 
the analysis. The Agency only needs to make relatively simple 
adjustments to this model to reflect changes in activities and 
conditions due to the standard, which, working through the model, then 
lead to changes in relevant health outcomes. There are three channels 
by which the standard generates benefits. First are estimated benefits 
due to the lowering of the PEL. Second are estimated benefits with 
further exposure reductions from the substitution of non-beryllium for 
beryllium-containing materials, ending workers' beryllium exposures 
entirely. This potential source of benefits is particularly significant 
with respect to OSHA's assumptions for how dental labs are likely to 
reduce exposures (see below). Finally, the model estimates benefits due 
to the ancillary programs that are required by the proposed standard. 
The last channel affects CBD and sensitization, endpoints which may be 
mitigated or prevented with the help of ancillary provisions such as 
dermal protection and medical surveillance for early detection, and for 
which the Agency has some information on the effects on risk of 
ancillary provisions. The benefits of ancillary provisions are not 
estimated for lung cancer because the benefits from reducing lung 
cancer are considered to be the result of reducing airborne exposure 
only and thus the ancillary provisions will have no separable effect on 
airborne exposures. The discussion here will concentrate on CBD as 
being the most important and complex endpoint, and most illustrative of 
other endpoints: The structure for other endpoints is the same; only 
the exposure response functions are different. Here OSHA will

[[Page 47708]]

discuss first the exposure-response model, then the structure of the 
year-to-year changes for a worker, then the estimated exposure 
distribution in the affected population and the risk model with the 
lowering of the PEL, and, last, the other adjustments for the ancillary 
benefits and the substitution benefits.
    The exposure response model is designed to translate beryllium 
exposure to risk of adverse health endpoints. In the case of beryllium 
sensitization and CBD, the Agency uses the cumulative exposure data 
from a beryllium manufacturing facility. Specifically, OSHA uses the 
quartile data from the Cullman plant that is presented in Table VI-7 of 
the Preliminary Risk Assessment in the preamble. The raw data from this 
study show cases of CBD with cumulative exposures that would represent 
an average exposure level of less than 0.1 [micro]g/m\3\ if exposed for 
10 years; show cases of CBD with exposures lasting less than one year; 
and show cases of CBD with actual average exposure of less than 0.1 
[micro]g/m\3\.
    Prevalence is defined as the percentage of persons with a condition 
in a population at a given point in time. The quartile data in Table 
VI-7 of the Preliminary Risk Assessment are prevalence percentages (the 
number of cases of illness documented over several years in the 319 
person cohort from the Cullman plant) at different cumulative exposure 
levels. The Cullman data do not cover persons who left the work force 
or what happened to persons who remained in the workforce after the 
study was completed. For the lifetime risk model, the prevalence 
percentages will be translated into incidence percentages--the 
estimated number of new cases predicted to occur each year. For this 
purpose OSHA assumed that the incidence for any given cumulative 
exposure level is constant from year to year and continues after 
exposure ceases.
    To calculate incidence from prevalence, OSHA assumed a steady state 
in which both the size of the beryllium-exposed affected population, 
exposure concentrations during employment and prevalence are constant 
over time. If these conditions are met, and turnover among workers with 
a condition is equal to turnover for workers without a condition, then 
the incidence rate will be equal to the turnover rate multiplied by the 
prevalence rate. If the turnover rate among persons with a condition is 
higher than the turnover rate for workers without the condition, then 
this assumption will underestimate incidence. This might happen if, in 
addition to other reasons for leaving work, persons with a condition 
leave a place of employment more frequently because their disabilities 
cause them to have difficulty continuing to do the work. If the 
turnover rate among persons with a condition is lower than the turnover 
rate for workers without the condition, then this assumption will 
overestimate incidence. This could happen if an employer provides 
special benefits to workers with the condition, and the employer would 
cease to provide these benefits if the employee left work.
    To illustrate, if 10 percent of the work force (including 10 
percent of those with the condition) leave each year and if the overall 
prevalence is at 20 percent, then a 2 percent (10 percent times 20 
percent) incidence rate will be needed in order to keep a steady 20 
percent group prevalence rate each year. OSHA's model assumes a 
constant 10 percent turnover rate (see later in this section for the 
rationale for this particular turnover rate). While turnover rates are 
not available for the specific set of employees in question, for 
manufacturing as a whole, the turnover rates are greater than 20 
percent, and greater than 30 percent for the economy as a whole (BLS, 
2013). For this analysis, OSHA assumed an effective turnover rate of 10 
percent. Different turnover rates will result in different incidence 
rates. The lower the turnover rate the lower the estimated incidence 
rate. This is a conservative assumption for the industries where 
turnover rates may be higher. However, some occupations/industries, 
such as dental lab technicians, may have lower turnover rates than 
manufacturing workers. Additionally, the typical dental technician even 
if leaving one workplace, has significant likelihood of continuing to 
work as a dental technician and going to another workplace that uses 
beryllium. OSHA welcomes comments on its turnover estimates and on 
sectors, such as dental laboratories, where turnover may be lower than 
ten percent.
    Using Table VI-7 of the Preliminary Risk Assessment, when a 
worker's cumulative exposure is below 0.147 ([mu]g/m\3\-years), the 
prevalence of CBD is 2.5 percent and so the derived annual risk would 
be 0.25 percent (0.10 x 2.5 percent). It will stay at this level until 
the worker has reached a cumulative exposure of 1.468, where it will 
rise to 0.80 percent.
    The model assumes a maximum 45-year (250 days per year) working 
life (ages 20 through 65 or age of death or onset of CBD, whichever is 
earlier) and follows workers after retirement through age 80. The 45-
year working life is based on OSHA's legal requirements and is longer 
than the working lives of most exposed workers. A shorter working life 
will be examined later in this section. While employed, the worker 
accumulates beryllium exposure at a rate depending on where the worker 
is in the empirical exposure profile presented in Chapter IV of the PEA 
(i.e., OSHA calculates a general risk model which depends on the 
exposure level and then plug in our empirical exposure distribution to 
estimate the final number of cases of various health outcomes). 
Following a worker's retirement, there is no increased exposure, just a 
constant annual risk resulting from the worker's final cumulative 
exposure.
    OSHA's model follows the population of workers each year, keeping 
track of cumulative exposure and various health outcomes. Explicitly, 
each year the model calculates: The increased cumulative exposure level 
for each worker versus last year, the incidence at the new exposure 
level, the survival rate for this age bracket, and the percentage of 
workers who have not previously developed CBD in earlier years.
    For any individual year, the equation for predicting new cases of 
CBD for workers at age t is:

    New CBD cases rate(t) = modeled incidence rate(t) * survival 
rate(t) * (1- currently have CBD rate(t)), where the variables used 
are:
    New CBD cases rate(t) is the output variable to be calculated;
    cumulative exposure(t) = cumulative exposure(t-1) + current 
exposure;
    modeled incidence rate(t) is a function of cumulative exposure; 
and
    survival rate(t) is the background survival rate from mortality 
due to other causes in the national population.

    Then for the next year the model updates the survival rate (due to 
an increase in the worker's age), incidence rate (due to any increased 
cumulative exposure), and the rate of those currently having CBD, which 
increases due to the new CBD case rate of the year before. This process 
then repeats for all 60 years.
    It is important to note that this model is based on the assumption 
that prevalence is explained by an underlying constant incidence, and 
as a result, prevalence will be different depending on the average 
number of years of exposure in the population examined and (though a 
sensitivity analysis is provided later) on the assumption of a maximum 
of 45 years of exposure. OSHA also examined (OSHA 2015c) a model in 
which prevalence is constant at the levels shown in Table VI-7 of the 
preliminary

[[Page 47709]]

risk assessment, with a population age (and thus exposure) distribution 
estimated based on an assumed constant turnover rate. OSHA solicits 
comment on this and other alternative approaches to using the available 
prevalence data to develop an exposure-response function for this 
benefits analysis.
    In the next step, OSHA uses its model to take into account the 
adoption of the lower proposed PEL. OSHA uses the exposure profile for 
workers as estimated in Chapter IV of the PEA for each of the various 
application groups. These exposure profiles estimate the number of 
workers at various exposure levels, specifically the ranges less than 
0.1 [mu]g/m\3\, 0.1 to 0.2, 0.2 to 0.5, 0.5 to 1.0, 1.0 to 2.0, and 
greater than 2.0 [mu]g/m\3\. Translating these ranges into exposure 
levels for the risk model, the model assumes an average exposure equal 
to the midpoint of the range, except for the lower end, where it was 
assumed to be equal to 0.1 [mu]g/m\3\, and the upper end, where it was 
assumed to be equal to 2.0 [mu]g/m\3\.
    The model increases the workers' cumulative exposure each year by 
these midpoints and then plugs these new values into the new case 
equation. This alters the incidence rate as cumulative exposure crosses 
a threshold of the quartile data. So then using the exposure profiles 
by application group from Chapter IV of the PEA, the baseline exposure 
flows through the life time risk model to give us a baseline number of 
cases. Next OSHA calculated the number of cases estimated to occur 
after the implementation of the proposed PEL of 0.2 [mu]g/m\3\. Here 
OSHA simply takes the number of workers with current average exposure 
above 0.2 [mu]g/m\3\ and set their exposure level at 0.2 [mu]g/m\3\; 
all exposures for workers exposed below 0.2 [mu]g/m\3\ stay the same. 
After adjusting the worker exposure profile in this way, OSHA goes 
through all the same calculations and obtains a post-standard number of 
CBD cases. Subtracting estimated post-standard CBD cases from estimated 
pre-standard CBD cases gives us the number of CBD cases that would be 
averted due to the proposed change in the PEL.
    Based on these methods, OSHA's estimate of benefits associated with 
the proposed rule does not include benefits associated with current 
compliance that have already been achieved with regard to the new 
requirements, or benefits obtained from future compliance with existing 
beryllium requirements. However, available exposure data indicate that 
few employees are currently exposed above the existing standard's PEL 
of 2.0 [mu]g/m\3\. To achieve consistency with the cost estimation 
method in chapter V, all employees in the exposure profile that are 
above 2.0 [mu]g/m\3\ are assumed to be at the 2.0 [mu]g/m\3\ level.
    There is also a component that applies only to dental labs. OSHA 
has preliminarily assumed, based on the estimates of higher costs for 
engineering controls than using substitutes presented in the cost 
chapter, that rather than incur the costs of compliance with the 
proposed standard, many dental labs are likely to stop using beryllium-
containing materials after the promulgation of the proposed 
standard.\24\ OSHA estimated earlier in this PEA that, for the 
baseline, only 25 percent of dental lab workers still work with 
beryllium. OSHA estimates that, if OSHA adopts the proposed rule, 75 
percent of the 25 percent still using beryllium will stop working with 
beryllium; their beryllium exposure level will therefore drop to zero. 
OSHA estimates that the 75 percent of workers will not be a random 
sample of the dental lab exposure profile but instead will concentrate 
among workers who are currently at the highest exposure levels because 
it would cost more to reduce those higher exposures into compliance 
with the proposed PEL. Under this judgment OSHA is estimating that the 
rule would eliminate all cases of CBD in the 75 percent of dental lab 
workers with the highest exposure levels. As discussed in the 
sensitivity analysis below, dental labs constitute a significant source 
of both costs and benefits to the rule (over 40 percent), and the 
extent to which dental laboratories substitute other materials for 
beryllium has significant effects on the benefits and costs of the 
rule. To derive its baseline estimate of cases of CBD in dental 
laboratories, OSHA (1) estimated baseline cases of CBD using the 
existing rate of beryllium use in dental labs without a projection of 
further substitution; (2) estimated cases of CBD with the proposed 
regulation using an estimate that 75 percent of the dental labs with 
higher exposure would switch to other materials and thus eliminate 
exposure to beryllium; and (3) estimated that the turnover rate in the 
industry is 10 percent. OSHA welcomes comments on all aspects of the 
analysis of substitution away from beryllium in the dental laboratories 
sector.
---------------------------------------------------------------------------

    \24\ In Chapter V (Costs) of the PEA, OSHA explored the cost of 
putting in LEV instead of substitution. The Agency costed an 
enclosure for 2 technicians: The Powder Safe Type A Enclosure, 32 
inch wide with HEPA filter, AirClean Systems (2011), which including 
operating and maintenance, was annualized at $411 per worker. This 
is significantly higher than the annual cost for substitution of 
$166 per worker, shown later in this section.
---------------------------------------------------------------------------

    Estimation results for both dental labs and non-dental workplaces 
appear in the table below.

                                       CBD Case Estimates, 45-Year Totals, Baseline and With PEL of 0.2 [mu]g/m\3\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                     Current beryllium exposure  ([mu]g/m\3\)
                                                                     ------------------------------------------------------------------------    Total
                                                                         < 0.1      0.1-0.2     0.2-0.5     0.5-1.0     1.0-2.0      > 2.0
--------------------------------------------------------------------------------------------------------------------------------------------------------
Baseline................................  Dental labs...............         827         636         432         608         155         466       3,124
                                          Non-dental................       5,912         631         738         287         112         214       7,893
                                                                     -----------------------------------------------------------------------------------
                                             Total..................       6,739       1,267       1,171         895         267         679      11,017
PEL = 0.2 [mu]g/m\3\....................  Dental labs...............         679           0           0           0           0           0         679
                                          Non-dental................       5,912         631         693         255          98         186       7,774
                                                                     -----------------------------------------------------------------------------------
                                             Total..................       6,591         631         693         255          98         186       8,454
Prevented by PEL reduction..............  Dental labs...............         148         636         432         608         155         466       2,444
                                          Non-dental................           0           0          45          32          14          27         119
                                                                     -----------------------------------------------------------------------------------
                                             Total..................         148         636         478         640         169         493       2,563
--------------------------------------------------------------------------------------------------------------------------------------------------------


[[Page 47710]]

    In contrast to this PEL component of the benefits, both the 
ancillary program benefits calculation and the substitution benefits 
calculation are relatively simple. Both are percentages of the 
lifetime-risk-model CBD cases that still occur in the post-standard 
world. OSHA notes that in the context of existing CBD prevention 
programs, some ancillary-provision programs similar to those included 
in OSHA's proposal have eliminated a significant percentage of the 
remaining CBD cases (discussed later in this chapter). If the ancillary 
provisions reduce remaining CBD cases by 90 percent for example, and if 
the estimated baseline contains 120 cases of CBD, and post-standard 
compliance with a lower PEL reduces the total to 100 cases of CBD, then 
90 of those remaining 100 cases of CBD would be averted due to the 
ancillary programs.
    OSHA assumed, based on the clinical experience discussed further 
below, that approximately 65 percent of CBD cases ultimately result in 
death. Later in this chapter, OSHA provides a sensitivity analysis of 
the effects of different values for assuming this percentage at 50 
percent and 80 percent on the number of CBD deaths prevented. OSHA 
welcomes comment on this assumption. OSHA's exposure-response model for 
lung cancer is based on lung cancer mortality data. Thus, all of the 
estimated cases of lung cancer in the benefits analysis are cases of 
premature death from beryllium-related lung cancer.
    Finally, in recognition of the uncertainty in this aspect of these 
models, OSHA presents a ``high'' estimate, a ``low'' estimate, and uses 
the midpoint of these two as our ``primary'' estimate. The low estimate 
is simply those CBD fatalities prevented due to everything except the 
ancillary provisions, i.e., both the reduction in the PEL and the 
substitution by dental labs. The high estimate includes both of these 
factors plus all the ancillary benefits calculated at an effectiveness 
rate of 90 percent in preventing cases of CBD not averted by the 
reduction of the PEL. The midpoint is the combination of reductions 
attributed to adopting the proposed PEL, substitution by dental labs, 
and the ancillary provisions calculated at an effectiveness rate of 
only 45 percent.
a. Chronic Beryllium Disease
    CBD is a respiratory disease in which the body's immune system 
reacts to the presence of beryllium in the lung, causing a progression 
of pathological changes including chronic inflammation and tissue 
scarring. Immunological sensitization to beryllium (BeS) is a precursor 
that occurs before early-stage CBD. Only sensitized individuals can go 
on to develop CBD. In early, asymptomatic stages of CBD, small 
granulomatous lesions and mild inflammation occur in the lungs. As CBD 
progresses, the capacity and function of the lungs decrease, which 
eventually affects other organs and bodily functions as well. Over time 
the spread of lung fibrosis (scarring) and loss of pulmonary function 
cause symptoms such as: A persistent dry cough, shortness of breath, 
fatigue, night sweats, chest and join pain, clubbing of fingers due to 
impaired oxygen exchange, and loss of appetite. In these later stages 
CBD can also impair the liver, spleen, and kidneys, and cause health 
effects such as granulomas of the skin and lymph nodes, and cor 
pulmonale (enlargement of the heart). The speed and extent of disease 
progression may be influenced by the level and duration of exposure, 
treatment with corticosteroids, and genetics, but these effects are not 
fully understood.
    Corticosteroid therapy, in workers whose beryllium exposure has 
ceased, has been shown to control inflammation, ease symptoms, and in 
some cases prevent the development of fibrosis. However, corticosteroid 
use can have adverse effects, including increased risk of infections; 
accelerated bone loss or osteoporosis; psychiatric effects such as 
depression, sleep disturbances, and psychosis; adrenal suppression; 
ocular effects; glucose intolerance; excessive weight gain; increased 
risk of cardiovascular disease; and poor wound healing. The effects of 
CBD, and of common treatments for CBD, are discussed in detail in this 
preamble at Section V, Health Effects, and Section VIII, Significance 
of Risk.
    OSHA's review of the literature on CBD suggests three broad types 
of CBD progression (see this preamble at Section V, Health Effects). In 
the first, individuals progress relatively directly toward death 
related to CBD. They suffer rapidly advancing disability and their 
death is significantly premature. Medical intervention is not applied, 
or if it is, does little to slow the progression of disease. In the 
second type, individuals live with CBD for an extended period of time. 
The progression of CBD in these individuals is naturally slow, or may 
be medically stabilized. They may suffer significant disability, in 
terms of loss of lung function--and quality of life--and require 
medical oversight their remaining years. They would be expected to lose 
some years of normal lifespan. As discussed previously, advanced CBD 
can involve organs and systems beyond the respiratory system; thus, CBD 
can contribute to premature death from other causes. Finally, 
individuals with the third type of CBD progression do not die 
prematurely from causes related to CBD. The disease is stabilized and 
may never progress to a debilitating state. These individuals 
nevertheless may experience some disability or loss of lung function, 
as well as side effects from medical treatment, and may be affected by 
the disease in many areas of their lives: Work, recreation, family, 
etc.\25\
---------------------------------------------------------------------------

    \25\ As indicated in the Health Effects section of this 
preamble: ``It should be noted, however, that treatment with 
corticosteroids has side-effects of their own that need to be 
measured against the possibility of progression of disease (Gibson 
et al., 1996; Zaki et al., 1987). Alternative treatments such as 
azathiopurine and infliximab, while successful at treating symptoms 
of CBD, have been demonstrated to have side-effects as well 
(Pallavicino et al., 2013; Freeman, 2012)''.
---------------------------------------------------------------------------

    In the analysis that follows, OSHA assumes, based on the clinical 
experience discussed below, that 35 percent of workers who develop CBD 
experience the third type of progression and do not die prematurely 
from CBD. The remaining 65 percent were estimated to die prematurely, 
whether from rapid disease progression (type 1) or slow (type 2). 
Although the proportion of CBD patients who die prematurely as a result 
of the disease is not well understood or documented at this time, OSHA 
believes this assumption is consistent with the information submitted 
in response to the RFI. Newman et al. (2003) presented a scenario for 
what they considered to be the ``typical'' CBD patient:

    We have included an example of a life care plan for a typical 
clinical case of CBD. In this example, the hypothetical case is 
diagnosed at age 40 and assumed to live an additional 33.7 years 
(approximately 5% reduced life expectancy in this model). In this 
hypothetical example, this individual would be considered to have 
moderate severity of chronic beryllium disease at the time of 
initial diagnosis. They require treatment with prednisone and 
treatment for early cor pulmonale secondary to CBD. They have 
experienced some, but not all, of the side effects of treatment and 
only the most common CBD-related health effects.

    In short, most workers diagnosed with CBD are expected to have 
shortened life expectancy, even if they do not progress rapidly and 
directly to death. It should be emphasized that this represents the 
Agency's best estimate of the mortality related to CBD based upon the 
current available evidence. As described in Section V, Health Effects, 
there is a substantial degree of uncertainty as to the prognosis for 
those contracting CBD, particularly as the relatively less severe

[[Page 47711]]

cases are likely not to be studied closely for the remainder of their 
lives.
    As mentioned previously, OSHA used the Cullman data set for 
empirical estimates of beryllium sensitization and CBD prevalence in 
its exposure response model, which translates beryllium exposure to 
risk of adverse health endpoints for the purpose of determining the 
benefits that could be achieved by preventing those adverse health 
endpoints.
    OSHA chose the cumulative exposure quartile data as the basis for 
this benefits analysis. The choice of cumulative quartiles was based in 
part on the need to use the cumulative exposure forecast developed in 
the model, and in part on the fact that in statistically fitted models 
for CBD, the cumulative exposure tended to fit the CBD data better than 
other exposure variables. OSHA also chose the quartile model because 
the outside expert who examined the logistic and proportional hazards 
models believed statistical modeling of the data set to be unreliable 
due to its small size. In addition, the proportional hazards model with 
its dummy variables by year of detection is difficult to interpret for 
purposes of this section. Of course regression analyses are often 
useful in empirical analysis. They can be a useful compact 
representation of a set of data, allow investigations of various 
variable interactions and possible causal relationships, have added 
flexibility due to covariate transformations, and under certain 
conditions can be shown to be statistically ``optimal.'' However, they 
are only useful when used in the proper setting. The possibility of 
misspecification of functional form, endogeneity, or incorrect 
distributional assumptions are just three reasons to be cautious about 
using regression analyses.
    On the other hand, the use of results produced by a quartile 
analysis as inputs in a benefits assessment implies that the analytic 
results are being interpreted as evidence of an exposure-response 
causal relationship. Regression analysis is a more sophisticated 
approach to estimating causal relationships (or even correlations) than 
quartile or other quantile analysis, and any data limitations that may 
apply to a particular regression-based exposure-response estimation 
also apply to exposure-response estimation conducted with a quartile 
analysis using the same data set. In this case, OSHA adopted the 
quartile analysis because the logistic regression analysis yielded 
extremely high prevalence rates for higher level of exposure over long 
time periods that some might not find credible. Use of the quartile 
analysis serves to show that there are significant benefits even 
without using an extremely high estimate of prevalence for long periods 
of exposure at high levels. As a check on the quartile model, the 
Agency performed the same benefits calculation using the logit model 
estimated by the Agency's outside expert, and these benefit results are 
presented in a separate OSHA background document (OSHA, 2015b). The 
difference in benefits between the two models is slight, and there is 
no qualitative change in final outcomes. The Agency solicits comment on 
these issues.
(1) Number of CBD Cases Prevented by the Proposed PEL
    To examine the effect of simply changing the PEL, including the 
effect of the standard on some dental labs to discontinue their use of 
beryllium, OSHA compared the number of CBD-related deaths (mortality) 
and cases of non-fatal CBD (morbidity) that would occur if workers were 
exposed for a 45-year working life to PELs of 0.1, 0.2, or 0.5 [mu]g/
m\3\ to the number of cases that would occur at levels of exposure at 
or below the current PEL. The number of avoided cases over a 
hypothetical working life of exposure for the current population at a 
lower PEL is then equal to the difference between the number of cases 
at levels of exposure at or below the current PEL for that population 
minus the number of cases at the lower PEL. This approach represents a 
steady-state comparison based on what would hypothetically happen to 
workers who received a specific average level of occupational exposure 
to beryllium during an entire working life. (Chapter VII in the PEA 
modifies this approach by introducing a model that takes into account 
the timing of benefits before steady state is reached.)
    As indicated in Table IX-11, the Agency estimates that there would 
be 16,240 cases of beryllium sensitization, from which there would be 
11,017, or about 70 percent, progressing to CBD. The Agency arrived at 
these estimates by using the CBD and BeS prevalence values from the 
Agency's preliminary risk analysis, the exposure profile at current 
exposure levels (under an assumption of full, or fixed, compliance with 
the existing beryllium PEL), and the model outlined in the previous 
methods of estimation section after a working lifetime of exposure. 
Applying the prior midpoint estimate, as explained above, that 65 
percent of CBD cases cause or contribute to premature death, the Agency 
predicts a total of 7,161 cases of mortality and 3,856 cases of 
morbidity from exposure at current levels; this translates, annually, 
to 165 cases of mortality and 86 cases of morbidity. At the proposed 
PEL, OSHA's base model estimates that, due to the airborne factor only, 
a total of 2,563 CBD cases would be avoided from exposure at current 
levels, including 1,666 cases of mortality and 897 cases of morbidity--
or an average of 37 cases of mortality and 20 cases of morbidity 
annually. OSHA has not estimated the quantitative benefits of 
sensitization cases avoided.
    OSHA requests comment on this analysis, including feedback on the 
data relied on and the approach and assumptions used. As discussed 
earlier, based on information submitted in response to the RFI, the 
Agency estimates that most of the workers with CBD will progress to an 
early death, even if it comes after retirement, and has quantified 
those cases prevented. However, given the evolving nature of science 
and medicine, the Agency invites public comment on the current state of 
CBD-related mortality.
    The proposed standard also includes provisions for medical 
surveillance and removal. The Agency believes that to the extent the 
proposal provides medical surveillance sooner and to more workers than 
would have been the case in the absence of the proposed standard, 
workers will be more likely to receive appropriate treatment and, where 
necessary, removal from beryllium exposure. These interventions may 
lessen the severity of beryllium-related illnesses, and possibly 
prevent premature death. The Agency requests public comment on this 
issue.
(2) CBD Cases Prevented by the Ancillary Provisions of the Proposed 
Standard
    The nature of the chronic beryllium disease process should be 
emphasized. As discussed in this preamble at Section V, Heath Effects, 
the chronic beryllium disease process involves two steps. First, 
workers become sensitized to beryllium. In most epidemiological studies 
of CBD conducted to date, a large percentage of sensitized workers have 
progressed to CBD. A certain percentage of the population has an 
elevated risk of this occurring, even at very low exposure levels, and 
sensitization can occur from dermal as well as inhalation exposure to 
beryllium. For this reason, the threat of beryllium sensitization and 
CBD persist to a substantial degree, even at very low levels of 
airborne beryllium exposure. It is therefore desirable not only to 
significantly reduce airborne beryllium exposure, but to avoid nearly 
any source

[[Page 47712]]

of beryllium exposure, so as to prevent beryllium sensitization.
    The analysis presented above accounted only for CBD-prevention 
benefits associated with the proposed reduction of the PEL, from 2 ug/
m\3\ to 0.2 ug/m\3\. However, the proposed standard also includes a 
variety of ancillary provisions--including requirements for respiratory 
protection, personal protective equipment (PPE), housekeeping 
procedures, hygiene areas, medical surveillance, medical removal, and 
training--that the Agency believes would further reduce workers' risk 
of disease from beryllium exposure. These provisions were described in 
Chapter I of the PEA and discussed extensively in Section XVIII of this 
preamble, Summary and Explanation of the Proposed Standard.
    The leading manufacturer of beryllium in the U.S., Materion 
Corporation (Materion), has implemented programs including these types 
of provisions in several of its plants and has worked with NIOSH to 
publish peer-reviewed studies of their effectiveness in reducing 
workers' risk of sensitization and CBD. The Agency used the results of 
these studies to estimate the health benefits associated with a 
comprehensive standard for beryllium.
    The best available evidence on comprehensive beryllium programs 
comes from studies of programs introduced at Materion plants in 
Reading, PA; Tucson, AZ; and Elmore, OH. These studies are discussed in 
detail in this preamble at Section VI, Preliminary Risk Assessment, and 
Section VIII, Significance of Risk. All three facilities were in 
compliance with the current PEL prior to instituting comprehensive 
programs, and had taken steps to reduce airborne levels of beryllium 
below the PEL, but their medical surveillance programs continued to 
identify cases of sensitization and CBD among their workers. Beginning 
around 2000, these facilities introduced comprehensive beryllium 
programs that used a combination of engineering controls, dermal and 
respiratory PPE, and stringent housekeeping measures to reduce workers' 
dermal exposures and airborne exposures. These comprehensive beryllium 
programs have substantially lowered the risk of sensitization among 
workers. At the times that studies of the programs were published, 
insufficient follow-up time had elapsed to report directly on the 
results for CBD. However, since only sensitized workers can develop 
CBD, reduction of sensitization risk necessarily reduces CBD risk as 
well.
    In the Reading, PA copper beryllium plant, full-shift airborne 
exposures in all jobs were reduced to a median of 0.1 ug/m\3\ or below, 
and dermal protection was required for production-area workers, 
beginning in 2000-2001 (Thomas et al., 2009). In 2002, the process with 
the highest exposures (with a median of 0.1 ug/m\3\) was enclosed, and 
workers involved in that process were required to use respiratory 
protection. Among 45 workers hired after the enclosure was built and 
respiratory protection instituted, one was found to be sensitized (2.2 
percent). This is more than an 80 percent reduction in sensitization 
from a previous group of 43 workers hired after 1992, 11.5 percent of 
whom had been sensitized by the time of testing in 2000.
    In the Tucson beryllium ceramics plant, respiratory and skin 
protection was instituted for all workers in production areas in 2000 
(Cummings et al., 2007). BeLPT testing in 2000-2004 showed that only 1 
(1 percent) of 97 workers hired during that time period was sensitized 
to beryllium. This is a 90 percent reduction from the prevalence of 
sensitization in a 1998 BeLPT screening, which found that 6 (9 percent) 
of 69 workers hired after 1992 were sensitized.
    In the Elmore, OH beryllium production and processing facility, all 
new workers were required to wear loose-fitting powered air-purifying 
respirators (PAPRs) in manufacturing buildings, beginning in 1999 
(Bailey et al., 2010). Skin protection became part of the protection 
program for new workers in 2000, and glove use was required in 
production areas and for handling work boots, beginning in 2001. Bailey 
et al. (2010) found that 23 (8.9 percent) of 258 workers hired between 
1993 and 1999, before institution of respiratory and dermal protection, 
were sensitized to beryllium. The prevalence of sensitization among the 
290 workers who were hired after the respiratory protection and PPE 
measures were put in place was about 2 percent, close to an 80 percent 
reduction in beryllium sensitization.
    In a response to OSHA's 2002 Request for Information (RFI), Lee 
Newman et al. from National Jewish Medical and Research Center (NJMRC) 
summarized results of beryllium program effectiveness from several 
sources. Said Dr. Newman (in response to Question #33):

    Q. 33. What are the potential impacts of reducing occupational 
exposures to beryllium in terms of costs of controls, costs for 
training, benefits from reduction in the number or severity of 
illnesses, effects on revenue and profit, changes in worker 
productivity, or any other impact measures than you can identify?
    A: From experience in [the Tucson, AZ facility discussed above], 
one can infer that approximately 90 percent of beryllium 
sensitization can be eliminated. Furthermore, the preliminary data 
would suggest that potentially 100 percent of CBD can be eliminated 
with appropriate workplace control measures.
    In a study by Kelleher 2001, Martyny 2000, Newman, JOEM 2001) in 
a plant that previously had rates of sensitization as high as 9.7 
percent, the data suggests that when lifetime weighted average 
exposures were below 0.02 [mu]g per cu meter that the rate of 
sensitization fell to zero and the rate of CBD fell to zero as well.
    In an unpublished study, we have been conducting serial 
surveillance including testing new hires in a precision machining 
shop that handles beryllium and beryllium alloys in the Southeast 
United States. At the time of the first screening with the blood 
BeLPT of people tested within the first year of hire, we had a rate 
of 6.7 percent (4/60) sensitization and with 50 percent of these 
individuals showing CBD at the time of initial clinical evaluation. 
At that time, the median exposures in the machining areas of the 
plant was 0.47 [mu]g per cu meter. Subsequently, efforts were made 
to reduce exposures, further educate the workforce, and increase 
monitoring of exposure in the plant. Ongoing testing of newly hired 
workers within the first year of hire demonstrated an incremental 
decline in the rate of sensitization and in the rate of CBD. For 
example, at the time of most recent testing when the median airborne 
exposures in the machining shop were 0.13 [mu]g per cu meter, the 
percentage of newly hired workers found to have beryllium 
sensitization or CBD was now 0 percent (0/55). Notably, we also saw 
an incremental decline in the percentage of longer term workers 
being detected with sensitization and disease across this time 
period of exposure reduction and improved hygiene practices.
    Thus, in calculating the potential economic benefit, it's 
reasonable to work with the assumption that with appropriate efforts 
to control exposures in the work place, rates of sensitization can 
be reduced by over 90 percent. (NJMRC, RFI Ex. 6-20)
    OSHA has reviewed these papers and is in agreement with Dr. 
Newman's testimony. OSHA judges Dr. Newman's estimate to be an upper 
bound of the effectiveness of ancillary programs and examined the 
results of using Dr. Newman's estimate that beryllium ancillary 
programs can reduce BeS by 90 percent, and potentially eliminate CBD 
where sensitization is reduced, because CBD can only occur where there 
is sensitization. OSHA applied this 90 percent reduction factor to all 
cases of CBD remaining after application of the reductions due to 
lowering the PEL alone. OSHA applied this reduction broadly because the 
proposed standard would require housekeeping and PPE related to skin 
exposure (18,000 of

[[Page 47713]]

28,000 employees will need PPE because of possible skin exposure) to 
apply to all or most employees likely to come in contact with beryllium 
and not just those with exposure above the action level. Table IX-11 
shows that there are 11,017 baseline cases of CBD and that the proposed 
PEL of 0.2 [micro]g/m\3\ would prevent 2,563 cases through airborne 
prevention alone. The remaining number of cases of CBD is then 8,454 
(11,017 minus 2,563). If OSHA applies the full ninety percent reduction 
factor to account for prevention of skin exposure (``non-airborne'' 
protections), then 7,609 (90 percent of 8,454 cases) additional cases 
of CBD would be prevented.
    The Agency recognizes that there are significant differences 
between the comprehensive programs discussed above and the proposed 
standard. While the proposed standard includes many of the same 
elements, it is generally less stringent. For example, the proposed 
standard's requirements for respiratory protection and PPE are 
narrower, and many provisions of the standard apply only to workers 
exposed above the proposed TWA PEL or STEL. However, many provisions, 
such as housekeeping and beryllium work areas, apply to all employers 
covered by the proposed standard. To account for these differences, 
OSHA has provided a range of benefits estimates (shown in Table IX-11), 
first, assuming that there are no ancillary provisions to the standard, 
and, second, assuming that the comprehensive standard achieves the full 
90-percent reduction in risk documented in existing programs. The 
Agency is taking the midpoint of these two numbers as its main estimate 
of the benefits of avoided CBD due to the ancillary provisions of the 
proposed standard. The results in Table IX-11 suggest that 
approximately 60 percent of the beryllium sensitization cases and the 
CBD cases avoided would be attributable to the ancillary provisions of 
the standard. OSHA solicits comment on all aspects of this approach to 
analyzing ancillary provisions and solicits additional data that might 
serve to make more accurate estimates of the effects of ancillary 
provisions. OSHA is interested in the extent of the effects of 
ancillary provisions and whether these apply to all exposed employees 
or only those exposed above or below a given exposure level.
(3) Morbidity Only Cases
    As previously indicated, the Agency does not believe that all CBD 
cases will ultimately result in premature death. While currently strong 
empirical data on this are lacking, the Agency estimates that 
approximately 35 percent of cases would not ultimately be fatal, but 
would result in some pain and suffering related to having CBD, and 
possible side effects from steroid treatment, as well as the dread of 
not knowing whether the disease will ultimately lead to premature 
death. These would be described as ``mild'' cases of CBD relative to 
the others. These are the residual cases of CBD after cases with 
premature mortality have been counted. As indicated in Table IX-11, the 
Agency estimates the standard will prevent 2,228 such cases (midpoint) 
over 45 years, or an estimated 50 cases annually.
b. Lung Cancer
    In addition to the Agency's determinations with respect to the risk 
of chronic beryllium disease, the Agency has preliminarily determined 
that chronic beryllium exposure at the current PEL can lead to a 
significantly elevated risk of (fatal) lung cancer. OSHA used the 
estimation methodology outlined at the beginning of this section. 
However, unlike with chronic beryllium disease, the underlying data 
were based on incidence of lung cancer and thus there was no need to 
address the possible limitations of prevalence data. The Agency also 
used lifetime excess risk estimates of lung cancer mortality, presented 
in Table VI-20 in Section VI of this preamble, Preliminary Risk 
Assessment, to estimate the benefits of avoided lung cancer mortality. 
The lung cancer risk estimates are derived from one of the best-fitting 
models in a recent, high-quality NIOSH lung cancer study, and are based 
on average exposure levels. The estimates of excess lifetime risk of 
lung cancer were taken from the line in Table VI-20 in the risk 
assessment labeled PWL (piecewise log-linear) not including 
professional and asbestos workers. This model avoids possible 
confounding from asbestos exposure and reduces the potential for 
confounding due to smoking, as smoking rates and beryllium exposures 
can be correlated via professional worker status. Of the three 
estimates in the NIOSH study that excluded professional workers and 
those with asbestos exposure, this model was chosen because it was at 
the midpoint of risk results.
    Table IX-11 shows the number of avoided fatal lung cancers for PELs 
of 0.2 [mu]g/m\3\, 0.1 [mu]g/m\3\, and 0.5 [mu]g/m\3\. At the proposed 
PEL of 0.2 [mu]g/m\3\, an estimated 180 lung cancers would be prevented 
over the lifetime of the current worker population. This is the 
equivalent of 4.0 cases avoided annually, given a 45-year working life 
of exposure.
    Combining the two major fatal health endpoints--for lung cancer and 
CBD-related mortality--OSHA estimates that the proposed PEL would 
prevent between 1,846 and 6,791 premature fatalities over the lifetime 
of the current worker population, with a midpoint estimate of 4,318 
fatalities prevented. This is the equivalent of between 41 and 151 
premature fatalities avoided annually, with a midpoint estimate of 96 
premature fatalities avoided annually, given a 45-year working life of 
exposure.
    Note that the Agency based its estimates of reductions in the 
number of beryllium-related diseases over a working life of constant 
exposure for workers who are employed in a beryllium-exposed occupation 
for their entire working lives, from ages 20 to 65. In other words, 
workers are assumed not to enter or exit jobs with beryllium exposure 
mid-career or to switch to other exposure groups during their working 
lives. While the Agency is legally obligated to examine the effect of 
exposures from a working lifetime of exposure and set its standard 
accordingly,\26\ in an alternative analysis purely for informational 
purposes, using the same underlying risk model for CBD, the Agency 
examined, in Chapter VII of the PEA, the effect of assuming that 
workers are exposed for a maximum of only 25 working years, as opposed 
to the 45 years assumed in the main analysis. While all workers are 
assumed to have less cumulative exposure under the 25-years-of-exposure 
assumption, the effective exposed population over time is 
proportionately increased.
---------------------------------------------------------------------------

    \26\ Section (6)(b)(5) of the OSH Act states: ``The Secretary, 
in promulgating standards dealing with toxic materials or harmful 
physical agents under this subsection, shall set the standard which 
most adequately assures, to the extent feasible, on the basis of the 
best available evidence, that no employee will suffer material 
impairment of health or functional capacity even if such employee 
has regular exposure to the hazard dealt with by such standard for 
the period of his working life.'' Given that it is necessary for 
OSHA to reach a determination of significant risk over a working 
life, it is a logical extension to estimate what this translates 
into in terms of estimated benefits for the affected population over 
the same period.
---------------------------------------------------------------------------

    A comparison of exposures over a maximum of 25 working years versus 
over a potentially 45-year working life shows variations in the number 
of estimated prevented cases by health outcome. For chronic beryllium 
disease, there is a substantial increase in the number of estimated 
baseline and prevented cases if one assumes that the typical maximum 
exposure period is 25 years, as opposed to 45. This reflects the

[[Page 47714]]

relatively flat CBD risk function within the relevant exposure range, 
given varying levels of airborne beryllium exposure--shortening the 
average tenure and increasing the exposed population over time 
translates into larger total numbers of people sensitized to beryllium. 
This, in turn, results in larger populations of individuals contracting 
CBD. Since the lung cancer model itself is based on average, as opposed 
to cumulative, exposure, it is not adaptable to estimate exposures over 
a shorter period of time. As a practical matter, however, over 90 
percent of illness and mortality attributable to beryllium exposure in 
this analysis comes from CBD.
    Overall, the 45-year-maximum-working-life assumption yields smaller 
estimates of the number of cases of avoided fatalities and illnesses 
than does the maximum-25-years-of-exposure assumption. For example, the 
midpoint estimates of the number of avoided fatalities and illnesses 
related to CBD under the proposed PEL of 0.2 [mu]g/m\3\ increases from 
92 and 50, respectively, under the maximum-45-year-working-life 
assumption to 145 and 78, respectively, under the maximum-25-year-
working-life assumption--or approximately a 57 to 58 percent 
increase.\27\
---------------------------------------------------------------------------

    \27\ Technically, this analysis assumes that workers receive 25 
years' worth of beryllium exposure, but that they receive it over 45 
working years, as is assumed by the risk models in the risk 
assessment. It also accounts for the turnover implied by 25, as 
opposed to 45, years of work. However, it is possible that an 
alternate analysis, which accounts for the larger number of post-
exposure worker-years implied by workers departing their jobs before 
the end of their working lifetime, might find even larger health 
effects for workers receiving 25 years' worth of beryllium exposure.

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[[Page 47715]]

[GRAPHIC] [TIFF OMITTED] TP07AU15.022


[[Page 47716]]


Step 2--Estimating the Stream of Benefits Over Time
    Risk assessments in the occupational environment are generally 
designed to estimate the risk of an occupationally related illness over 
the course of an individual worker's lifetime. As demonstrated 
previously in this section, the current occupational exposure profile 
for a particular substance for the current cohort of workers can be 
matched up against the expected profile after the proposed standard 
takes effect, creating a ``steady state'' estimate of benefits. 
However, in order to annualize the benefits for the period of time 
after the beryllium rule takes effect, it is necessary to create a 
timeline of benefits for an entire active workforce over that period.
    While there are various approaches that could be taken for modeling 
the workforce, there seem to be two polar extremes. At one extreme, one 
could assume that none of the benefits occur until after the worker 
retires, or at least 45 years in the future. In the case of lung 
cancer, that period would effectively be at least 55 years, since the 
45 years of exposure must be added to a 10-year latency period during 
which it is assumed that lung cancer does not develop.\28\ At the other 
extreme, one could assume that the benefits occur immediately, or at 
least immediately after a designated lag. However, based on the various 
risk models discussed in this preamble at Section VI, Risk Assessment, 
which reflect real-world experience with development of disease over an 
extended period of time, it appears that the actual pattern occurs at 
some point between these two extremes.
---------------------------------------------------------------------------

    \28\ This assumption is consistent with the 10-year lag 
incorporated in the lung cancer risk models used in OSHA's 
preliminary risk assessment.
---------------------------------------------------------------------------

    At first glance, the simplest intermediate approach would be to 
follow the pattern of the risk assessments, which are based in part on 
life tables, and observe that typically the risk of the illness grows 
gradually over the course of a working life and into retirement. Thus, 
the older the person exposed to beryllium, the higher the odds that 
that person will have developed the disease.
    However, while this is a good working model for an individual 
exposed over a working life, it is not very descriptive of the effect 
of lowering exposures for an entire working population. In the latter 
case, in order to estimate the benefits of the standard over time, one 
has to consider that workers currently being exposed to beryllium are 
going to vary considerably in age. Since the calculated health risks 
from beryllium exposure depend on a worker's cumulative exposure over a 
working lifetime, the overall benefits of the proposed standard will 
phase in over several decades, as the cumulative exposure gradually 
falls for all age groups, until those now entering the workforce reach 
retirement and the annual stream of beryllium-related illnesses reaches 
a new, significantly lowered ``steady state.'' \29\ That said, the 
near-term impact of the proposed rule estimated for those workers with 
similar current levels of cumulative exposure will be greater for 
workers who are now middle-aged or older. This conclusion follows in 
part from the structure of the relative risk model used for lung cancer 
in this analysis and the fact that the background mortality rates for 
lung cancer increase with age.
---------------------------------------------------------------------------

    \29\ Technically, the RA lung cancer model is based on average 
exposure, Nonetheless, as noted in the RA, the underlying studies 
found lung cancer to be significantly related to cumulative 
exposure. Particularly since the large majority of the benefits are 
related to CBD, the Agency considers this fairly descriptive of the 
overall phase-in of benefits from the standard.
---------------------------------------------------------------------------

    In order to characterize the magnitude of benefits before the 
steady state is reached, OSHA created a linear phase-in model to 
reflect the potential timing of benefits. Specifically, OSHA estimated 
that, for all non-cancer cases, while the number of cases of beryllium-
related disease would gradually decline as a result of the proposed 
rule, they would not reach the steady-state level until 45 years had 
passed. The reduction in cases estimated to occur in any given year in 
the future was estimated to be equal to the steady-state reduction (the 
number of cases in the baseline minus the number of cases in the new 
steady state) times the ratio of the number of years since the standard 
was implemented and a working life of 45 years. Expressed 
mathematically:

Nt = (C-S) x (t/45),

Where Nt is the number of non-malignant beryllium-related 
diseases avoided in year t; C is the current annual number of non-
malignant beryllium-related diseases; S is the steady-state annual 
number of non-malignant beryllium-related diseases; and t represents 
the number of years after the proposed standard takes effect, with t 
<= 45.

    In the case of lung cancer, the function representing the decline 
in the number of beryllium-related cases as a result of the proposed 
rule is similar, but there would be a 10-year lag before any reduction 
in cancer cases would be achieved. Expressed mathematically, for lung 
cancer:

Lt = (Cm-Sm) x ((t-10)/45)),

Where 10 <= t <= 55 and Lt is the number of lung cancer 
cases avoided in year t as a result of the proposed rule; 
Cm is the current annual number of beryllium-related lung 
cancers; and Sm is the steady-state annual number of 
beryllium-related lung cancers.

    This model was extended to 60 years for all the health effects 
previously discussed in order to incorporate the 10-year lag, in the 
case of lung cancer, and a maximum-45-year working life, as well as to 
capture some occupationally-related disease that manifests itself after 
retirement.\30\ As a practical matter, however, there is no overriding 
reason for stopping the benefits analysis at 60 years. An internal 
analysis by OSHA indicated that, both in terms of cases prevented, and 
even with regard to monetized benefits, particularly when lower 
discount rates are used, the estimated benefits of the standard are 
larger on an annualized basis if the analysis extends further into the 
future. The Agency welcomes comment on the merit of extending the 
benefits analysis beyond the 60-years analyzed in the PEA.
---------------------------------------------------------------------------

    \30\ The left-hand columns in the tables in Appendix VII-A of 
the PEA provide estimates using this model of the stream of 
prevented fatalities and illnesses due to the proposed beryllium 
rule.
---------------------------------------------------------------------------

    In order to compare costs to benefits, OSHA assumes that economic 
conditions remain constant and that annualized costs--and the 
underlying costs--will repeat for the entire 60-year time horizon used 
for the benefits analysis (as discussed in Chapter V of the PEA). OSHA 
welcomes comments on the assumption for both the benefit and cost 
analysis that economic conditions remain constant for sixty years. OSHA 
is particularly interested in what assumptions and time horizon should 
be used instead and why.
Separating the Timing of Mortality
    In previous sections, OSHA modeled the timing and incidence of 
morbidity. OSHA's benefit estimates are based on an underlying CBD-
related mortality rate of 65 percent. However, this mortality is not 
simultaneous with the onset of morbidity. Although mortality from CBD 
has not been well studied, OSHA believes, based on discussions with 
experienced clinicians, that the average lag for a larger population 
has a range of 10 to 30 years between morbidity and mortality. The 
Agency's review of Workers Compensation data related to beryllium 
exposure from the Office of Worker Compensation Programs (OWCP) 
Division of Energy Employees Occupational Illness Compensation is 
consistent with this range. Hence, for the purposes of this

[[Page 47717]]

proposal, OSHA estimates that mortality occurs on average 20 years 
after the onset of CBD morbidity. Thus, for example, the prevented 
deaths that would have occurred in year 21 after the promulgation of 
the rule are associated with the CBD morbidity cases prevented in year 
one. OSHA requests comment on this estimate and range.
    The Agency invites comment on each of these elements of the 
analysis, particularly on the estimates of the expected life expectancy 
of a patient with CBD.
Step 3--Monetizing the Benefits of the Proposed Rule
    To estimate the monetary value of the reductions in the number of 
beryllium-related fatalities, OSHA relied, as OMB recommends, on 
estimates developed from the willingness of affected individuals to pay 
to avoid a marginal increase in the risk of fatality. While a 
willingness-to-pay (WTP) approach clearly has theoretical merit, it 
should be noted that an individual's willingness to pay to reduce the 
risk of fatality would tend to underestimate the total willingness to 
pay, which would include the willingness of others--particularly the 
immediate family--to pay to reduce that individual's risk of fatality.
    For estimates using the willingness-to-pay concept, OSHA relied on 
existing studies of the imputed value of fatalities avoided based on 
the theory of compensating wage differentials in the labor market. 
These studies rely on certain critical assumptions for their accuracy, 
particularly that workers understand the risks to which they are 
exposed and that workers have legitimate choices between high- and low-
risk jobs. These assumptions are far from obviously met in actual labor 
markets.\31\ A number of academic studies, as summarized in Viscusi & 
Aldy (2003), have shown a correlation between higher job risk and 
higher wages, suggesting that employees demand monetary compensation in 
return for a greater risk of injury or fatality. The estimated trade-
off between lower wages and marginal reductions in fatal occupational 
risk--that is, workers' willingness to pay for marginal reductions in 
such risk--yields an imputed value of an avoided fatality: The 
willingness-to-pay amount for a reduction in risk divided by the 
reduction in risk.\32\
---------------------------------------------------------------------------

    \31\ On the former assumption, see the discussion in Chapter II 
of the PEA on imperfect information. On the latter, see, for 
example, the discussion of wage compensation for risk for union 
versus nonunion workers in Dorman and Hagstrom (1998).
    \32\ For example, if workers are willing to pay $90 each for a 
1/100,000 reduction in the probability of dying on the job, then the 
imputed value of an avoided fatality would be $90 divided by 1/
100,000, or $9,000,000. Another way to consider this result would be 
to assume that 100,000 workers made this trade-off. On average, one 
life would be saved at a cost of $9,000,000.
---------------------------------------------------------------------------

    OSHA has used this approach in many recent proposed and final 
rules. Although this approach has been criticized for yielding results 
that are less than statistically robust (see, for example, Hintermann, 
Alberini and Markandya, 2010), a more recent WTP analysis, by Kniesner 
et al. (2012), of the trade-off between fatal job risks and wages, 
using panel data, seems to address many of the earlier econometric 
criticisms by controlling for measurement error, endogeneity, and 
heterogeneity. In conclusion, the Agency views the WTP approach as the 
best available and will rely on it to monetize benefits.\33\ OSHA 
welcomes comments on the use of willingness-to-pay measures and 
estimates based on compensating wage differentials.
---------------------------------------------------------------------------

    \33\ Note that, consistent with the economics literature, these 
estimates would be for reducing the risk of an acute (immediate) 
fatality. They do not include an individual's willingness to pay to 
avoid a higher risk of illness prior to fatality, which is 
separately estimated in the following section.
---------------------------------------------------------------------------

    Viscusi & Aldy (2003) conducted a meta-analysis of studies in the 
economics literature that use a willingness-to-pay methodology to 
estimate the imputed value of life-saving programs and found that each 
fatality avoided was valued at approximately $7 million in 2000 
dollars. Using the GDP Deflator (U.S. BEA, 2010), this $7 million base 
number in 2000 dollars yields an estimate of $8.7 million in 2010 
dollars for each fatality avoided.\34\
---------------------------------------------------------------------------

    \34\ An alternative approach to valuing an avoided fatality is 
to monetize, for each year that a life is extended, an estimate from 
the economics literature of the value of that statistical life-year 
(VSLY). See, for instance, Aldy and Viscusi (2007) for discussion of 
VSLY theory and FDA (2003), pp. 41488-9, for an application of VSLY 
in rulemaking. OSHA has not investigated this approach, but welcomes 
comment on the issue.
---------------------------------------------------------------------------

    In addition to the benefits that are based on the implicit value of 
fatalities avoided, workers also place an implicit value on 
occupational injuries or illnesses avoided, which reflect their 
willingness to pay to avoid monetary costs (for medical expenses and 
lost wages) and quality-of-life losses as a result of occupational 
illness. Chronic beryllium disease and lung cancer can adversely affect 
individuals for years, or even decades, in non-fatal cases, or before 
ultimately proving fatal. Because measures of the benefits of avoiding 
these illnesses are rare and difficult to find, OSHA has included a 
range based on a variety of estimation methods.
    For both CBD and lung cancer, there is typically some permanent 
loss of lung function and disability, on-going medical treatments, side 
effects of medicines, and major impacts on one's ability to work, 
marry, enjoy family life, and quality of life.
    While diagnosis with CBD is evidence of material impairment of 
health, placing a precise monetary value on this condition is 
difficult, in part because the severity of symptoms may vary 
significantly among individuals. For that reason, for this preliminary 
analysis, the Agency employed a broad range of valuation, which should 
encompass the range of severity these individuals may encounter.
    Using the willingness-to-pay approach, discussed in the context of 
the imputed value of fatalities avoided, OSHA has estimated a range in 
valuations (updated and reported in 2010 dollars) that runs from 
approximately $62,000 per case--which reflects estimates developed by 
Viscusi and Aldy (2003), based on a series of studies primarily 
describing simple accidents--to upwards of $5 million per case--which 
reflects work developed by Magat, Viscusi, and Huber (1996) for non-
fatal cancer. The latter number is based on an approach that places a 
willingness-to-pay value to avoid serious illness that is calibrated 
relative to the value of an avoided fatality. OSHA previously used this 
approach in the Preliminary Economic Analysis (PEA) supporting its 
respirable crystalline silica proposal (2013) and in the Final Economic 
Analysis (FEA) supporting its hexavalent chromium final rule (2006), 
and EPA (2003) used this approach in its Stage 2 Disinfection and 
Disinfection Byproducts Rule concerning regulation of primary drinking 
water. Based on Magat, Viscusi, and Huber (1996), EPA used studies on 
the willingness to pay to avoid nonfatal lymphoma and chronic 
bronchitis as a basis for valuing a case of nonfatal cancer at 58.3 
percent of the value of a fatal cancer. OSHA's estimate of $5 million 
for an avoided case of non-fatal cancer is based on this 58.3 percent 
figure.
    The Agency believes this range of estimates, between $62,000 and $5 
million, is descriptive of the value of preventing morbidity associated 
with moderate to severe CBD that ultimately results in premature death. 
\35\
---------------------------------------------------------------------------

    \35\ There are several benchmarks for valuation of health 
impairment due to beryllium exposure, using a variety of techniques, 
which provide a number of mid-range estimates between OSHA's high 
and low estimates. For a fuller discussion of these benchmarks, see 
Chapter VII of the PEA.

---------------------------------------------------------------------------

[[Page 47718]]

    While the Agency has estimated that 65 percent of CBD cases will 
result in premature mortality, the Agency has also estimated that 
approximately 35 percent of CBD cases will not result in premature 
mortality. However, the Agency acknowledges that it is possible there 
have been new developments in medicine and industrial hygiene related 
to the benefits of early detection, medical intervention, and greater 
control of exposure achieved within the past decade. For that reason, 
as elsewhere, the Agency requests comment on these issues.
    Also not clear are the negative effects of the illness in terms of 
lost productivity, medical costs, and potential side-effects of a 
lifetime of immunosuppressive medication. Nonetheless, the Agency is 
assigning a valuation of $62,000 per case, to reflect the WTP value of 
a prevented injury not estimated to precede premature mortality. The 
Agency believes this is conservative, in part because, with any given 
case of CBD, the outcome is not known in advance, certainly not at the 
point of discovery; indeed much of the psychic value of preventing the 
cases may come from removing the threat of premature mortality. In 
addition, as previously noted, some of these cases could involve 
relatively severe forms of CBD where the worker died of other causes; 
however, in those cases, the duration of the disease would be 
shortened. While beryllium sensitization is a critical precursor of 
CBD, this preliminary analysis does not attempt to assign a separate 
value to sensitization itself.
    Particularly given the uncertainties in valuation on these 
questions, the Agency is interested in public input on the issue of 
valuing the cost to society of morbidity associated with CBD, both in 
cases preceding mortality, and those that may not result in premature 
mortality. The Agency is also interested in comments on whether it is 
appropriate to assign a separate valuation to prevented sensitization 
cases in their own right, and if so, how such cases should be valued.
a. Summary of Monetized Benefits
    Table IX-12 presents the estimated annualized (over 60 years, using 
a 0 percent discount rate) benefits from each of these components of 
the valuation, and the range of estimates, based on uncertainty of the 
prevention factor (i.e., the estimated range of prevented cases, 
depending on how large an impact the rule has on cases beyond an 
airborne-only effect), and the range of uncertainty regarding valuation 
of morbidity. (Mid-point estimates of the undiscounted benefits for 
each of the first 60 years are provided in the middle columns of Table 
VII-A-1 in Appendix VII-A at the end of Chapter VII in the PEA. The 
estimates by year reach a peak of $3.5 billion in the 60th year. Note 
that, by using a 60-year time-period, OSHA is not including any 
monetized fatality benefits associated with reduced worker CBD cases 
originating after year 40 because the 20-year lag takes these CBD 
fatalities beyond the 60-year time horizon. To this extent, OSHA will 
have underestimated benefits.)
    As shown in Table IX-12, the full range of monetized benefits, 
undiscounted, for the proposed PEL of 0.2 [micro]g/m\3\ runs from $291 
million annually, in the case of the lowest estimate of prevented cases 
of CBD, and the lowest valuation for morbidity, up to $2.1 billion 
annually, for the highest of both. Note that the value of total 
benefits is more sensitive to the prevention factor used (ranging from 
$430 million to $1.6 billion, given estimates at the midpoint of the 
morbidity valuation) than to the valuation of morbidity (ranging from 
$666 million to $1.3 billion, given estimates at the midpoint of 
prevention factor).
    Also, the analysis illustrates that most of the morbidity benefits 
are related to CBD and lung cancer cases that are ultimately fatal. At 
the valuation and case frequency midpoint, $663 million in benefits are 
related to mortality, $226 million are related to morbidity preceding 
mortality, and $4.3 million are related to morbidity not preceding 
mortality.

[[Page 47719]]

[GRAPHIC] [TIFF OMITTED] TP07AU15.023

b. Adjustment of WTP Estimates to Reflect Rising Real Income Over Time
    OSHA's estimates of the monetized benefits of the proposed rule are 
based on the imputed value of each avoided fatality and each avoided 
beryllium-related disease. As previously discussed, these, in turn, are 
derived from a worker's willingness to pay to avoid a fatality (with an 
imputed value per fatality avoided of $8.7 million in 2010 dollars) and 
to avoid a beryllium-related disease (with an imputed value per disease 
avoided of between $62,000

[[Page 47720]]

and $5 million in 2010 dollars). To this point, these imputed values 
have been assumed to remain constant over time. However, two related 
factors suggest that these values will tend to increase over time.
    First, economic theory indicates that the value of reducing life-
threatening and health-threatening risks--and correspondingly the 
willingness of individuals to pay to reduce these risks--will increase 
as real per capita income increases. With increased income, an 
individual's health and life becomes more valuable relative to other 
goods because, unlike other goods, they are without close substitutes 
and in relatively fixed or limited supply. Expressed differently, as 
income increases, consumption will increase but the marginal utility of 
consumption will decrease. In contrast, added years of life (in good 
health) is not subject to the same type of diminishing returns--
implying that an effective way to increase lifetime utility is by 
extending one's life and maintaining one's good health (Hall and Jones, 
2007).
    Second, real per capita income has broadly been increasing 
throughout U.S. history, including recent periods. For example, for the 
period 1950 through 2000, real per capita income grew at an average 
rate of 2.31 percent a year (Hall and Jones, 2007),\36\ although real 
per capita income for the recent 25-year period 1983 through 2008 grew 
at an average rate of only 1.3 percent a year (U.S. Census Bureau, 
2010). More important is the fact that real U.S. per capita income is 
projected to grow significantly in future years. For example, the 
Annual Energy Outlook (AEO) projections, prepared by the Energy 
Information Administration (EIA) in the Department of Energy (DOE), 
show an average annual growth rate of per capita income in the United 
States of 2.7 percent for the period 2011-2035.\37\ The U.S. 
Environmental Protection Agency prepared its economic analysis of the 
Clean Air Act using the AEO projections. OSHA believes that it is 
reasonable to use the same AEO projections employed by DOE and EPA, and 
correspondingly projects that per capita income in the United States 
will increase by 2.7 percent a year.
---------------------------------------------------------------------------

    \36\ The results are similar if the historical period includes a 
major economic downturn (such as the United States has recently 
experienced). From 1929 through 2003, a period in U.S. history that 
includes the Great Depression, real per capita income still grew at 
an average rate of 2.22 percent a year (Gomme and Rupert, 2004).
    \37\ The EIA used DOE's National Energy Modeling System (NEMS) 
to produce the Annual Energy Outlook (AEO) projections (EIA, 2011). 
Future per capita GDP was calculated by dividing the projected real 
gross domestic product each year by the projected U.S. population 
for that year.
---------------------------------------------------------------------------

    On the basis of the predicted increase in real per capita income in 
the United States over time and the expected resulting increase in the 
value of avoided fatalities and diseases, OSHA has adjusted its 
estimates of the benefits of the proposed rule to reflect the 
anticipated increase in their value over time. This type of adjustment 
has been recognized by OMB (2003), supported by EPA's Science Advisory 
Board (EPA, 2000), and applied by EPA \38\. OSHA proposes to accomplish 
this adjustment by modifying benefits in year i from [Bi] to 
[Bi * (1 + k)\i\], where ``k'' is the estimated annual 
increase in the magnitude of the benefits of the proposed rule.
---------------------------------------------------------------------------

    \38\ See, for example, EPA (2003, 2008).
---------------------------------------------------------------------------

    What remains is to estimate a value for ``k'' with which to 
increase benefits annually in response to annual increases in real per 
capita income, where ``k'' is equal to ``(1+g) * ([eta])'', ``g'' is 
the expected annual percentage increase in real per capita income, and 
``[eta]'' is the income elasticity of the value of a statistical life. 
Probably the most direct evidence of the value of ``k'' comes from the 
work of Costa and Kahn (2003, 2004). They estimate repeated labor 
market compensating wage differentials from cross-sectional hedonic 
regressions using census and fatality data from the Bureau of Labor 
Statistics for 1940, 1950, 1960, 1970, and 1980. In addition, with the 
imputed income elasticity of the value of life on per capita GNP of 1.7 
derived from the 1940-1980 data, they then predict the value of an 
avoided fatality in 1900, 1920, and 2000. Given the change in the value 
of an avoided fatality over time, it is possible to estimate a value of 
``k'' of 3.4 percent a year from 1900-2000; of 4.3 percent a year from 
1940-1980; and of 2.5 percent a year from 1980-2000.
    Other, more indirect evidence comes from estimates in the economics 
literature of ``[eta]'', the income elasticity of the value of a 
statistical life. Viscusi and Aldy (2003) performed a meta-analysis on 
0.2 wage-risk studies and concluded that the confidence interval upper 
bound on the income elasticity did not exceed 1.0 and that the point 
estimates across a variety of model specifications ranged between 0.5 
and 0.6. Applied to a long-term increase in per capita income of about 
2.7 percent a year, this would suggest a value of ``k'' of about 1.5 
percent a year.
    More recently, Kniesner, Viscusi, and Ziliak (2010), using panel 
data quintile regressions, developed an estimate of the overall income 
elasticity of the value of a statistical life of 1.44. Applied to a 
long-term increase in per capita income of about 2.7 percent a year, 
this would suggest a value of ``k'' of about 3.9 percent a year.
    Based on the preceding discussion of these three approaches for 
estimating the annual increase in the value of the benefits of the 
proposed rule and the fact that the projected increase in real per 
capita income in the United States has flattened in recent years and 
could flatten in the long run, OSHA suggests a conservative value for 
``k'' of approximately two percent a year. The Agency invites comment 
on this estimate and on estimates of the income elasticity of the value 
of a statistical life.
    The Agency believes that the rising value, over time, of health 
benefits is a real phenomenon that should be taken into account in 
estimating the annualized benefits of the proposed rule. Table IX-13, 
in the following section on discounting benefits, shows estimates of 
the monetized benefits of the proposed rule (under alternative discount 
rates) with this estimated increase in monetized benefits over time. 
The Agency invites comment on this adjustment to monetized benefits.
c. The Discounting of Monetized Benefits
    As previously noted, the estimated stream of benefits arising from 
the proposed beryllium rule is not constant from year to year, both 
because of the 45-year delay after the rule takes effect until all 
active workers obtain reduced beryllium exposure over their entire 
working lives and because of, in the case of lung cancer, a 10-year 
latency period between reduced exposure and a reduction in the 
probability of disease. An appropriate discount rate \39\ is needed to 
reflect the timing of benefits over the 60-year period after the rule 
takes effect and to allow conversion to an equivalent steady stream of 
annualized benefits.
---------------------------------------------------------------------------

    \39\ Here and elsewhere throughout this section, unless 
otherwise noted, the term ``discount rate'' always refers to the 
real discount rate--that is, the discount rate net of any 
inflationary effects.
---------------------------------------------------------------------------

1. Alternative Discount Rates for Annualizing Benefits
    Following OMB (2003) guidelines, OSHA has estimated the annualized 
benefits of the proposed rule using separate discount rates of 3 
percent and 7 percent. Consistent with the Agency's own practices in 
recent rulemakings, OSHA has also estimated, for benchmarking purposes, 
undiscounted benefits--that is, benefits using a zero percent discount 
rate.

[[Page 47721]]

    The question remains, what is the ``appropriate'' or ``preferred'' 
discount rate to use to monetize health benefits? The choice of 
discount rate is a controversial topic, one that has been the source of 
scholarly economic debate for several decades. However, in simplest 
terms, the basic choices involve a social opportunity cost of capital 
approach or social rate of time preference approach.
    The social opportunity cost of capital approach reflects the fact 
that private funds spent to comply with government regulations have an 
opportunity cost in terms of foregone private investments that could 
otherwise have been made. The relevant discount rate in this case is 
the pre-tax rate of return on the foregone investments (Lind, 1982, pp. 
24-32).
    The rate of time preference approach is intended to measure the 
tradeoff between current consumption and future consumption, or in the 
context of the proposed rule, between current benefits and future 
benefits. The individual rate of time preference is influenced by 
uncertainty about the availability of the benefits at a future date and 
whether the individual will be alive to enjoy the delayed benefits. By 
comparison, the social rate of time preference takes a broader view 
over a longer time horizon--ignoring individual mortality and the 
riskiness of individual investments (which can be accounted for 
separately).
    The usual method for estimating the social rate of time preference 
is to calculate the post-tax real rate of return on long-term, risk-
free assets, such as U.S. Treasury securities (OMB, 2003, p. 33). A 
variety of studies have estimated these rates of return over time and 
reported them to be in the range of approximately 1-4 percent.
    In accordance with OMB Circular A-4 (2003), OSHA presents benefits 
and net benefits estimates using discount rates of 3 percent 
(representing the social rate of time preference) and 7 percent (a rate 
estimated using the social cost of capital approach). The Agency is 
interested in any evidence, theoretical or applied, that would inform 
the application of discount rates to the costs and benefits of a 
regulation.
2. Summary of Annualized Benefits under Alternative Discount Rates
    Table IX-13 presents OSHA's estimates of the sum of the annualized 
benefits of the proposed rule, using alternative discount rates of 0, 
3, and 7 percent, with the suggested adjustment for increasing 
monetized benefits in response to annual increases in per capita income 
over time.
    Given that the stream of benefits extends out 60 years, the value 
of future benefits is sensitive to the choice of discount rate. The 
undiscounted benefits in Table IX-13 range from $291 million to $2.1 
billion annually. Using a 7 percent discount rate, the annualized 
benefits range from $60 million to $591 million. As can be seen, going 
from undiscounted benefits to a 7 percent discount rate has the effect 
of cutting the annualized benefits of the proposed rule by about 74 
percent.
    Taken as a whole, the Agency's best preliminary estimate of the 
total annualized benefits of the proposed rule--using a 3 percent 
discount rate with an adjustment for the increasing value of health 
benefits over time--is between $158 million and $1.2 billion, with a 
mid-point value of $576 million.

[[Page 47722]]

[GRAPHIC] [TIFF OMITTED] TP07AU15.024

Step 4: Net Benefits of the Proposed Rule
    OSHA has estimated, in Table IX-14, the monetized and annualized 
net benefits of the proposed rule (with a PEL of 0.2 [mu]g/m\3\), based 
on the benefits and costs previously presented. Table IX-14 also 
provides estimates of annualized net benefits for alternative PELs of 
0.1 and 0.5 [mu]g/m\3\. Both the proposed rule and the alternatives PEL 
options have the same ancillary provisions and an action level equal to 
half of the PEL in both cases.
    Table IX-14 is being provided for informational purposes only. As 
previously noted, the OSH Act requires the Agency to set standards 
based on eliminating significant risk to the extent feasible. An 
alternative criterion of maximizing net (monetized) benefits may result 
in very different regulatory outcomes. Thus, this analysis of net 
benefits has not been used by OSHA as the basis for its decision 
concerning the choice of a PEL or of other ancillary requirements for 
the proposed beryllium rule.
    Table IX-14 shows net benefits using alternative discount rates of 
0, 3, and 7 percent for benefits and costs, having previously included 
an adjustment to monetized benefits to reflect increases in real per 
capita income over time. OSHA has relied on a uniform discount rate 
applied to both costs and benefits. The Agency is interested in any 
evidence, theoretical or applied, that would support or refute the 
application of differential discount rates to the costs and benefits of 
a regulation.
    As previously noted in this section, the choice of discount rate 
for annualizing benefits has a significant effect on annualized 
benefits. The same is true for net benefits. For example, the net 
benefits using a 7 percent discount rate for benefits are considerably 
smaller than the net benefits using a 3 percent discount rate, 
declining by over half under all scenarios. (Conversely, as noted in 
Chapter V of the PEA, the choice of discount rate for annualizing costs 
has a relatively minor effect on annualized costs.)
    Based on the results presented in Table IX-14, OSHA finds:
     While the net benefits of the proposed rule vary 
considerably--depending on the choice of discount rate used to 
annualize benefits and on whether the benefits being used are in the 
high, midpoint, or low range--benefits exceed costs for the proposed 
0.2 [mu]g/m\3\ PEL in all cases that OSHA considered.

[[Page 47723]]

     The Agency's best estimate of the net annualized benefits 
of the proposed rule--using a uniform discount rate for both benefits 
and costs of 3 percent--is between $120 million and $1.2 billion, with 
a midpoint value of $538 million.
     The alternative of a 0.5 [mu]g/m\3\ PEL has lower net 
benefits under all assumptions, whereas the effect on net benefits of 
the 0.1 [mu]g/m\3\ PEL is mixed, relative to the proposed 0.2 [mu]g/
m\3\ PEL. However, for these alternative PELs, benefits were also found 
to exceed costs in all cases that OSHA considered.
[GRAPHIC] [TIFF OMITTED] TP07AU15.025

Incremental Benefits of the Proposed Rule
    Incremental costs and benefits are those that are associated with 
increasing the stringency of the standard. A comparison of incremental 
benefits and costs provides an indication of the relative efficiency of 
the proposed PEL and the alternative PELs. Again, OSHA has conducted 
these calculations for informational purposes only and has not used 
these results as the basis for selecting the PEL for the proposed rule.
    OSHA provides, in Table IX-15, estimates of the net benefits of the 
alternative 0.1 and 0.5 [mu]g/m\3\ PELs. The incremental costs, 
benefits, and net benefits of meeting a 0.5[mu]g/m\3\ PEL and then 
going to a 0.2 [mu]g/m\3\ PEL (as well as meeting a 0.2 [mu]g/m\3\ PEL 
and then going to a 0.1 [mu]g/m\3\ PEL--which the Agency has not yet 
determined is feasible), for alternative discount rates of 3 and 7 
percent, are presented in Table IX-15. Table IX-15 breaks out costs by 
provision and benefits by type of disease and by morbidity/mortality. 
As Table IX-15 shows, at a discount rate of 3 percent, a PEL of 0.2 
[mu]g/m\3\, relative to a PEL of 0.5 [mu]g/m\3\, imposes additional 
costs of $4.4 million per year; additional benefits of $172.7 million 
per year; and additional net benefits of $168.2 million per year. The 
proposed PEL of 0.2 [mu]g/m\3\ also has higher net benefits, relative 
to a PEL of 0.5 [mu]g/m\3\, using a 7 percent discount rate.
    Table IX-15 demonstrates that, regardless of discount rate, there 
are net benefits to be achieved by lowering exposures from the current 
PEL of 2.0 [mu]g/m\3\ to 0.5 [mu]g/m\3\ and then, in turn, lowering 
them further to 0.2 [mu]g/m\3\. However, the majority of the benefits 
and costs attributable to the proposed rule are from the initial effort 
to lower exposures to 0.5 [mu]g/m\3\. Consistent with the previous 
analysis, net benefits decline across all increments as the discount 
rate for annualizing benefits increases. As also shown in Table IX-15, 
there is a slight positive net incremental benefit from going from a 
PEL of 0.2 [mu]g/m\3\ to 0.1 [mu]g/m\3\ for a discount rate of 3 
percent, and a slight negative net increment for a discount rate of 7 
percent. (Note that these results are for OSHA's midpoint estimate of 
benefits, although as indicated in Table IX-14, this is not universal 
across all estimation parameters.)
    In addition to examining alternative PELs, OSHA also examined 
alternatives to other provisions of the standard. These regulatory 
alternatives are discussed Section IX.H of this preamble.

[[Page 47724]]

[GRAPHIC] [TIFF OMITTED] TP07AU15.026

Step 5: Sensitivity Analysis
    In this section, OSHA presents the results of two different types 
of sensitivity analysis to demonstrate how robust the estimates of net 
benefits are to changes in various cost and benefit parameters. In the 
first type of sensitivity analysis, OSHA made a series of isolated 
changes to individual cost and benefit input parameters in order to 
determine their effects on the Agency's estimates of annualized costs, 
annualized benefits, and annualized net benefits. In the second type of

[[Page 47725]]

sensitivity analysis--a so-called ``break-even'' analysis--OSHA also 
investigated isolated changes to individual cost and benefit input 
parameters, but with the objective of determining how much they would 
have to change for annualized costs to equal annualized benefits. For 
both types of sensitivity analyses, OSHA used the annualized costs and 
benefits obtained from a three-percent discount rate as the reference 
point.
    Again, the Agency has conducted these calculations for 
informational purposes only and has not used these results as the basis 
for selecting the PEL for the proposed rule.
a. Analysis of Isolated Changes to Inputs
    The methodology and calculations underlying the estimation of the 
costs and benefits associated with this rulemaking are generally linear 
and additive in nature. Thus, the sensitivity of the results and 
conclusions of the analysis will generally be proportional to isolated 
variations in a particular input parameter. For example, if the 
estimated time that employees need to travel to (and from) medical 
screenings were doubled, the corresponding labor costs would double as 
well.
    OSHA evaluated a series of such changes in input parameters to test 
whether and to what extent the general conclusions of the economic 
analysis held up. OSHA first considered changes to input parameters 
that affected only costs and then changes to input parameters that 
affected only benefits. Each of the sensitivity tests on cost 
parameters had only a very minor effect on total costs or net costs. 
Much larger effects were observed when the benefits parameters were 
modified; however, in all cases, net benefits remained significantly 
positive. On the whole, OSHA found that the conclusions of the analysis 
are reasonably robust, as changes in any of the cost or benefit input 
parameters still show significant net benefits for the proposed rule. 
The results of the individual sensitivity tests are summarized in Table 
IX-16 and are described in more detail below.
    In the first of these sensitivity tests, where OSHA doubled the 
estimated portion of employees in need of protective clothing and 
equipment (PPE), essentially doubling the estimated baseline non-
compliance rate (e.g., from 10 to 20 percent), and estimates of other 
input parameters remained unchanged, Table IX-16 shows that the 
estimated total costs of compliance would increase by $1.4 million 
annually, or by about 3.7 percent, while net benefits would also 
decline by $1.4 million annually, from $538.2 million to $536.8 million 
annually.
    In a second sensitivity test, OSHA increased the estimated unit 
cost of ventilation from $13.18 per cfm for most sectors to $25 per cfm 
for most sectors. As shown in Table IX-16, if OSHA's estimates of other 
input parameters remained unchanged, the total estimated costs of 
compliance would increase by $2.0 million annually, or by about 5.3 
percent, while net benefits would also decline by $2.0 million 
annually, from $538.2 million to $536.2 million annually.

[[Page 47726]]

[GRAPHIC] [TIFF OMITTED] TP07AU15.027

    In a third sensitivity test, OSHA increased the estimated share of 
workers showing signs and symptoms of CBD from 15 to 25 percent, 
thereby adding these workers to the group eligible for medical 
surveillance and assuming that they would not be otherwise eligible for 
another reason (working in a regulated area, exposed during an 
emergency, etc.). As shown in Table IX-16, if OSHA's estimates of other 
input parameters remained unchanged, the total estimated costs of 
compliance would increase by $1.5 million annually, or by about 4.1 
percent, while net benefits would also decline by $1.5 million 
annually, from $538.2 million to $536.7 million annually.
    In a fourth sensitivity test, OSHA increased its estimated 
incremental time per workers for housekeeping by 50

[[Page 47727]]

percent. As shown in Table IX-16, if OSHA's estimates of other input 
parameters remained unchanged, the total estimated costs of compliance 
would increase by $5.4 million annually, or by about 14.4 percent, 
while net benefits would also decline by $5.4 million annually, from 
$538.2 million to $532.8 million annually.
    In a fifth sensitivity test, OSHA increased the estimated number of 
establishments needing engineering controls. For this sensitivity test, 
if less than 50 percent of the establishments in an industry needed 
engineering controls, OSHA doubled the percentage of establishments 
needing engineering controls. If more than 50 percent of establishments 
in an industry needed engineering controls, then OSHA increased the 
percentage of establishment needing engineering control to 100 percent. 
The purpose of this sensitivity analysis was to check the importance of 
using a methodology that treated 50 percent of workers in a given 
occupation exposed above the PEL as equivalent to 50 percent of 
facilities lacking adequate exposure controls. As shown in Table IX-16, 
if OSHA's estimates of other input parameters remained unchanged, the 
total estimated costs of compliance would increase by $4.5 million, or 
by about 11.9 percent, while net benefits would also decline by $4.5 
million, from $538.2 million to $533.7 million annually.
    The Agency also performed sensitivity tests on several input 
parameters used to estimate the benefits of the proposed rule. In the 
first two tests, in an extension of results previously presented in 
Table IX-12, the Agency examined the effect on annualized net benefits 
of employing the high-end estimate of the benefits, as well as the low-
end estimate, specifically examining the effect on undiscounted 
benefits of varying the valuation of individual morbidity cases. Table 
IX-16 presents the effect on annualized net benefits of using the 
extreme values of these ranges: the high morbidity valuation case and 
the low morbidity valuation case. For the low estimate of valuation, 
the benefits decline by 37.7 percent, to $359 million annually, 
yielding net benefits of $321 million annually. As shown, using the 
high estimate of morbidity valuation, the benefits rise by 77.0 percent 
to $1.0 billion annually, yielding net benefits of $982 million 
annually.
    In a third sensitivity test of benefits, the Agency examined the 
effect of removing the component for the estimated rising value of 
health and safety over time. This would reduce the benefits by 54.6 
percent, or $314 million annually, lowering the net benefits to $224 
million annually.
    In Chapter VII of the PEA the Agency examined the effect of raising 
the discount rate for costs and benefits to 7 percent. Raising the 
discount rate to 7 percent would increase costs by $1.5 million 
annually and lower benefits by $320.5 million annually, yielding 
annualized net benefits of $216.2 million.
    Also in Chapter VII of the PEA the Agency performed a sensitivity 
analysis of dental lab substitution. In the PEA, OSHA estimates that 75 
percent of the dental laboratory industry will react to a new standard 
on beryllium by substituting away from using beryllium to the use of 
other materials. Substitution is not costless, and Chapter V of the PEA 
estimates the increased cost due to the higher costs of using non-
beryllium alloys. These costs are smaller than the avoided costs of the 
ancillary provisions and engineering controls. Thus, as indicated in 
Table VII-8 of the PEA, the benefits of the proposal would be lower and 
the costs higher if there were less substitution out of beryllium in 
dental labs. The lowest net benefits would occur if labs were unable to 
substitute out beryllium-containing materials at all, and had to use 
ventilation to control exposures. In this case, the proposal would 
yield only $420 million in net benefits. The highest net benefits, 
larger than assumed for OSHA's primary estimate, would be if all dental 
labs substituted out of beryllium-containing materials as a result of 
the proposal; as a result, the proposal would yield $573 million in net 
benefits. Another possibility is a scenario is which technology and the 
market move along rapidly away from using beryllium-containing 
materials, independently of an OSHA rule, and the proposal itself would 
therefore produce neither costs nor benefits in this sector. If dental 
labs are removed from the PEA, the net benefits for the proposal--for 
the remaining industry sectors--decline to $284 million. This analysis 
demonstrates, however, that regardless of any assumption regarding 
substitution in dental labs, the proposal would generate substantially 
more monetized benefits than costs.
    Finally, the Agency examined in Chapter VII of the PEA the effects 
of changes in two important inputs to the benefits analysis: the factor 
that transforms CBD prevalence rates into incidence rates, needed for 
the equilibrium lifetime risk model, and the percentage of CBD cases 
that eventually lead to a fatality.
    From the Cullman dataset, the Agency has estimated the prevalence 
of CBD cases at any point in time as a function of cumulative beryllium 
exposure. In order to utilize the lifetime risk model, which tracks 
workers over their working life in a job, OSHA has turned these 
prevalence rates into an incidence rate, which is the rate of 
contracting CBD at a point in time. OSHA's baseline estimate of the 
turnover rate in the model is 10 percent. In Table VII-10 in the PEA, 
OSHA also presented alternative turnover rates of 5 percent and 20 
percent. A higher turnover rate translates into a higher incidence 
rate, and the table shows that, from a baseline midpoint estimate with 
10 percent turnover the number of CBD cases prevented is 6,367, while 
raising the turnover rate to 20 percent causes this midpoint estimate 
to rise to 11,751. Conversely, a rate of 5 percent lowers the number of 
CBD cases prevented to 3,321. Translated into monetary benefits, the 
table shows that the baseline midpoint estimate of $575.8 million now 
ranges from $314.4 million to $1,038 million.
    Also in TableVII-10 of the PEA, the Agency looked at the effects of 
varying the percentage of CBD cases that eventuate in fatality. The 
Agency's baseline estimate of this outcome is 65 percent, with half of 
this occurring relatively soon, and the other half after an extended 
debilitating condition. The Agency judged that a reasonable range to 
investigate was a low of 50 percent and a high of 80 percent, while 
maintaining the shares of short-term and long-term endpoint fatality. 
At a baseline of 65 percent, the midpoint estimate of total CBD cases 
prevented is 4,139. At the low end of 50 percent mortality this 
estimate lowers to 3,183 while at the high end of 80 percent mortality 
this estimate rises to 5,094. Translated into monetary benefits, the 
table shows that the baseline midpoint estimate of $575.8 million now 
ranges from $500.1 million to $651.5 million.
b. ``Break-Even'' Analysis
    OSHA also performed sensitivity tests on several other parameters 
used to estimate the net costs and benefits of the proposed rule. 
However, for these, the Agency performed a ``break-even'' analysis, 
asking how much the various cost and benefits inputs would have to vary 
in order for the costs to equal, or break even with, the benefits. The 
results are shown in Table IX-17.
    In one break-even test on cost estimates, OSHA examined how much 
total costs would have to increase in order for costs to equal 
benefits. As shown in Table IX-17, this point would

[[Page 47728]]

be reached if costs increased by $538.2 million, or by 1,431 percent.
    In a second test, looking specifically at the estimated engineering 
control costs, the Agency found that these costs would need to increase 
by $566.7 million, or 6,240 percent, for costs to equal benefits.
    In a third sensitivity test, on benefits, OSHA examined how much 
its estimated monetary valuation of an avoided illness or an avoided 
fatality would need to be reduced in order for the costs to equal the 
benefits. Since the total valuation of prevented mortality and 
morbidity are each estimated to exceed the estimated costs of $38 
million, an independent break-even point for each is impossible. In 
other words, for example, if no value is attached to an avoided illness 
associated with the rule, but the estimated value of an avoided 
fatality is held constant, the rule still has substantial net benefits. 
Only through a reduction in the estimated net value of both components 
is a break-even point possible.
    The Agency, therefore, examined how large an across-the-board 
reduction in the monetized value of all avoided illnesses and 
fatalities would be necessary for the benefits to equal the costs. As 
shown in Table IX-17, a 94 percent reduction in the monetized value of 
all avoided illnesses and fatalities would be necessary for costs to 
equal benefits, reducing the estimated value to $733,303 per fatality 
prevented, and an equivalent percentage reduction to about $4,048 per 
illness prevented.
    In a fourth break-even sensitivity test, OSHA estimated how many 
fewer beryllium-related fatalities and illnesses would be required for 
benefits to equal costs. Paralleling the previous discussion, 
eliminating either the prevented mortality or morbidity cases alone 
would be insufficient to lower benefits to the break-even point. The 
Agency therefore examined them as a group. As shown in Table IX-17, a 
reduction of 96 percent, for both simultaneously, is required to reach 
the break-even point--90 fewer fatalities prevented annually, and 46 
fewer beryllium-related illnesses-only cases prevented annually.
    Taking into account both types of sensitivity analysis the Agency 
performed on its point estimates of the annualized costs and annualized 
benefits of the proposed rule, the results demonstrate that net 
benefits would be positive in all plausible cases tested. In 
particular, this finding would hold even with relatively large 
variations in individual input parameters. Alternately, one would have 
to imagine extremely large changes in costs or benefits for the rule to 
fail to produce net benefits. OSHA concludes that its finding of 
significant net benefits resulting from the proposed rule is a robust 
one.
    OSHA welcomes input from the public regarding all aspects of this 
sensitivity analysis, including any data or information regarding the 
accuracy of the preliminary estimates of compliance costs and benefits 
and how the estimates of costs and benefits may be affected by varying 
assumptions and methodological approaches. OSHA also invites comment on 
the risk analysis and risk estimates from which the benefits estimates 
were derived.

[[Page 47729]]

[GRAPHIC] [TIFF OMITTED] TP07AU15.028

H. Regulatory Alternatives

    This section discusses various regulatory alternatives to the 
proposed OSHA beryllium standard. Executive Order 12866 instructs 
agencies to ``select those approaches that maximize net benefits 
(including potential economic, environmental, public health and safety, 
and other advantages; distributive impacts; and equity), unless a 
statute requires another regulatory approach.'' The OSH Act, as 
interpreted by the courts, requires health regulations to reduce 
significant risk to

[[Page 47730]]

the extent feasible. Nevertheless OSHA has examined possible regulatory 
alternatives that may not meet its statutory requirements.
    Each regulatory alternative presented here is described and 
analyzed relative to the proposed rule. Where appropriate, the Agency 
notes whether the regulatory alternative, to be a legitimate candidate 
for OSHA consideration, requires evidence contrary to the Agency's 
preliminary findings of significant risk and feasibility. To facilitate 
comment, OSHA has organized some two dozen specific regulatory 
alternatives into five categories: (1) Scope; (2) exposure limits; (3) 
methods of compliance; (4) ancillary provisions; and (5) timing.
1. Scope Alternatives
    The first set of regulatory alternatives would alter scope of the 
proposed standard--that is, the groups of employees and employers 
covered by the proposed standard. The scope of the current beryllium 
proposal applies only to general industry work, and does not apply to 
employers when engaged in construction or maritime activities. In 
addition, the proposed rule provides an exemption for those working 
with materials that contain beryllium only as a trace contaminant (less 
than 0.1percent composition by weight).\40\
---------------------------------------------------------------------------

    \40\ Employers engaged in general industry activities exempted 
from the proposed rule must still ensure that their employees are 
protected from beryllium exposure above the current PEL, as listed 
in 29 CFR 1910.1000 Table Z-2.
---------------------------------------------------------------------------

    As discussed in the explanation of paragraph (a) in Section XVIII 
of this preamble, Summary and Explanation of the Proposed Standard, 
OSHA is considering alternatives to the proposed scope that would 
increase the range of employers and employees covered by the standard. 
OSHA's review of several industries indicates that employees in some 
construction and maritime industries, as well as some employees who 
deal with materials containing less than 0.1 percent beryllium, may be 
at significant risk of CBD and lung cancer as a result of their 
occupational exposures. Regulatory Alternatives #1a, #1b, #2a, and #2b 
would increase the scope of the proposed standard to provide additional 
protection to these workers.
    Regulatory Alternative #1a would expand the scope of the proposed 
standard to also include all operations in general industry where 
beryllium exists only as a trace contaminant; that is, where the 
materials used contain less than 0.1 percent beryllium by weight. 
Regulatory Alternative #1b is similar to Regulatory Alternative #1a, 
but exempts operations where beryllium exists only as a trace 
contaminant and the employer can show that employees' exposures will 
not meet or exceed the action level or exceed the STEL. Where the 
employer has objective data demonstrating that a material containing 
beryllium or a specific process, operation, or activity involving 
beryllium cannot release beryllium in concentrations at or above the 
proposed action level or above the proposed STEL under any expected 
conditions of use, that employer would be exempt from the proposed 
standard except for recordkeeping requirements pertaining to the 
objective data. Alternative #1a and Alternative #1b, like the proposed 
rule, would not cover employers or employees in construction or 
shipyards.
    OSHA has identified two industries with workers engaged in general 
industry work that would be excluded under the proposed rule but would 
fall within the scope of the standard under Regulatory Alternatives #1a 
and #1b: Primary aluminum production and coal-fired power generation. 
Beryllium exists as a trace contaminant in aluminum ore and may result 
in exposures above the proposed permissible exposure limits (PELs) 
during aluminum refining and production. Coal fly ash in coal-powered 
power plants is also known to contain trace amounts of beryllium, which 
may become airborne during furnace and baghouse operations and might 
also result in worker exposures. See Appendices VIII-A and VIII-B at 
the end of Chapter VIII in the PEA for a discussion of beryllium 
exposures and available controls in these two industries.
    As discussed in Appendix IV-B of the PEA, beryllium exposures from 
fly ash high enough to exceed the proposed PEL would usually be coupled 
with arsenic exposures exceeding the arsenic PEL. Employers would in 
that case be required to implement all feasible engineering controls, 
work practices, and necessary PPE (including respirators) to comply 
with the OSHA Inorganic Arsenic standard (29 CFR 1910.1018)--which 
would be sufficient to comply with those aspects of the proposed 
beryllium standard as well. The degree of overlap between the 
applicability of the two standards and, hence, the increment of costs 
attributable to this alternative are difficult to gauge. To account for 
this uncertainty, the Agency at this time is presenting a range of 
costs for Regulatory Alternative #1a: From no costs being taken for 
ancillary provisions under Regulatory Alternative #1a to all such costs 
being included. At the low end, the only additional costs under 
Regulatory Alternative #1a are due to the engineering control costs 
incurred by the aluminum smelters (see Appendix VIII-A).
    Similarly, the proposed beryllium standard would not result in 
additional benefits from a reduction in the beryllium PEL or from 
ancillary provisions similar to those already in place for the arsenic 
standard, but OSHA does anticipate some benefits will flow from 
ancillary provisions unique to the proposed beryllium standard. To 
account for significant uncertainty in the benefits that would result 
from the proposed beryllium standard for workers in primary aluminum 
production and coal-fired power generation, OSHA estimated a range of 
benefits for Regulatory Alternative #1a. The Agency estimated that the 
proposed ancillary provisions would avert between 0 and 45 percent \41\ 
of those baseline CBD cases not averted by the proposed PEL. Though the 
Agency is presenting a range for both costs and benefits for this 
alternative, the Agency judges the degree of overlap with the arsenic 
standard is likely to be substantial, so that the actual costs and 
benefits are more likely to be found at the low end of this range. The 
Agency invites comment on all these issues.
---------------------------------------------------------------------------

    \41\ As discussed in Chapter VII of the PEA, OSHA used 45 
percent to develop its best estimate.
---------------------------------------------------------------------------

    Table IX-18 presents, for informational purposes, the estimated 
costs, benefits, and net benefits of Regulatory Alternative #1a using 
alternative discount rates of 3 percent and 7 percent. In addition, 
this table presents the incremental costs, incremental benefits, and 
incremental net benefits of this alternative relative to the proposed 
rule. Table IX-18 also breaks out costs by provision, and benefits by 
type of disease and by morbidity/mortality.
    As shown in Table IX-18, Regulatory Alternative #1a would increase 
the annualized cost of the rule from $37.6 million to between $39.6 and 
$56.0 million using a 3 percent discount rate and from $39.1 million to 
between $41.3 and $58.1 million using a 7 percent discount rate. OSHA 
estimates that regulatory Alternative #1a would prevent as few as an 
additional 0.3 (i.e., almost one fatality every 3 years) or as many as 
an additional 31.8 beryllium-related fatalities annually, relative to 
the proposed rule. OSHA also estimates that Regulatory Alternative #1a 
would prevent as few as an additional 0.002 or as many as an additional 
9 beryllium-related non-fatal illnesses annually, relative to the 
proposed rule. As a result, annualized benefits in monetized

[[Page 47731]]

terms would increase from $575.8 million to between $578.0 and $765.2 
million, using a 3 percent discount rate, and from $255.3 million to 
between $256.3 and $339.3 million using a 7 percent discount rate. Net 
benefits would increase from $538.2 million to between $538.4 and 
$709.2 million using a 3 percent discount rate and from $216.2 million 
to somewhere between $215.1 to $281.2 million using a 7 percent 
discount rate. As noted in Appendix VIII-B of Chapter VIII in the PEA, 
the Agency emphasizes that these estimates of benefits are subject to a 
significant degree of uncertainty, and the benefits associated with 
Regulatory Alternative #1a arguably could be a small fraction of OSHA's 
best estimate presented here.
    OSHA estimates that the costs and the benefits of Regulatory 
Alternative #1b will be somewhat lower than the costs of Regulatory 
Alternative #1a, because most--but not all--of the provisions of the 
proposed standard are triggered by exposures at the action level, 8-
hour time-weighted average (TWA) PEL, or STEL. For example, where 
exposures exist but are below the action level and at or below the 
STEL, Alternative #1a would require employers to establish work areas; 
develop, maintain, and implement a written exposure control plan; 
provide medical surveillance to employees who show signs or symptoms of 
CBD; and provide PPE in some instances. Regulatory Alternative #1b 
would not require employers to take these measures in operations where 
they can produce objective data demonstrating that exposures are below 
the action level and at or below the STEL. OSHA only analyzed costs, 
not benefits, for this alternative, consistent with the Agency's 
treatment of Regulatory Alternatives in the past. Total costs for 
Regulatory Alternative #1b versus #1a, assuming full ancillary costs, 
drop from to $56.0 million to $49.9 million using a 3 percent discount 
rate, and from $58.1 million to $51.8 million using a 7 percent 
discount rate.
BILLING CODE 4510-26-P

[[Page 47732]]

[GRAPHIC] [TIFF OMITTED] TP07AU15.029

    Regulatory Alternative #2a would expand the scope of the proposed 
standard to include employers in construction and maritime. For 
example, this alternative would cover abrasive blasters, pot tenders, 
and

[[Page 47733]]

cleanup staff working in construction and shipyards who have the 
potential for airborne beryllium exposure during blasting operations 
and during cleanup of spent media. Regulatory Alternative #2b would 
update 29 CFR 1910.1000 Tables Z-1 and Z-2, 1915.1000 Table Z, and 
1926.55 Appendix A so that the proposed TWA PEL and STEL would apply to 
all employers and employees in general industry, shipyards, and 
construction, including occupations where beryllium exists only as a 
trace contaminant. For example, this alternative would cover abrasive 
blasters, pot tenders, and cleanup staff working in construction and 
shipyards who have the potential for significant airborne exposure 
during blasting operations and during cleanup of spent media. The 
changes to the Z tables would also apply to workers exposed to 
beryllium during aluminum refining and production, and workers engaged 
in maintenance operations at coal-powered utility facilities. All 
provisions of the standard other than the PELs, such as exposure 
monitoring, medical removal, and PPE, would be in effect only for 
employers and employees that fall within the scope of the proposed 
rule.\42\ Alternative #2b would not be as protective as Alternative #1a 
or Alternative #1b for employees in aluminum refining and production or 
coal-powered utility facilities because the other provisions of the 
proposed standard would not apply.
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    \42\ However, many of the occupations excluded from the scope of 
the proposed beryllium standard receive some ancillary provision 
protections from other rules, such as Personal Protective Equipment 
(29 CFR 1910 subpart I, 1915 subpart I, 1926.28, also 1926 subpart 
E), Ventilation (including abrasive blasting) (Sec. Sec.  1926.57 
and 1915.34), Hazard Communication (Sec.  1910.1200), and specific 
provisions for welding (parts 1910 subpart Q, 1915 subpart D, and 
1926 subpart J).
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    As discussed in the explanation of proposed paragraph (a) in this 
preamble at Section XVIII, Summary and Explanation of the Proposed 
Standard, abrasive blasting is the primary application group in 
construction and maritime industries where workers may be exposed to 
beryllium. OSHA has judged that abrasive blasters and their helpers in 
construction and maritime industries have the potential for significant 
airborne exposure during blasting operations and during cleanup of 
spent media. Airborne concentrations of beryllium have been measured 
above the current TWA PEL of 2 [mu]g/m\3\ when blast media containing 
beryllium are used as intended (see Appendix IV-C in the PEA for 
details).
    To address high concentrations of various hazardous chemicals in 
abrasive blasting material, employers must already be using engineering 
and work practice controls to limit workers' exposures and must be 
supplementing these controls with respiratory protection when 
necessary. For example, abrasive blasters in the construction industry 
fall under the protection of the Ventilation standard (29 CFR 1926.57). 
The Ventilation standard includes an abrasive blasting subsection (29 
CFR 1926.57(f)), which requires that abrasive blasting respirators be 
worn by all abrasive blasting operators when working inside blast-
cleaning rooms (29 CFR 1926.57(f)(5)(ii)(A)), or when using silica sand 
in manual blasting operations where the nozzle and blast are not 
physically separated from the operator in an exhaust-ventilated 
enclosure (29 CFR 1926.57(f)(5)(ii)(B)), or when needed to protect 
workers from exposures to hazardous substances in excess of the limits 
set in Sec.  1926.55 (29 CFR 1926.57(f)(5)(ii)(C); ACGIH, 1971). For 
maritime, standard 29 CFR 1915.34(c) covers similar requirements for 
respiratory protection needed in blasting operations. Due to these 
requirements, OSHA believes that abrasive blasters already have 
controls in place and wear respiratory protection during blasting 
operations. Thus, in estimating costs for Regulatory Alternatives #2a 
and #2b, OSHA judged that the reduction of the TWA PEL would not impose 
costs for additional engineering controls or respiratory protection in 
abrasive blasting (see Appendix VIII-C of Chapter VIII in the PEA for 
details). OSHA requests comment on this issue--in particular, whether 
abrasive blasters using blast material that may contain beryllium as a 
trace contaminant are already using all feasible engineering and work 
practice controls, respiratory protection, and PPE that would be 
required by Regulatory Alternatives #2a and #2b.
    In the estimation of benefits for Regulatory Alternative #2a, OSHA 
has estimated a range to account for significant uncertainty in the 
benefits to this population from some of the ancillary provisions of 
the proposed beryllium standard. It is unclear how many of the workers 
associated with abrasive blasting work would benefit from dermal 
protection, as comprehensive dermal protection may already be used by 
most blasting operators. It is also unclear whether the housekeeping 
requirements of the proposed standard would be feasible to implement in 
the context of abrasive blasting work, and to what extent they would 
benefit blasting helpers, who are themselves exposed while performing 
cleanup activities. OSHA estimated that the proposed ancillary 
provisions would avert between 0 and 45 percent of those baseline CBD 
cases not averted by the proposed PEL.
    These considerations also lead the Agency to present a range for 
the costs of this alternative: From no costs being estimated for 
ancillary provisions under Regulatory Alternative #2a to including all 
such costs. Based on the considerations discussed above, the Agency 
judges that costs and benefits at the low end of this range are more 
likely to be correct. The Agency invites comment on these issues.
    In addition, OSHA believes that a small number of welders in the 
maritime industry may be exposed to beryllium via arc and gas welding 
(and none through resistance welding). The number of maritime welders 
was estimated using the same methodology as was used to estimate the 
number of general industry welders. Brush Wellman's customer survey 
estimated 2,000 total welders on beryllium-containing products (Kolanz, 
2001). Based on ERG's assumption of 4 welders per establishment, ERG 
estimated that a total of 500 establishments would be affected. These 
affected establishments were then distributed among the 26 NAICS 
industries with the highest number of IMIS samples for welders that 
were positive for beryllium. To do this, ERG first consulted the BLS 
OES survey to determine what share of establishments in each of the 26 
NAICS employed welders and estimated the total number of establishments 
that perform welding regardless of beryllium exposure (BLS, 2010a). 
Then ERG distributed the 500 affected beryllium welding facilities 
among the 26 NAICS based on the relative share of the total number of 
establishments performing welding. Finally, to estimate the number of 
welders, ERG used the assumption of four welders per establishment. 
Based on the information from ERG, OSHA estimated that 30 welders would 
be covered in the maritime industry under this regulatory alternative. 
For these welders, OSHA used the same controls and exposure profile 
that were used to estimate costs for arc and gas welders in Chapter V 
of the PEA. ERG judged there to be no construction welders exposed to 
beryllium due to a lack of any evidence that the construction sector 
uses beryllium-containing products or electrodes in resistance welding. 
OSHA solicits comment and any relevant data on beryllium exposures for 
welders in construction and maritime employment.
    Estimated costs and benefits for Regulatory Alternative #2a are 
shown in Table IX-18a. Regulatory Alternative

[[Page 47734]]

#2a would increase costs from $37.6 million to between $37.7 and $55.3 
million, using a 3 percent discount rate, and from $39.1 million to 
between $39.2 and $57.3 million using a 7 percent discount rate. 
Annualized benefits would increase from $575.8 million to between 
$575.9 and $675.3 million using a 3 percent discount rate, and from 
$255.3 million to between $255.4 and $299.4 million using a 7 percent 
discount rate. Net benefits would change from $538.2 million to between 
$538.2 and $620.0 million using a 3 percent discount rate, and from 
$216.2 million to between $216.1 and $242.1 million using a 7 percent 
discount rate.