[Federal Register Volume 61, Number 214 (Monday, November 4, 1996)]
[Rules and Regulations]
[Pages 56746-56856]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-27791]



[[Page 56745]]


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Part II





Department of Labor





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Occupational Safety and Health Administration



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29 CFR Part 1910, et al.



Occupational Exposure to 1,3-Butadiene; Final Rule

  Federal Register / Vol. 61, No. 214 / Monday, November 4, 1996 / 
Rules and Regulations  

[[Page 56746]]



DEPARTMENT OF LABOR

Occupational Safety and Health Administration

29 CFR Parts 1910, 1915 and 1926

[Docket No. H-041]
RIN 1218-AA83


Occupational Exposure to 1,3-Butadiene

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

ACTION: Final rule.

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

SUMMARY: This final standard amends the Occupational Safety and Health 
Administration's (OSHA) occupational standard that regulates employee 
exposure to 1,3-Butadiene (BD). The basis for this action is a 
determination by the Assistant Secretary, based on animal and human 
data, that OSHA's current permissible exposure limit (PEL) which 
permits employees to be exposed to BD in concentrations up to 1,000 
parts BD per million parts of air (1,000 ppm) as an eight-hour time-
weighted average (TWA) does not adequately protect employee health. 
OSHA's new limits reduce the PEL for BD to an 8-hour TWA of 1 ppm and a 
short term exposure limit (STEL) of 5 ppm for 15 minutes. An ``action 
level'' of 0.5 ppm as an 8-hour TWA is included in the standard as a 
mechanism for exempting an employer from some administrative burdens, 
such as employee exposure monitoring and medical surveillance, in 
instances where the employer can demonstrate that the employee's 
exposures are consistently at very low levels. In order to reduce 
exposures and protect employees, OSHA's BD standard includes 
requirements such as engineering controls, work practices and personal 
protective equipment, measurement of employee exposures, training, 
medical surveillance, hazard communication, regulated areas, emergency 
procedures and recordkeeping.

DATES: The effective date of these amendments is February 3, 1997. 
Start-up date for engineering controls is November 4, 1998, and for the 
exposure goal program November 4, 1999. Affected parties do not have to 
comply with the information collection requirements in 
Sec. 1910.1051(d) exposure monitoring, Sec. 1910.1051(f) methods of 
compliance, Sec. 1910.1051(g) exposure goal program, Sec. 1910.1051(h) 
respiratory protection, Sec. 1910.1051(j) emergency situations, 
Sec. 1910.1051(k) medical screening and surveillance, Sec. 1910.1051(l) 
communication of BD hazards to employees; and Sec. 1910.1051(m) 
recordkeeping until the Department of Labor publishes a Federal 
Register notice informing the public that OMB has approved these 
information requirements under the Paperwork Reduction Act of 1995.
    Other Dates: Written comments on the paperwork requirements of this 
final rule must be submitted on or before January 3, 1997.

ADDRESSES: In accordance with 28 U.S.C. 2112(a), the Agency designates 
the following party to receive petitions for review of this regulation: 
Associate Solicitor for Occupational Safety and Health, Office of the 
Solicitor, Room S-4004, U.S. Department of Labor, 200 Constitution 
Ave., NW., Washington, DC 20210. These petitions must be filed no later 
than the 59th calendar day following promulgation of this regulation; 
see section 6(f) of the Occupational Safety and Health Act of 1970 (OSH 
Act), 29 CFR 1911.18(d), and United Mine Workers of America v. Mine 
Safety and Health Administration, 900 F.2d 384 (D.C. Circ. 1990).
    Comments regarding the paperwork burden of this regulation, which 
are being solicited by the Agency as required by the Paperwork 
Reduction Act of 1995, are to be submitted to the Docket Office, Docket 
No. ICR 96-13, U.S. Department of Labor, Room N-2625, 200 Constitution 
Ave., NW., Washington, DC 20210, telephone (202) 219-7894. Written 
comments limited to 10 pages or less in length may also be transmitted 
by facsimile to (202) 219-5046.

FOR FURTHER INFORMATION CONTACT: Ms. Anne Cyr, OSHA Office of Public 
Affairs, United States Department of Labor, Room N-3641, 200 
Constitution Avenue, NW., Washington, DC. 20210, Telephone (202) 219-
8151. Copies of the referenced information collection request are 
available for inspection and copying in the Docket Office and will be 
mailed to persons who request copies by telephoning Vivian Allen at 
(202) 219-8076. For electronic copies of the 1,3-Butadiene Information 
Collection Request, contact OSHA's WebPage on Internet at http://
www.osh.gov/.

I. Collection of Information; Request for Comment

    This final 1,3-Butadiene standard contains information collection 
requirements that are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act (PRA95) 44 U.S.C. 3501 
et seq. (see also 5 CFR part 1320). PRA95 defines collection of 
information to mean, ``the obtaining, causing to be obtained, 
soliciting, or requiring the disclosure to third parties or the public 
of facts or opinions by or for an agency regardless of form or 
format.'' (44 U.S.C. 3502(3)(A))
    The title, the need for and proposed use of the information, a 
summary of the collections of information, description of the 
respondents, and frequency of response required to implement the 
required information collection is described below with an estimate of 
the annual cost and reporting burden (as required by 5 CFR 
1320.5(a)(1)(iv) and 1320.8(d)(2)). Included in the estimate is the 
time for reviewing instructions, gathering and maintaining the data 
needed, and completing and reviewing the collection of information.
    OSHA invites comments on whether the proposed collection of 
information:
     Ensures that the collection of information is necessary 
for the proper performance of the functions of the agency, including 
whether the information will have practical utility;
     Estimates the projected burden accurately, including 
whether the methodology and assumptions used are valid;
     Enhances the quality, utility, and clarity of the 
information to be collected; and
     Minimizes the burden of the collection of information on 
those who are to respond, including the use of appropriate automated, 
electronic, mechanical, or other technological collection techniques or 
other forms of information technology, e.g., permitting electronic 
submissions of responses.
    Title: 1,3-Butadiene, 29 CFR 1910.1051.
    Description: The final 1,3-Butadiene (BD) Standard is an 
occupational safety and health standard that will minimize occupational 
exposure to BD. The standard's information collection requirements are 
essential components that will protect employees from occupational 
exposure. The information will be used by employers and employees to 
implement the protection required by the standard. OSHA will use some 
of the information to determine compliance with the standard.
    Summary of the Collection of Information: The collections of 
information contained in the standard include the provisions concerning 
objective data; exposure monitoring records and employee notification 
of exposure monitoring results; written plans for compliance, 
respiratory protection, exposure goal, emergency situations; 
information to the physician; employee medical exams and medical

[[Page 56747]]

records; respirator fit-testing records; record of training program; 
employee access to monitoring and medical records; and transfer of 
records to NIOSH.
    Respondents: The respondents are employers whose employees may have 
occupational exposure to BD above the action level. The main industries 
affected are 1,3-Butadiene Polymer Production, Monomer purification of 
1,3-Butadiene, Stand-Alone Butadiene Terminals, and Crude 1,3-Butadiene 
Producers.
    Frequency of Response: The frequency of monitoring and notification 
of monitoring results will be dependent on the results of the initial 
and subsequent monitoring events and the number of different job 
classifications with BD exposure. The Compliance Plan is required to be 
established and updated as necessary and reviewed at least annually. 
The Exposure Goal Program, Respiratory Protection Program, and 
Emergency Plans are required to be established and updated as 
necessary. For those using respirators, respirator fit testing is 
required initially, and at least annually thereafter. The frequency of 
the medical examinations will be dependent on the number of employees 
who will be exposed at or above the action level, or in emergency 
situations. A record of the training program is required to be 
maintained. Those employers using objective data in lieu of monitoring 
must maintain records of the objective data relied upon. The employer 
must maintain exposure monitoring and medical records, which includes 
information provided to the physician or other licensed health care 
professional, in accordance with 29 CFR 1910.20. Fit-Test records must 
be maintained for respirator users until the next fit test is 
administered.
    Total Estimated Cost: First Year $820,388; Second Year $658,949; 
and Third and Recurring Years $75,890.
    Total Burden Hours: The total burden hours for the first year is 
estimated to be 8,077; for the second year, the burden is estimated to 
be 5,342; and for the third and recurring years, the burden is 
estimated to be 1,587. The Agency has submitted a copy of the 
information collection request to OMB for its review and approval. 
Interested parties are requested to send comments regarding this 
information collection to the OSHA Docket Office, Docket No. ICR 96-13, 
U.S. Department of Labor, Room N-2625, 200 Constitution Avenue, NW, 
Washington, DC 20210. Written comments limited to 10 pages or fewer may 
also be transmitted by facsimile to (202) 219-5046.
    Comments submitted in response to this notice will be summarized 
and included in the request for Office of Management and Budget 
approval of the final information collection request; they will also 
become a matter of public record.
    Copies of the referenced information collection request are 
available for inspection and copying in the OSHA Docket Office and will 
be mailed to persons who request copies by telephoning Vivian Allen at 
(202) 219-8076. Electronic copies of the 1,3-Butadiene information 
collection request are available on the OSHA WebPage on the Internet at 
http://www.osha.gov/.

Federalism

    This standard has been reviewed in accordance with Executive Order 
12612, 52 FR 41685 (October 30, 1987), regarding Federalism. This Order 
requires that agencies, to the extent possible, refrain from limiting 
State policy options, consult with States prior to taking any actions 
only when there is clear constitutional authority and the presence of a 
problem of national scope. The Order provides for preemption of State 
law only if there is a clear Congressional intent for the Agency to do 
so. Any such preemption is to be limited to the extent possible.
    Section 18 of the Occupational Safety and Health Act (OSH Act), 
expresses Congress' clear intent to preempt State laws with respect to 
which Federal OSHA has promulgated occupational safety or health 
standards. Under the OSH Act, a State can avoid preemption only if it 
submits, and obtains Federal approval of, a plan for the development of 
such standards and their enforcement. Occupational safety and health 
standards developed by such State Plan-States must, among other things, 
be at least as effective in providing safe and healthful employment and 
places of employment as the Federal standards. Where such standards are 
applicable to products distributed or used in interstate commerce, they 
may not unduly burden commerce and must be justified by compelling 
local conditions. (See section 18(c)(2).)
    The final BD standard is drafted so that employees in every State 
will be protected by general, performance-oriented standards. States 
with occupational safety and health plans approved under section 18 of 
the OSH Act will be able to develop their own State standards to deal 
with any special problems which might be encountered in a particular 
state. Moreover, the performance nature of this standard, of and by 
itself, allows for flexibility by States and employers to provide as 
much leeway as possible using alternative compliance.
    This final rule of BD addresses a health problem related to 
occupational exposure to BD which is national in scope.
    Those States which have elected to participate under section 18 of 
the OSH Act would not be preempted by this regulation and will be able 
to deal with special, local conditions within the framework provided by 
this performance-oriented standard while ensuring that their standards 
are at least as effective as the Federal Standard.

State Plans

    The 23 States and 2 territories with their own OSHA-approved 
occupational safety and health plans must adopt a comparable standard 
within 6 months of the publication of this final standard for 
occupational exposure to 1,3-butadiene or amend their existing 
standards if it is not ``at least as effective'' as the final Federal 
standard. The states and territories with occupational safety and 
health state plants are: Alaska, Arizona, California, Connecticut (for 
State and local government employees only), Hawaii, Indiana, Iowa, 
Kentucky, Maryland, Michigan, Minnesota, Nevada, New Mexico, New York 
(for State and local government employees only), North Carolina, 
Oregon, Puerto Rico, South Carolina, Tennessee, Utah, Vermont, 
Virginia, the Virgin Islands, Washington, and Wyoming. Until such time 
as a State standard is promulgated, Federal OSHA will provide interim 
enforcement assistance, as appropriate, in these states and 
territories.

SUPPLEMENTARY INFORMATION:

I. Table of Contents

    The preamble to the final standard on occupational exposure to BD 
discusses events leading to the final rule, physical and chemical 
properties of BD, manufacture and use of BD, health effects of 
exposure, degree and significance of the risk presented, an analysis of 
the technological and economic feasibility, regulatory impact and 
regulatory flexibility analysis, and the rationale behind the specific 
provisions set forth in the proposed standard. The discussion follows 
this outline:

I. Table of Contents
II. Pertinent Legal Authority
III. Events Leading to the Final Standard
IV. Chemical Identification, Production, and Use
    A. Monomer
    B. Polymers
V. Health Effects

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    A. Introduction
    B. Carcinogenicity
      1. Animal Studies
      2. Epidemiologic Studies
    C. Reproductive Effects
    D. Other Relevant Studies
VI. Quantitative Risk Assessment
VII. Significance of Risk
VIII. Summary of the Final Economic Analysis
IX. Environmental Impact
X. Summary and Explanation of the Proposed Standard
    A. Scope and Application
    B. Definitions
    C. Permissible Exposure Limits
    D. Exposure Monitoring
    E. Regulated Areas
    F. Methods of Compliance
    G. Exposure Goal Program
    H. Respiratory Protection
    I. Personal Protective Equipment
    J. Emergency Situations
    K. Medical Screening and Surveillance
    L. Hazard Communication
    M. Recordkeeping
    N. Dates
    O. Appendices
XI. Final Standard and Appendices
Appendix A: Substance Safety Data Sheet for 1,3-Butadiene
Appendix B: Substance Technical Guidelines for 1,3-Butadiene
Appendix C: Medical Screening and Surveillance for 1,3-Butadiene
Appendix D: Sampling and Analytical Method for 1,3-Butadiene
Appendix E: Respirator Fit Testing Procedures
Appendix F: Medical Questionnaires

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 to 
promulgate and enforce occupational safety and health standards. U.S.C. 
655(a) (authorizing summary adoption of existing consensus and federal 
standards within two year of Act's enactment), 655(b) (authorizing 
promulgation of standards pursuant to notice and comment), 654(b) 
(requiring employers to comply with OSHA standards.)
    A safety or health standard is a standard ``which requires 
conditions, or the adoption or use of one or more practices, means, 
methods, operations, or processes, reasonably necessary or appropriate 
to provide safe or healthful employment or places of employment.'' 29 
U.S.C. 652(8).
    A standard is reasonably necessary or appropriate within the 
meaning of Section 652(8) if it substantially reduces or eliminates 
significant risk, and is economically feasible, technologically 
feasible, cost effective, consistent with prior Agency action or 
supported by a reasoned justification for departing from prior Agency 
actions, supported by substantial evidence, and is better able to 
effectuate the Act's purposes than any national consensus standard it 
supersedes. See 58 FR 16612-16616 (March 30, 1993).
    The Supreme Court has noted that a reasonable person would consider 
a fatality risk of 1/1000 over a 45-year working lifetime to be a 
significant risk. Industrial Union Dep't v. American Petroleum 
Institute, 448 U.S. 607, 646 (1980) (benzene standard). OSHA agrees 
that a fatality risk of 1/1000 over a working lifetime is well within 
the range of risk that reasonable people would consider significant. 
See e.g., International Union, UAW v. Pendergrass, 878 F.2d 389 (D.C. 
Cir. 1989) (formaldehyde standard); Building and Constr. Trades Dep't, 
AFL-CIO v. Brock, 838 F.2d 1258, 1265 (D.C. Cir. 1988) (asbestos 
standard).
    A standard is technologically feasible if the protective measures 
it requires already exist, can be brought into existence with available 
technology, or can be created with technology that can reasonably be 
expected to be developed. American Textile Mfrs. Institute v. OSHA, 452 
U.S. 490, 513 (1981) (``ATMI''), American Iron and Steel Institute v. 
OSHA, 939 F.2d 975, 980 (D.C. cir. 1991) (``AISI'').
    A standard is economically feasible if industry can absorb or pass 
on the cost of compliance without threatening its long term 
profitability or competitive structure. See ATMI, 452 U.S. at 530 n. 
55; AISI, 939 F. 2d at 980.
    A standard is cost effective if the protective measures it requires 
are the least costly of the available alternatives that achieve the 
same level of protection. ATMI, 453 U.S. at 514 n. 32; International 
Union, UAW v. OSHA, 37 F. 3d 665, 668 (D.C. Cir. 1994) (``LOTO III'').
    All standards must be highly protective. See 58 FR 16614-16615; 
LOTO III, 37 F. 3d at 668. However, health standards must also meet the 
``feasibility mandate'' of Section 6(b)(5) of the Act, 29 U.S.C. 
655(b)(5). Section 6(b)(5) requires OSHA to select ``the most 
protective standard consistent with feasibility'' that is needed to 
reduce significant risk when regulating health hazards. ATMI, 452 U.S. 
at 509.
    Section 6(b)(5) also directs OSHA to base health standards on ``the 
best available evidence,'' including research, demonstrations, and 
experiments. 29 U.S.C. 655(b)(5). OSHA shall consider ``in addition to 
the attainment of the highest degree of health and safety protection * 
* * the latest scientific data * * * feasibility and experience gained 
under this and other health and safety laws.'' Id.
    Section 6(b)(7) of the Act authorizes 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).
    Finally, whenever practical, standards shall ``be expressed in 
terms of objective criteria and of the performance desired.'' Id.

III. Events Leading to the Final Standard

    The standard adopted for BD by OSHA in 1971 pursuant to Section 
6(a) of the OSH Act, 29 U.S.C. 655 from an existing Walsh-Healey 
Federal Standard required employers to assure that employee exposure 
does not exceed 1,000 ppm determined as an 8-hour TWA (29 CFR 
1910.1000, Table Z-1). The source of the Walsh-Healey Standard was the 
Threshold Limit Value (TLV) for BD developed in 1968 by the American 
Conference of Governmental Industrial Hygienists (ACGIH). This TLV was 
adopted by the ACGIH to prevent irritation and narcosis.
    In 1983, the National Toxicology Program (NTP) released the results 
of an animal study indicating that BD causes cancer in rodents. (Ex. 
20) Based on the strength of the results of this animal study, ACGIH in 
1983 classified BD as an animal carcinogen and in 1984 recommended a 
new TLV of 10 ppm. (Ex. 2-4) Based on the same evidence, on February 9, 
1984, the National Institute for Occupational Safety and Health (NIOSH) 
published a Current Intelligence Bulletin (CIB) recommending that BD be 
regarded as a potential occupational carcinogen, teratogen and a 
possible reproductive hazard. (Ex. 23-17) On January 5, 1984, OSHA 
published a Request for Information (RFI) jointly with the 
Environmental Protection Agency. (EPA) (49 FR 844) EPA also announced 
the initiation of a 180 day review under the authority of section 4(f) 
of the Toxic Substance Control Act (TSCA) (49 FR 845) to determine 
``whether to initiate appropriate action to prevent or reduce the risk 
from the chemical or to find that the risk is not unreasonable.'' 
Comments were to be submitted to OSHA by March 5, 1984. On April 4, 
1984, OSHA extended the comment period until further notice. (49 FR 
13389)
    Petitions for an Emergency Temporary Standard (ETS) of 1 ppm or 
less for workers' exposure to BD were submitted to OSHA on January 23, 
1984, by the United Rubber, Cork, Linoleum and

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Plastic Workers of America (URW), the Oil, Chemical and Atomic Workers 
(OCAW), the International Chemical Workers Union (ICWU), and the 
American Federation of Labor and Congress of Industrial Organizations 
(AFL-CIO). (Ex. 6-4) On March 7, 1984, OSHA denied the petitions on the 
ground that the Agency was still evaluating the health data to 
determine whether regulatory action was appropriate.
    Based on its 180-day review of BD, EPA published, on May 15, 1984, 
an Advance Notice of Proposed Rulemaking (ANPR) (49 FR 20524) to 
announce the initiation of a regulatory action by the EPA to determine 
and implement the most effective means of controlling exposures to the 
chemical BD under the TSCA. EPA was working with OSHA because available 
evidence indicated that exposure to BD occurs primarily within the 
workplace.
    Information received in response to this ANPR was used by EPA to 
develop risk assessments. Subsequently, EPA identified BD as a probable 
human carcinogen (Group B2) according to EPA's classification of 
carcinogens, and concluded that current exposures during the 
manufacturing of BD and its processing into polymers presented an 
unreasonable risk of injury to human health. (Ex. 17-4) Additionally, 
EPA determined that the risks associated with exposure to BD may be 
reduced to a sufficient extent by action taken under the OSH Act. 
Following these findings, EPA, in accordance with section 9(a) of TSCA, 
on October 10, 1985 (50 FR 41393), referred BD to OSHA to give this 
Agency an opportunity to regulate the chemical under the OSH Act. EPA 
requested that OSHA determine whether the risks described in the EPA 
report may be prevented or reduced to a sufficient extent by action 
taken under the OSH Act and then if such a determination is made, OSHA 
issue an order declaring whether the manufacture and use of BD 
described in the EPA report present the risk therein described. EPA 
asked OSHA to respond within 180 days, by April 8, 1986. (50 FR 41393)
    On December 27, 1985, OSHA published a notice soliciting public 
comments on EPA's referral report. (50 FR 52952) Based on all the 
available information, OSHA, on April 11, 1986, responded to the EPA 
referral report by making a preliminary determination (50 FR 12526) 
that a revised OSHA standard limiting occupational exposure to BD could 
prevent or reduce the risk of exposure to a sufficient extent and that 
such risks had been accurately described by EPA in the report. On 
October 1, 1986, OSHA published an ANPR (51 FR 35003) to initiate a 
rulemaking within the meaning of section 9(a) of TSCA. The Agency 
requested that comments be submitted by December 30, 1986. Twenty-four 
comments, some of them containing new information, were received in 
response to the ANPR. (Ex. 28-1 to 28-24) Six additional comments were 
received after the deadline. (Ex. 29-1 to 29-6)
    OSHA reviewed the available data and conducted risk assessment, 
regulatory impact and flexibility analyses. These analyses demonstrate 
that the proposed standard was technologically and economically 
feasible and substantially reduced the significant risk of cancers and 
other adverse health effects.
    On August 10, 1990, OSHA published its proposed rule to regulate 
occupational exposure to 1,3-butadiene. (55 FR 32736) Based on the 
Agency's review of studies of exposed animals and epidemiologic studies 
and taking into account technologic and economic feasibility 
considerations, OSHA proposed a permissible exposure limit (PEL) of 2 
ppm as an 8-hour time-weighted average and a short term exposure limit 
(STEL) of 10 ppm for a 15 minute sampling period. Also included in the 
proposal was an ``action level'' of 1 ppm which triggered certain 
provisions of the standard such as medical surveillance and training.
    OSHA convened public hearings in Washington, DC., on January 15-23, 
1991, and in New Orleans, Louisiana, on February 20-21, 1991. The post-
hearing period for the submission of briefs, arguments and summations 
was to end July 22, 1991, but was extended by the Administrative Law 
Judge to December 13, 1991, in order to give participants time to 
review new data on low-dose exposures submitted by NTP and a 
quantitative risk assessment done by NIOSH. The comment period closed 
February 10, 1992.
    In the Fall of 1992, the International Agency for Research on 
Cancer (IARC) published the results of the Working Group on the 
Evaluation of Carcinogenic Risks to Humans, which reviewed the 
carcinogenic potential of BD and concluded that:

    There is limited evidence for the carcinogenicity in humans of 
1,3-butadiene * * * There is sufficient evidence for the 
carcinogenicity in experimental animals * * * (Ex. 125)

IARC stated that its overall evaluation led it to conclude that ``1,3-
butadiene is probably carcinogenic to humans (Group 2A).'' (Ex. 125)
    To assist OSHA in issuing a final rule for BD, representatives of 
the major unions and industry groups involved in the production and use 
of BD submitted the outline of a voluntary agreement reached by the 
parties dated January 29, 1996, outlining provisions that they agreed 
upon and recommended be included in the final rule. The letter 
transmitting the agreement was signed by J.L. McGraw for the 
International Institute of Synthetic Rubber Producers (IISRP), Michael 
J. Wright for the United Steelworkers of America (USWA), and Michael 
Sprinker (CWU). The committee that worked on the issues also included 
Joseph Holtshouser of the Goodyear Tire and Rubber Company, Carolyn 
Phillips of the Shell Chemical Company, representing the Chemical 
Manufacturers Association, Robert Richmond of the Firestone Synthetic 
Rubber and Latex Company, and Louis Beliczky (formerly of the URW) and 
James L. Frederick of the SWA.
    The agreement proposed a change in the permissible exposure limits, 
additional provisions for exposure monitoring, and an exposure goal 
program designed to reduce exposures below the action level. It also 
set forth other modifications to the scope, respiratory protection, 
communication of hazards, medical surveillance, and start-up dates 
sections of the final rule.
    On March 8, 1996 OSHA published the labor/industry joint 
recommendations and re-opened the record for 30 days to allow the 
public to comment. (61 FR 9381) In response to requests from the 
parties to the agreement, the comment period was extended to April 26, 
1996. (61 FR 15205)
    At the beginning of the comment period, OSHA placed in the 
rulemaking record an epidemiologic study of BD exposed workers by 
Delzell, et al. sponsored by IISRP, along with IARC volume 127 
``Butadiene and Styrene Assessment of Health Hazards,'' a published 
paper by Santos-Burgoa, et al. entitled ``Lymphohematopoietic Cancer in 
Styrene-Butadiene Polymerization Workers,'' and abstracts from a 
symposium entitled ``Evaluation of Butadiene and Isoprene Health 
Risks.'' (Ex. 117-1; 117-2; 117-3; 117-4) The epidemiological study had 
also been submitted to the EPA in compliance with provisions of the 
Toxic Substances Control Act.
    In response to the re-opening of the BD record, 18 sets of comments 
were received. The parties to the labor/industry agreement submitted a 
draft regulatory text which put their recommendations into specific 
requirements. The outline and the

[[Page 56750]]

subsequent draft regulatory text are solely the work product of the 
negotiating committee. OSHA was neither a party to nor present at the 
negotiations.
    While the responses to the record re-opening helped clarify the 
intent of the negotiating parties, the rationales behind several of the 
changes were not fully explained.
    On September 16, 1996, Judge John M. Vittone, for Judge George C. 
Pierce who presided over the BD hearings, closed the record of the 
public hearing on the proposed standard for 1,3-butadiene and certified 
it to the Assistant Secretary of Labor. (Ex. 135)

IV. Chemical Identification, Production and Use

A. Monomer

    The chemical 1,3-butadiene (BD) (Chemical Abstracts Registry Number 
106-99-0) is a colorless, noncorrosive, flammable gas with a mild 
aromatic odor at standard ambient temperature and pressure. It has a 
chemical formula of C4H6, a molecular weight of 54.1, and a 
boiling point of -4.7  deg.C at 760 mm Hg, a lower explosive limit of 
2%, and an upper explosive limit of 11.5%. Its vapor density is almost 
twice that of air. It is slightly soluble in water, somewhat soluble in 
methanol and ethanol, and readily soluble in less polar organic 
solvents such as hexane, benzene, and toluene. (Ex. 17-17) It is highly 
reactive, dimerizes to 4-vinylcyclohexene, and polymerizes easily. 
Because of its low odor threshold, high flammability and explosiveness, 
BD has been handled with extreme care in the industry.
    In the United States BD has been produced commercially by three 
processes: Catalytic dehydrogenation of n-butane and n-butene, 
oxidative dehydrogenation of n-butene, and recovery as a by-product 
from the C4 co-product stream from the steam cracking process used 
to manufacture ethylene, which is the major product of the 
petrochemical industry. For economic reasons, almost all BD currently 
made in the U.S. is produced by the ethylene co-product process.
    In the steam cracking process for ethylene, a hydrocarbon feedstock 
is diluted with steam then heated rapidly to a high temperature by 
passing it through tubes in a furnace. The output stream, containing a 
broad mixture of hydrocarbons from the pyrolysis reactions in the 
cracking tubes plus unreacted components of feedstock, is cooled and 
then processed through a series of distillation and other separation 
operations in which the various products of the cracking operation are 
separated for disposal, recycling or recovery.
    The cracking process produces between 0.02 to 0.3 pounds of BD per 
pound of ethylene, depending upon the composition of the feedstock. BD 
is recovered from the C4 stream by the separation operations. The 
C4 stream contains from 30 to 50% BD plus butane, butenes and 
small fractions of other hydrocarbons. This crude BD stream from the 
ethylene unit may be refined in a unit on site, or transferred to 
another location, a monomer plant, owned by the same or a different 
company, to produce purified BD.
    Regardless of the source of the crude BD-ethylene co-product, 
(dehydrogenation, or blending of C4 streams from other sources), 
the processes used by different companies to refine BD for subsequent 
use in polymer production are similar. Extractive distillation is used 
to effect the basic separation of BD from butanes and butenes and 
fractional distillation operations are used to accomplish other related 
separations. A typical monomer plant process is described below.
    C3 and C4 acetylene derivatives, present in the C4 
co-product stream, are converted to olefins by passing the stream 
through a hydrogenation reactor. The stream is then fed to an 
extractive distillation column to separate the BD from butanes and 
butenes. Several different solvents have been employed for this 
operation, including n-methylpyrrolidone, dimethylformamide, furfural, 
acetonitrile, dimethylacetamide, and cuprous ammonium acetate solution. 
The BD, extracted by the solvent, is stripped from it in the solvent 
recovery column, then fed to another fractionation column, the 
methylacetylene column, to have residual acetylene stripped out. The 
bottom stream from the methylacetylene column, containing the BD, is 
fed to the BD rerun column, from which the purified BD product is taken 
off overhead. The solvent, recovered in the solvent recovery column, is 
recycled to the extractive distillation column with part of it 
distilled to keep down the level of polymer. (Ex. 17-17)
    A stabilizer is added to the monomer to inhibit formation of 
polymer during storage. It is stored as a liquid under pressure, 
sometimes refrigerated to reduce the pressure, generally stored in a 
tank farm in diked spheres. It is shipped to polymer manufacturers and 
other users by pipeline, barge, tank car, or tank truck.
    BD is a major commodity product of the petrochemical industry. 
Total U.S. production of BD in 1991 was 3.0 billion pounds. Although BD 
is a toxic flammable gas, its simple chemical structure with low 
molecular weight and high chemical reactivity make it a useful building 
block for synthesizing other products. In ``1,3-Butadiene Use and 
Substitutes Analysis,'' EPA identified 140 major, minor and potential 
uses of BD in the chemical industry. (Ex. 17-15)
    Over 60% of the BD consumed in the United States is used in the 
manufacture of rubber, about 12% in making adiponitrile which in turn 
is used to make hexamethylenediamine (HMDA), a component of Nylon, 
approximately 8% in making styrene-butadiene copolymer latexes, 
approximately 7% in producing polychloroprene, and about 6% in 
producing acrylonitrile-butadiene-styrene (ABS) resins. Lesser amounts 
are consumed in the production of rocket propellants, specialty 
copolymer resins and latexes for paint, coatings and adhesive 
applications, and hydrogenated butadiene-styrene polymers used as 
lubricating oil additives. Some nonpolymer applications include the 
manufacture of the agricultural fungicides, Captan and Captofol, the 
industrial solvent sulfolane, and anthroquinone dyes.

B. Polymers

    BD based synthetic elastomers are manufactured by polymerizing BD 
by itself, by polymerizing BD with other monomers to produce 
copolymers, and by producing mixtures of these polymers. The largest-
volume product is the copolymer of styrene and BD, styrene-butadiene 
rubber, followed in volume by polybutadiene, polychloroprene, and 
nitrile rubber. Polybutadiene is the polymer of BD monomer by itself. 
Polychloroprene is made by polymerizing chloroprene, produced by 
chlorination of BD. Nitrile rubbers are copolymers of acrylonitrile and 
BD.
    Four general types of processes are used in polymerizing BD and its 
copolymers: emulsion, suspension, solution and bulk polymerization. In 
emulsion and suspension polymerization, the monomers and the many 
chemicals used to control the reaction are finely dispersed or 
dissolved in water. In solution polymerization, the monomers are 
dissolved in an organic solvent such as hexane, pentane, toluene. In 
bulk polymerization, the monomer itself serves as solvent for the 
polymer. The polymer product, from which end-use products are 
manufactured, is produced in the form of polymer crumb (solid 
particles), latex (a milky suspension in water), or cement (a 
solution).

[[Page 56751]]

    Emulsion polymerization is the principal process used to make 
synthetic rubber. A process for the manufacture of styrene-butadiene 
crumb is typical of emulsion processes. Styrene and BD are piped to the 
process area from the storage area. The BD is passed through a caustic 
soda scrubber to remove the inhibitors which were added to prevent 
premature polymerization. The fresh BD monomer streams are mixed with 
styrene, aqueous emulsifying agents, activator, catalyst, and modifier, 
and then fed to the first of a train of reactors. The reaction proceeds 
stepwise in the series of reactors to around 60% conversion of monomer 
to polymer. In the cold process, the reactants are chilled and the 
reactor temperature is maintained at 4 deg.C to 7 deg.C (40 deg.F to 
45 deg.F) and pressure at 0 to 15 psig; in the hot rubber process, 
temperature and pressure are around 50 deg.C (122 deg.F) and 40 to 60 
psig, respectively.
    The latex from the reactor train is flashed to evaporate unreacted 
BD which is compressed, condensed and recycled. Uncondensed vapors are 
absorbed in a kerosene absorber before venting and the absorbed BD is 
steam stripped or recovered from the kerosene by some other operation. 
The latex stream is passed through a steam stripper, operated under 
vacuum, to remove and recover unreacted styrene. The styrene and water 
in the condensate are separated by decanting. The styrene phase is 
recycled to the process. Noncondensibles from the stripping column 
contain some BD and are directed through the BD recovery operations.
    Stripped latex, to which an antioxidant has been added, is pumped 
to coagulation vessels where dilute sulfuric acid and sodium chloride 
solution are added. The acid and brine mixture breaks the emulsion, 
releasing the polymer in the form of crumb. Sometimes carbon black and 
oil are added during the coagulation step since better dispersion is 
obtained than by mixing later on.
    The crumb and water slurry from the coagulation operation is 
screened to separate the crumb. The wet crumb is pressed in rotary 
presses to squeeze out most of the entrained water then dried with hot 
air on continuous dry belt dryers. The dried product is baled and 
weighed for shipment.
    Production of styrene-butadiene latex by the emulsion 
polymerization process is similar to that for crumb but is usually 
carried out on a smaller scale with fewer reactors. For some but not 
all products, the reaction is run to near completion, monomer removal 
is simpler and recovery may not be practiced.
    Polybutadiene rubber is usually produced by solution 
polymerization. Inhibitor is removed from the monomer by caustic 
scrubbing. Both monomer and solvent are dried by fractional 
distillation, mixed in the desired ratio and dried in a desiccant 
column. Polymerization is conducted in a series of reactors using 
initiators and catalysts and is terminated with a shortstop solution. 
The solution, called rubber cement, is pumped to storage tanks for 
blending. Crumb is precipitated by pumping the solution into hot water 
under violent agitation. Solvent and monomer are recovered by stripping 
and distillation similar to those previously described. The crumb is 
screened, dewatered, dried and baled.
    Polychloroprene (neoprene) elastomers are manufactured by 
polymerizing chloroprene in an emulsion polymerization process similar 
to that used for making styrene-butadiene rubber. The monomer, 
chloroprene (2-chloro-BD), is made by chlorination of BD to make 3,4-
dichlorobutene, and dehydrochlorination of the latter.
    Nitrile rubbers, copolymers of acrylonitrile and BD, are produced 
by emulsion polymerization similar to that used to make styrene-
butadiene rubber.
    Substantial amounts of BD are used in the production of two other 
large volume polymers: Nylon resins and ABS resin. Dupont manufactures 
adiponitrile from BD and uses the product to make hexamethylenediamine 
which is polymerized in making Nylon resins and fibers, including Nylon 
6,6. Acrylonitrile, BD and styrene are the monomers used to make ABS 
resin which is a major thermoplastic resin. Chemically complex 
emulsion, suspension and bulk polymerization processes are used by 
different producers to make ABS polymer.

V. Health Effects

A. Introduction

    The toxicity of BD was long considered to be low and non-
cumulative. Thus, the OSHA standard for BD was 1,000 ppm on the basis 
of its irritation of mucous membranes and narcosis at high levels of 
exposure. However, in the 1980s, carcinogenicity studies indicated BD 
is clearly a carcinogen in rodents. In 1986, the American Conference of 
Governmental Industrial Hygienists (ACGIH) was prompted by these 
studies to lower the workplace threshold limit value (TLV) from 1,000 
to 10 ppm. (Ex. 2-5)
    Rodent studies are now conclusive that BD is an animal carcinogen. 
Further, a consistent body of epidemiologic studies have also shown 
increased mortality from hematopoietic cancers associated with BD 
exposure among BD-exposed production and styrene/BD rubber polymer 
workers. Complementary studies of metabolic products and genotoxicity 
support these cancer findings. OSHA was also concerned about evidence 
that BD affects the germ cell as well as the somatic cell, and what 
potential reproductive toxicity might result from exposure to BD. Since 
BD itself does not appear to be carcinogenic, but must be metabolized 
to an active form, OSHA also reviewed studies on the metabolism of BD 
to determine wether they might help explain the observed differences in 
cancer incidence among species.
    The following sections discuss the effects of BD exposure, both in 
human and animal systems.

B. Carcinogenicity

1. Animal Studies
    In the proposed BD rule, OSHA discussed the results of two lifetime 
animal bioassays, one on the Sprague-Dawley rat and one in the 
B6C3F1 mouse. (55 FR 32736 at 32740) Both studies found evidence 
of BD carcinogenicity, with the greater response in the mouse. The rat 
study involved exposure levels of 0, 1000, or 8000 ppm BD, starting at 
five weeks of age, to groups of 100 male and 100 female Sprague-Dawley 
rats for 6 hours per day, five days per week, for 105 weeks. Mortality 
was increased over controls in the 1,000 ppm exposed female rats and in 
both of the male rat exposure groups. Significant tumor response sites 
in the male rats included exocrine adenomas and carcinomas (combined) 
of the pancreas in the highest exposure group (3, 1, and 11 tumors in 
the 0, 1000, and 8000 ppm groups, respectively); and Leydig-cell tumors 
of the testis (0, 3, and 8 in the same groups, respectively). In the 
female rats, the significantly increased tumor response also occurred 
in the highest exposure group; cancers seen included follicular-cell 
adenomas and carcinomas (combined) of the thyroid gland (0,4, and 11 
tumors in the three exposure groups, respectively), and benign and 
malignant (combined) mammary gland tumors (50, 79, and 81 in the same 
exposure groups). To a lesser degree there were also sarcomas of the 
uterus (1, 4, 5 tumors in the three exposure groups), and Zymbal gland 
(0, 0, 4 tumors in the same exposure groups, respectively). While only 
high

[[Page 56752]]

exposure group tumor response for some of these sites was statistically 
significant, trend tests were also significant.
    In contrast to the generally less than 10% increase in tumor 
response seen in the Sprague-Dawley rat at levels far above BD 
metabolic saturation, the carcinogenic response to BD in the 
B6C3F1 mouse in the National Toxicology Program study (NTP I) was 
extensive. (Ex. 23-1) In this study, groups of 50 male and 50 female 
mice were exposed via inhalation to 0, 625 or 1250 ppm BD for 6 hours 
per day, 5 days per week in a study originally designed to last 2 
years. However, the high carcinogenic response included multiple 
primary cancers, with short latent periods, and led to early study 
termination (60-61 weeks) due to high cancer mortality in both the 625 
ppm and 1250 ppm exposure groups of both sexes. This mortality was due 
mainly to lymphocytic lymphomas and hemangiosarcomas of the heart, both 
of which were typically early occurring and quickly fatal. This large 
and rapidly fatal carcinogenic response led to both the NTP and 
industry to undertake additional studies to better understand the 
mechanisms involved.
    Some commenters have associated qualitative or quantitative 
differences in mouse and rat BD carcinogenicity with the differences in 
rat and mouse BD metabolism. Many studies published and submitted to 
the BD record since the proposed rule have sought to better 
characterize the metabolic, distributional, and elimination processes 
involved, and some have attributed species differences (at least in 
part) to the metabolic differences. These will be addressed separately 
in the metabolism section.
    Another factor hypothesized to account for differences between 
mouse and rat BD carcinogenicity was the role of activation of 
ecotropic retrovirus in hematopoietic tissues on tumor response in the 
B6C3F1 mouse. This virus is endogenous to the B6C3F1 mouse 
and was hypothesized to potentiate the BD lymphoma response in this 
strain. To study this hypothesis Irons and co-workers exposed both (60) 
B6C3F1 male (those with the endogenous virus) and (60) NIH Swiss 
male (those without the endogenous virus) mice to either 0 or 1250 ppm 
BD, for 6 hours./day, 5 days per week for 52 weeks. (Ex. 32-28D) A 
third group of 50 B6C3F1 male mice received 1250 ppm for 12 weeks 
only and was observed until study termination at 52 weeks. The results 
of the study showed significantly increased thymic lymphomas in all 
exposed groups but significantly greater response in the B6C3F1 
mouse--1 tumor/60 (2%) in the control (zero exposure) group, 10/48 
(21%) in the 12 week exposure group, and 34/60 (57%) in the 52 week 
exposure group--vs. the NIH Swiss mice, which developed 0 tumors/60 in 
the control group, and 8 tumors/57 (14%) in the BD exposed group. 
Hemangiosarcomas of the heart were also observed in both strains 
exposed to BD for 52 weeks--5/60 (8%) in the B6C3F1 mice vs. 1/57 
in the NIH Swiss mice. (Ex. 32-28D). The B6C3F1 response was very 
similar to the NTP I high exposure group response, verifying that 
earlier study. The qualitatively similar lymphoma responses of the two 
strains also confirmed that the mouse hematopoietic system is highly 
susceptible to the carcinogenic effects of BD, although quantitatively 
the strains may differ. The 21% 1-year lymphoma response in the 12-week 
stop-exposure B6C3F1 group also increased concerns about high 
concentration, short duration exposures.
NTP II Study
    Concurrent with the industry studies, the NTP, in order to better 
characterize the dose-response and lifetime experience, conducted a 
second, much larger research effort over a much broader dose range. 
(Ex. 90; 96) These toxicology and carcinogenesis studies included a 
100-fold lower (6.25 ppm) low exposure group than NTP I, several 
intermediate exposure groups, a study of dose-rate effects using 
several high-concentration partial lifetime (stop-) exposure groups, 
and planned interim sacrifice groups. Other parts of the study included 
clinical pathology studies (with the 9- and 15-month interim 
sacrifices, metabolism studies, and examination of tumor bearing 
animals for activated oncogenes).
    For the lifetime carcinogenesis studies, groups of 70 B6C3F1 
mice of each sex were exposed via inhalation to BD at levels of 0, 
6.25, 20, 62.5, 200, or 625 ppm (90 of each sex in this highest group) 
for 6 hours per day, 5 days per week for up to 2 years. Up to 10 
randomly selected animals in each group were sacrificed after 9 and 15 
months of exposure, and these animals were assessed for both 
carcinogenicity and hematologic effects.
    For the stop-exposure study, different groups of 50 male mice were 
exposed 6 hours per day, 5 days per week to concentrations of either 
200 ppm for 40 weeks, 625 ppm for 13 weeks, 312 ppm for 52 weeks, or 
625 ppm for 26 weeks. Following the BD exposure period, the exposed 
animals were then observed for the remainder of the 2-year study. The 
first two stop-exposure groups received a total exposure (concentration 
times duration) of 8,000 ppm-weeks, while the latter two groups 
received approximately 16,000 ppm-weeks of exposure. For the analysis 
discussed below, groups are compared both with each other for dose-rate 
effects and with the lifetime (2 year) exposure groups for recovery 
effects.
Methodology
    Male mice were 6-8 weeks old and female mice were 7-8 weeks old 
when the exposures began. Animals were exposed in individual wire mesh 
cage units in stainless steel Hazelton 2000 chambers (2.3 m\3\). The 
exposure phase extended from January, 1986 to January, 1988. Animals 
were housed individually; water was available ad libitum; NIH-07 diet 
feed was also available ad libitum except during exposure periods. 
Animals were observed twice daily for moribundity and mortality; 
animals were weighed weekly for the first 13 weeks and monthly 
thereafter. Hematology included red blood cell count (RBC), and white 
blood cell count (WBC). The study was conducted in compliance with the 
Food and Drug Administration (FDA) Good Laboratory Practice Regulations 
with retrospective quality assurance audits.
    The results of the study are presented below for the two-year and 
stop-exposure study. Between study group comparisons are made where it 
is deemed appropriate. Emphasis is placed on the neoplastic effects.

Results

Two-Year Study
    While body weight gains in both exposed male and female mice were 
similar to those of the control groups, exposure related malignant 
neoplasms were responsible for decreased survival in all exposure 
groups of both sexes exposed to concentrations of 20 ppm or above. 
Excluding the interim sacrificed animals, the two-year survival 
decreased uniformly with increasing exposure for females (37/50, 33/50, 
24/50, 11/50, 0/50, 0/70), and nearly uniformly for males (35/50, 39/
50, 24/50, 22/50, 4/50, 0/70). As with the earlier NTP study, all 
animals in the 625 ppm group were dead by week 65, mostly as a result 
of lymphomas or hemangiosarcomas of the heart. The 200 ppm exposure 
groups of both sexes also had much higher mortality, but significantly 
less than that of the 625 ppm group. The survival of the lowest 
exposure group (6.25 ppm) was slightly better than controls for the 
male mice, slightly less for the female mice. Mean

[[Page 56753]]

survival for the males was an exposure-related 597, 611, 575, 558, 502, 
and 280 days; for the females it was similarly 608, 597, 573, 548, 441, 
and 320 days. This decreased survival with increasing exposure was 
almost totally due to tumor lethality.
Carcinogenicity
    Nine different sites showed primary tumor types associated with 
butadiene exposures, seven in the male mice and eight in the female 
mice. These were lymphoma, hemangiosarcoma of the heart, combined 
alveolar-bronchiolar adenoma and carcinoma, combined forestomach 
papilloma and carcinoma, Harderian gland adenoma and adenocarcinoma, 
preputial gland adenoma and carcinoma (males only), hepatocellular 
adenoma and carcinoma, and mammary and ovarian tumors (females only). 
These are shown in Table V-1 adapted from Melnick et al. (Ex. 125) From 
this table it is seen that six of these tumor sites are statistically 
significantly increased in the highest exposed males and five were 
statistically significantly increased in the highest exposed females. 
Two additional sites which showed significant increases at lower 
exposures showed decline at the highest exposures because other tumors 
were more rapidly fatal. At 200 ppm preputial gland adenoma and 
carcinoma combined were significantly increased in males (p<.05; 0/70 
(0%) control vs. 5/70 (7%) in the 200 ppm group) and hepatocellular 
adenoma and carcinoma were increased for both exposed males and 
females. At the lowest exposure concentration, 6.25 ppm, only female 
mouse lung tumors (combined adenoma and carcinoma) showed statistical 
significance (p<.05; 4/70 (6%) in controls vs. 15/70 (21%) in the 6.25 
ppm group); these tumors in female mice showed a monotonic increase 
with increasing exposure up to 200 ppm. At 20 ppm female mouse 
lymphomas and liver tumors also reached statistical significance 
(lymphomas, p<.05; 10/70 (15%) in controls vs. 18/70 (26%) in the 20 
ppm group; liver tumors, p<.05; 17/70 (24%) in controls vs. 23/70 (33%) 
in the 20 ppm group), and at 62.5 ppm, tumors at several other sites 
were also significantly increased. In general, while there were some 
differences in amount of tumor response between the male and female 
mice, there is fairly consistent pattern of tumor type in mice of both 
sexes for the six non-sexual organ sites.

         Table V-1.--Tumor Incidences (I) and Percentage Mortality-Adjusted Tumor Rates (R) in Mice Exposed to 1,3-Butadiene For up to 2 Years.         
                                                                 [Adapted from Ex. 125]                                                                 
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                    Exposure concentration (ppm)                        
                                                                           -----------------------------------------------------------------------------
                      Tumor                                  Sex                 0           6.25          20          62.5         200          625    
                                                                           -----------------------------------------------------------------------------
                                                                               I     Rc     I     R      I     R      I     R      I     R      l     R 
--------------------------------------------------------------------------------------------------------------------------------------------------------
Lymphoma........................................  M                           4/70    8    3/70    6    8/70   19   11/70  a25    9/70  a27   69/90  a97
                                                  F                          10/70   20   14/70   30  a18/70   41   10/70   26   19/70  a58   43/90  a89
Heart--Hemangiosarcoma..........................  M                           0/70    0    0/70    0    1/70    2    5/70  a13   20/70  a57    6/90  a53
                                                  F                           0/70    0    0/70    0    0/70    0    1/70    3   20/70  a64   26/90   84
Lung--Alveolar-bronchiolar adenoma and carcinoma  M                          22/70   46   23/70   48   20/70   45   33/70  a72   42/70  a87   12/90  a73
Forestomach--Papilloma and carcinoma............  F                           4/70    8   15/70  a32   19/70  a44   27/70  a61   32/70  a81   25/90  a83
Harderian gland--Adenoma and adenocarcinoma.....  M                           1/70    2    0/70    0    1/70    2    5/70   13   12/70  a36   13/90  a75
                                                  F                           2/70    4    2/70    4    3/70    8    4/70   12    7/70  a31   28/90  a85
Preputial gland--Adenoma and carcinoma..........  M                           6/70   13    7/70   15   11/70   25   24/70  a53   33/70  a77    7/90  a58
                                                  F                           9/70   18   10/70   21    7/70   17   16/70  a40   22/70  a67    7/90   48
Liver--Hepatocellular adenoma and carcinoma.....  M                           0/70    0    0/70    0    0/70    0    0/70    0    5/70  a17    0/90    0
Mammary gland--Adenocarcinoma...................  M                          31/70   55   27/70   54   35/70   68   32/70   69   40/70  a87   12/90   75
Ovary--Benign and malignant granulosa-cell        F                          17/70   35   20/70   41   23/70  a52   24/70  a60   20/70  a68    3/90   28
 tumors.                                                                                                                                                
                                                  F                           0/70    0    2/70    4    2/70    5    6/70  a16   13/70  a47   13/90  a66
                                                  F                           1/70    2    0/70    0    0/70    0    9/70  a24   11/70  a44    6/90   44
--------------------------------------------------------------------------------------------------------------------------------------------------------
a Increased compared with chamber controls (0 ppm), p < 0.05, based on logistic regression analysis.                                                    
b The Working Group noted that the incidence in control males and females was in the range of that in historical controls (Haseman et al., 1985).       
c Mortality adjusted tumor rates are adjusted for competing causes of mortality, such as death due to other tumors, whose rates differ by exposure      
  group.                                                                                                                                                

    Hemangiosarcoma of the heart, with metastases to other organs was 
first observed at 20 ppm in 1 male (the historical controls for this 
strain are 1/2373 in males and 1/2443 in females), in 5 males and 1 
female at 62.5 ppm and in 20 males and 20 females at 200 ppm; at 625 
ppm these tumor rates leveled off as other tumors, especially lymphomas 
became dominant. Lymphatic lymphomas increased to statistical 
significance first in females at 20 ppm and were usually rapidly fatal, 
the first tumor appearing at week 23, most likely preempting some of 
the later appearing tumors in the higher exposure groups. Because of 
the plethora of primary tumors and the different time patterns observed 
to onset of each type, several tumor dose-response trends do not appear 
as strong as they would otherwise be.
Non-Neoplastic Effects
    Several non-cancer toxic effects were noted in the exposed groups, 
reflecting many of the same target sites for which the neoplastic 
effects were seen. (Ex. 90; 96; 125).
    Although the reported numbers differ slightly in the different 
exhibits, generally dose-related increases in hyperplasia were observed 
in the heart, lung, forestomach, and Harderian gland, both in the two-
year study (both sexes) and in the stop-exposure study (conducted in 
males only). In addition, testicular atrophy was observed in both the 
two-year and stop-exposure male mice, but remained in the 6%-10% range 
except for the 2-year, 625 ppm

[[Page 56754]]

group where it was 74%. Ovarian germinal hyperplasia (2/49 (control), 
3/49 (6.25 ppm), 8/48 (20 ppm), 15/50 (62.5 ppm), 15/50 (200 ppm), 18/
79 (625 ppm), ovarian atrophy (4/49, 19/49, 32/48, 42/50, 43/50, 69/
79), and uterine atrophy (1/50, 0/49, 1/50, 1/49, 8/50, 41/78) were 
also dose related, with ovarian atrophy significantly increased at the 
lowest BD exposure of 6.25 ppm. These toxic effects to the reproductive 
organs are discussed in greater detail in the reproductive effects 
section of this preamble. Bone marrow atrophy was noted only in the 
highest exposure groups, occurring in 23/73 male mice and 11/79 female 
mice.

Stop-Exposure Study

    As with the 2-year study, the body weights of the four treated 
groups in the stop-exposure study were similar to controls. All 
exposure groups exhibited markedly lower survival than controls, and 
only slightly better survival than that of the comparable full lifetime 
exposure groups. Mortality appeared to be more related to total dose 
than to exposure concentration. Most deaths were caused by tumors.

Neoplastic Effects

    All of these stop-exposure groups exhibited a very similar tumor 
profile to that of the lifetime high exposure groups, with the lone 
exception of liver tumors, which were increased only in the lifetime 
exposure group; all the other multiple primary tumors were observed at 
significantly increased levels in both the stop- and lifetime-exposure 
groups, Table V-2. (Ex. 125) In addition, the 625 ppm, 26 week exposure 
group had higher rates for several of the tumor types compared to the 
lifetime 625 ppm group, possibly because of the shorter exposure 
group's slightly better survival. The most prevalent tumor type, 
lymphoma, also showed a dose-rate effect, as the tumor incidence was 
greater for exposure to short-term higher concentrations compared with 
a lower long-term exposure (p=.01; 24/50 at 625 ppm for 13 weeks vs. 
12/50 at 200 ppm for 40 weeks: p<.0001; 37/50 at 625 ppm for 26 weeks 
vs. 15/50 at 312 ppm for 52 weeks). The same pattern was seen with 
forestomach tumors and preputial gland carcinomas. Conversely, the 
hemangiosarcomas of the heart and alveolar-bronchiolar tumors showed an 
opposite trend, as lower exposures for a longer time yielded a 
significantly higher incidence of these tumors than the same cumulative 
exposures over a shorter time (survival-adjusted, as opposed to the raw 
incidence lung tumor rates actually suggest no dose-response trends). 
These inconsistent trends with the different tumor sites may be the 
result of multiple mechanisms of carcinogenicity or partially due to 
the rapid fatality caused by lymphocytic lymphomas in the short-term 
high-exposure groups. As with the lifetime study, angiosarcomas of the 
heart and lymphomas presented competing risks in the highly exposed 
mice.

 Table V-2.--Tumor Incidences (I) and Percentage Mortality-Adjusted Tumor Rates (R) in Male Mice Exposed to 1,3-
  Butadiene in Stop-Exposure Studies. (After Exposures Were Terminated, Animals Were Placed in Control Chambers 
                                    Until the End of the Study at 104 Weeks.)                                   
                                             [Adapted from Ex. 125]                                             
----------------------------------------------------------------------------------------------------------------
                                                                             Exposure                           
                                                ----------------------------------------------------------------
                                                      0         200 ppm,     625 ppm,     312 ppm,     625 ppm, 
                     Tumor                      -------------    40 wk        13 wk        52 wk        26 wk   
                                                             ---------------------------------------------------
                                                    I    R c     I     R      I     R      I     R      I     R 
----------------------------------------------------------------------------------------------------------------
Lymphoma.......................................    4/70    8   12/50  a 3                                       
                                                                        5   24/50  a 6                          
                                                                                     1   15/50  a 5             
                                                                                                  5   37/50  a 9
                                                                                                               0
Heart--Hemang-iosarcoma........................    0/70    0    7/50  a47    7/50  a 3                          
                                                                                     1   33/50  a 8             
                                                                                                  7   13/50  a 7
                                                                                                               6
Lung--Alveolar-bronchiolar adenoma and                                                                          
 carcinoma.....................................   22/70   46   35/50  a 8                                       
                                                                        8   27/50  a 8                          
                                                                                     7   32/50  a 8             
                                                                                                  8   18/50  a 8
                                                                                                               9
Forestomach--Squamous-cell papilloma and                                                                        
 carcinoma.....................................    1/70    2    6/50  a 2                                       
                                                                        0    8/50  a 3                          
                                                                                     3   13/50  a 5             
                                                                                                  2   11/50  a 6
                                                                                                               3
Harderian gland--Adenoma and adenocarcinoma....    6/70   13   27/50  a 7                                       
                                                                        2   23/50  a 8                          
                                                                                     2   28/50  a 8             
                                                                                                  6   11/50  a 7
                                                                                                               0
Preputial gland--Carcinoma.....................    0/70    0    1/50    3    5/50  a21    4/50  a 2             
                                                                                                  1    3/50  a 3
                                                                                                               1
Kidney--Renal tubular adenoma..................    0/70    0    5/50  a 1                                       
                                                                        6    1/50    5    3/50  a 1             
                                                                                                  5    1/50  11 
----------------------------------------------------------------------------------------------------------------
From Melnick et al (1990).                                                                                      
 AAaIncreased compared with chamber controls (0ppm), p<0.05, based on logistic regression analysis.             
 cMortality adjusted tumor rates are adjusted for competing causes of mortality, such as death due to other     
  tumors, whose rates differ by exposure group.                                                                 

Activated Oncogenes

    The presence of activated oncogenes in the exposed groups which 
differ from those seen in tumors in the control group can help in 
identifying a mechanistic link for BD carcinogenicity. Furthermore, 
certain activated oncogenes are seen in specific human tumors and K-ras 
is the most commonly detected oncogene in humans. In independent 
studies, tumors from this study were evaluated for the presence of 
activated protooncogenes. (Ex. 129) Activated K-ras oncogenes were 
found in 6 of 9 lung adenocarcinomas, 3 of 12 hepatocellular cancers 
and 2 of 11 lymphomas in BD exposed mice. Nine of these 11 K-ras 
mutations, including all six of those seen in lung tumors, were G to C 
conversions in codon 13. Activation of K-ras genes by codon 13 
mutations has not been detected in lung or liver tumors or lymphomas in 
unexposed B6C3F1 mice, but activation by codon 12 mutation was 
observed in 1 of 10 lung tumors in unexposed mice. (Ex. 129)

Conclusion

    All of the four animal bioassays (one rat, three mouse) find a 
clear carcinogenic response; together they provide sufficient evidence 
to declare BD a known animal carcinogen and a probable human 
carcinogen. The three mouse studies, all with a positive lymphoma 
response, further support a finding that the mouse is a good model for 
BD related lymphatic/hematopoietic and other site tumorigenicity. The 
most recent NTP II study confirms and strengthens the previous NTP I 
and Irons et al. mouse studies, and presents clear evidence that BD is 
a potent multisite carcinogen in B6C3F1 mice of both sexes. (Ex. 
23-1;32-28D, Irons) The finding of lung tumors at exposures as low as 
6.25 ppm, 100 fold lower than the lowest exposure of the NTP I study 
and a level that is in the occupational exposure range, increases 
concern for workers' health. Two other concerns

[[Page 56755]]

raised by both the second NTP and the Irons et al. studies are, (1) 
substantial carcinogenicity is found with less-than-lifetime exposures 
(as low as 12 or 13 weeks) for lymphomas and hemangiosarcomas, at least 
at higher concentrations, and, (2) for lymphomas and at least two other 
sites, there appears to be a dose-rate effect, where exposure to higher 
concentrations for a shorter time yields higher tumor response (by a 
factor of as much as 2-3) than a comparable total exposure spread over 
a longer time. These findings suggest that even short-term exposures 
should be as low as possible. Positive studies for genotoxicity and the 
detection of activated K-ras oncogenes in several of these tumors 
induced in mice, including lymphomas, liver, and lung, suggest a 
mutagenic mechanism for carcinogenicity, and support reliance on a 
linear low-dose extrapolation procedure (on the basis of the multistage 
mutagenesis theory of carcinogenicity), at least for these tumor sites. 
The finding of activated K-ras oncogenes in these mouse tumors may also 
be relevant to humans, because K-ras is the most commonly detected 
oncogene in humans.
    The different dose-rate trends for different tumor sites suggest 
that different mechanisms are involved at different sites. The 
observation of a highly nonlinear exposure-response for lymphomas at 
exposure levels of 625 ppm and above suggests a secondary high-exposure 
mechanism as well, not merely a metabolic saturation, as is suspected 
with the high-exposure saturation seen in Sprague-Dawley rats. (Ex. 34-
6, Owen and Glaister) The picture emerges of BD as a potent genotoxic 
multisite carcinogen in mice, far more potent in mice than in rats.
    With respect to appropriate tumor sites for risk extrapolation from 
mouse to humans, Melnick and Huff have presented information comparing 
animal tumor response for five known or suspected human carcinogens--
BD, benzene, ethylene oxide, vinyl chloride, and acrylonitrile. (Ex. 
117-2) BD, benzene, and ethylene oxide all have strong occupational 
epidemiology evidence of increased lymphatic/hematopoietic cancer (LHC) 
mortality and all three cause both LHC, lung, Harderian gland, and 
mammary gland tumors in mice, plus several other primary tumors (see 
Table V-3). Only BD and vinyl chloride cause mouse hemangiosarcomas, BD 
in the heart and vinyl chloride in the liver. In rats, while all five 
carcinogens cause tumors at multiple sites, only brain and Zymbal gland 
tumors are associated with as many as four of the compounds. In general 
mice and rats are affected at different tumor sites by these 
carcinogens. LHC, lung, Harderian gland, mammary gland and, possibly 
hemangiosarcomas are sites in mice which correlate well with human LHC. 
This suggests that mice, rats and humans may have different target 
sites for the same carcinogen, but that compounds which are multisite 
carcinogens in the mouse and rat are likely to be human carcinogens as 
well. Based on BD's strong LHC association in humans, and its multisite 
carcinogenicity in the mouse, including occurrence at several of the 
same target sites seen with other carcinogens, OSHA concludes that the 
mouse is a good animal model for predicting BD carcinogenesis in 
humans.

   Table V-3.--Sites at Which Neoplasms are Caused by 1,3-Butadiene in Mice and Rats: Comparison With Results of Studies With Benzene, Ethylene Oxide,  
                                                            Vinyl Chloride and Acrylonitrile                                                            
                                                                    [From Ex. 117-2]                                                                    
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                         1,3-Butadiene          Benzene         Ethylene oxide      Vinyl chloride       Acrylonitrile  
                        Site                         ---------------------------------------------------------------------------------------------------
                                                        Mice      Rats      Mice      Rats      Mice      Rats      Mice      Rats      Mice      Rats  
--------------------------------------------------------------------------------------------------------------------------------------------------------
Lymphatic/hematopoietic.............................                                                       NS           
Lung................................................                                                                    
Heart...............................................  f                                             a a                                                           
Harderian gland.....................................                                                                            
Ovary...............................................                                                                                    
Mammary gland.......................................                                                    
Preputial gland.....................................                                                                                    
Brain...............................................                                                                    
Zymbal gland........................................                                                            
Uterus..............................................                                                                            
Pancreas............................................                                                                                            
Testis..............................................                                                                                            
Thyroid gland.......................................                                                                                            
--------------------------------------------------------------------------------------------------------------------------------------------------------
NS, not studied.                                                                                                                                        
Hemangiosarcoma.                                                                                                                                        

2. Epidemiologic Studies
    (i) Introduction. OSHA has concluded that the epidemiologic studies 
contained in this record, as well as the related hearing testimony and 
record submissions, show that occupational exposure to BD is associated 
with an increased risk of death from cancers of the Lymphohematopoietic 
(LH) system. However, in contrast to the available toxicologic data, 
our understanding of BD epidemiology is based on
observational studies, not experimental ones. In other words, the 
investigators who conducted these epidemiologic studies did not have 
control over the exposure status of the individual workers. They were, 
nonetheless, able to select the worker populations and the 
observational study design.
    Cohort and case control studies are two types of observational 
study designs. Each of these designs has strengths and weaknesses that 
should be considered when the results are
interpreted. Cohort studies, for example, have the advantages of 
decreasing the chance of selection bias regarding exposure status and 
providing a more complete description of all health outcomes subsequent 
to exposure. The disadvantages of cohort studies include the large 
number of subjects that are needed to study rare diseases and the 
potentially long duration required for follow-up. By comparison, case 
control studies are well suited for the study of rare diseases and they 
require fewer

[[Page 56756]]

subjects. The disadvantages of case control studies, however, include 
the difficulty of selecting an appropriate control group(s), and the 
reliance on recall or records for information on past exposures. 
Regardless of the selected observational study design, the greatest 
limitation of occupational epidemiologic studies is their ability to 
measure and classify exposure.
    In spite of the inherent limitations of observational epidemiologic 
studies, guidelines have been developed for judging causal association 
between exposure and outcome. Criteria commonly used to distinguish 
causal from non-causal associations include: Strength of the 
association as measured by the relative risk ratio or the odds ratio; 
consistency of the association in different populations; specificity of 
the association between cause and effect; temporal relationship between 
exposure and disease which requires that cause precede effect; biologic 
plausibility of the association between exposure and disease; the 
presence of a dose-response relationship between exposure and disease; 
and coherence with present knowledge of the natural history and biology 
of the disease. These criteria have been considered by OSHA in the 
development of its conclusion regarding the association between BD and 
cancer of the LH system.
    As stated previously, each type of epidemiologic study design has 
strengths and weaknesses. Since epidemiologic studies are observational 
and not experimental, each study will also have inherent strengths and 
weaknesses; there is no perfect epidemiologic study. The most 
convincing evidence of the validity and reliability of any 
epidemiologic study comes with replication of the study's results.
    There are six major epidemiologic studies in the record that have 
examined the relationship between occupational exposure to BD and human 
cancer. These studies include: A North Carolina study of rubber workers 
(Ex. 23-41; 23-42; 23-4; 2-28; 23-27; 23-3); a Texaco study of workers 
at a BD production facility in Texas (Ex. 17-33; 34-4; 34-4); a NIOSH 
study of two plants in the styrene-butadiene rubber (SBR) industry (Ex. 
2-26; 32-25); the Matanoski cohort study of workers in SBR 
manufacturing (Ex. 9; 34-4); the nested case-control study of workers 
in SBR manufacturing conducted by Matanoski and Santos-Burgoa (Ex. 23-
109); and a follow-up study of synthetic rubber workers recently 
completed by Delzell et al. (Ex. 117-1). Several comments in the record 
have concluded that these studies demonstrate a positive association 
between occupational exposure to BD and LH cancers. However, OSHA has 
been criticized by the Chemical Manufacturers Association (CMA) and the 
International Institute of Synthetic Rubber Producers, Inc. (IISRP) for 
its interpretation of these studies as showing a positive association; 
the chief criticisms will be discussed below. (Ex. 112 and 113)
    OSHA's final consideration of the BD epidemiologic studies is 
organized and presented according to what have been identified as key 
issues. These are the epidemiologic issues that were raised and 
considered throughout the rulemaking. They are also the issues most 
pertinent to OSHA's conclusions. These key issues surrounding BD 
exposure and LH cancer are: Evidence of an association; observation of 
a dose-response relationship; observation of short latency periods; the 
potential role of confounding exposures and the observed study results; 
the biological basis for grouping related LH cancers; relevance of 
subgroup analyses; and appropriateness of selected reference 
populations.
    (ii) Evidence of an Association Between BD and LH Cancer. Each of 
the studies listed above contributes to the epidemiologic knowledge 
upon which OSHA's conclusion regarding the relationship of BD exposure 
and LH cancer has been developed.
    (a) North Carolina Studies. This series of studies was undertaken 
to examine work-related health problems of a population of workers in a 
major tire manufacturing plant. They were not designed to look 
specifically at the health hazards of BD. (Tr. 1/15/91, p. 117) 
However, in a work area that involved the production of elastomers, 
including SBR, relative risks of 5.6 for lymphatic and hematopoietic 
malignancies and 3.7 for lymphatic leukemia were found among workers 
employed for more than five years. The International Agency for 
Research on Cancer (IARC) evaluation concluded that this study suggests 
an association between lymphatic and hematopoietic malignancy and work 
in SBR manufacturing. (Tr. 1/15/91, p. 117) However, the IISRP asserted 
that these studies do not provide ``meaningful evidence of an 
association between butadiene and cancer.'' (Ex. 113, p. A-23) OSHA 
recognizes that the researchers who conducted these studies 
acknowledged that the workers may have had exposures to organic 
solvents, including benzene, a known leukemogen, as pointed out by the 
IISRP. (Ex. 113, p. A-24)
    (b) Texaco Study. The two Texaco studies examined mortality of a 
population of workers in a BD manufacturing facility in Texas. (Ex. 17-
33; 34-4 Vol. III, H-2; Divine 34-4, Vol. III, H-1) A qualitative 
method of exposure classification, based on department codes and expert 
consensus judgement, was used in the Downs study. (Ex. 17-33; 34-4, 
Vol. III, H-2) From this methodology four exposure groups were defined: 
Low exposure, which included utility workers, welders, electricians, 
and office workers; routine exposure, which included process workers, 
laboratory personnel, and receiving, storage and transport workers; 
non-routine exposure, which included skilled maintenance workers; and 
unknown exposure, which included supervisors and engineers. It is 
OSHA's opinion that although this is a crude approach to exposure 
classification, there are important findings in this study that 
contribute to our understanding of BD epidemiology.
    In the Downs study (Ex. 34-4, Vol. III, H-2) the standardized 
mortality ratio (SMR) for all causes of death in the entire study 
cohort was low (SMR 80; p < .05) when compared to national population 
rates. However, a statistically significant excess of deaths was 
observed for lymphosarcoma and reticulum cell sarcoma combined (SMR 
235; 95% confidence interval (CI) = 101,463) when compared with 
national population rates. (The issue of reference population selection 
is discussed below in paragraph (viii).)
    When analyzed by duration of employment, the SMR for the category 
of all LH neoplasms was higher in workers with less than five years 
employment (SMR = 167) than for those with more than five years 
employment (SMR = 127). (Ex. 34-4, Vol. III, H-2) However, neither of 
these findings was statistically significant. Alternatively, it has 
been suggested that perhaps the short-term workers were wartime 
workers, and that these workers were actually exposed to higher levels 
of BD, albeit for a shorter time. (Tr. 1/15/91, p. 119)
    Analyses of the four exposure groups also showed elevated but not 
statistically significant SMRs. The routine exposure group had a SMR of 
187 for all LH neoplasms, explained primarily by excesses in Hodgkin's 
disease (SMR = 197) and other lymphomas (SMR = 282). (Ex. 34-4, Vol. 
III, H-2) Those workers in the non-routine exposure group also had an 
elevated SMR for all LH neoplasms (SMR = 167), with excess mortality 
for Hodgkin's disease (SMR = 130), leukemias (SMR = 201), and other

[[Page 56757]]

lymphomas (SMR = 150) (Ex. 34-4, Vol. III, H-2).
    These data were updated by Divine by extending the period of 
follow-up from 1979 through 1985. (Ex. 34-4, Vol. III, H-1) The SMR for 
all causes of mortality remained low (SMR = 84, 95% CI = 79,90), as it 
did for mortality from all cancers (SMR = 80, 95% CI = 69,94). (Ex. 34-
4, Vol. III, H-1) However, the SMR for lymphosarcoma and 
reticulosarcoma combined was elevated and statistically significant 
(SMR = 229, 95% CI = 104,435). This finding was consistent with the 
previous analyses done by Downs. (Tr. 1/15/91, p. 120).
    Exposure group analyses were also consistent with the previous 
findings by Downs. The highest levels of excess mortality from 
lymphatic and hematopoietic malignancy were again seen in the routine 
and non-routine exposure groups. The routine exposure group that was 
``ever employed'' had a statistically significant excess of 
lymphosarcoma (SMR = 561, 95% CI = 181,1310), that accounted for most 
of the LH excess. (Ex. 34-4, Vol. III, H-1) The cohort of workers 
employed before 1946 (wartime workers) also demonstrated a 
statistically significant excess of mortality due to lymphosarcoma and 
reticulosarcoma combined (SMR = 269, 95% CI = 108,555). (Ex. 34-4, Vol. 
III, H-2)
    In summary, the Texaco study provides several notable results. The 
first of these is the consistently elevated mortality for 
lymphosarcoma. This finding is consistent with excess lymphomas 
observed in experimental mice. (Ex. 23-92) Second, the excess risk of 
mortality was found in the routine and non-routine exposure groups. 
Based on the types of jobs held by workers in these two exposure 
groups, this finding suggests that the incidence of lymphatic 
malignancy is highest in the groups with the heaviest occupational 
exposure to BD. (Tr. 1/15/91, p. 121) The third notable result of this 
study was the significantly elevated rate of malignancy in workers 
employed for fewer than 10 years.
    (c) NIOSH Study. The NIOSH study was undertaken in January 1976 in 
response to the report of deaths of two male workers from leukemia. 
(Ex. 2-26; 32-25) These workers had been employed in two adjacent SBR 
facilities (Plant A and Plant B) in Port Neches, Texas. The hypothesis 
tested by this study is that:

    Employment in the SBR production industry was associated, 
specifically, with an increased risk of leukemia and, more 
generally, with an increased risk of other malignancies of 
hematopoietic and lymphatic tissue. (Ex. 2-26)

This study did not specifically examine the association between BD and 
all LH cancers. Thus, OSHA agrees with the criticism that this study by 
itself did not demonstrate that occupational exposure to BD causes 
cancer. (Ex. 113, pp. A-13, A-19) However, the findings in this study 
are consistent with the patterns observed in the other epidemiologic 
studies discussed in this section. In Plant A, the overall mortality 
was significantly decreased (SMR=80, p<0.05). (Ex. 2-26) The SMR for 
all malignant neoplasms was also decreased (SMR=78), but this result 
was not statistically significant. (Ex. 2-26) The SMR for LH cancers 
was elevated (SMR=155), as it was for lymphosarcoma and reticulum cell 
sarcoma (SMR=181) and leukemia (SMR=203), but none of these results was 
statistically significant. (Ex. 2-26)
    The pattern of mortality for a subgroup of wartime workers was also 
examined for the Plant A population. For this subgroup of white males, 
employed at least six months between the beginning of January 1943 and 
the end of December 1945, there was an elevated SMR for lymphatic and 
hematopoietic neoplasms (SMR = 212) that was statistically significant 
at the level of 0.050-19, 20-99, 100-199, and 200+, 
respectively. (Ex. 117-1, pp. 68-69; 158) Poisson regression analyses 
were also conducted using varying exposure categories of BD ppm-years. 
These analyses demonstrated a stronger and more consistent relationship 
between BD and leukemia than between styrene and leukemia. (Ex. 117-1, 
p. 69, 159) Although a clearly positive relationship between BD ``peak-
years'' and leukemia was observed from additional Poisson regression 
analyses, even after controlling for BD ppm-years, styrene ppm-years, 
and styrene peak-years, the dose-response relationship was less clear. 
(Ex. 117-1, pp. 71, 162)
    In summary, one of the most important findings of the research of 
Delzell et al. was strong and consistent evidence that employment in 
the SBR industry produced an excess of leukemia. In the authors own 
words:

    This study found a positive association between employment in 
the SBR industry and leukemia. The internal consistency and 
precision of the result indicate that the association is due to 
occupational exposure. The most likely causal agent is BD or a 
combination of BD and [styrene]. Exposure to [benzene] did not 
explain the leukemia excess. (Ex. 117-1, p. 85)

    (g) Summary. These studies provide a current body of scientific 
evidence regarding the association between BD and LH cancers. As 
previously discussed, two of the criteria commonly used to determine 
causal relationships are consistency of the association and strength of 
the association. The consistency criterion for causality refers to the 
repeated observation of an association in different populations under 
different circumstances. Consistency is perhaps the most striking 
observation to be made from this collection of studies: ``[E]very one 
of these studies to a greater or lesser extent finds excess rates of 
deaths from tumors of the lymphatic and hematopoietic system.'' (Tr. 1/
15/91, p. 129)
    Strength of the association is determined by the magnitude and 
precision of the estimate of risk. In general, the greater the risk 
estimate, e.g., SMR or odds ratio, and the narrower the confidence 
intervals around that estimate, the more probable the causal 
association. In the nested case-control study, although the confidence 
intervals were wide, the odds ratios provide evidence of a strong 
association between leukemia and occupational exposure to BD.
    (iii) Observation of a Dose-Response Relationship. A dose-response 
relationship is present when an increase in the measure of effect 
(response), e.g., SMR or odds ratio, is positively correlated with an 
increase in the exposure, i.e., estimated dose. When such a 
relationship is observed, it is given serious consideration in the 
process of determining causality. However, the absence of a dose-
response relationship does not necessarily indicate the absence of a 
causal relationship.
    OSHA has been criticized for its conclusion that the epidemiologic 
data suggest a dose-response relationship. (Ex. 113) The IISRP offers a 
different interpretation of the data. In their opinion, the data 
provide a ``consistent finding of an inverse relationship between 
duration of employment and cancer mortality.'' (Ex. 113, A-34) This 
observation is further described by John F. Acquavella, Ph.D., Senior 
Epidemiology Consultant, Monsanto Company, as ``the paradox of 
butadiene epidemiology.'' (Ex. 34-4, Vol. I, Appendix A) This 
interpretation assumes that cumulative occupational exposure to BD will 
increase with duration of employment, and, thus, cancer mortality will 
increase with increasing duration of employment. (Ex. 113, A-35-39)
    In OSHA's opinion, this is an erroneous assumption; the 
epidemiologic data for BD tell a different story. For the workers in 
these epidemiologic studies, it is unlikely that occupational exposure 
to BD was constant over the duration of employment. According to 
Landrigan, BD exposures were most likely higher during the war years 
than they were in subsequent years. (Tr. 1/15/91, p.146) It is logical 
that exposures would be especially intense during this time period 
because of wartime production pressures, the process of production 
start-up in a new industry, and the general lack of industrial hygiene 
controls during that phase of industrial history. Unfortunately, 
without quantitative industrial hygiene monitoring data, the true 
levels of BD exposure for wartime workers cannot be ascertained. In the 
absence of such data, however, OSHA believes it is reasonable to 
consider wartime workers as a highly exposed occupational subgroup. 
(Tr. 1/15/91, p. 121; Tr. 1/16/91, pp. 225-227) Thus, the excess 
mortality seen among these workers provides another piece of the 
evidence to support a dose-response relationship between occupational 
exposure to BD and LH cancers.
    Additional support that excess mortality, among workers exposed to 
BD, is dose-related can be found in the analyses of the work area 
exposure groups. The studies by Divine, Matanoski, and Matanoski and 
Santos-Burgoa all provide evidence that excess mortality is greatest 
among production workers. (Ex. 34-4, Vol. III, H-1; 34-4, Vol. III, H-
6; 23-109, respectively) Production workers are typically the most 
heavily exposed workers to potentially toxic substances. (Ex. 34-4)
    The most compelling data that support the existence of a dose-
response relationship for occupational exposure to BD and LH cancers 
are those in the study by Delzell et al. (Ex. 117-1) Analysis of the 
cumulative time-weighted BD exposure in ppm-years indicates a relative 
risk for all leukemias that increases positively with increasing 
exposure. This relationship is present even with statistical adjustment 
for age, years since hire, calendar period, race, and exposure to 
styrene. It is OSHA's opinion that identification of a positive dose-
response in an epidemiologic study is a very powerful observation in 
terms of causality.
    (iv) Observation of Short Latency Periods. Short latency periods, 
i.e., time from initial BD exposure to death, were seen in two 
epidemiologic studies. In the NIOSH study, three of the six leukemia 
cases had a latency period from three to four years. (Ex. 2-26) 
Additionally, five of these six workers were employed prior to 1945. 
(Ex. 2-26)

[[Page 56762]]

In the Texaco study update, a latency of less than 10 years was seen in 
four of the nine non-Hodgkin's lymphoma (lymphosarcoma) cases, and 
seven of these workers were also employed during the wartime years. 
(Ex. 34-4, Vol. III, H-1)
    According to OSHA's expert witness, Dr. Dennis D. Weisenburger,

these findings are contrary to the accepted belief that, if a 
carcinogen is active in an environment, one should expect the * * * 
SMRs to be higher for long-term workers than for short-term workers 
(i.e., larger cumulative dose). (Ex. 39, p. 9)

Thus, it has been argued that these findings appear to lack coherence 
with what is known of the natural history and biology of LH cancers. 
(Ex. 113, A-40-42) Furthermore, these findings have been interpreted as 
evidence against a causal association between BD and these LH cancers. 
(Ex. 113, A-42)
    In OSHA's opinion, there are other possible explanations for these 
observations. First, as proffered by Dr. Weisenburger, a median latency 
period of about seven years has been found for leukemia in studies of 
atomic bomb victims, radiotherapy patients, and chemotherapy patients 
who have received high-dose, short-term exposures. (Ex. 39) In 
contrast, Dr. Weisenburger points out that low-dose exposure to an 
environmental carcinogen, such as benzene, has a median latency period 
for leukemia of about 15-20 years. (Ex. 39) He concludes that short-
term, high-dose exposures may be associated with a short latency 
period, whereas long-term, low-dose exposures may be associated with a 
long latency period.
    Second, the occurrence of short latency periods for LH cancer 
mortality in these two studies was concentrated in workers first 
employed during the wartime years. As previously discussed, it is 
possible that exposure to BD during the wartime years was greater than 
in subsequent years. (Ex. 39; Tr. 1/15/91, p. 121) Dr. Weisenburger 
suggests that the ``short latency periods for LH cancer in these 
studies may be explained by intense exposures to BD over a relatively 
short time period.'' (Ex. 39, p. 10)
    In his testimony, Dr. Landrigan, another OSHA expert witness, makes 
the point that ``duration of employment is really only a crude 
surrogate for total cumulative exposures, not itself a measure of 
exposure.'' (Tr. 1/15/91, p. 121) In other words, it is possible that 
short-term workers employed during the wartime years may have actually 
had heavier exposures to BD than long-term workers. (Tr. 1/15/91, pp. 
115-205) On cross-examination, Dr. Landrigan cautioned against 
``assuming that duration of exposure directly relates to total 
cumulative exposure.'' (Tr. 1/15/91, p. 180) He also emphatically 
stated that an increased cancer risk in short-term workers would not be 
inconsistent with a causal association. (Tr. 1/15/91, p. 204)
    (v) The Potential Role of Confounding Exposures and Observed 
Results. In epidemiologic studies ``confounding'' may lead to invalid 
results. Confounding occurs when there is a mixing of effects. More 
specifically, confounding may produce a situation where a measure of 
the effect of an exposure on risk, e.g., SMR, RR, is distorted because 
of the association of the exposure with other factors that influence 
the outcome under study.
    For example, the IISRP has suggested that confounding exposures 
from other employment were responsible for the LH cancers observed in 
the studies of BD epidemiology. (Ex. 113, A-43) This argument is based 
on the past practice of using petrochemical industry workers, who may 
have also been exposed to benzene, to start up the SBR and BD 
production plants. The IISRP finds support for this position in the 
observation of elevated SMRs in short-term workers employed during the 
wartime years, precisely those most likely to be cross-employed. (Ex. 
113, A-43)
    However, there are a number of research methods in occupational 
epidemiology that are available to control potential confounding 
factors. Research methods that eliminate the effect of confounding 
variables include: Matching of cases and controls; adjustment of data; 
and regression analyses. In the nested case-control study, for example, 
cases and controls were matched on variables that otherwise might have 
confounded the study results. In the testimony provided by Santos-
Burgoa, he states that the ``matching scheme allowed us to control for 
potential confounders and concentrate only on exposure variations.'' 
(Ex. 40, p. 12)
    On cross-examination, Landrigan also addressed the potential role 
of confounding exposures and the observed study results. First, he 
observed that Dr. Philip Cole, Professor, Department of Epidemiology, 
School of Public Health, University of Alabama at Birmingham, one of 
the outspoken critics of OSHA's proposed rule, found no evidence for 
confounding in his review of the Matanoski study. (Tr. 1/15/91, p. 178) 
Second, Dr. Landrigan dismissed the notion of previous exposure to 
benzene as the causative agent for the observed results in the short-
term workers. (Tr. 1/15/91, p. 178-179)
    In their analyses of mortality patterns by estimated monomer 
exposure, Delzell et al. used Poisson regression to control for 
potential confounding factors. (Ex. 117-1) As previously stated, the 
analyses conducted to determine the association between BD ppm-years 
and leukemia indicated a positive dose-response relationship, even 
after controlling for styrene ppm-years, age, years since hire, 
calendar period, and race. In the opinion of the investigators, benzene 
exposure did not explain the excess of leukemia risk, and BD is the 
most likely causal agent. (Ex. 117-1, p. 85)
    (vi) The Biological Basis for Grouping Related LH Cancers. The 
epidemiologic studies that have examined the association between 
occupational exposure to BD and excess mortality have grouped related 
LH cancers in their analyses. This approach has been criticized as 
evidence of a lack of ``consistency with respect to cell type'' which 
``argues against a common etiologic agent.'' (Ex. 113, A-45) In other 
words, these critics suggest that the relationship between BD and 
excess mortality does not meet the specificity of association 
requirement for a causal relationship. This requirement states that the 
likelihood of a causal relationship is strengthened when an exposure 
leads to a single effect, not multiple effects, and this finding also 
occurs in other studies.
    More specifically, OSHA has been criticized for its position that 
``broad categories such as `leukemia' or `all LHC' should be used to 
evaluate the epidemiologic data.'' (Ex. 113, A-46) Dr. Cole, for 
example, commented that:

    It is a principle of epidemiology--and of disease investigation 
in general--that entities should be divided as finely as possible in 
order to maximize the prospect that one has delineated a homogeneous 
etiologic entity. Entities may be grouped for investigative purposes 
only when there is substantial evidence that they share a common 
etiology. (Ex. 63, p. 11)

It is Dr. Cole's opinion that LH cancers are ``distinct diseases'' with 
``heterogeneous and multifactorial'' etiologies. (Ex. 63, p. 47)
    Dr. Weisenburger, OSHA's expert in hematopathology, provided 
testimony to the contrary. (Ex. 39, pp. 7-8) According to Dr. 
Weisenburger, ``LH (cancer) cannot be readily grouped into `etiologic' 
categories, since the precise etiologies and pathogenesis of LH 
(cancer) are not well understood.'' (Ex. 39, p. 7) In his opinion, 
because LH cancers are ``closely related to one

[[Page 56763]]

another and arise from common stem cells and/or progenitor cells, it is 
valid to group the various types of LH (cancer) into closely-related 
categories for epidemiologic study.'' (Ex. 39, p.7)
    The issue of grouping related LH cancers to observe a single effect 
was also addressed by Dr. Landrigan in his testimony. (Tr. 1/15/91, pp. 
131-133) The first point raised by Dr. Landrigan is that the 
``diagnostic categories [for LH cancers] are imprecise and * * * 
overlapping.'' (Tr. 1/15/91, p. 131) For example, he explained that in 
clinical practice transitions of lymphomas and myelomas into leukemias 
may be observed. In such a case, one physician may record the death as 
due to lymphoma and another may list leukemia as the cause of death. 
(Tr. 1/15/91, p. 131-132) Additionally, Dr. Landrigan testified that 
``some patients with lymphomas or multiple myeloma may subsequently 
develop leukemia as a result of their treatments with radiation or 
cytotoxic drugs.'' (Tr. 1/15/91, p. 132)
    These recordings of disease transition are further complicated by 
the historical changes that have occurred in nomenclature and The 
International Classification of Diseases (ICD) coding. According to Dr. 
Landrigan,

certain lymphomas and * * * leukemias, such as chronic lymphatic 
leukemia are now considered by some investigators * * * to represent 
different clinical expressions of the same neoplastic process. There 
have been recent immunologic and cytogenetic studies which indicate 
that there are stem cells which appear to have the capacity to 
develop variously into all the various sorts of hematopoietic cells 
including T-lymphocytes, plasma cells, granulocytes, erythrocytes, 
and monocytes. (Tr. 1/15/91, p. 132)

Dr. Landrigan summarized his testimony on this issue by stating that 
``these different types of cells share a common ancestry * * * there is 
good biologic reason to think that they would have etiologic factors in 
common.'' (Tr. 1/15/91, pp. 132-133)
    OSHA maintains the opinion, which is well supported by the record, 
that there is a biological basis and a methodologic rationale for 
grouping related LH cancers. Furthermore, OSHA rejects the criticism 
that the observation of different subtypes of LH cancers argues against 
the consistency and specificity of the epidemiologic findings.
    (vii) Relevance of Worker Subgroup Analyses. OSHA has been 
criticized for focusing on and emphasizing the ``few positive results'' 
seen in the results of worker subgroup analyses. (Ex. 113, A-48) It has 
been pointed out, for example, that in the update of the Matanoski 
cohort study ``there were hundreds of SMRs computed in that study and 
it's not surprising that one or two or even more would be found to be 
statistically significant even when there is in fact nothing going 
on.'' (Tr. 1/22/91, p. 1444) Additionally, it has been suggested that 
OSHA has ignored the ``clearly overall negative results'' of the 
epidemiologic studies. (Ex. 113, A-48)
    OSHA agrees with the observation that when many statistical 
analyses are done on a database, it is possible that some positive 
results may be due to chance. However, OSHA rejects criticism that the 
Agency has inappropriately concentrated on the positive results and 
disregarded the negative results. It is OSHA's opinion that there is a 
compelling pattern of results in the epidemiologic studies.
    Furthermore, a reasonable explanation for the elevated SMR for 
black production workers in the update of the Matanoski cohort study is 
that this subset of the population actually had heavy exposure to BD. 
Support for this explanation can be found in the industrial hygiene 
survey results of Fajen et al. (Ex. 34-4) In this case, then, the risk 
for excess mortality would be concentrated in a small subset of 
otherwise very healthy and unexposed workers that would be diluted when 
analyses are based on the entire group being studied. The only way to 
observe the risk in the most highly exposed subset would be to analyze 
the data by subgroups of the population.
    (viii) Appropriateness of Selected Reference Populations. OSHA also 
has been criticized for ``ignor[ing] the fact that most of the 
epidemiologic studies of butadiene-exposed workers only used U.S. 
cancer mortality rates for comparison to worker mortality.'' (Ex. 113, 
A-49) The significance of this criticism is based on the observation by 
Downs that ``use of local (mortality) rates (for comparison) tended to 
bring the SMRs closer to 100.'' (Ex. 17-33, p.14) This finding results 
from cancer rates along the Texas Gulf coast that are higher than 
national rates. (Ex. 17-33) In other words, it has been argued that 
national comparison rates artificially inflate the SMRs, while local 
rates provide a more accurate picture of the mortality experience of 
workers with occupational exposure to BD. (Ex. 113, A-50)
    Dr. Landrigan captured the essence of this issue in his testimony 
on cross-examination,

    This is a perennial debate in epidemiology of whether to use 
local comparison rates or regional or national, and there's [sic] 
arguments [to] go both ways. (Tr. 1/15/91, p. 154)

He presented several arguments for using national rates. First, U.S. 
mortality rates are based on the entire population, so they are more 
stable. Second, national rates are more commonly used, so it is easier 
to compare results from different studies.
    On the other hand, the argument in favor of using local rates 
centers on the fact that people in a local area may truly be different 
from the total population or a regional population(s). Thus, comparing 
a local subpopulation with the entire local population may provide more 
accurate results. However, the weakness in this argument was 
highlighted by Dr. Landrigan when he said that,

* * * if there are factors acting in the local population, such as 
environmental pollution that may elevate rates in the local area so 
that they are closer to the rates in the occupationally exposed 
population, then theoretically at least one could argue that the 
local population is overmatched, too similar to the employee 
population and that the use of the national comparison group 
actually give [sic] a better reflection of reality. (Tr. 1/15/91, p. 
155)

In fact, he went on to point out that the BD plants have been 
identified by the Environmental Protection Agency (EPA) as ``major'' 
polluters of the local environment with BD. (Tr. 1/15/91, p. 155)
    OSHA acknowledges that there are pros and cons to both approaches 
of reference population selection. However, in the study by Delzell et 
al. mortality data of the USA cohort subgroup were analyzed using both 
state, i.e., local, general population rates and USA general population 
rates. (Ex. 117-1) As previously stated, there was little difference in 
the overall pattern of these analyses. (Ex. 117-1, p. 60) Additionally, 
the Santos-Burgoa and Matanoski nested case control study used the most 
appropriate comparison group of all: Those employed at the same 
facilities. (Ex. 23-109 and 34-4, Vol. III, H-4) Thus, given the 
available data in the record, OSHA is of the opinion that it cannot 
ignore the findings of excess mortality that are based on national 
comparison rates.
    (ix) Summary and Conclusions. (a) Summary. Table V-4 lists the 
criteria that can be used to judge the presence of a causal association 
between occupational exposure to BD and cancer of the 
lymphohematopoietic system. When the available epidemiologic study 
results are examined in this way, there is strong evidence for 
causality. The data fulfill all of the listed criteria: Temporal 
relationship; consistency;

[[Page 56764]]

strength of association; dose-response relationship; specificity of 
association; biological plausibility; and coherence.
    In his testimony, OSHA's epidemiologist expert witness agreed that 
there is ``definite evidence for the fact that occupational exposure to 
1,3-Butadiene can cause human cancer of the hematopoietic and lymphatic 
organs.'' (Tr. 1/15/91, p. 133) Dr. Weisenburger, OSHA's expert witness 
in hematopathology, also concluded that ``it would be prudent to treat 
BD as though it were a human carcinogen.'' (Ex. 39, p. 11)

      Table V-4.--Evidence That 1,3-Butadiene Is a Human Carcinogen     
------------------------------------------------------------------------
           Criterion for causality                    Met by  BD        
------------------------------------------------------------------------
Temporal relationship.......................  Yes.                      
Consistency.................................  Yes.                      
Strength of association.....................  Yes.                      
Dose-response relationship..................  Yes.                      
Specificity of association..................  Yes.                      
Biological plausibility.....................  Yes.                      
Coherence...................................  Yes.                      
------------------------------------------------------------------------

    (b) Conclusion. On the basis of the foregoing analysis, OSHA 
concludes that there is strong evidence that workplace exposure to BD 
poses an increased risk of death from cancers of the 
lymphohematopoietic system. The epidemiologic findings supplement the 
findings from the animal studies that demonstrate a dose-response for 
multiple tumors and particularly for lymphomas in mice exposed to BD.

C. Reproductive Effects

    In addition to the established carcinogenic effects of BD exposure, 
various reports have led to concern about the potential reproductive 
and developmental effects of exposure to BD. The term reproductive 
effects refers to those on the male and female reproductive systems and 
the term developmental refers to effects on the developing fetus.
    Male reproductive toxicity is generally defined as the occurrence 
of adverse effects on the male reproductive system that may result from 
exposure to chemical, biological, or physical agents. Toxicity may be 
expressed as alterations to the male reproductive organs and/or related 
endocrine system. For example, toxic exposures may interfere with 
spermatogenesis (the production of sperm), resulting in adverse effects 
on number, morphology, or function of sperm. These may adversely affect 
fertility. Human males produce sperm from puberty throughout life and 
thus the risk of disrupted spermatogenesis is of concern for the entire 
adult life of a man.
    Female reproductive toxicity is generally defined as the occurrence 
of adverse effects on the female reproductive system that may result 
from exposure to chemical, biological, or physical agents. This 
includes adverse effects in sexual behavior, onset of puberty, 
ovulation, menstrual cycling, fertility, gestation, parturition 
(delivery of the fetus), lactation or premature reproductive senescence 
(aging).
    Developmental toxicity is defined as adverse effects on the 
developing organism that may result from exposure prior to conception 
(either parent), during prenatal development, or postnatally to the 
time of sexual maturation. Developmental effects induced by exposures 
prior to conception may occur, for example, when mutations are 
chemically induced in sperm. If the mutated sperm fertilizes an egg, 
adverse developmental effects may be manifested in developing fetuses. 
Mutations may also be induced in the eggs. The major manifestations of 
developmental toxicity include death of the developing fetus, 
structural abnormality, altered growth and function deficiency.
    To determine whether an exposure condition presents a developmental 
or reproductive hazard, there are two categories of research studies on 
which to rely: Epidemiologic, or studies of humans, and toxicologic, or 
experimental studies of exposed animals or other biologic systems.
    Many outcomes such as early embryonic loss or spontaneous abortion 
are not easily detectable in human populations. Further, some adverse 
effects may be quite rare and require very large study populations in 
order to have adequate statistical power to detect an effect, if in 
fact one is present. Often, these populations are not available for 
study. In addition, there are fewer endpoints which may be feasibly 
measured in humans as compared to laboratory animals. For example, 
early embryonic loss is difficult to measure in the study of humans, 
but can be measured easily in experimental animals. There are no human 
studies available to address reproductive and developmental effects of 
BD exposure to workers. Thus, evidence on the reproductive and 
developmental toxicity of BD comes from toxicologic studies performed 
using primarily mice.
    Animal studies have proved useful for studying reproductive/
developmental outcomes to predict human risk. A very important 
advantage to the toxicological approach is the ability of the 
experimenter to fully quantitate the exposure concentration and 
conditions of exposure. Although extrapolation of risk to humans on a 
qualitative basis is accepted, quantitative extrapolation of study 
results is more complex.
    In his testimony, OSHA's witness, Dr. Marvin Legator, an 
internationally recognized genetic toxicologist from the University of 
Texas Medical Branch in Galveston, cautioned that in assessing risk 
``humans in general have proven to be far more sensitive than animals * 
* * to agents characterized as developmental toxicants.'' (Ex. 72) He 
also noted that ``of the 21 agents considered to be direct human 
developmental toxins, in 19 * * * the human has been shown to be more 
sensitive than the animal * * *'' He also pointed to the possibility 
that sub-groups of the human population may be even more highly 
sensitive than the population average.
    OSHA believes that the animal inhalation studies designed to 
determine the effect of BD on the reproduction and development of these 
animals indicate that BD causes adverse effects in both the male and 
female reproductive systems and produces adverse developmental effects. 
These studies are briefly summarized and discussed below.

Toxicity to Reproductive Organs

    In the first NTP bioassay, an increased incidence of testicular 
atrophy was observed in male mice exposed to BD atmospheric 
concentrations of 625 ppm. (Ex. 23-1) In female mice, an increased 
incidence of ovarian atrophy was observed at 625 and 1,250 ppm. These 
adverse effects were confirmed in reports of the second NTP study, 
which used lower exposure concentrations. The latter lifetime bioassay 
exposed male and female B3C6F1 mice to 0, 6.25, 20, 62.5, 200, and 625 
ppm BD. (Ex. 114, p 115) See Table V-5. Testicular atrophy in males was 
significantly increased at the highest dose tested, 625 ppm, and 
reduced testicular weight was observed from BD exposures of 200 ppm. 
(Ex. 96) These latter data are not shown in the Table. In female mice 
at terminal sacrifice, 103 weeks, ovarian atrophy was significantly 
increased at all exposure levels including the lowest dose tested, 6.25 
ppm, compared with controls. Evidence of ovarian toxicity was also seen 
during interim sacrifices, but in these cases was the result of higher 
exposure levels. After 65 weeks of exposure, 90% of the mice exposed to 
62.5 ppm experienced ovarian atrophy.

[[Page 56765]]



                                            Table V-5.--Ovarian and Testicular Atrophy in Mice Exposed to BD                                            
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                    Exposure concentration (ppm)                                        
            Lesion               Weeks of  -------------------------------------------------------------------------------------------------------------
                                 exposure           0                 6.25               20               62.5               200               625      
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                                        
(5) Incidence (%)                                                                                                                                       
                                           -------------------------------------------------------------------------------------------------------------
Testicular atrophy...........           40  0/10(0)            NE                 NE                NE                0/10(0)           6/10(60)        
                                        65  0/10(0)            NE                 NE                NE                0/10(0)           4/7(57)         
                                       103  1/50(2)            3/50(6)            4/50(8)           2/48(4)           6/49(12)          53/72(74)       
Ovarian atrophy..............           40  0/10(0)            NE                 NE                0/10(0)           9/10(90)          8/8(100)        
                                        65  0/10(0)            0/10(0)            1/10(10)          9/10(90)          7/10(70)          2/2(100)        
                                       103  4/49(8)            19/49(39)          32/48(67)         42/50(84)         43/50(86)         69/79(87)       
--------------------------------------------------------------------------------------------------------------------------------------------------------
NE, not examined microscopically.                                                                                                                       
Source: Ex. 114.                                                                                                                                        

    Extensive comments on the BD induced ovarian atrophy were received 
from Dr. Mildred Christian, a toxicologist who offered testimony on 
behalf of the Chemical Manufacturers Association. She questioned the 
relevance of using the data from studies of mice to extrapolate risk of 
ovarian atrophy to humans because most of the evidence was observed 
among the animals who were sacrificed after the completion of the 
species reproductive life and only after prolonged exposure to 6.25 ppm 
and 20 ppm (Ex. 118-13, Att 3, p. 4) On the other hand, Drs. Melnick 
and Huff, toxicologists from the National Institute of Environmental 
Health Sciences stated that: ``Even though ovarian atrophy in the 6.25 
ppm group was not observed until late in the study when reproductive 
senescence likely pertains, the dose-response data clearly establish 
the ovary as a target organ of 1,3-butadiene toxicity at concentrations 
as low as 6.25 ppm, the lowest concentration studied.'' (Ex. 114, p. 
116) In addition, it should be noted that an elevated incidence of 
ovarian atrophy was observed at periods of interim sacrifice of female 
mice exposed to 20 ppm that took place at the 65 week exposure period, 
a time prior to the ages when senescence would be expected to have 
occurred. NIOSH also accepted Dr. Melnick's view that mice exposed to 
6.25 ppm BD demonstrated ovarian atrophy. (Ex. 32-35) OSHA remains 
concerned about the ovarian atrophy demonstrated at low exposure levels 
in the NTP study. Thus, OSHA concludes that exposure to relatively low 
levels of BD resulted in the induction of ovarian atrophy in mice.

Sperm-Head Morphology Study

    NTP/Battelle investigators also described sperm head morphology 
findings using B6C3F1 mice exposed as described in the dominant 
lethal study mentioned below, e.g., exposures to 200, 1000 and 5000 ppm 
BD. The mice were sacrificed in the fifth week post-exposure and 
examined for gross lesions of the reproductive system. (Ex. 23-75) The 
study authors chose this interval as having the highest probability for 
detecting sperm abnormalities. Epididymal sperm suspensions were 
examined for morphology. The percentage of morphologically abnormal 
sperm heads was significantly increased in the mice exposed at 1,000 
ppm and 5,000 ppm, but not for those exposed to 200 ppm. The study 
authors concluded that ``these significant differences in the 
percentage of abnormalities between control mice and males exposed to 
1000 and 5000 ppm [BD] indicated that their late spermatogonia or early 
spermatocytes were sensitive to this chemical.'' (Ex. 23-75, p. 16)
    In reviewing this study, Dr. Mildred Christian stated that these 
results are not necessarily correlated with developmental abnormalities 
or reduced fertility and are ``reversible in nature'' and that the 
observed differences are ``biologically insignificant.'' (Ex. 76, p. 
14) In its submission, the Department of Health Services of California 
said: ``A conclusion as to the reproductive consequences of these 
abnormalities cannot be made from this study.'' (Ex. 32-168) In 
reviewing Dr. Christian's comments, OSHA is in agreement that the 
observation of a significant excess of sperm head abnormalities as a 
result of BD exposure is not necessarily correlated with the 
development of abnormal fetuses or of reduced fertility; however, the 
Anderson study, which did evaluate fetal abnormality and reduced 
fertility, demonstrated a significant excess of both fetal abnormality 
plus early and late fetal mortality as a result of male mice exposure 
to BD. (Ex. 117-1, P. 171) These observations of fetal mortality could 
only occur as a result of an adverse effect on the sperm. In response 
to Dr. Christian's comment that the sperm head abnormality observed in 
the study is reversible, the reversibility would be dependent upon 
cessation of exposure. Since workers may be exposed to BD on a daily 
basis, the significance of reversibility may be moot.

Developmental Toxicity

Dominant Lethal Studies
    A dominant lethal study was conducted by Battelle/NTP to assess the 
effects of a 5-day exposure of male CD-1 mice to BD atmospheric 
concentrations of 0, 200, 1,000 and 5,000 ppm BD for 6 hours per day on 
the reproductive capacity of the exposed males during an 8-week post-
exposure period. (Ex 23-74) If present, dominant lethal effects are 
expressed as either a decrease in the number of implantations or as an 
increase in the incidence of intrauterine death, or both, in females 
mated to exposed males. Dominant lethality is thought to arise from 
lethal mutations in the germ cell line that are dominantly expressed 
through mortality to the offspring. In this study, the only evidence of 
toxicity to the adult male mouse was transient and occurred over a 20 
to 30 minute period following exposure at 5,000 ppm. Males were then 
mated to a different female weekly for 8 weeks. After 12 days, females 
were killed and examined for reproductive status. Uteri were examined 
for number, position and status of implantation. Females mated to the 
BD-exposed males during the first 2 weeks post-exposure were described 
as more likely than control animals to have increased numbers of dead 
implantations per pregnancy.
    For week one, the percentage of dead implantations in litters sired 
by males exposed to 1,000 ppm was significantly higher than controls. 
There were smaller increases at 200 ppm and 1000 ppm that were not 
statistically significant. The percentage of females with two or more 
dead implantations was significantly higher than the control value for 
all three exposure groups. For week two, the numbers of dead 
implantations per

[[Page 56766]]

pregnancy in litters sired by males exposed to 200 ppm and 1000 ppm 
were also significantly increased, but not for those exposed to 5000 
ppm. No significant increases in the end points evaluated were observed 
in weeks three to eight. These results suggested to the authors that 
the more mature cells (spermatozoa and spermatids) may be adversely 
altered by exposure to BD. (Ex. 23-74)
    The State of California Department of Health Services concluded 
that the above mentioned study showed no adverse effect from exposure 
to BD, with the possible exception of the increase in intrauterine 
death seen as a result of male exposures to 1000 ppm BD at the end of 
one week post exposure. (Ex. 32-16) Since values for the 5000 ppm 
exposure group were not significantly elevated for this same period of 
follow up, the California Department of Health thought the biological 
significance of the results of the 1000 ppm exposure was questionable. 
(Ex. 32-16) On the other hand, Dr. Marvin Legator stressed the low 
sensitivity of the dominant lethal assay which, he felt was due to the 
endpoint-lethality. He expressed the opinion that the studies were 
``consistent with an effect on mature germ cells.'' (Ex. 72) He felt 
that since an effect was observable in this relatively insensitive 
assay that only the ``tip of the iceberg'' was observed, and that 
``[t]ransmissible genetic damage, displaying a spectrum of abnormal 
outcomes can be anticipated at concentrations (of BD) below those 
identified in the dominant lethal assay procedure.'' (Ex. 72, p. 17)
    The dominant lethal effect of BD exposure was more recently 
confirmed by Anderson et al. in 1993. (Ex. 117-1, p. 171) They studied 
CD-1 mice using a somewhat modified study design. Two exposure regimens 
were used. In the first, ``acute study,'' male mice were exposed to 0 
(n=25), 1250 (n=25), or 6250 (n=50) ppm BD for 6 hours only. Five days 
later they were caged with 2 untreated females. One female was allowed 
to deliver her litter and the other was killed on day 17 of gestation 
and examined for the number of live fetuses, number of early and late 
post-implantation deaths and the number and type of any gross 
malformation. The authors stated that sacrifice on day 17 (rather than 
the standard days 12 through 15) allowed examination of near-term 
embryos for survival and abnormalities. The mean number of implants per 
female was reduced compared with controls at both concentrations of BD, 
but was statistically significant only at 1250 ppm. Neither post-
implantation loss nor fetal abnormalities were significantly increased 
at either concentration. The authors concluded that ``a single 6-hour 
acute exposure to butadiene was insufficient to elicit a dominant 
lethal effect.'' (Ex. 117-1, p. 171)
    In the second phase of the study, the ``subchronic study,'' CD-1 
mice were exposed to 0 (n=25), 12.5 (n=25), or 1250 (n=50) ppm BD for 6 
hours per day, 5 days per week, for 10 weeks. They were then mated. The 
higher 1250 ppm BD exposure resulted in significantly reduced numbers 
of implantations and in significantly increased numbers of dominant 
lethal mutations expressed as both early and late deaths. See Table V-
6. Non-lethal mutations expressed as birth abnormalities were also 
observed in live fetuses (3/312; 1 hydrocephaly and 2 runts).
    The lower exposure (12.5 ppm) did not result in decreases in the 
total number of implants, nor in early deaths; however, the frequencies 
of late deaths and fetal abnormalities (7/282; 3 exencephalies in 1 
litter and one in another, two runts and one with blood in the amniotic 
sac) were significantly increased.
    The authors felt that their finding of increased late deaths and 
fetal abnormalities at a subchronic, low exposure of 12.5 ppm was the 
main new finding of the study. They noted that these adverse health 
effects were increased 2-3 fold over historical controls. In evaluating 
these latter two studies OSHA notes that while there was no 
demonstrable effect on dominant lethality as a result of a single 
exposure to 1250 ppm BD, subchronic exposure to 12.5 ppm, the lowest 
dose tested, resulted in the induction of dominant lethal mutations and 
perhaps non-lethal mutations. (Ex 117-1, p 171) OSHA has some 
reservations about whether or not the fetal abnormalities observed in 
the Anderson et al. ``subchronic'' study were actually caused by non-
lethal mutations or by some other mechanism because they were observed 
in only a few of the litters produced by the mice. (Ex. 117-1, p. 171)

                                                                 Table V-6.--Effect of BD on Reproductive Outcomes in CD-1 Mice                                                                 
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                           Implantations                   Early deaths                     Late deaths             Late deaths including dead           Abnormal fetuses       
                                 ------------------------------------------------------------------------------------------------             fetuses            -------------------------------
                                                                                                                                 --------------------------------                               
                                  No.             Mean            No.            Mean a           No.            Mean a           No.            Mean a           No.            Mean a         
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Control.........................  278  12.091.276      13  0.0500.0597      0  .........................    2  0.0070.0222      0  .........................
12.5............................  306  12.752.507      16  0.0530.0581      7  0.23**0.038      8  0.0260.0424     b7  0.024*0.062  
1250 ppm........................  406  10.68**3.103    87  0.204***0161     6  0.014***0.032    7  0.0160.339      c3  0.011**0.043<
                                                                                                        4                                                               l                       
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
* Significantly different from control at: *p0.05; **p0.01; ***p0.001 (by analysis of variance and least significance test on arc-sine transform data).        
a Per implantation.                                                                                                                                                                             
b Four exencephalies (three in one litter), two runts (70% and 60% of mean body weight of others in litter; total litter sizes 7 and 9, respectively one fetus with blood in amniotic
  sac but no obvious gross malformation (significance of difference not altered if this fetus is excluded).                                                                                     
c One hydrocephaly, two runts (71% and 75% of mean body weight of others in litter; total litter sizes; 2 and 11, respectively).                                                                

    A dominant lethal test was also performed by Adler et al. (Ex. 126) 
Male(102/E1XC3H/E1)F1 male mice were exposed to 0 and 1300 ppm BD. 
They were mated 4 hours after the end of exposure with untreated virgin 
females. Females were inspected for the presence of a vaginal plug 
every morning. Plugged females were replaced by new females. The mating 
continued for four consecutive weeks. At pregnancy day 14-16 the 
females were killed and uterus contents were evaluated for live and 
dead implants. Exposure of male mice to 1300 ppm BD caused an increase 
of dead implants during the first to the third mating week after 5 days 
of exposure. The dead implantation rate was significantly different 
from the concurrent controls only during the second mating week. Adler 
et al. concluded that dominant lethal mutations were induced by BD in 
spermatozoa and late stage spermatids and that these findings confirmed 
the results of the Battelle/NTP study which showed effects on the same 
stages of

[[Page 56767]]

sperm development. (Ex. 23-74) The authors were of the opinion that BD 
may induce heritable translocations in these germ cell stages.
    The earliest reproductive study reported on BD was conducted by 
Carpenter et al. in 1944. (Ex. 23-64) In this study, male and female 
rats were exposed by inhalation to 600, 2,300 or 6,700 ppm BD, 7.5 
hours per day, six days per week for an 8-month period. Although this 
study was not specifically designed as a reproductive study, the 
fertility and the number of progeny were recorded. No significant 
effects due to BD exposure were noted for either the number of litters 
per female animal or for the number of pups per litter.
    In the Hazelton study, Sprague-Dawley (SD) rats were exposed by 
inhalation to 0, 200, 1,000 or 8,000 ppm BD on days 6 though 15 of 
gestation. (Ex. 2-32) There were dose-related effects on maternal body 
weight gain, fetal mean weight and crown-to-rump length. Post-
implantation loss was slightly higher in all BD-exposed groups. In 
addition, there were significant increases in hematoma in pups in the 
200 and 1,000 ppm exposure groups. In the 8,000 ppm exposure group, a 
significantly increased number of pups had lens opacities and there was 
an increased number of opacities per animal. According to the authors, 
the highest exposure groups also had a significantly increased number 
of fetuses with skeletal variants, a higher incidence of bipartite 
thoracic centra, elevated incidence of incomplete ossification of the 
sternum, higher incidence of irregular ossification of the ribs, and 
``other abnormalities of the skull, spine, long bones, and ribs.'' The 
authors concluded that the fetal response was not indicative of a 
teratogenic effect, but was the result of maternal toxicity.
    In the Battelle/NTP study, pregnant Sprague-Dawley (SD) rats and 
pregnant Swiss mice were exposed to 0, 40, 200, or 1,000 ppm BD for 6 
hours per day from day 6 through day 15 of gestation. (Ex. 23-72) 
Animals were sacrificed and examined one day before expected delivery. 
In the rat, very little effect was noted; in the 1,000 ppm exposure 
group only there was evidence of maternal toxicity, i.e., depressed 
body weight gains during the first 5 days of exposure. No evidence of 
developmental toxicity was observed in the SD rats evaluated in the 
study, e.g., the number of live fetuses per litter and the number of 
intrauterine deaths were within normal limits.
    In the mouse, exposure to the above mentioned concentrations did 
not result in significant maternal toxicity, with the exception of a 
reduction in extra-gestational weight gain for the 200 ppm and 1000 ppm 
BD exposed dams. In the female mice, there was a significant depression 
of fetal body weight only at the 200 and 1,000 ppm exposure levels. 
Fetal body weight for male pups was reduced at all exposure 
concentrations, including the 40 ppm exposure level, even though 
evidence of maternal toxicity was not observed at this exposure 
concentration. No significant differences were noted in incidence of 
malformations among the groups. However, the incidence of supernumerary 
ribs and reduced ossification of sternebrae was significantly increased 
in litters of mice exposed to 200 and 1,000 ppm BD.
    In reviewing these data, Drs. Melnick and Huff noted that since 
maternal body weight gain was reduced at the 200 and 1000 ppm exposure 
levels and body weights of male fetuses were reduced at the 40, 200, 
and 1000 exposure levels ``[t]he male fetus is more susceptible than 
the dam to inhaled 1,3-butadiene.'' (Ex. 114, p. 116) They further 
stated that ``the results of the study in mice reveal that a toxic 
effect of 1,3-butadiene was manifested in the developing organism in 
the absence of maternal toxicity.'' On the basis of this study, the 
authors concluded that ``1,3-butadiene does not appear to be 
teratogenic in either the rat or the mouse, but there is some 
indication of fetotoxicity in the mouse.'' (Ex. 23-72)
    On the other hand, Dr. Mildred Christian was of the opinion that 
the significant decrease in male mouse fetal weight gain in the 40 ppm 
exposure group was not a selective effect of BD on the conceptus, but 
rather was a result of the statistical analysis used which she 
considered inappropriate. (Ex. 118-13, Att. 3, p. 6) She was also of 
the opinion that the larger litter sizes in the 40 ppm exposure group 
as compared with the control group contributed to the statistical 
finding. Dr. Christian, however, did not present any specific 
information on the type of analysis used for statistical testing that 
she thought made the results inappropriate. In general, one would 
expect that the evaluation of data from larger litter sizes would give 
one more confidence in the statistical findings.
    In reviewing the same study, the State of California, Department of 
Health Services was more cautious. It stated that ``The increased 
incidence of reduced ossifications and the fetal weight reductions in 
the absence of apparent maternal toxicity in the 40- and 200-ppm groups 
is evidence of fetotoxicity * * * in the Swiss (CD-1) mouse.'' After 
reviewing the study results and arguments about the study, OSHA 
concluded that the NTP study provides evidence of fetotoxicity in the 
mouse. (Ex. 23-72)

Mouse spot test

    Adler et al. (1994) conducted a spot test in mice. (Ex. 126) The 
spot test is an in vivo method for detecting somatic cell mutations. A 
mutation in a melanoblast is detected as a coat color spot on the 
otherwise black fur of the offspring. Pregnant females were exposed to 
0 or 500 ppm BD for 6 hours per day on pregnancy days 8, 9, 10, 11 and 
12. They were allowed to come to term and to wean their litters. 
Offspring were inspected for coat color spots at ages 2 and 3 weeks. 
Gross abnormalities were also recorded. Exposure to a concentration of 
500 ppm did not cause any embryotoxicity, nor were gross abnormalities 
observed. The BD exposure, however, significantly increased the 
frequency of coat color spots in the offspring. This study demonstrates 
that BD exposure is capable of causing transplacentally induced somatic 
cell mutations that can result in a teratogenic effect in mice.

Summary of Reproductive and Developmental Effect

    OSHA has limited its discussion on reproductive and developmental 
hazards to a qualitative evaluation of the data. This approach was 
chosen because no generally accepted mathematical model for estimating 
reproductive/developmental risk on a quantitative basis was presented 
during the rulemaking. For example, the CMA Butadiene panel disagreed 
with OSHA's findings in the proposal regarding the potential 
reproductive and developmental risks presented by BD exposure using an 
uncertainty factor approach. (See Ex. 112) They cited Dr. Christian's 
conclusion that the mouse possessed a ``special sensitivity'' to BD and 
should not be used as a model on which to base risk estimates.
    The agency has determined, however, that animal studies, taken as a 
whole, offer persuasive qualitative evidence that BD exposure can 
adversely effect reproduction in both male and female rodents. The 
Agency also notes that BD is mutagenic in both somatic and germ cells. 
(Ex. 23-71; Ex. 114; Ex. 126)
    Some evidence of maternal and developmental toxicity was seen in 
rats exposed to BD, but the concentrations used were much higher than 
those that elicited a response in mice. (Ex. 118-13, Att. 3, p. 2) In 
mice, evidence of fetotoxicity was observed in either the presence or 
absence of maternal toxicity, the latter evidence being

[[Page 56768]]

provided by decreased fetal body weight in male mice whose dams were 
exposed to 40 ppm BD, the lowest dose tested in the study. In addition, 
a teratogenic effect was observed in mice (coat color spot test) as a 
result of transplacentally induced somatic cell mutation.
    OSHA is also concerned about the observation of a significant 
excess of sperm head abnormalities as a result of BD exposure, even 
though this expression of toxicity is not necessarily correlated with 
the development of abnormal fetuses or of reduced fertility. The 
Anderson study, which did evaluate reduced fertility and fetal 
abnormality, demonstrated a significant excess of both early and late 
fetal mortality and perhaps fetal abnormality as a result of male mice 
exposure to BD. (Ex. 117-1, P. 171) This observation could only occur 
as a result of an adverse effect on the sperm. Two additional studies 
also provide evidence of dominant lethality as a result of male 
exposure to BD. (Ex. 23-74; Ex. 126) The observation of germ cell 
effects is supported by additional evidence of genotoxicity in somatic 
cells, as demonstrated by positive results in the micronucleus test and 
in the mouse spot test. (Ex. 126)
    Some of the adverse effects related to reproductive and 
developmental toxicity in the mouse, e.g., ovarian atrophy, testicular 
atrophy, reduced testicular weight, abnormal sperm heads, dominant 
lethal effects, were acknowledged by Dr. Christian, but she urged the 
Agency not to rely on these findings because of negative study results 
in other species, or because positive findings in other species 
required much higher exposure levels. (Ex. 118-13, Att. 3, p. 1)
    For example, a CMA witness has argued that the diepoxide is 
responsible for the ovarian atrophy observed in relation to low level 
BD exposure (6.25 ppm). (Ex. 118-13, Att. 3) However, the monoepoxide 
could also play a role in the ovarian atrophy and evidence indicates 
that humans can form the monoepoxide of BD and that humans have the 
enzymes present that could cause conversion to the diepoxide. Therefore 
on a qualitative basis, the observation of ovarian atrophy in the mouse 
is meaningful in OSHA's view. In addition, the metabolic factors 
related to testicular atrophy, malformed sperm and dominant lethal 
mutations in the mouse are not known. (See section on in vitro 
metabolic studies.) These observations further support the findings in 
mice as being meaningful for humans on a qualitative basis. The mouse 
spot test which demonstrates a somatic cell mutation leading to a 
teratogenic effect inconsistent with data showing the ability of BD to 
cause adverse effects on chromosomes and hprt mutations in humans 
exposed to BD.
    OSHA also notes that studies of workers exposed to low 
concentrations of BD demonstrated a significant excess of chromosomal 
breakage and an inability to repair DNA damage. Thus, BD exposure seems 
capable of inducing genetic damage in humans as a result of low level 
exposure. Therefore, the mouse studies which demonstrate genetic damage 
(mutations) in both somatic and germinal cells seem to be a better 
model on a qualitative basis than the rat for predicting these adverse 
effects in humans.

D. Other Relevant Studies

1. Acute Hazards
    At very high concentrations, BD produces narcosis with central 
nervous system depression and respiratory paralysis. (Ex. 2-11) 
LC50 values (the concentration that produces death in 50 percent 
of the animals exposed) were reported to be 122,170 ppm (12.2%     v/v) 
in mice exposed for 2 hours and 129,000 ppm (12.9% v/v) in rats exposed 
for 4 hours. (Ex. 2-11, 23-91) These concentrations would present an 
explosion hazard, thus limiting the likelihood that humans would risk 
any such exposure except in extreme emergency situations. Oral 
LD50 values (oral dose that results in death of 50 percent of the 
animals) of 5.5 g/kg body weight for rats and 3.2 g/kg body weight for 
mice have been reported. (Ex. 23-31) These lethal effects occur at such 
high doses that BD would not be considered ``toxic'' for purposes of 
Appendix A of OSHA's Hazard Communication Standard (29 CFR 1910.1200), 
which describes a classification scheme for acute toxicity based on 
lethality data.
    At concentrations somewhat above the previous permissible exposure 
level of 1,000 ppm, BD is a sensory irritant. Concentrations of several 
thousand ppm were reported to cause irritation to the skin, eyes, nose, 
and throat. (Ex. 23-64, 23-94) Two human subjects exposed to BD for 8 
hours at 8000 ppm reported eye irritation, blurred vision, coughing, 
and drowsiness. (Ex. 23-64)
2. Systemic Effects
    In the preamble to the proposal, OSHA reviewed the literature to 
discern the systemic effects of BD exposure. (55 FR 32736 at 32755) 
OSHA discussed an IARC review which briefly examined several studies 
from the former Soviet Union. In these, various adverse effects, such 
as hematologic disorders, liver enlargement and liver and bile-duct 
diseases, kidney malfunctions, laryngotracheitis, upper respiratory 
tract irritation, conjunctivitis, gastritis, various skin disorders and 
a variety of neurasthenic symptoms, were ascribed to occupational 
exposure to BD. (Ex. 23-31) OSHA and IARC have found these studies to 
be of limited use primarily due to their lack of exposure information. 
Except for sensory irritant effects and hematologic changes, evidence 
from studies of other exposed groups have failed to confirm these 
observations.
    Melnick and Huff summarized the observed non-neoplastic effects of 
BD exposure in the NTP I and NTP II mouse bioassays. They listed the 
following effects associated with exposure of B6C3F \1\ mice to BD for 
6 hours per day 5 days per week for up to 65 weeks:

* * * epithelial hyperplasia of the forestomach, endothelial 
hyperplasia of the heart, alveolar epithelial hyperplasia, 
hepatocellular necrosis, testicular atrophy, ovarian atrophy and 
toxic lesions in nasal tissues (chronic inflammation, fibrosis, 
osseous and cartilaginous metaplasia, and atrophy of the olfactory 
epithelium.) (Ex. 114, p. 114)

They noted that the nasal lesions were seen only in the group of male 
mice exposed to 1250 ppm BD and that no tumors were observed at this 
site. Further, Melnick and Huff suggested that some of the 
proliferative lesions observed in the bioassay might represent pre-
neoplastic changes.
    The findings of testicular and ovarian atrophy are discussed more 
fully in the Reproductive Effects section of this preamble,.
    Nephropathy, or degeneration of the kidneys, was the most common 
non-carcinogenic effect reported for male rats in the Hazelton 
Laboratory Europe (HLE) study in which rats were exposed to 1000 or 
8000 ppm BD for 6 hours per day, 5 days per week for up to 2 years. 
Nephropathy was one of the main causes of death for the high dose 
males. (Ex. 2-31, 23-84) The combined incidence of marked or severe 
nephropathy was significantly elevated in the high dose group over 
incidence in the low dose group and over incidence in the controls 
(p<.001). HLE's analysis of ``certainly fatal'' nephropathy shows a 
significant dose-related trend (p<.05), but when ``uncertainly fatal'' 
cases were included, the trend disappeared.
    The HLE study authors concluded that the interpretation of the 
nephropathy incidence data was equivocal. They stated that ``an 
increase in the prevalence of the more severe grades of nephropathy, a 
common age-

[[Page 56769]]

related change in the kidney, was considered more likely to be a 
secondary effect associated with other unknown factors and not to 
represent a direct cytotoxic effect of the test article on the 
kidney.''
    Upon reviewing the HLE rat study for the proposed rule, OSHA 
expressed concern that only 75% of the low-dose male rats in the HLE 
study exhibited nephropathy, while 87% of the control rats had some 
degree of nephropathy, suggesting low-dose male rats were less 
susceptible to kidney degeneration than control rats, thereby 
decreasing the comparability between rats in the low-dose and control 
groups. (55 FR 32736 at 32744) Dr. Robert K. Hinderer, in testifying 
for the CMA BD Panel, countered that the NTP I mouse study also had 
``selected instances where the response in the test group (was) lower 
than that in the controls'' and that ``* * * (o)ne cannot look at 
single or a few individual site responses to evaluate the health status 
or overall effect of the chemical.'' (Ex. 51) OSHA agrees that there 
may be some variability in background response rates for specific 
outcomes. However, the Agency believes that it is important to assess 
the impact of the variability in background response rates when drawing 
conclusions about dose-related trends in the data. This was not done in 
the HLE study nephropathy analysis.
    Other non-carcinogenic effects observed in the HLE rat study were 
elevated incidence of metaplasia in the lung of high dose male rats at 
terminal sacrifice as compared with incidence in male controls at 
terminal sacrifice, and a significant increase in high dose male rat 
kidney, heart, lung, and spleen weights over the organ weights in 
control male rats.
3. Bone Marrow Effects
    There was a single study of BD-exposed humans discussed in the 
proposal--a study by Checkoway and Williams that examined 163 hourly 
production workers who were employed at the SBR facility studied by 
McMichael et al.. (described more fully in the Epidemiology Section of 
this Preamble.) (Ex. 23-4, 2-28).
    Exposure to BD, styrene, benzene, and toluene was measured in all 
areas of the plant. BD and styrene concentrations, 20 (0.5-65) ppm and 
13.7 (0.14-53) ppm, respectively, were considerably higher in the Tank 
Farm than in other departments. In contrast, benzene exposures, 
averaging 0.03 ppm, and toluene concentrations, averaging 0.53 ppm, 
were low in the Tank Farm. The authors compared the hematologic 
profiles of Tank Farm workers (n=8) with those of the other workers 
examined.
    The investigation focused on two potential effects, bone marrow 
depression and cellular immaturity. Bone marrow depression was 
suspected if there were lower levels of erythrocytes, hemoglobin, 
neutrophils, and platelets. Cellular immaturity was suggested by 
increases in reticulocyte and neutrophil band form values.
    Although the differences were small, adjusted for age and medical 
status, hematologic parameters in the Tank Farm workers differed from 
those of the other workers. Except for total leukocyte count, the 
hematologic profiles of the Tank Farm workers were consistent with an 
indication of bone marrow depression. The Tank Farm workers also had 
increases in band neutrophils, a possible sign of cellular immaturity, 
but no evidence that increased destruction of reticulocytes was the 
cause.
    While acknowledging the limitations of the cross-sectional design 
of the study, the authors felt, nevertheless, that their results were 
``suggestive of possible biological effects, the ultimate clinical 
consequences of which are not readily apparent.'' OSHA finds any 
evidence of hematological changes in workers exposed at BD levels well 
below the existing permissible limit (1000 ppm) to be of concern since 
such information suggests the inadequacy of the present exposure limit. 
However, this cross-sectional study involved only 8 workers with 
relatively high levels of exposure to BD and low levels of exposure to 
benzene, so it is quite insensitive to minor changes in hematologic 
parameters.
    In a review of BD-related studies, published in 1986, an IARC 
Working Group felt the study of Checkoway and Williams could not be 
considered indicative of an effect of BD on the bone marrow (Ex. 2-28). 
In 1992, IARC concluded that the ``changes cannot be interpreted as an 
effect of 1,3-butadiene on the bone marrow particularly as alcohol 
intake was not evaluated.'' (Ex. 125, p. 262)
    In light of the more recent animal studies that were not available 
to IARC, however, OSHA believes that the bone marrow is a target of BD 
toxicity. Furthermore, the fact that changes in hematologic parameters 
could be distinguished in workers exposed to BD at 20 ppm indicates 
that such measurements may prove a sensitive indicator of excessive 
exposure to BD.
    In testimony for the CMA BD Panel, Dr. Michael Bird stated his 
conclusion that the hematological differences between the 8 tank farm 
workers and the lesser exposed group of workers was not ``statistically 
significant by the usual conventional statistics.'' (Tr. 1/18/1991, p. 
1078) He believed that although the raw data were not available, the 
reported means were within the historical and expected range for these 
parameters. (Tr. 1/18/1991, p., 1078) In contrast, OSHA concludes from 
this study that the hematologic differences observed in BD-exposed 
workers, although small, are suggestive of an effect of BD on human 
bone marrow under occupational exposure conditions.
    Thus OSHA considers the Checkoway and Williams study to be 
suggestive of hematologic effects in humans, but does not regard it as 
definitive. No other potential systemic effects of BD exposure on this 
population were addressed in the Checkoway and Williams study.
    In 1992, Melnick and Huff reviewed the toxicologic studies of BD 
exposure in laboratory animals. (Ex. 114) Only slight to no systemic 
effects were observed in an early study of rats, guinea pigs, rabbits 
and a dog exposed to BD up to 6,700 ppm daily for 8 months. (Ex. 23-64) 
The study of Sprague Dawley rats exposed to doses of BD up to 8,000 ppm 
daily for 13 weeks also did not result in hematologic, biochemical, 
neuromuscular, nor urinary effects. However, there were marked effects 
seen in exposed mice.
    Epidemiologic studies of the styrene-butadiene rubber (SBR) 
industry suggest that workers exposed to BD are at increased risk of 
developing leukemia or lymphoma, two forms of hematologic malignancy 
(see preamble section on epidemiology). Consequently, investigators 
have looked for evidence of hematopoietic toxicity resulting from BD 
exposure in animals and in workers. For example, Irons and co-workers 
at CIIT found that exposure of male B6C3F1 mice to 1,250 ppm of BD 
for 6-24 weeks resulted in macrocytic-megaloblastic anemia, an increase 
in erythrocyte micronuclei and leukopenia, principally due to 
neutropenia. Bone marrow cell types overall were not altered, but there 
was an increase in the number of cells in the bone marrow of exposed 
mice due to an increase in DNA synthesis. (Ex. 23-12)
    Melnick and Huff also reviewed the available information on bone 
marrow toxicity. (Ex. 114, p. 114) Table V-7 represents the reported 
findings of a study of 10 B6C3F1 mice sacrificed after 6.25-625 
ppm exposure to BD for 40 weeks. The authors concluded that these data 
demonstrated a concentration-dependent decrease in red blood cell 
number, hemoglobin concentration, and packed red cell

[[Page 56770]]

volume at BD exposure levels from 62.5 to 625 ppm. The effects were not 
observed at 6.25 and 20 ppm exposure levels. Melnick and Kohn also 
noted the increase in mean corpuscular volume in mice exposed at 625 
ppm, and suggested that this and other observations (such as those of 
Tice (Ex. 32-38D)) who observed a decrease in the number of dividing 
cells in mice and decreased rate of their division), suggested that BD 
exposure led to a suppression of hematopoiesis in bone marrow. Melnick 
and Huff concluded that this, in turn, led to release of large immature 
cells from sites such as the spleen, which was considered indicative of 
macrocytic megaloblastic anemia by Irons. They concluded that these 
findings ``(establish) the bone marrow as a target of 1,3-butadiene 
toxicity in mice.'' (Ex. 114, p. 115)

       Table I.--Hematologic Changes in Male B6C3F1 Mice Exposed for 6 Hours/Day, 5 Days/Week for 40 Weeks      
----------------------------------------------------------------------------------------------------------------
                                                  Red blood cell                                                
                BD exposure (ppm)                  count  ( x 10    Hemoglobin     Volume packed   Mean corpus- 
                                                      \6\/ul)      conc.  (g/dl)    RBC (ml/dl)      cular vol  
----------------------------------------------------------------------------------------------------------------
0...............................................  10.4a 9.9a 15.9a 45.9a 9.6a 15.6a 45.4a 7.6a 13.5a 39.9a 53.2a Different from chamber control (0 ppm), P<0.05. Results of treated groups were compared to those of control   
  groups using Dunnett's t-test.                                                                                

4. Mutagenicity and Other Genotoxic Effects
    OSHA discussed the genotoxic effects of BD exposure in some detail 
in the proposal. (55 FR 32736 at 32760) Briefly, BD is mutagenic to 
Salmonella typhimurium strains TA 1530 and TA 1535 when activated with 
S9 liver fraction of Wistar rats treated with phenobarbital or Arochlor 
1254. These bacterial strains are sensitive to base-pair substitution 
mutagens. Since the liver fraction is required to elicit the positive 
mutagenic response, BD is not a direct-acting mutagen and likely must 
be metabolized to an active form before becoming mutagenic in this test 
system. IARC published an extensive list of ``genetic and related 
effects of 1,3-butadiene.'' (Ex. 125) They noted in summarizing the 
data that BD was negative in tests for somatic mutation and 
recombination in Drosophila, and that neither mouse nor rat liver from 
animals exposed to 10,000 ppm BD showed evidence of unscheduled DNA 
synthesis.
    As OSHA described in the proposed rule, and Tice et al. reported in 
1987, BD is a potent in vivo genotoxic agent in mouse bone marrow cells 
that induced chromosomal aberrations and sister chromatid exchange in 
marrow cells and micronuclei in peripheral red blood cells. (55 FR 
52736 at 52760) Some of these effects were evident at exposures as low 
as 6.25 ppm (6 hours/day, 10 days). However, similar effects were not 
observed in rat cells exposed to higher levels of BD (10,000 ppm for 2 
days).
    Sister chromatid exchange is a recombinational event in which 
nucleic acid is exchanged between the two sister chromatids in each 
chromosome. It is thought to result from breaks or nicks in the DNA. 
Irons et al. described micronuclei as ``* * * chromosome fragments or 
chromosomes remaining as the result of non-dysjunctional event. Their 
presence in the circulation is frequently associated with megaloblastic 
anemia.'' (Ex. 23-12).
    In a subsequent study, Filser and Bolt exposed B6C3F1 mice to 
the same 3 concentrations of BD, 6.25, 62.5 or 625 for 6 hours/day, 5 
days/week, for 13 weeks. (Ex. 23-10) Peripheral blood samples were 
taken from 10 animals per group and scored for polychromatic 
erythrocytes (PCE) and micronucleated normochromatic erythrocytes (MN-
NCE). The MN-NCE response, which reflects an accumulated response, was 
significantly increased in both sexes at all concentrations of BD, 
including 6.25 ppm.
    Certain metabolites of BD also produce genotoxic effects. These are 
detailed in a number of reviews (see for example, Ex. 114, 125). 
Briefly, epoxybutene (the monoepoxide) is mutagenic in bacterial 
systems in the absence of exogenous metabolic activation. Epoxybutene 
also reacts with DNA, producing two structurally identical adducts and 
has been shown to induce sister chromatid exchanges in Chinese hamster 
ovary cells and in mouse bone marrow in vivo.
    IARC in its review concluded that the diepoxide, 1,2,:3,4-
diepoxybutane, induced DNA crosslinks in mouse hepatocytes and, like 
epoxybutene, is mutagenic without metabolic activation. As discussed 
below, BD diepoxide also induced SCE and chromosomal aberrations in 
cultured cells.
    A human cross-sectional study involving a limited number of workers 
in a Texas BD plant indicated genotoxic effects. (Ex. 118-2D) 
Peripheral lymphocytes were cultured from 10 non-smoking workers and 
from age- and gender-matched controls who worked in an area of very low 
BD exposure (0.03 ppm). Production areas in the plant had a mean 
exposure of 3.5 ppm BD, with most exposed workers in this sample 
experiencing exposure of approximately 1 ppm BD.
    Standard assays for chromosomal aberrations and a gamma irradiation 
challenge assay that was designed to detect DNA repair deficiencies 
were performed. The results of the standard assay indicated that the 
exposed group had a higher frequency of cells with chromosome 
aberrations and higher chromatid breaks compared with the control 
group. This difference was not statistically significant. In the 
challenge assay, the exposed group had a statistically significant 
increased frequency of aberrant cells, chromatid breaks, dicentrics 
(chromosomes having 2 centromeres) and a marginally significant higher 
frequency of chromosomal deletions than controls. Au and co-workers 
concluded that cells exposed to BD are likely to have more difficulty 
in repairing radiation induced damage. (Ex. 118-2D)
    To determine the mutagenic potential of both BD and its three 
metabolite epoxides, Cochrane and Skopek studied effects in human 
lymphoblastoid cells (TK6) and in splenic T cells from exposed 
B6C3F1 mice. (Ex. 117-2, p. 195) TK6 cells were exposed for 24 
hours to epoxybutene (0-400 uM), 3,4-epoxy-1,2-butanediol (0-800 uM), 
or diepoxybutane (0-6 uM). All

[[Page 56771]]

metabolites were mutagenic at both the hprt (hypoxanthine-guanine 
phosphoribosyl transferase) and tk (thymidine kinase) loci, with 
diepoxybutane being active at concentrations 100 times lower than 
epoxybutane or epoxybutanediol.
    They also studied mice exposed to 625 ppm BD for 2 weeks and found 
a 3-fold increase in hprt mutation frequency in splenic T cells 
compared with controls. They also intended to give daily IP doses of 
epoxybutene (60, 80 or 100 mg/kg) or diepoxybutane (7, 14, or 21 mg/kg) 
every other day for three days. However, only animals given the lowest 
dose of the diepoxide received three doses because of lethality. After 
two weeks of expression time, cells were isolated for determination of 
mutation frequency. Both exposure regimens resulted in increased 
mutation frequency. For example, at the highest exposure to 
epoxybutene, the average mutation frequency was 8.6 x 10\6\, while the 
diepoxide exposed group had a frequency of 13 x 10\6\, compared to a 
control mutation frequency of 1.2 x 10\6\.
    Cochrane and Skopek used denaturing gradient gel electrophoresis to 
study the nature of the splenic T cell hprt mutants in the DNA. They 
found about half were frameshift mutations. A potential ``hotspot'' was 
also described in which a plus one (+1) frameshift mutation in a run of 
six guanine bases was observed in four BD-exposed mice, in four 
expoxybutene-exposed mice and in two mice exposed to the diepoxide. 
They observed both G:C and A:T base pair substitutions in the epoxide 
treated group; however, similar to the findings of Recio, et al. 
(described below), A:T substitutions were observed only in the BD-
treated group. The authors offered no hypothesis for this observation. 
These researchers also noted a significant correlation of dicentrics 
with the presence of a BD metabolite, (1,2-dihydroxy-4-(N-acetyl-
cysteinyl-S)butane) in the urine of exposed workers. They further 
concluded that:

    This study indicates that the workers had exposure-induced 
mutagenic effects. Together with the observation of gene mutation in 
a subset of the population, this study indicates that the current 
occupational exposure to butadiene may not be safe to workers. (Ex. 
118-2D)

    An abstract by Hallberg submitted to the Environmental Mutagenesis 
Society describes a host-cell reaction assay in which lymphocytes 
transfected with a plasmid with an inactive chloramphenicol acetyl 
transferase (CAT) reporter gene were challenged to repair the damaged 
plasmid and reactivate the CAT gene. No effect was noted among cells of 
workers exposed to 0.3 ppm benzene; however, BD-exposed workers (mean 
exposure 3 ppm) had significantly reduced DNA repair capacity 
(p=0.001). The authors believed that this finding confirmed the DNA 
repair defect due to BD exposure observed in the Au et al. study's 
challenge assay. (Ex. 118-2D)
    Ward and co-workers reported the results of a preliminary study to 
determine whether a biomarker for BD exposure and a biomarker for the 
genetic effect of BD exposure could be detected in BD-exposed workers. 
(Ex. 118-12A) The biomarker for exposure was excretion of a urinary 
metabolite of BD, (1,2-dihydroxy-4-(n- acetylcysteinyl-S)butane. The 
genetic biomarker was the frequency of lymphocytes containing mutations 
at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus. 
Study subjects included 20 subjects from a BD production plant and 9 
from the authors' university; all were verified non-smokers. Seven 
workers were in areas or at jobs that were ``considered likely to 
expose them to higher levels of butadiene than in other parts of the 
plant.'' Ten worked in areas where the likelihood of BD exposure was 
low. Three ``variable'' employees worked in both types of jobs or 
areas. hprt assays of 6 of the 7 high exposure group and 5 of the 6 
non-exposed groups were completed at the time of the report. Air 
sampling was used to estimate exposure. In the production area, the 
mean was approximately 3.5 ppm, with most samples below 1 ppm. In the 
central control area (lower exposure) the mean was 0.03 ppm. The 
frequency of mutant lymphocytes in the high-exposure group compared 
with either the low- or no-exposure group was significantly increased. 
The low- and non-exposed groups were not significantly different from 
each other in mutant frequencies.
    Similarly, the concentration of the BD metabolite in urine was 
significantly greater in the high exposure group than in the lower- or 
non-exposed groups. There was a strong correlation among exposed 
subjects between the level of metabolite in urine and the frequency of 
the hprt mutants (r=0.85). (Ex. 118-2A)
    Another study of humans for potential cytogenetic effects of BD 
exposure was reported recently by Sorsa et al. in which peripheral 
blood was drawn from 40 BD production facility workers and from 30 
controls chosen from other departments of the same plants, roughly 
matched for age and smoking habits. (Ex. 124) Chromosome aberrations, 
micronuclei and sister-chromatid exchanges were analyzed. No exposure 
related effects were seen in any of the cytogenetic endpoints. The 
typical exposure was reported as less than 3 ppm. (Ex. 124)
    Among the limited number of human studies involving BD exposed 
workers is that of Osterman-Golker who evaluated post-exposure adduct 
formation in the hemoglobin of mice, rats, and a small number of 
workers. (Ex. 117-2, p. 127) Mice and rats were exposed at 0, 2, 10, or 
100 ppm for 6 hours per day, 5 days per week for 4 weeks and their 
blood tested for the presence and quantity of the BD metabolite, 1,2-
epoxybutene, forming an adduct with the N-terminal valine of 
hemoglobin. The result was a linear response for mice at 2, 10 and 100 
ppm; and, for rats at 2 and 10 ppm, with the 100 ppm dose group 
deviating from linearity. In addition, while the adduct level per gram 
of globin in the 100 ppm rats was about 4 times lower than the level 
observed in mice exposed to 100 ppm BD, at lower exposures, the adduct 
levels were similar.
    In the portion of the study dealing with effects on humans, blood 
was taken from four workers in two areas of a chemical production plant 
with known BD exposure, and five workers from two non-production areas 
where BD concentrations were low. In the higher exposure area, the mean 
BD exposure was about 3.5 ppm, as determined by environmental sampling. 
The lower exposure areas had a mean BD level of about 0.03 ppm. On a 
mole of adduct per gram of hemoglobin level, the adduct levels in the 
higher BD exposed workers were 70 to 100 times lower than those of 
either the rat or mice exposed at the 2 ppm level discussed above. 
Production workers had adduct levels ranging from 1.1 to 2.6 pmol/g 
globin. Most controls in the study were below the level of detection of 
the assay (0.5 pmol adduct/ g globin). (Two heavy smokers reported from 
a previous study had higher adduct levels than non-smokers; their 
levels approached those observed in BD exposed workers and were 
consistent with the amount of BD in mainstream smoke.)
    Similar results for mice and rats exposed to BD were reported by 
Albrecht et al. (Ex. 117-2, p. 135) In this study which exposed the 
rodents to 0, 50, 200, 500 or 1300 ppm for 6 hours/day, for 5 
consecutive days, BD monoepoxide adduct levels in the hemoglobin of 
mice were about five times that of the rat at most BD exposure 
concentrations. Humans were not studied in this report.
    Another observation pertaining to human cytogenetics with 
potentially important implications for BD-induced

[[Page 56772]]

human disease is contained in a report by Wiencke and Kelsey. (Ex. 117-
2, p. 265) These researchers studied the impact of the BD metabolite, 
diepoxybutane, exposure on sister chromatid exchange (SCE) frequencies 
in several groups of human blood cell cultures (n=173 healthy workers). 
They discovered that the study populations were bimodally distributed 
according to their sensitivity to induction of SCEs when cell cultures 
were exposed to 6 uM diepoxybutane. Wiencke and Kelsey reported that 
they had observed in earlier studies that ``genetic deficiency of 
glutathione S-transferase type u leads to bimodal induction of SCEs by 
epoxide substrates of the isozyme'' and that cells from individuals 
with the deficiency had SCE induction scores that were significantly 
higher than those observed in the general population. (Ex. 117-2, p. 
271) Approximately 20% of the tested groups were sensitive to induction 
of SCE and the remaining 80% were relatively insensitive.1 
Subsequent testing indicated that the sensitive population was also 
sensitive to induction of chromosomal aberrations by diepoxybutane with 
significant increases in the frequencies of chromatid deletions, 
isochromatid deletions, chromatid exchanges and total aberrations. The 
relevance of these findings in not yet clear; however, they may 
indicate that certain subsets of the population are more highly 
susceptible to the effects of this mutagenic metabolite of BD.
---------------------------------------------------------------------------

     1 For example, in the 58 newspaper workers tested, 24% had 
greater than 95 SCE/cell, while the remaining 76% had fewer than 80 
SCE/cell.
---------------------------------------------------------------------------

    Recio et al. used transgenic mice containing a shuttle vector with 
a recoverable lac 1 gene to study in vivo mutagenicity of BD and the 
spectrum of mutations produced in various tissues. (Ex. 118-7D) Mice 
were exposed to 62.5, 625 or 1250 ppm BD for 4 weeks (5 days/week, 6 
hours/day). The investigators extracted DNA from bone marrow and 
determined mutagenicity at the lac 1 transgene.
    The mutant DNA was sequenced. Dose-dependent mutagenicity--up to a 
3-fold increase over air controls--was observed among mice exposed at 
625 or 1250 ppm. Although a number of differences in patterns were 
noted, the most striking was that sequence analysis indicated an 
increased frequency of in vivo point mutations induced by BD exposure 
at adenine and thymine (A:T) base pairs following inhalation.
    In further studies of BD-exposed transgenic mice, Sisk and co-
workers exposed male B6C3F1 mice to 0, 62.5, 625, or 1250 ppm, BD 
for 4 weeks (6 hour/day, 6 days/week). (Ex. 118-7Q) Bone marrow cells 
were isolated and mutation frequency and spectrum evaluated. Lac 1 
mutation frequencies were significantly increased at all 3 exposure 
levels and were dose-responsive in the 62.5 and 625 ppm BD-exposed 
mice, compared to controls. A plateau in mutation frequencies was 
observed at 1250 ppm BD-exposed mice, perhaps indicating saturation or 
mutant loss due to the effects of high level exposure.
    When the mutants were sequenced, several from the same animal were 
found to have identical mutations. Although they might have arisen 
independently, Sisk et al. felt that this was likely due to clonal 
expansion of a bone marrow cell with a mutated lac 1 gene.
    As had Recio et al., Sisk et al. observed a higher frequency of 
mutations at A:T sites in the exposed mice DNA, compared with controls. 
A:T to G:C transitions comprised only 2% of the background mutations, 
but made up 15% of those in the exposed mice.
    Sisk et al. concluded that their observation coupled with in vitro 
studies `` * * * suggest that BD may mutate hematopoietic stem cells.'' 
(Ex. 118-7Q, p. 476)
    As discussed in the animal carcinogenicity section in this 
preamble, BD-induced mouse tumors have been found to have activated 
proto-oncogenes. Specifically, the K-ras oncogene is activated and is 
the most commonly detected oncogene in humans. (Ex. 129)
    OSHA concludes that BD is mutagenic in a host of tests which show 
point and frameshift mutations, hprt mutations, chromosome breakage, 
and SCEs in both animals and humans. The data suggest that mice are 
more susceptible than rats to these alterations. In addition, certain 
subsets of the human population may be more susceptible to the effects 
of BD exposure than others (based on the Wiencke and Kelsey study of 
human blood cell cultures, Ex. 117-2, p. 265). OSHA further notes with 
concern the fact that the data suggest that BD exposure at relatively 
low levels adversely affects DNA repair mechanisms in humans and is 
associated with mutational effects.
5. Metabolism
    In vitro genotoxicity studies have shown that BD is mutagenic only 
after it is metabolically activated. Biotransformation is probably also 
important to the carcinogenicity of this gas. It is thought that the 
formation of epoxides, specifically epoxybutene, also termed the 
``monoepoxide'' and 1,2:3,4-diepoxybutane, termed the ``diepoxide,'' is 
required for activity and that the reaction is cytochrome P450 mediated 
2. Both the mono- and diepoxide are mutagenic in the Salmonella 
assay, with the diepoxide being more active. The reactive epoxides can 
bind to DNA, and formation of DNA adducts is hypothesized to initiate a 
series of events leading to malignancy.
---------------------------------------------------------------------------

     2  Cytochrome is defined as any of a class of hemoproteins 
whose principal biologic function is electron transport by virtue of 
a reversible valency change of its heme iron. Cytochromes are widely 
distributed in animal and plant tissues.
---------------------------------------------------------------------------

    As described earlier, for most cancer sites, mice are more 
sensitive than rats to the carcinogenic effects of BD exposure. Studies 
of the metabolism of BD have been undertaken in an attempt to elucidate 
the contributions of dose-metric factors for the observed differences 
in carcinogenicity between the species.
    Much of the research in this area has been performed at the 
Chemical Industry Institute of Toxicology and in German laboratories. 
Work on metabolism of BD was described by OSHA in the 1990 proposal. 
(55 FR 32736 at 32756) OSHA reviewed the current literature in the 
record and concluded:
    1. The rate of metabolism of BD in mice is approximately twice that 
in rats;
    2. Mice accumulate more radiolabelled BD equivalents in a 6 hour 
exposure than do rats at the same concentration;
    3. Mice have about twice the concentration of the metabolite (1,2-
epoxy-3-butene) (BMO) in blood as rats exposed at similar 
concentrations;
    4. Over a wide range of exposures, mice received a larger amount of 
inhaled BD per unit body weight than rats, and had a higher 
concentration of BMO in the blood than rats (As expected, because of 
body size differences and breathing rates, and some enzymology);
    5. BD is readily absorbed and widely distributed in tissues of both 
mice and rats, with tissue concentrations per umole BD inhaled higher 
in mice than in rats, by factors of 15-fold or more;
    6. While there are species differences in the amount of BD 
metabolism at various sites, both mice and rats metabolize BD to the 
same reactive metabolites suspected of being ultimate carcinogens.
    In comments on OSHA's proposal, Dr. Michael Bird of Exxon testified 
on behalf of the CMA BD Task Group that the mouse ``will attain a 
significantly higher amount of the epoxides over a longer period of 
time than the rat. . . or primate when exposed to butadiene.''

[[Page 56773]]

(Ex. 52, p. 27) Dr. Bird concluded that the differences in metabolism 
of BD in the species help ``explain the greater sensitivity of the 
mouse to BD carcinogenic activity.'' He further concluded that the 
differences in rates of enzyme mediated processes indicate non-human 
primates have lower internal concentrations of BD or BMO, and ``man is 
more similar to the primate with respect to 1,2-epoxy-3-butene 
formation than the rat or mouse.'' (Ex. 52, p. 22) He argued that the 
mouse may be ``uniquely sensitive `` to BD carcinogenicity due to its 
greater uptake, faster BD metabolism and ``elimination of the epoxide 
1,2-epoxy-3-butene is saturable in mice but not in rats.'' (Ex. 52, p. 
21) He felt this observation correlated well with the observed 
cytogenetic and bone marrow response (seen in mouse, but not rats.)
    Others hold an opposing view, e.g., Melnick and Kohn argued that 
``[b]ecause the rat appears to be exceptionally insensitive to 
leukemia/lymphoma induction, the mouse must be considered as the more 
appropriate model for assessing human risk for lymphatic and 
hematopoietic cancers.'' (Ex. 130, p. 160)
    Dr. Bird urged OSHA to use the monkey data of Dahl, et al. which 
indicated that the retention rate for BD in primates is over 6 times 
lower than that for the mouse, in ``drawing any firm conclusions about 
the cancer risk to humans.'' (Ex. 52, p. 36) During the public hearing, 
the work of Dahl was presented as a preliminary report. (Ex. 44) Dahl 
exposed 3 cynomolgus monkeys to BD and measured uptake and metabolism. 
Each animal was exposed to three concentrations of C14-labeled BD, 
progressing from 10,300 to 8000 ppm with at least 3 months separating 
the re-exposure of each monkey. Post-exposure blood was taken. Each 
animal's breathing frequency and tidal volume was measured.
    Dahl and co-workers found BD uptake to be lower in monkeys than in 
rats. The reported blood levels of the epoxides were also lower in the 
monkey than the levels reported by Bond et al. in rats and mice.
    Dahl et al. attempted to quantitate total BD metabolites through 
collection of feces, urine and exhaled material though use of cryogenic 
traps. Measurement of residual labeled material retained in the animals 
at the end of the 96 hour post exposure period was not determined. HPLC 
(high-performance liquid chromatography) identification of the trapped 
material (at 95 C) indicated that only 5 to 15% of the radioactivity 
was present as monoepoxide.
    Melnick and Huff, in reviewing this study, found its significance 
``clouded'' because only three animals of unknown age were studied and 
there was uncertainty about the ability of vacuum line cryogenic 
distillation alone to identify and quantitate BD metabolites. (Ex. 114, 
p. 133) In testimony at the public hearing, Dr. James Bond of CIIT 
acknowledged the limitations of the use of vacuum-line cryogenic 
distillation as follows:

    * * * there will be some material no matter what kind of vacuum 
you apply to it * * * simply will not move into the traps. That's 
referred to as non-volatile material.
    We don't know what that material is and I think that's an 
important component of this study, because, in fact, in many cases 
it can represent 70 to 80 percent of the material that actually 
distills out. (Tr. 1/22/91, p. 1553)

    Melnick and Huff were also concerned that only the monkeys, not the 
mice or rats, were anesthetized during exposure and question what 
impact that might have had on respiratory rates and cardiac output and 
what the influence might be on inhalation pharmacokinetics of BD. (Ex. 
114, p. 133) In their 1992 review, Melnick and Huff concluded that 
studies to date have not revealed species pharmacokinetic differences 
of sufficient magnitude ``to account for the reported different toxic 
or carcinogenic responses in one strain of rats compared to two strains 
of mice.'' (Ex. 114, p. 134) In post hearing comments Dr. David A. 
Dankovic of NIOSH reviewed this topic and concluded ``* * * the most 
prudent course is to base 1,3-butadiene risk assessments on the 
external exposure concentration, unless substantial improvements are 
made in the methodology used for obtaining `internal' dose estimates.'' 
(Ex. 101, Att. 2, p. 5)
Recent Studies
    Recent studies have focused on the metabolism of BD to the 
epoxides, epoxybutene and diepoxybutane, and their detoxification by 
epoxide hydrolase and glutathione. Bond et al. recently reviewed BD 
toxicologic data. (Ex. 118-7G) Epoxybutene and diepoxybutane were 
reported to be carcinogenic to mice and rats via skin application and/
or subcutaneous injection, with the diepoxide having more carcinogenic 
potency. Bond et al. also concluded that the diepoxide is more 
mutagenic than the monoepoxide by a factor of nearly 100 on a molar 
basis. The diepoxide also induces genetic damage in vitro mammalian 
cells (Chinese hamster ovary cells and human peripheral blood 
lymphocytes). These studies are summarized in this preamble discussion 
of reproductive effects.
In vitro metabolic studies
    In 1992 Csanady et al. reported use of microsomal and cytosolic 
preparations from livers and lungs of Sprague-Dawley rats, B6C3F1 
mice and humans to examine cytochrome P450-dependent metabolism of BD. 
(Ex. 118-7AA) The preparations were placed in sealed vials and BD was 
injected by use of a gas-tight syringe. Air samples were taken from the 
head space at 5 minute intervals and analyzed by gas chromatography for 
epoxybutene.
    Cytochrome P450-dependent metabolism of the monoepoxide to the 
diepoxide was examined. Enzyme mediated hydrolysis of BMO by epoxide 
hydrolase was measured. (Non-enzyme mediated hydrolysis was determined 
using heat-inactivated tissue and none was observed.) Second order rate 
constants were determined using 100 mM monoepoxide and 10 mM GSH. The 
human samples were quite variable, with rates ranging from 14 to 98 
nmol/min/mg protein.
    The maximum rates for BD oxidation to monoepoxide (Vmax) were 
determined to be highest for mouse liver microsomes 3 (2.6 nmol/mg 
protein/min); the Vmax values for humans were intermediate, at 1.2 
nmol/mg protein/min; the Vmax values for rats was 0.6 nmol/mg protein/
min. For lung microsomes, the Vmax in the mouse was found to be similar 
to the mouse liver rate, but over 10-fold greater than that of either 
humans or rats.
---------------------------------------------------------------------------

    \3\ A microsome is defined as one of the finely granular 
elements of protoplasm, resulting from fragmentation 
(homogenization) of the endoplasmic reticulum.
---------------------------------------------------------------------------

    From these data Csanady et al. calculated a ratio of activation to 
detoxification for each species tested. These values, expressed as mg 
cytosolic protein/gm liver [glutathione-S-transferase is a cytosolic 
enzyme], resulted in the determination of an overall 
activation:detoxification ratio of 12.3 for the mouse, 1.3 for the rat, 
and 4.4 for the human samples.
    If these in vitro liver microsomal studies can be extrapolated to 
the whole animal in vivo, then this implies, as pointed out by Kohn and 
Melnick, that the mouse produces 2.8 times as much BMO per mol of BD as 
the human and that the human activation:detoxification ratio is 3.4 
times that of the rat. However, the Csanady et al. study demonstrated a 
wide variability in BD metabolic activity among the 3 human liver 
microsomes, and a 60-fold variation was found in 10 human liver

[[Page 56774]]

samples by Seaton et al. (Ex. 118-7N) Kohn and Melnick noted that this 
human variability in CYP2E1, the P450 enzyme primarily responsible for 
the activity, suggests that a ``* * * fraction of the human population 
may be as sensitive to butadiene as mice are.'' (Ex. 131, p. 620).
    A study similar to that of Csanady et al., reported by Duescher and 
Elfarra in 1994, determined that the Vmax/Km ratios for BD metabolism 
in human and mouse liver microsome were similar and were nearly 3 to 
3.5 fold higher than the ratio obtained with rat liver microsomes. (Ex. 
128) Duescher and Elfarra suggest that differences between their 
results and those of Csanady et al. may have been due in part to 
experimental methodology differences, such as incubation and assay 
methods. Duescher and Elfarra found that two P450 isozymes, 2A6 and 
2EI, were most active in forming BMO of the 7 isozymes tested. They 
concluded that since human liver microsomes oxidized BD at least as 
efficiently as mouse liver microsomes (and much more so than rat liver 
microsomes), this ``suggests that if [BMO] formation rate is the 
primary factor which leads to toxicity, humans may be at higher risk of 
expressing BD toxicity than mice or rats, and that the mouse may be the 
more appropriate animal model for assessing toxicity.'' Duescher and 
Elfarra felt that since P450/2A6 appears to play a major role in BD 
oxidation in human liver microsomes, and that it is more similar to 
that of mouse P450/2A5 than to rat P450/2A1, the mouse may be a better 
model to use in assessing human risk.
    In 1994 Himmelstein et al. hypothesized that ``[S]pecies 
differences in metabolic activation and detoxification most likely 
contribute to the difference in carcinogenic potency of BD by 
modulating the circulating blood levels of the epoxides.'' (Ex. 118-13, 
Att 3) To address this, Himmelstein and colleagues looked at the levels 
of BD, BMO, and BDE in blood of rats and mice exposed at 62.5, 625, or 
1250 ppm BD. Samples were collected at 2, 3, 4, and 6 hours of exposure 
for BD and BMO and at 3 and 6 h for the BDE. Blood was collected from 
mice by cardiac puncture and from rats through an in-dwelling jugular 
cannula. Melnick and Huff criticized earlier studies which failed to 
use in-dwelling cannulae.

    Because steady state levels of [monoepoxide] are lower in rats 
than in mice and because the metabolic elimination rate for this 
compound is 5 times faster in rats than in mice, any delay in 
obtaining immediate blood samples would have a much greater effect 
on analyses in blood samples obtained from rats than those obtained 
from mice. (Ex. 114, p. 133)

    Himmelstein et al. found that the concentration of BD in blood was 
not directly proportional to the inhaled concentration of BD, 
suggesting that the uptake of BD was saturable at the highest inhaled 
concentration. In both rats and mice BD and the BMO blood levels were 
at steady state at 2, 3, 4 and 6 hours of exposure and declined rapidly 
when exposure ceased. This is consistent with exhalation being the 
primary route of elimination of BD. (Ex. 118-7B)
    Genter and Recio used Western blot and immunohistochemical analyses 
to detect P450/2E1 in bone marrow of B6C3F1 mice. (Ex. 118-7T) 
Although both methods detected the presence of the protein in livers of 
both male and female mice, non was seen in the bone marrow. The limits 
of detection were not stated in the report. The author hypothesized the 
BD might be converted to the monoepoxide in the liver prior to uptake 
by the bone marrow or that another pathway (e.g., myeloperoxidase) is 
responsible for BD oxidation in the marrow. Recio and Genter suggest 
that the greater sensitivity of mice to BD-induced carcinogenicity can 
be explained in part by the higher levels of both epoxides in the blood 
of mice compared with that of rats.
    Himmelstein et al. furthered this work in 1995 in a report in which 
they determined levels of the epoxides in livers and lungs of mice and 
rats exposed to BD. (Ex. 118-7/O) Animals were exposed at 625 or 1250 
ppm of BD for 3 or 6 hours. Himmelstein et al. found that in mice 
exposed to this regimen, the monoepoxide levels were higher in lungs 
than in livers. Rats at 625 and 1250 ppm had lower concentrations of 
BMO in lungs and livers than mice. When rats were exposed to 8000 ppm 
BD, the maximum concentration of BMO in the lung and liver was nearly 
the same. The diepoxide levels in lungs of mice exposed at 625 and 1250 
ppm were 0.71 and 1.5 nmol/g respectively. The diepoxide was not 
detected in livers or lungs of rats exposed at any tested level.
    Himmelstein et al. also observed depletion of glutathione in liver 
and lung samples from both rodent species. Following 6 hours of 
exposure, the lungs of mice exhibited greater depletion of GSH than 
mouse liver, rat liver or rat lung at all concentrations of BD tested. 
The conclusion reached by the study authors was that their data 
indicate that GSH depletion is associated with tissue burden of the 
epoxides and that this target organ dosimetry might help explain some 
of the non-concordance of cancer sites observed between the species. 
OSHA notes, however, that while % GSH depletion was highest in the 
mouse lung, the major increase in depletion was at 1250 ppm BD, while 
lung tumor incidence was increased in the female mice at 6.25 ppm and 
in male mice at 62.5 ppm. Depletion of glutathione was dependent on 
concentration and duration of BD exposure.
    Himmelstein et al. stressed the importance of the fact that the 
diepoxide was detected in the mouse lung but was not quantifiable in 
the mouse liver, and stated that if the diepoxide was formed in the 
liver, it is rapidly detoxified or otherwise moved out of the liver. 
They also found that depletion of glutathione was greater in mouse than 
rat tissues for similar inhaled concentrations of BD and concluded that 
conjugation of the monoepoxide with glutathione by glutathione S-
transferase is an important detoxification step.
    In contrast to rats and mice, lungs and livers from humans had much 
faster rates of microsomal monoepoxide hydrolysis by epoxide hydrolase 
compared to cytosolic conjugation with glutathione by the transferase. 
(Ex. 118-7AA)
    Thornton-Manning et al. in 1995 examined the production and 
disposition of monoepoxide and diepoxide in tissues of rats and mice 
exposed at 62.5 ppm BD. (Ex. 118-13, Att. 3) They found monoepoxide was 
above background in blood, bone marrow, heart, lung, fat, spleen and 
thymus tissues of mice after 2 or 4 hours of exposures to BD. In rats, 
levels of monoepoxide were increased in blood, fat, spleen and thymus 
tissues. No increase in monoepoxide in rat lung was observed. The more 
mutagenic diepoxide was detected in all tissues of the mice examined 
immediately following 4 hours of exposure. It was detected in heart, 
lung, fat, spleen and thymus of rats, but at levels 40- to 160-fold 
lower than those seen in mice.
    In mice, the level of diepoxide exceeded the monoepoxide levels 
immediately after exposure in such target organs as the heart and 
lungs. Thornton-Manning et al. concluded that the high concentrations 
of diepoxide in heart and lungs they observed suggested to them that 
this compound may be particularly important in BD-induced 
carcinogenesis.
    The study authors noted that neither epoxide was detected in rats' 
liver and was present only in quite low concentrations in the livers of 
mice. Thornton-Manning et al. found this

[[Page 56775]]

surprising since epoxides present in blood in the liver should have 
yielded values greater than those observed in the liver samples. They 
hypothesized that it might be due to prior metabolism of the epoxides 
before reaching the liver or it might be an artifact due to post-
exposure metabolism of the epoxides in the liver.
    Thornton-Manning et al. did not detect the monoepoxide in rat 
lungs, and found the diepoxide level to be quite low. In contrast, in 
the mice they found both epoxides present in lung tissue, with the 
monoepoxide level present at a concentration less than expected using 
blood volume values, and the diepoxide level agreeing with that 
expected as a function of blood volume. Thornton-Manning et al. 
concluded that these results ``* * * suggest that the lung is capable 
of metabolizing BDO, but perhaps is less active in metabolizing 
BDO2. (Ex. 118-13, Att. 3) Moreover, Thornton-Manning et al. 
believed that although BD is oxidatively metabolized by similar 
metabolic pathways in the rats and mice, the quantitative differences 
in tissue levels between species may be responsible for the increased 
carcinogenicity of BD in mice.

  Table V-8.--Tissue Levels [pmol/gm tissue, meanS.E.] of Epoxybutene and Diepoxybutane in Rats and 
                          Mice Following a 4-Hour Exposure to 62.5 ppm BD by Inhalation                         
----------------------------------------------------------------------------------------------------------------
                                                                     Epoxybutene              Diepoxybutane     
                           Tissue                            ---------------------------------------------------
                                                                  Rats         Mice         Rats         Mice   
----------------------------------------------------------------------------------------------------------------
Blood.......................................................  361...............................................  0.2; n=3 or 4 for each determination.       
  Adapted from Ex. 118-13, Att. 3.                                                                              

    These data are shown in Table V-8.
    Seaton et al. examined the activities of cDNA-expressed human 
cytochrome P450 (CYP) isozymes for their ability to oxidize epoxybutene 
to diepoxybutane. (Ex. 118-7N) They also determined the rate of 
formation of the diepoxide by samples of human liver microsomes (n=10) 
and in mice and rat liver microsomes. Seaton et al. found that two of 
the cytochrome P450 isozymes, CYP2E1 and CYP3A4, catalyzed oxidation of 
80 uM of monoepoxide to detectable levels of diepoxide, and that CYP2E1 
catalyzed the reaction at higher levels of monoepoxide (5mM), 
suggesting the predominance of 2E1 activity at low substrate 
concentrations. Hepatic microsomes from all 3 species formed the 
diepoxide when incubated with the monoepoxide. Seaton et al. 
hypothesized that the difference between these results and those of 
Csanady et al. (who did not detect the diepoxide when the monoepoxide 
was substrate in a similar microsomal assay) was due to differences in 
experimental methodology.
    Seaton et al. noted a 25-fold variability in Vmax/Km among the 4 
human livers. They reported that Vmax/Km for oxidation of the 
monoepoxide to the diepoxide for the 4 human samples was 3.8, 1.2, 1.3 
and 0.15, while that of the pooled rat samples was 2.8, and the mouse 
ratio was 9.2.
    The authors, using available data, calculated an overall 
activation/detoxification ratio (Vmax/Km for oxidation of BD to the 
monoepoxide) taking into account hydrolysis of the monoepoxide by 
epoxide hydrolase and conjugation with glutathione. The activation/
detoxification ratio was estimated at 1295 for the mouse, 157 for rats 
and 230 for humans. However, Melnick and Kohn point out that ``when 
yields of microsomal and cytosolic protein content and liver size were 
considered, the activation to detoxification ratio was only 2.8 times 
greater in mice than in humans and 3.4 times greater in humans than in 
rats. These ratios do not take into account inter-individual 
variability in the activities of the enzymes involved.'' (Ex. 131)
    Recently, Seaton et al. studied production of the monoepoxide in 
whole airways isolated from mouse and rat lung. (Ex. 118-7C) They 
explained the impetus to use fresh intact tissue by stating that lung 
subcellular fractions, as employed in experiments by Csanady et al., 
described above, contained mixtures of cell type ``so that the 
metabolizing capacities of certain cell populations may have been 
masked.'' They anticipated that use of airway tissue would allow more 
precise quantitation of differences in lung metabolism of BD.
    Whole airways or bronchioles isolated from both male B6C3F1 
mice and male Sprague-Dawley rats were incubated for 60 min with 34 um 
BD. Levels of 10.45.6 nmol epoxybutene/mg protein were 
detected in mouse lungs, while 2-3 nmol/mg protein was observed in rat 
lung airway regions. Seaton et al. noted that while the species 
differences ``are not dramatic,'' they may in part contribute to the 
differences in carcinogenicity observed in mice and rats.
    To characterize conjugation of BD metabolites with glutathione 
(GSH), Boogard et al. prepared cytosol from lungs and livers of rats 
and mice and from 6 human donor livers and incubated them with 0.1 to 
100 mM diepoxide and labeled glutathione (GSH). (Ex. 118-7J) NMR 
(nuclear mass resonance) and HPLC techniques were used to characterize 
and quantitate conjugate formation.
    Non-enzymatic reaction was concluded to be negligible. The 
conjugation rates (Vmax) in mouse and rat livers were similar and 10-
fold greater than those observed in the human samples. The initial rate 
of conjugation (Vmax) was much higher in mouse than rat lung. Both 
rodent species exhibited higher initial rates of conjugation than 
human. This led Boogard et al. to conclude that the higher diepoxide 
levels observed in BD-exposed mice compared with rats ``are not due to 
differences in hepatic or pulmonary GSH conjugation of BDE (the 
diepoxide),'' and further that since humans oxidize BD to the epoxides 
at a low rate, the low activity of GSH conjugation of the diepoxide in 
human liver cytosol demonstrated in this study ``will not necessarily 
lead to increased BDE (diepoxide) levels in humans

[[Page 56776]]

potentially exposed to BD.'' They also pointed out the need to 
determine the rate of BDE detoxification by other means, specifically 
by epoxide hydrolase in all three species.
Studies of Urinary Metabolites of BD
    Two metabolites of BD have been identified in urine of exposed 
animals by Sabourin et al. (Ex. 118-13 Att. 3) These are 1,2-dihydroxy-
4-N-acetylcysteinyl-S-)-butane, designated MI, and MII, which is 1-
hydroxy-2-N-acetylcysteinyl-S-)-3-butene. (Ex. 118-13-Att. 3)
    These mercapturic acids are formed by addition of glutathione (GSH) 
at either the double bond (MI) or the epoxide (MII). MI is thought to 
form by conjugation of GSH with butenediol, the hydrolysis product of 
the monoepoxide, while MII is thought to form from conjugation of the 
monoepoxide with GSH.
    Sabourin et al. measured MI and MII in urine from rats, mice, 
hamster and monkeys. Mice were observed to excrete 3 to 4 times as much 
MII as MI, while the hamsters and rats produced about 1.5 times as much 
MII as MI. The monkeys produced primarily MI.
    The ratio of formation of metabolite I to the total formation of 
the two mercapturic acids, MI and MII, correlated well with the known 
hepatic epoxide hydrolase activity in the different species, suggesting 
that the monoepoxide undergoes more rapid conjugation with glutathione 
in the mouse than in the hamster or rats, and that the least rapid 
conjugation occurs in the monkey. The epoxide availability is inversely 
related to the hepatic activity of epoxide hydrolase, which removed the 
epoxide by hydrolysis.
    In 1994, Bechtold et al. published a paper describing a comparison 
of these metabolites between mice, rats, and humans.\4\ In workers 
exposed to historical atmospheric concentrations of 3 to 4 ppm BD, 
Bechtold measured urine levels of MI and MII by use of isotope-dilution 
gas chromatography, and found MI, but not MII, to be readily 
detectable. Bechtold et al. found that employees who worked in 
production areas (having 3-4 ppm BD exposure) could be distinguished by 
this assay from outside controls and that low level human exposure to 
BD resulted in formation of epoxide.
---------------------------------------------------------------------------

    \4\ A preliminary study on the human population of this study is 
described in the section of this preamble dealing with the genetic 
toxicology of BD exposure.
---------------------------------------------------------------------------

    Bechtold et al. stated in their abstract that since monkeys 
displayed a higher ratio of MI to MI + MII than mice did, and ``because 
humans are known to have epoxide hydrolase activities more similar to 
those of monkeys than mice, we postulated that after inhalation of 
butadiene, humans would excrete predominantly MI and little MII.'' (Ex. 
118-13 Att. 3) Their observations suggested that the predominant 
pathway for clearance of the monoepoxide in humans is by hydrolysis 
rather than conjugation with glutathione.
    Bechtold et al. found when mice and rats were exposed to 11.7 ppm 
BD for 4 hours and the ratio of the two metabolites was then measured, 
for mice, the ratio of MI to MI  MII (or the % of total 
which is MI) was 20%, that of rats was 52%, while humans exhibited more 
than 97% MI. These data also indicate the predominance of clearance by 
hydrolysis pathways rather than GSH conjugation in the human.
    Nauhaus et al. used NMR techniques to study urinary metabolites of 
rats and mice exposed to ([(1,2,3,4)-13C]-butadiene). (Ex. 118-7I) 
They characterized metabolites in mouse and rat urine following 
exposure by inhalation to approximately 800 ppm BD for 5 hours. Urine 
was collected over 20 hours from exposed and control animals, 
centrifuged and frozen.
    The findings of this study are quite extensive and are briefly 
summarized as follows. Nine metabolites were detected and chemically 
identified in mouse urine and 5 in that of rats. Five were similar in 
the 2 species, though differing markedly in concentration. One was 
unique to the rat and four to the mouse. Nauhaus et al. observed that 
``when normalized to body weight (umol/kg body weight), the amount of 
diepoxide-derived metabolites was four times greater in mouse urine 
than in rat urine.'' They further hypothesized that ``the greater body 
burden of (diepoxide) in the mouse and the ability of rats to detoxify 
[it] though hydrolysis may be related to the greater toxicity of BD in 
the mouse.'' Nauhaus et al. found that both mice and rats conjugated 
the monoepoxide with glutathione, but the rat preferentially conjugated 
at the two carbon, while the mouse preferentially conjugated at the one 
carbon. Additionally, the finding of a metabolite of 3-butenal, a 
proposed intermediate in the oxidation of BD to crotonaldehyde, an 
animal carcinogen, is suggestive of an alternative carcinogenic pathway 
for BD. In general, this study supports the in vitro findings of 
Csanady et al. who reported similar rates for BMO conjugation with 
glutathione between rats and mice. (Ex. 118-7AA)
Interaction of Butadiene With Other Chemicals
    Bond et al. described use of available data to simulate the 
potential interaction of BD with other workplace chemicals. (Ex. 118-
7V) Specifically they modeled potential interaction assuming 
competitive inhibition of BD metabolism by styrene, benzene and 
ethanol. The model predicted that co-exposure to styrene would reduce 
the amount of BD metabolized, but that because of its relative 
insolubility, BD would not effectively inhibit styrene metabolism. 
Benzene, which, like BD, is metabolized by P450/2E1, was also predicted 
to be a highly effective inhibitor of BD metabolism because of its 
solubility in tissues. The models predicted that ethanol would have 
only a marginal effect on BD metabolism at concentrations of BD 
``relevant to human exposure.''
    BD and styrene co-exposures often occur in the SBR industry and 
both are metabolized by oxidation to active metabolites, in major part, 
by cytochrome P450/2E1. To determine the metabolic effect of joint 
exposure to BD and styrene, Levans and Bond developed and compared two 
PBPK models, one with one oxidative pathway and competition between BD 
and styrene and the other with two oxidation pathways for both BD and 
styrene. (Ex. 118-7E) For model validation, Levans and Bond exposed 
male mice to mixtures of BD and styrene of 100 or 1000 ppm BD and 50, 
100 or 250 ppm styrene for 8 hours. They used chamber inlet and outlet 
concentrations to calculate uptake and, when steady-state was reached, 
calculated the rate of metabolism. They analyzed blood for styrene, 
styrene oxide, epoxybutene and diepoxybutane by GC-MS.
    Leavens and Bond found BD metabolism was inhibited when mice were 
co-exposed to styrene. The inhibition approached maximum value at co-
exposure concentrations of styrene above 100 ppm.
    The report also described the preliminary development of 
pharmacokinetic models to simulate the observed rate of BD metabolism 
in co-exposed mice. Their results supported the hypothesis that ``more 
than one isozyme of P450 metabolized BD and styrene and competition 
does not occur between BD and styrene for all isozymes.'' They were 
unable to accurately predict blood concentrations of styrene following 
exposure, and felt that `` perhaps the diepoxide may inhibit metabolism 
of styrene by competing for the same P450 enzyme.''

[[Page 56777]]

    Although preliminary in nature and reflecting effects of relatively 
high exposures, these observations of interactions between styrene and 
BD exposure may have implications for the observed pattern of BD-
induced effects in human populations jointly exposed. Specifically, the 
cancer effects seen in SBR production workers may underestimate the 
effects of BD with no styrene or benzene exposure.
Pharmacokinetic Modeling of BD Metabolism
    In a recent publication, Bond et al. reviewed the results of 
application of a number of physiologically-based pharmacokinetic (PBPK) 
dosimetry models. (Ex. 118-7M) They noted that three of the models 
which included monoepoxide disposition (Kohn and Melnick, Johanson and 
Filser, Medinsky) predicted that, for any BD exposure concentration, 
steady-state monoepoxide levels will be higher for mice than for rats. 
Bond et al. further observed that ``while the three models accurately 
predict BD uptake in rats and mice, they overestimate the circulating 
blood concentrations of (monoepoxide) in these species compared to 
those experimentally measured by Himmelstein.'' Their results also led 
Bond et al. to conclude that the disagreement between model predictions 
for the monoepoxide and experimental data suggests that the structure 
and/or parameter values employed in these models are not accurate for 
predicting blood levels of BD epoxides, and conclusions based on model 
predictions of BD epoxide levels in blood or tissue may be wrong.'' 
(Ex. 118-7M, p. 168) OSHA agrees with these authors that BD epoxide 
levels should not be used in assessing risk. In the discussion, the 
authors pointed to the need for inclusion of diepoxide toxicokinetics 
(as well as that of the monoepoxide) in future modeling exercises, 
since they believe the diepoxide to be the ultimate carcinogenic 
metabolite of BD.
    Kohn and Melnick, in a recent publication, used available data and 
attempted to apply a PBPK model to see whether it was consistent with 
observed in vivo uptake and metabolism. (Ex. 131) The model included 
compartments for rapidly and for slowly perfused tissues. Rate 
equations for monoepoxide formation, its hydrolysis, and for 
conjugation with glutathione were included.
    Kohn and Melnick acknowledged numerous sources of uncertainty in 
applying the model to the data (in which there are many gaps), 
necessitating various assumptions. Their calculations led them to 
conclude that the ``model reproduces whole-body observations for the 
mouse and rat'' and that it predicts that ``inhalation uptake of 
butadiene and formation and retention of epoxybutene are controlled to 
a much greater extent by physiological parameters than by biochemical 
parameters. . . `` (Ex. 131)
    When Kohn and Melnick interchanged the biochemical parameters in 
the mouse and human models to see if ``the differences in calculated 
net uptake of butadiene among the three species were due to differences 
in metabolic activity,'' they found that use of human parameters in the 
mouse model decreased the level of absorption of BD, but not to a level 
as low as that of the human. Kohn and Melnick noted that the model 
predictions of epoxybutene levels in the heart and lung of mice and 
rats failed to account for the observation that mice, but not rats, 
develop tumors at these sites. Kohn and Melnick suggested that factors 
other than epoxybutene levels, not accounted for in the model, are 
probably crucial to induction of carcinogenesis.
Conclusions
    Many metabolism studies have been conducted both in vitro and in 
vivo, mostly in mice and rats, to determine the BD metabolic, 
distribution, and elimination processes, and these studies have been 
extended in attempts to explain, at least in part, the greater 
carcinogenic potency of BD in the mouse, whether the mouse or the rat 
is a better surrogate for human cancer and reproductive risk 
assessment, and what is the proper dose-metric to use in dose-response 
assessments. The question of whether the mouse or the rat is a better 
model for the human on the basis of tumor response is partly addressed 
in the risk assessment section of this preamble. This section more 
specifically considers whether these metabolic studies in total can 
explain the different cancer responses and potencies observed in the 
mouse, rat, and human. What is clear throughout the record is that most 
scientists who study the topic consider not BD itself, but the major 
epoxide metabolites of BD, BMO and BDE and 1, 2-epoxybutane-3,4-diol, 
to be the putative carcinogenic agents. Most of this research has 
focused on the relative species production of BMO and BDE. Both BMO and 
BDO have been reported in early studies to be carcinogenic to mice and 
rats via skin application and/or subcutaneous injection, with BDO being 
somewhat more potent. (Ex. 23-88, Ex. 125).
    Metabolism of BD to BMO in both the liver and lung of mice, rats 
and humans is by the P450 oxidation pathway, with CYP2E1 and CYP1A6 
being the major enzymes. Based on the studies reviewed by OSHA, overall 
the mouse metabolizes BD to the monoepoxide and the diepoxide in these 
organs at a faster rate than do the rat and human. This is supported by 
the following evidence: (1) The mouse has higher BMO and BDE levels in 
blood, lung, and liver (i.e., see Ex. 118-7S, Ex. 118-7D, and Ex. 118-
13), which are the target organs for cancer in the mouse but not the 
rat; (2) the mouse has higher in vitro lung and liver microsome Vmax/Km 
ratios for both BD and BMO metabolism than do rats or humans (Ex. 118-
7AA); and (3) the mouse has higher hemoglobin-BMO adduct levels than 
rats and much higher levels than humans. (Ex. 118-7Y) A major exception 
to the findings of these studies is the study by Duescher and Elfarra, 
who found the in vitro BD Vmax/km ratios to be the same in mice and 
human liver microsomes and 3-4 times higher than they were in rats, 
suggesting that mice and humans have similar BD metabolic potential, at 
least in the liver. (Ex. 128) Large variations, about 60 fold, were 
found among 10 human liver microsome BD metabolic activities. (Ex. 118-
7N) A recent BD in vitro metabolism study by Seaton et al. on whole rat 
and mouse lung airway isolates found that the mouse produced about 
twice the amount of BMO as the rat (this difference could not explain 
the difference between mouse and rat tumor incidence). (Ex. 118-7C)
    BMO and BDE were also measured in heart, spleen, thymus, and bone 
marrow (target sites for mouse but not rat tumors) following 4 hour BD 
inhalation exposure (62.5 ppm) to mice and rats. (Ex. 118-13) In these 
tissues, mouse BMO and BDE levels were 3 to 55 fold higher than rat 
levels for the same metabolites, although the mice organ levels of 
these metabolites correlated poorly with the mouse target organ cancer 
response at this exposure level. Only high BDE levels in the mouse lung 
were consistent with the mortality adjusted cancer incidence (see 
hazard identification--animal studies section, Ex. 114). This suggests 
that BD metabolite tissue levels can, at best, only partly explain 
differences in carcinogenic response. Differences in both species and 
tissue sensitivity must also be accounted for.
    The Thornton-Manning and other studies also provided information 
about BD elimination. (Ex. 118-7I) With higher experimental exposure 
levels, the major route of elimination of BD is via expiration. 
Elimination of BMO occurs

[[Page 56778]]

by different pathways in different species and different organs. At 
higher BD exposure concentrations, some BMO is expired. The mouse liver 
and lung appear to eliminate BMO predominantly by direct conjugation 
with GSH 5. For the rat there is approximately equal elimination 
by the GSH and EH mediated pathways, while for the human and monkey 
hydrolysis to butanediol is the major pathway for excretion. ( Ex. 118-
13 Att. 3) This species elimination pathway difference is a partial 
explanation for the higher levels of both BMO and BDE seen in the 
mouse, assuming that most of the BD metabolism takes place in the 
liver. With respect to the bone marrow BD distribution and metabolism, 
mouse levels of the BD metabolites in the bone marrow were lower than 
at any of the other target organs studied. (Ex. 118-13) In vitro 
studies by Gentler and Recio have found no detectable P4502E1 in the 
bone marrow of B6C3F1 mice. (Ex. 118-7T) These authors conclude 
that this ``suggests that BD is converted to BMO outside of bone marrow 
and is subsequently concentrated in bone marrow, or that the conversion 
of BD to BMO occurs by an alternate enzymatic pathway within the bone 
marrow.'' The latter appears to be the more likely since Maniglier-
Poulet and co-workers showed that in vitro BD metabolism to BMO in both 
B6C3F1 mouse and human bone marrow occur by a peroxidase-mediated 
process and not via the P450 cytochrome system. (Ex. L-133) Since in 
their system both human and mouse bone marrow generated about the same 
amount of BMO/cell, this suggests that both BD distribution to bone 
marrow and local metabolic reactions should be considered in species-
to-species extrapolations and in PBPK modeling.
---------------------------------------------------------------------------

    \5\ One exception: Seaton et al. found evidence ``that in mouse 
airways hydrolysis of BMO by epoxide hydrolase (EH) contributes to 
BMO detoxification to a greater extent than does glutathione 
conjugation.'' (Ex. 118-7C)
---------------------------------------------------------------------------

    Inclusion of bone marrow local reactions becomes even more 
important when considering the animal species to use for modeling human 
cancer. BD is genotoxic in the bone marrow of mice, but not in rats. 
(Tice et al. 1987; Cunningham et al. 1986, reported in Ex. 131) BD and 
BMO have been implicated as affecting primitive hematopoietic bone 
marrow stem and progenitor cells related to both T-cell leukemia and 
anemia in the mouse. (Irons et al., 1993, in Ex. 117-2) BD causes 
lymphoma in mice, but no lymphoma or leukemia in rats even at 8,000 
ppm. Furthermore, the body of epidemiologic evidence strongly indicates 
that BD exposure poses an increased risk of human leukemia (see the 
epidemiologic section and especially Ex. 117-1).
    Fat storage of BD during exposure, and release following cessation 
of exposure, is also a major concern, both in estimating target organ 
levels and in determining species differences. There is little in the 
record on the effect of fat storage and release. In the Thornton-
Manning study discussed above, both mouse and rat fat levels of both 
BMO and BDE declined rapidly following cessation of exposure, 
suggesting little lingering effect. However, Kohn and Melnick present a 
model in which post-exposure release of BD from the fat would result in 
extended epoxide production in humans in contrast with the mouse. (Ex. 
131)
    Bond et al. suggest that the more rapid metabolism of BD to BMO in 
the mouse, and the more rapid EH BMO elimination pathways in the rat 
and human may be an explanation for lower, if any, BDE levels seen in 
rat and human liver microsomes and why BD will not be carcinogenic to 
humans at exposure levels seen in the environment or the workplace. 
(Ex. 130) They also conclude that ``Since significant tumor induction 
in male rats occurs only at 8000 ppm BD, BMO levels are probably not 
predictive of a carcinogenic response.'' Thornton-Manning et al. 
characterize the peak levels of BDE in the mouse lung and heart as 
being either greater than or equivalent to peak levels of BMO, and 
suggest ``that the formation of BDE may be more important than the 
formation of BMO in the ultimate carcinogenicity of BD.'' (Ex. 118-13) 
However, BMO levels in these organs were also quite high, and were 
higher than BDE levels in blood and bone marrow, target organs for 
hematopoietic system cancers. OSHA believes that the evidence is not 
sufficient to dismiss the potential contribution of BMO to mouse, rat 
or human carcinogenicity; to conclude that BDE should be considered 
more actively carcinogenic than BMO; or to find that BDE levels are 
sufficiently characterized in either mouse or human tissue to be used 
as the dose metric for BD human risk assessment.
    Thus, OSHA concludes, based on the body of metabolic and other 
evidence presented, and the above discussion, that the mouse is a 
suitable animal model for the human for BD cancer risk assessment 
purposes, and that metabolism of BD to active metabolites is probably 
necessary for carcinogenicity. However, while the uptake, distribution, 
and metabolism of BD to active carcinogenic agents are important, local 
BD metabolic reactions and specific species sensitivities appear to 
have at least as large an impact on BD potency in the various species. 
This is likely to be especially true in the human, whose metabolic 
processes appear to be much more variable with respect to BD. Thus, 
although the metabolism studies provide insight into BD's metabolic 
processes in various species and organs (with the possible exception of 
mouse lung tumorigenicity related to lung BDE levels and protein cross 
linking), OSHA finds that too many questions remain unanswered, both 
with PBPK modeling efforts and with actual in vivo measurements (and 
the lack of such measurements in humans) to base a quantitative risk 
assessment on BD metabolite level equivalence between mice and humans. 
(Ex. L-132)

VI. Quantitative Risk Assessment

A. Introduction

    In 1980, the United States Supreme Court ruled on the necessity of 
a risk assessment in the case of Industrial Union Department, AFL-CIO 
v. American Petroleum Institute, 448 U.S. (607), the ``Benzene 
Decision.'' The United States Supreme Court concluded that the 
Occupational Safety and Health (OSH) Act requires, prior to issuance of 
a standard, that the new standard be based on substantial evidence in 
the record considered as a whole, that there is a significant risk of 
health impairment at existing permissible exposure limits (PELs) and 
that issuance of the standard will significantly reduce or eliminate 
that risk. The Court stated that, before the Secretary of Labor can 
promulgate any permanent health or safety standard, he 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. (448 U.S. 642)
    In 1981, the Court's ruling on the OSHA's Cotton Dust Standard 
(American Textile Manufacturers Institute v. Donovan, 452 U.S. 490 
(1981)) reaffirmed its previous position in the Benzene Decision, that 
a risk assessment is not only appropriate, but that OSHA is required to 
identify significant health risk to workers and to determine if a 
proposed standard will achieve a reduction in that risk, and OSHA as a 
matter of policy agrees that assessments should be put into 
quantitative terms to the extent possible.
    For this rulemaking, OSHA has conducted a quantitative risk 
assessment to estimate the excess risk for cancer and consequently for 
premature deaths associated with

[[Page 56779]]

exposure to an 8-hour time-weighted-average (TWA), 5 days/week, 50 
weeks/year, 45-year exposure to BD at concentrations ranging from 0.1 
to 5 ppm, the range of permissible exposure limits (PELs) considered by 
OSHA in this rulemaking. The data used in the quantitative risk 
assessment were from a National Toxicology Program (NTP) chronic 
inhalation study in which B6C3F1 mice of both sexes were 
exposed to either ambient air or BD exposure concentrations ranging 
from 6.25 to 200 ppm, known as NTP II. (Ex. 90) For seven gender-tumor 
site combinations, multistage Weibull time-to-tumor models were fit to 
these NTP II data. The best fitting models were chosen via a log-
likelihood ratio test.
    OSHA's maximum likelihood estimate (MLE) of the excess risk of 
developing cancer and subsequent premature death as a result of an 8-
hour TWA occupational lifetime exposure to 2 ppm BD, the PEL proposed 
by OSHA in 1990, was 16.2 per 1,000 workers, based on the most 
sensitive gender-tumor site combination, female mouse lung tumors. If 
the occupational lifetime 8-hour time-weighted-average (TWA) exposure 
level is lowered to 1 ppm BD, based on female mouse lung tumors, the 
estimate of excess cancer and premature death drops to 8.1 per 1,000 
workers. In other words, an 8-hour TWA lifetime occupational exposure 
reduction from 2 ppm to 1 ppm BD would be expected to prevent, on 
average, 8 additional cases of cancer and probable premature deaths per 
1,000 exposed workers. Based on the individual tumor site dose-response 
data, which were best characterized by a 1-stage Weibull time-to-tumor 
model, (male-lymphoma, male-lung, female-lymphoma and ovarian), on 
average, one would expect there to be between 1 and 6 fewer excess 
cases of cancer per 1,000 workers based on a 8-hour TWA occupational 
lifetime exposure to BD at 1 ppm versus BD at 2 ppm. Estimates of 
leukemia deaths at the former 8-hour TWA PEL of 1,000 ppm of BD, for an 
occupational lifetime, are not presented because contemporary BD 
exposures are generally far lower than this level.

B. Assessment of Carcinogenic Risk

1. Choice of Data Base for Quantitative Risk Assessment
    The choice of data provides the platform for a quantitative risk 
assessment (QRA). Either animal studies which evaluate the dose-
response relationship between BD exposure and tumorigenesis or 
epidemiological dose-response data may be suitable sources of data.
    Estimates of the quantitative risks to humans can be based on the 
experience of animals from a chronic lifetime exposure study. Chronic 
lifetime inhalation bioassays with rats and mice generally last 2 years 
or two-thirds of the lifespan of the animal. (Ex. 114) These types of 
studies provide insight into the nature of the relationship between 
exposure concentration, duration and resulting carcinogenic response 
under a controlled environment. Furthermore, some researchers have 
estimated a variety of measures of dose of BD, including inhaled and 
absorbed dose as well as BD metabolites, to estimate human risks based 
on the observed dose-response relationship of animals in a bioassay; 
the form of the dose used in a dose-response analyses is called the 
dose-metric.
    The carcinogenicity of lifetime inhalation of BD was studied in 
Sprague-Dawley rats by the International Institute of Synthetic Rubber 
Producers (IISRP) and in B6C3F1 mice by the National 
Toxicology Program. The IISRP sponsored a two-year inhalation bioassay 
of Sprague-Dawley rats performed at Hazelton Laboratories Europe (HLE). 
(Ex. 2-31) Groups of 110 male and female Sprague-Dawley rats were 
exposed for 6-hours per day, 5 days per week to 0, 1,000, or 8,000 
parts per million (ppm) of BD. The males were exposed for 111 weeks and 
the females for 105 weeks. Statistically significant increased rates of 
tumors were found in both male and female rats. Among exposed male 
rats, there were increased occurrences of pancreatic and testicular 
tumors and among the exposed female rats there were higher incidence 
rates of uterine, zymbal gland, mammary and thyroid tumors than in the 
control groups.
    The National Toxicology Program (NTP) has performed two chronic 
inhalation bioassays using B6C3F1 mice. (Ex. 23-1; 90; 
96) The first study, NTP I, was intended to be a two-year bioassay, 
exposing groups of 50 male and female mice to 0, 625, or 1,250 ppm of 
BD for a 6-hour day, 5 days/week. The study was prematurely curtailed 
at 60 weeks for the males 61 weeks for the females caused by an 
unusually high cancer mortality rate due to malignant neoplasms in 
multiple organs. Despite some weaknesses in the way the study was 
conducted, the results of this study show that BD is clearly 
carcinogenic in these mice, with statistically significant increases in 
malignant lymphomas, heart hemangiosarcomas, lung tumors, and 
forestomach tumors in comparison to the controls for exposed male and 
female mice. (Ex. 90)
    The second NTP BD chronic inhalation bioassay, NTP II, had groups 
of 70 (except for the group exposed to the highest concentration, which 
contained 90) male and female mice exposed to concentrations of 0, 
6.25, 20, 62.5, 200 and 625 ppm for 6 hours/day, 5 days/week for up to 
104 weeks. The NTP II bioassay provided lower exposures, closer to 
prevailing occupational exposure levels, than the NTP I and HLE chronic 
inhalation studies. The NTP II supported the pattern of carcinogenic 
response found in NTP I. Both male and female mice exposed to BD 
developed tumors at multiple sites including: lymphomas, heart 
hemangiosarcomas, and tumors of the lung, liver, forestomach, and 
Harderian gland (an accessory lacrimal gland at the inner corner of the 
eye in animals; they are rudimentary in man). Reproductive tissues were 
also adversely affected. Among the exposed males there were significant 
increases in tumors of the preputial gland; among females there were 
significant increases in the incidence of ovarian and mammary tumors.
    In 1996, a retrospective cohort study by Delzell and co-workers of 
about 18,000 men who worked in North American synthetic rubber plants 
was submitted to OSHA. (Ex. 117-1) In this study researchers derived 
estimates of occupational exposure to BD using a variety of resources, 
such as work histories, engineering data, production notes, and 
employees' institutional memories. In their October 2, 1995 report Dr. 
Delzell et al., characterized their effort as follows:

    Retrospective quantitative exposure estimation was done to 
increase the power of the study to detect associations and to assist 
with the assessment of the impact of specific exposure levels on 
mortality from leukemia and  other  lymphopoietic  cancers.  (Ex.     
117-1)

In April 1996, Dr. Delzell expressed concern with possible 
discrepancies between estimated cumulative exposures and actual 
measurements. (Ex. 118-2) OSHA believes that in a well-conducted study, 
retrospective exposure estimates can be reasonable surrogates for true 
exposures; misclassifications or uncertainty can decrease the precision 
of the risk estimates derived from such a study, but the problem must 
be severe and widespread to invalidate the basic findings.
    At the time of publication of the proposed standard on occupational 
exposure to BD (August 1990), only the NTP I mouse and HLE rat 
bioassays were available for quantitative risk assessments (QRA). 
Presented in Table

[[Page 56780]]

V-9 is an overview of authorship and data sets used in the various QRAs 
submitted to the OSHA docket. With one exception, the rest of the QRA's 
in the BD Docket have relied on animal chronic exposure lifetime 
bioassays. Each of the five risk assessments discussed in the proposal 
based its quantitative risk assessment on one or both of the higher-
exposure chronic bioassays (exposure groups exposed to BD 
concentrations ranging between 625-8,000 ppm). (Exs. 17-5; 17-21; 23-
19; 28-14; 29-3; 32-27) The three QRAs conducted using bioassay data 
subsequent to the publication of the NTP II study used NTP II data with 
exposures of 6.25-625 ppm BD, closer to actual occupational exposures, 
for calculating their best estimates of risk. (Exs. 90; 118-1b; 32-16)
    A summary of each of the ten QRA's follows:

    Table V-9.--Summary Table of Quantitative Risk Assessments (QRAs) In Order of Their Review in the OSHA BD   
                                                    Standard                                                    
----------------------------------------------------------------------------------------------------------------
           Exhibit                             Author                                   Data-set                
----------------------------------------------------------------------------------------------------------------
90..........................  National Institute for Occupational       NTP II a bioassay (preliminary).        
                               Safety and Health (NIOSH) (Preliminary).                                         
118-1b......................  NIOSH...................................  NTP II bioassay.                        
118-1.......................  NIOSH...................................  Delzell et al. epidemiological study.   
17-21.......................  United States EPA Carcinogen Assessment   NTP I b and HLE c bioassays;            
                               Group (CAG).                              Epidemiological based on Fajen Exposure
                                                                         Data.                                  
32-27.......................  California Occupational Health Program    NTP I; HLE bioassays Epidemiological    
                               (COHP) of the California Department of    based on Fajen Exposure Data           
                               Health services (CDHS).                                                          
32-16.......................  Shell Oil Corporation...................  NTP I, NTP II and HLE bioassays.        
17-5........................  United States EPA Office of Toxic         NTP I bioassay.                         
                               Substances (OTS).                                                                
23-19.......................  ICF/Clement Inc.........................  NTP I bioassay.                         
29-3........................  Center for Technology, Policy, and        NTP I and HLE bioassays.                
                               Industrial Development at the                                                    
                               Massachusetts Institute of Technology.                                           
28-14.......................  Environ Inc.............................  HLE bioassay.                           
----------------------------------------------------------------------------------------------------------------
a NTP II, The National Toxicology Program, Technical Report 434, 2-year bioassay of B6C3F1 mice to 5 exposure   
  groups receiving between 6.25 and 625 parts per million (ppm) of BD                                           
b NTP I, The National Toxicology Program, prematurely terminated longtime bioassay of B6C3F1 mice to 2 exposure 
  groups receiving either 625 or 1,200 ppm of BD                                                                
c HLE, Hazelton Laboratories Europe's, lifetime bioassay of Sprague Dawley rats, exposed groups received 1,000  
  ppm of BD or 8,000 ppm of BD                                                                                  

NIOSH-Quantitative Risk Assessments based on NTP II
    In the early 1990's, two QRAs were conducted sequentially by the 
National Institutes for Occupational Safety and Health (NIOSH). One was 
a preliminary and the other a final, with the latter using final 
pathology data for histiocytic sarcomas and one particular type of 
lymphoma from NTP II. In 1991, NIOSH submitted a preliminary QRA using 
the then preliminary NTP II tumor pathology data for various individual 
organ sites (8 from the female mice and 6 from the male mice) to 
estimate excess cancer risk at different BD exposures over an 
occupational lifetime. (Ex. 90) For all gender-tumor site analyses, 
NIOSH excluded the 625 ppm exposure group in its best estimate of risk 
since the plethora of competing tumors 6 in this high exposure 
group provide less information for a dose-response analysis of 
individual tumor sites than do data from some of the lower exposure 
groups. Another reason for the exclusion was that the dose-time-
response relationship in mice is saturated for exposures above 500 ppm 
and the data would thus provide very little additional information for 
low dose extrapolation. NIOSH's QRA relied on an allometric conversion 
of body weight to the three-quarters power, (mg/kg)\3/4\, and equated a 
900-day-old mouse to a 74-year old human. To avoid duplication of 
risks, NIOSH presented only maximum likelihood estimates based on the 
aggregate of all types of lymphomas even though dose-response data were 
also available for the lymphocytic lymphoma subset.
---------------------------------------------------------------------------

    \6\ Competing tumors refers to the lack of opportunity of a 
later developing tumor to express itself due to the occurrence of 
early developing lethal tumor; Among the 625 ppm exposure group 
lymphocytic lymphomas were mortal early developing tumors which 
prevented later developing disease such as heart hemangiosarcomas 
from possibly developing.
---------------------------------------------------------------------------

    Of the fourteen gender-tumor site data sets NIOSH modeled to 
extrapolate animal data to humans, 12 (86%) yielded excess risks 
greater than 2 cancer deaths per 1,000 workers, given an 8-hour TWA 
lifetime occupational exposure of 1 ppm BD. Estimates of excess risks 
to workers based on the best fitting models for each of the six dose-
time-response relationships for male tumor sites were between 0.4 and 
15.0 per 1,000 workers assuming an 8-hour TWA, 45 year occupational 
exposure to 1 ppm BD. Among estimates based on male mice's dose-
response data, the lowest and highest excess risk estimates were from 
the heart hemangiosarcoma and Harderian gland dose-response 
relationships, respectively. For estimates of excess risk based on 
either gender's set of individual tumor dose-response relationships, 
only the heart hemangiosarcoma data predicted a risk of less than 1 per 
1,000 workers with an occupational lifetime exposure of 1 ppm: these 
data predicted 0.4 and 3 x 10-3 excess cancer cases per 1,000 
workers based on the best fitting models for male and female mice, 
respectively.
    Based on tissue sites in females, the excess risk estimates for 8-
hour TWA occupational lifetime exposure to 1 ppm BD range between 4 and 
31 per 1,000 workers.
    NIOSH presented its findings for lifetime exposure to 2 ppm as 
follows:

    Based on tumors at the most sensitive site, the female mouse 
lung [assuming (mg/kg)\3/4\ conversion], our maximum likelihood 
estimates of the projected human increased risk of cancer due to a 
lifetime occupational exposure to BD at a TWA PEL of 2 ppm is 
approximately 60 in 1,000 (workers). (Ex. 90)

    For the linear models, if scaling were on a (mg/kg) basis rather 
than the (mg/kg)\3/4\ used by NIOSH for allometric conversion, the 
revised estimate of excess cancer risk for an 8-hour TWA occupational 
lifetime exposure to 2 ppm BD would decrease approximately 6 fold to 
9.2 per 1,000 workers based on the same female mouse lung tumor data.
    In 1993, NIOSH finalized its estimates of excess risk caused by 
occupational exposure based on the tumorigenesis

[[Page 56781]]

experience of mice in the NTP II study. (Ex. 118-1B) The rounded 
maximum likelihood estimates (MLE) from the final QRA are presented in 
Table V-10. NIOSH expanded the gender-tumor sites to include 
histiocytic sarcoma for both male and female mice. NIOSH chose to 
present only its risk estimate based on lymphocytic lymphoma, rather 
than an assessment based on the aggregate of lymphomas. In the 
preliminary and final NIOSH QRAs, 1-stage time-to-tumor models'' 
rounded estimates of risk associated with lifetime exposure to 1 ppm BD 
ranged from 1 to 30 excess cancer cases per 1,000 workers, with 
estimates based on the male-lymphocytic lymphoma and the female-lung 
dose-response data providing the lower and upper ends of the range of 
risk, respectively.
    As part of its sensitivity analyses, NIOSH derived the estimates of 
risk based on (1) equating a human lifespan to a mouse equivalent age 
of 784 days, a figure OSHA has used, and (2) equating a human lifespan 
to a mouse lifespan of 900 days (a figure more often used by NIOSH.) 
The best estimates of risk equating human lifespan to a mouse lifespan 
of 784 days were lower, by about one-third, than those assuming a human 
lifespan equivalency to 900 days for the mouse, all else held constant.

    Table V-10.--NIOSH's a Final Quantitative Risk Assessment's (QRA)   
 Maximum Likelihood Estimates (M.L.E.s) b per 1,000 Workers of Lifetime 
 Excess Risk Due to an Occupational c Exposure to 1 ppm of BD Using Best
Fitting Models, as Designated by Number of Stages of the Weibull Time-to-
                               Tumor Model                              
------------------------------------------------------------------------
                                                         MLE, Final QRA 
                   Gender-tumor site                        (Stages)    
------------------------------------------------------------------------
Male mouse:                                             ................
    Forestomach.......................................          0.03 (2)
    Harderian gland...................................            10 (1)
    Heart hemangiosarcoma.............................           0.5 (2)
    Histiocytic sarcoma...............................             8 (1)
    Liver.............................................             4 (1)
    All Lymphoma......................................                NA
    Lymphocytic lymphoma..............................           0.9 (1)
    Lung..............................................            10 (1)
Female mouse:                                           ................
    Forestomach.......................................             5 (1)
    Harderian Gland...................................             7 (1)
    Heart hemangiosarcoma.............................      3 x 10-3 (3)
    Histiocytic sarcoma...............................            10 (1)
    Liver.............................................             7 (1)
    All lymphoma......................................                NA
    Lymphocytic lymphoma..............................             9 (1)
    Lung..............................................            30 (1)
    Mammary...........................................             4 (1)
    Ovarian...........................................            9 (1) 
------------------------------------------------------------------------
a Based on NTP II, excluding the 625 ppm exposure category, equating a  
  900-day-old mouse to a 74-year old human and assuming an allometric   
  conversion of (mg/kg)3/4.                                             
b Rounded to one significant figure.                                    
c Occupational lifetime is an 8-hour time-weighted-average, 40-hours per
  week, 50-weeks per year, time-weighted-average (TWA) for 45-years.    

The Carcinogen Assessment Group QRA
    The Carcinogen Assessment Group (CAG) and the Reproductive Effects 
Assessment Group of the Office of Health and Environmental Assessment 
at the United States Environmental Protection Agency (EPA) also 
conducted an assessment of the mutagenicity and carcinogenicity of BD. 
(Ex. 17-21) In its quantitative risk assessment, CAG used both male and 
female response data from the two chronic bioassays available at the 
time, NTP I with B6C3F1 mice and the HLE Sprague Dawley 
rat study. The CAG analysis is based on EPA's established procedures 
for quantitative risk analyses, which fit the total number of animals 
with significantly increased or highly unusual tumors with the 
linearized multistage model and use the upper 95% confidence interval. 
Mice dying before week 20 and rats dying during the first year of the 
study (before the observation of the first tumor) were eliminated from 
the analysis to adjust for non-tumor differential mortality.
    The dose-metric was based on a preliminary report by the Lovelace 
Inhalation Toxicology Research Institute of its six-hour exposure study 
in B6C3F1 mice and Sprague Dawley rats at different 
concentrations of BD, roughly corresponding to the concentrations used 
in NTP I and HLE, with total internal BD equivalent dose expressed as a 
function of inhalation exposure concentration. Then CAG estimated the 
amount and percent of BD retained for various exposure concentrations 
in these bioassays. These internal dose-estimates were then 
extrapolated to humans based on animal-to-human ppm air concentration 
equivalence.
    CAG adjusted risk estimates from the mouse study by a factor of 
(study duration/lifetime) \3\ to account for less-than-lifetime 
observations, since the NTP I study was prematurely terminated at 60 
weeks for males and 61 weeks for females due to predominating cancer 
mortality. CAG extrapolated the short lifespan mouse data to an 
expected mouse lifetime, 104 weeks, in order to estimate lifetime risk 
to humans.
    CAG estimated all risks based on continuous exposure to BD, 24 
hours per day, 365 days per year, for a 70-year lifetime. The 
incremental unit risk estimates for the female mouse were about eight 
times as high as those for the female rat; for the males, the 
incremental unit risk estimate for mice was about 200 times as high as 
for rats. The CAG final incremental unit risk estimate of 0.64 
(ppm)-1 is based on the geometric mean of the upper-limit slope 
estimates for male and female mice and would predict an upper limit of 
640 excess cancers per 1,000 people exposed to 1 ppm continuously 
throughout their lifetime, 70 years. Extrapolating this same estimate 
to an equivalent 45-year working lifetime of 240 work days per

[[Page 56782]]

year at an 8-hour TWA exposure to 1 ppm BD would yield an upper-limit 
risk estimate of 90 excess cancers per 1,000 workers. If the working 
day is assumed to require one-half (10m \3\) the daily tidal volume, 
the total amount of air inhale, the excess would be 135 cancers per 
1,000 workers.
California Occupational Health Program (COHP) QRA
    In 1990, five years after the CAG conducted its quantitative risk 
assessment, the California Occupational Health Program (COHP) produced 
its estimates of risk with a similar assessment of the carcinogenicity 
of BD, using the same available bioassays, with more recent information 
on BD risk in humans, pharmacokinetic (PK) modeling, and animal low 
exposure absorption efficiency. (Ex. 32-16) Using three separate dose-
metrics for each bioassay and multistage models to characterize the 
basic dose-response relationship, CAG presented several quantitative 
estimates of incremental lifetime unit risks. Quantal lifetime response 
multistage models were fit to the data. COHP, like NIOSH, used the 
individual data with a multistage Weibull time-to-tumor model to 
characterize the dose response relationship. COHP stated that it also 
fit Mantel-Bryan and log-normal models to the data, and that the 
multistage models gave a better fit; the results obtained with these 
other models were not reported.
    COHP performed calculations on each primary tumor site separately, 
and also did calculations on the pool of primary tumors that showed 
significantly increased tumor incidences. For their main dose-metric, 
COHP refined the CAG approach, using a revised estimate of low-exposure 
absorption via inhalation. COHP also included an estimate of the PK 
model derived BD monoepoxide metabolites, but de-emphasized their use 
by stating that these were ``presented for comparative purposes only.'' 
The third dose-metric was straight ppm for animal-to-human species 
conversion (adjusting for duration of exposure). COHP stated:

(COHP) followed standard EPA practice and assumed that a certain 
exposure concentration in ppm or mg/m 3 in experimental animals 
was equivalent to the same exposure concentration in humans. (Ex. 
32-16)

Like CAG, COHP also adjusted for less than lifetime survival in the NTP 
I mouse study, by using a cubic power of time, (study duration/
lifetime) \3\. COHP's potency estimate adjustment for the male mouse 
study with 60-week survival was 5.21; for the 61-week female mouse 
survival the adjustment was 4.96.
    With all the combinations of sites, species, sexes, models, and 
dose-metrics, COHP presented over 60 potency estimates for the rat and 
over 100 for the mouse. As with the CAG and other analyses, the 
estimates based on NTP I were typically one to two orders of magnitude 
greater than those based on the rat for similar dose-metrics, models 
and total tumors. COHP chose the estimates based on the male mouse as 
final indicators of human risk based on the ``superior quality of the 
mouse study.'' From these estimates, using the quantal form of the 
multistage model, COHP chose ``the upper bound for plausible excess 
cancer risk to humans.'' COHP's final cancer potency estimate of 0.32 
(ppm)-1 presented in units of continuous lifetime exposure, is 
based on all significant tumors in the male mouse and uses the internal 
BD equivalent dose conversion factor of 0.54 mg/kg-d/ppm for the mouse 
and animal-to-human ppm equivalency. COHP's final potency estimate was 
one-half the value of 0.64 (ppm)-1 calculated by the CAG; the 
difference is due mainly to a low exposure absorption modification by 
COHP. The continuous lifetime exposure potency factor converts to a 
working lifetime risk of 45 to 67 excess cancers per 1,000 workers, 
exposed to 1 ppm of BD at an 8-hour TWA over a 45 year working 
lifetime.
    COHP, like CAG, attempted to determine whether its animal-based 
risk extrapolation could predict the leukemia mortality observed in 
epidemiology studies. Following the approach employed by CAG in its 
analyses of the Meinhardt (1982) study, the COHP compared its estimates 
of risk from bioassays to the then most recent epidemiological studies 
of Downs et al. (1987) and Matanoski and Schwartz (1987). Both COHP and 
CAG used MLEs based on mouse lymphoma for comparing the animal-derived 
potency estimates with the occupational response. In addition, neither 
COHP nor CAG used the upward adjustment factor of approximately 5 to 
correct for the less-than-lifetime duration of NTP I. Because neither 
of these epidemiology studies (Downs et al. (1987) or Matanoski and 
Schwartz (1987)) had recorded exposure estimates, the COHP relied on 8-
hr TWA estimates of 1 and 10 ppm taken at different but similar plants 
reported by Fajen et al. (1986). For lifetime unit risk estimates, COHP 
used the initial MLE of 0.0168 (ppm)-1 derived from the male mouse 
lymphoma analysis, unadjusted for less-than-lifetime survival. This 
part of the analysis also assumed that a lymphocytic outcome in the 
animals would equate to leukemia death in humans. These assumptions 
yielded a range of 6 to 21 predicted lymphocytic cancer deaths (for 1 
and 10 ppm exposures) versus the 8 observed by Downs et al.
Office of Toxic Substances (OTS) QRA
    The Office of Toxic Substances (OTS), U.S. Environmental Protection 
Agency (EPA) conducted a quantitative risk assessment using only the 
NTP I data. (Ex. 17-5) The reasons cited for this choice include: (1) 
The mouse is a more sensitive test species for BD than the rat; (2) a 
quality control review had been done for the mouse bioassay at the time 
OTS wrote its risk assessment whereas none was available for the rat 
bioassay; (3) greater amount of histopathological data was available 
for the NTP I study than for the HLE rat study; and (4) the type of BD 
feedstock used by NTP I had a much lower dimer concentration than the 
BD used by HLE (increased dimer concentration results in the lowering 
of availability of BD for metabolism to the mono- and di-epoxides, 
which are thought to be the carcinogenic agents). To compensate for 
early termination of the NTP I study, OTS adjusted dose by a factor of 
(study duration/lifetime).\3\ Butadiene ppm exposure concentration was 
used as the measure of dose and mouse-to-human species extrapolation 
was also on a ppm equivalence basis. OTS estimated cancer risks based 
on heart hemangiosarcoma and pooled tumors (grouping of sites showing 
statistically significant elevated incidence rates) tumors using a 1-
stage quantal model. Workplace exposures to BD were converted to 
estimated lifetime average daily doses. Since the NTP I study was 
curtailed at 61 weeks, tumor incidence rates were adjusted for survival 
by life-table methods. Cancer risks were based on administered dose of 
BD and not delivered dose to various target organs. (Ex. 17-5) 
Estimated 95% upper confidence-limits for the excess risk of cancer 
from an occupational lifetime exposure to an 8-hour TWA of 1 ppm BD, 
for 240 days/year for 40 years, ranged between 10 and 30 per 1,000 
workers, based on pooled tumor incidence for female and male animals, 
respectively.
ICF/Clement Estimates
    In 1986, ICF/Clement (ICF) estimated the risk of cancer associated 
with occupational exposure to BD. (Ex. 23-19) ICF determined that only 
the NTP I data were suitable for a risk assessment based on animal 
data, (NTP II data were not available at that time) based on ICF/

[[Page 56783]]

Clement's concern over the discrepancies between HLE's summary 
statistics and individual counts. ICF chose to use individual tumor 
type data for some of its analyses. ICF fitted a linearized multistage 
quantal model to the NTP I data. Based on a preliminary study by Bond 
(a senior toxicologist at the Chemical Industry Institute of 
Toxicology), ICF adjusted the NTP I exposure concentrations for percent 
retention which varied inversely from 100% at 1 ppm to 5% at 1,000 ppm.
    ICF assumed ppm as the proper dose-metric and ppm to ppm for the 
mouse-to-human species extrapolation factor. (Exs. 23-86; 23-19) The 
95% upper confidence limit estimates of risk based on pooled female 
tumor data with a lifetime occupational exposure was 200 per 1,000 
workers at 1 ppm BD, and 400 per 1,000 workers at 5 ppm BD; the non-
proportionality reflects the assumption of lower percentage retentions 
at higher concentrations.
Massachusetts Institute of Technology (MIT) QRA
    Hattis and Wasson at the Center for Technology, Policy, and 
Industrial Development at MIT conducted pharmacokinetic/mechanism-based 
analyses of the carcinogenic risk associated with BD. (Ex. 29-3) The 
analyses include both HLE and NTP I data. Key elements, such as 
partition coefficients for blood/air and tissue/blood, were not 
available to be measured and had to be estimated. The best estimate of 
excess risk of cancer given a lifetime occupational exposure of 1 ppm 
BD 8-hr TWA was 5 per 1,000 workers based on the NTP I female mouse 
data set, incorporating pharmacokinetic models which set the blood/air 
partition coefficient to 0.2552. Based on the HLE female rat data with 
a blood/air partition coefficient of 0.2552, an excess risk was 
estimated to be 0.4 additional cases of cancer for every 1,000 workers 
at an 8-hour TWA, occupational lifetime exposure to 1 ppm BD.
Environ QRA
    Environ conducted a quantitative risk assessment based on the HLE 
rat bioassay data. (Ex. 28-14) Environ noted that the relatively high 
BD concentrations of the earlier bioassays (HLE with groups exposed to 
8,000 and 1,000 ppm BD and NTP I with exposures of 1,250 and 625 ppm 
BD) made it difficult to extrapolate risks to the relevant, lower 
exposure levels of BD in occupational settings. Environ stated that 
among B6C3F1 mice, metabolic saturation occurs with 8-
hour TWA BD concentrations greater than 500 ppm; thus, the time-dose-
response relationship is different at higher doses than at lower doses. 
Environ stated that the methodological problems and the high early 
mortality shown in the NTP I data contributed to the uncertainty of its 
relevance to human risks and therefore chose to use the HLE rat 
bioassay data instead. Environ believes that human metabolism of BD is 
more similar to that in the Sprague-Dawley rat than in the 
B6C3F1 mouse. Extrapolated risks were based on estimates 
of absorbed dose, expressed in mg/kg, as defined in the Bond et al. 
(1986) absorption study. (Ex. 23-86)
    Environ used the HLE female rats to estimate the extra lifetime 
risk of developing cancer given an occupational lifetime 8-hr TWA 
exposure to 1 ppm BD. Using MLEs from multistage, Weibull, and Mantel-
Bryan models, based on the total number of female rats with 
significantly increased tumors, Environ's predicted occupational 
lifetime risks were 0.575 (Multistage), 0.576 (Weibull), and 0.277 
(Mantel-Bryan) per 1,000 workers.
Shell Oil Company QRA
    Shell Oil Company estimated excess cancer risks by the multistage 
quantal and the Weibull time-to-tumor models based on female heart 
hemangiosarcomas and pooled malignant tumors from the NTP II study. 
Shell estimated human risks based on various assumptions, correcting 
for BD retention and/or relative human epoxide dose. Shell stated that 
the Weibull time-to-tumor model better characterized risks since it was 
able to fully utilize available dose-response data, including time 
until onset of tumors and latency (time from initiation until detection 
of tumor). (Ex. 32-27) Shell used

    * * * crude time-to-tumor data consisting of early deaths to 40- 
weeks, 40-week interim sacrifices, deaths to 65- weeks, 65-week 
interim sacrifices, death to 104- weeks and terminal sacrifices * * 
* in-lieu of individual animal data [for NTP II data]. (Ex. 32-27)

OSHA believes that the true dose-response relationship is obscured by 
Shell's use of crude time-to-tumor data and its grouping of early 
deaths to 40 weeks, deaths to 65 weeks and deaths to 104 weeks; 
instead, dose-time-tumor response data for each individual mouse should 
have been used.
    Shell did not explain why it chose one model over the other. For 
example, without explanation, Shell dropped the highest exposure group, 
625 ppm, when estimating lifetime occupational risk for all of its 
Weibull time-to-tumor models and dropped additional dose groups when 
using some multistage quantal models. Moreover, estimates of excess 
risk were presented only for 5-stage Weibull time-to-tumor models, 
although there is no discussion of correct model specifications. For 
example, no reasons are given for choosing the 5-stage model rather 
than another. Also, Shell does not support its estimation that the 
latency between the induction of a tumor and its observation is for the 
pooled female mice malignant tumors and 40-weeks for the female mice 
heart hemangiosarcomas.
    Based on the Shell analyses, extrapolating from pooled malignant 
female mice tumors, assuming 10% human BD retention efficiency at 2 
ppm, and on a 5-stage Weibull time-to-tumor model, one would expect 18 
excess cancers per 1,000 workers given an 8-hour TWA occupational 
lifetime exposure of 2 ppm BD. Based on the same data set, but assuming 
a mouse-to-human species conversion factor based on an epoxide ratio of 
590 (mouse-to-monkey) in addition to a 10% BD retention efficiency 
factor, the estimate of excess risk of cancer drops to 0.3 cases per 
1,000 workers with an 8-hour TWA occupational lifetime exposure of 2 
ppm. Using the same pooled malignant female mice tumors, but assuming 
the blood epoxide estimates of the Dahl et al. study and an 8-hour TWA 
lifetime occupational BD exposure of 2 ppm, the estimate of excess risk 
of cancer is slightly lower, 0.24 per 1,000 workers. The excess risk 
estimates based on female hemangiosarcomas and a 5-stage Weibull time-
to-tumor model and occupational lifetime exposure to 2 ppm of BD were: 
(a) 6.4 x 10-8 (assuming a 10% BD retention factor); (B) 
6.2 x 10-15 (assuming a 10% BD retention factor and an epoxide 
ration of 590); and (c) 1.3 x 10-11 (assuming the blood epoxide 
estimates of the Dahl et al. study).
    Shell also presented the Environ Inc. QRA based on the HLE Sprague-
Dawley rat bioassay and made similar adjustments for BD retention and 
blood epoxide to those it made for the NTP II B6C3F1 
mice data. As had Environ, Shell stated that the dose- response of the 
rat is more relevant than that of the mice in predicting risk in 
humans. Shell concluded that the risk estimates derived from HLE 
Sprague Dawley rat data should be given greater weight than those based 
on the B6C3F1 mouse data.
NIOSH's QRA Based on the Delzell et al. Study
    NIOSH estimated the excess risk of workers developing leukemia 
based on the Delzell et al. preliminary estimates of occupational 
exposure categories of a retrospective cohort study. (Exs. 117-1; 118-
1) NIOSH derived excess risks from

[[Page 56784]]

the best fitting relative risk (RR) model, the square root model, as 
fit by Delzell et al. who adjusted for age, years since hire, and 
calendar period. The preferred final model specified by Delzell et al. 
was:

Relative Risk=1+0.17 x (BD ppm-years)0.5

Under this model the age-cause specific leukemia death rates (ACSDR) 
are a function of cumulative occupational exposure up to that age. The 
occupational ACSDRs are a multiplicative function of background ACSDR 
times the BD-caused relative increase (0.17 * BD ppm-years) in 
leukemia. These total ACSDRs were then applied to an actuarial program 
which adjusted for competing risks to estimate lifetime excess risk of 
leukemia associated with 45-year 8-hour TWA occupational exposures for 
a number of PELs for BD. Estimates of background rates of leukemia and 
all causes of death were taken from the mortality rates for all males, 
20 to 65 years of age, from the 1989 Vital Statistics of the United 
States. This model estimates the excess risk of leukemia death, given 
an occupational lifetime exposure of 2 ppm of BD, as 11 per 1,000 
workers. Lowering the 8-hour TWA occupational lifetime BD PEL to 1 ppm, 
on average, one would expect there to be 8 excess leukemia deaths per 
1,000 workers over a working lifetime.
    In most animal bioassays, exposure to chemical carcinogens is 
usually associated with an elevated tumor incidence at only one or two 
target tissues. BD is of great concern because significantly increased 
incidences of tumors at multiple sites and doses were observed in both 
rats and mice.
    OSHA's final risk assessment is based upon the NTP II bioassay. 
(Exs. 90; 96) In NTP II, the following tumor sites' incidence rates 
were elevated: Heart, lymph nodes, lung, forestomach, Harderian gland, 
preputial gland, liver, ovaries and mammary gland. The NTP II bioassay 
was preferred over the NTP I mouse and the HLE rat bioassay for several 
reasons. First, most of the exposure levels for NTP II (6.25, 20, 62.5 
and 200 ppm) were closer to current occupational exposure levels than 
were those in the other bioassays (625; 1,000 and 8,000 ppm); studies 
with higher than typical occupational exposure concentrations may lead 
to difficulties in extrapolating the effects to the lower 
concentrations of BD which typically occur in current occupational 
settings. Furthermore, for doses (625 to 8,000 ppm) above the metabolic 
saturation level of 500 ppm, the biologically effective doses are not 
proportional to ppm exposure concentrations. Second, the NTP II mice 
were successfully randomized to exposure groups and their individual 
pathology reports were consistently coded. The randomization of the 
bioassay mouse population lends to the internal validity of the study 
through the similar composition of experimental and control groups. 
Third, Good Laboratory Practices were followed, as verified by audits. 
Fourth, there was a clear dose-response relationship for several cancer 
sites. Fifth, since the carcinogenic mechanism is still unknown, OSHA 
conservatively estimates excess risk to humans based on the experience 
of the more sensitive animal species unless there is specific evidence 
indicating that the choice of that species is inappropriate. Sixth, 
risk assessment results based on the preliminary findings from the most 
recent epidemiologic study suggest that the B6C3F1 mouse 
is a reasonable species to use for quantitative risk assessment. (Ex. 
118-1)
    For its risk assessment, OSHA has focused exclusively on those 
tumor sites that are scientifically pertinent. From the NTP II study, 
the range of excess cancer risk associated with a lifetime occupational 
exposure to BD is estimated based on the dose-response relationships of 
four target tissues, three common to both genders: Heart 
(hemangiosarcoma), lung, and lymphoma, and one, ovarian tumors, 
observed in one gender only. OSHA's focus on these four individual 
target tissues is based not on an objection to the use of other tissue 
tumors and sites but rather on the judgment that the chosen animal 
sites are appropriate because they include both rare (e.g., heart 
hemangiosarcoma) and common tumors (e.g., lung) and those sites with 
the lowest (heart hemangiosarcoma) and highest incidence rates 
(lymphatic).
    Three of the target organs chosen for the QRA demonstrated a 
significantly elevated tumor incidence in both male and female animals; 
ovarian tumor incidence was also significantly elevated in female 
animals. For both male and female mice, heart hemangiosarcomas were 
selected for modeling because there is virtually no background 
incidence of heart hemangiosarcoma among untreated mice in the NTP 
control population; only 0.04% of unexposed B6C3F1 mice 
develop heart hemangiosarcoma, and thus any observed increase in the 
incidence of heart hemangiosarcoma could be attributed to BD exposure. 
(Ex. 114, p. 121) The earlier developing lymphocytic lymphoma caused a 
significant number of mice to die. Therefore, leaving mice are left at 
risk for the later developing tumor, heart hemangiosarcoma. (Ex. 114, 
p. 123) This situation is known as competing risk (the lack of 
opportunity for later developing tumors to express themselves because 
an earlier developing tumor has already caused the death of the animal. 
The occurrence of heart hemangiosarcomas in the NTP study is even more 
notable because of these competing risks.
    In the absence of definitive, pharmacokinetic information, OSHA has 
estimated excess risks to humans based on the most sensitive species-
sex-tumor site. Lung tumors are the most sensitive sites for both male 
and female B6C3F1 mice and, as such, were included in 
OSHA's final risk assessment.
    Ovarian tumors are an example of the group of reproductive tumors 
which also had significantly increased incidence rates among the 
animals in the NTP II bioassay. Other significantly increased incidence 
rates were seen in testicular, preputial and mammary tumors.
    The increased risk of developing leukemia that has been observed in 
the epidemiological studies suggests that lymphomas might be the most 
relevant tumor site in animals for estimating the quantitative cancer 
risk to workers. Some have suggested that the high rate of lymphoma 
among B6C3F1 mice might have been due to the presence of 
the murine retro virus (MuLV) and have asserted that the presence of 
this virus in B6C3F1 mice may be partially responsible 
for the incidence of thymic lymphoma. For example, in 1990, Dr. Richard 
Irons reported,

    A major difference between NIH Swiss and B6C3F1 
mice is their respective exotropic retro viral background (MuLV) * * 
* Chronic exposure to BD (at 1250 ppm) for up to a year resulted in 
a fourfold difference in the incidence of thymic lymphoma between 
B6C3F1 mice and NIH Swiss mice * * * The role of 
endogenous retro virus (MuLV) in the etiology of chemically induced 
murine leukemogenesis is presently not understood. (Ex. 23-104)

Dr. Melnick of the National Toxicology Program testified during his 
public hearing statement,

    In terms of the difference in response between the 
B6C3F1 mouse or the NIH Swiss Mouse, you must be 
aware that the study is not a complete cancer study. It's a one-year 
exposure. We do not know the full response in the NIH Swiss mouse if 
it were conducted as a cancer study (about 2-years). (Tr. 1/16/91, 
p. 382)

    Furthermore, NIOSH stated: ``It is not known whether the retro 
virus activation mechanism is operative at the lower exposure 
concentrations of 1,3-butadiene [below 1250 ppm].'' (Ex. 90)

[[Page 56785]]

There is no information in the record to show that retrovirus insertion 
into the B6C3F1 mice of the NTP II study led to the 
induction of lymphoma. Nor is there information indicating that the 
murine retro virus may have led to an enhancement of butadiene-induced 
lymphomas in B6C3F1 mice. The development of thymic 
lymphoma in BD-exposed NIH Swiss mice that do not have this endogenous 
virus argues against the virus alone inducing the lymphomas observed in 
the BD-exposed B6C3F1 mice. (Ex. 23-104)
    Tables V-11 and V-12 show the breakdown of microscopically examined 
tissues included in OSHA's QRA, by exposure concentration and death 
disposition of female and male mice. As illustrated in the tables, 
microscopic examination varied by tissue type, exposure group, means of 
death, and gender. Microscopic examinations of all tissues were made 
for all natural deaths, and moribund and terminal sacrifices, 
irrespective of exposure group.
    For each gender-exposure-group, 10 animals were sacrificed at 40 
and 65 weeks. Microscopic evaluations were not made for all tissue 
types among interim sacrifices (40 and 65 weeks). Among early 
sacrifices (40 weeks) for the 6.25 and 20 ppm exposure groups, there 
were no microscopic examinations of the relevant tissues. For the 65-
week female sacrifices at the 6.25 and 20 ppm dose levels only lung and 
ovarian tissues were examined microscopically. No microscopic 
evaluations were made for male 65-week sacrifices at the 6.25 ppm 
exposure level, but at the 20 ppm exposure level, animals were 
microscopically examined for heart hemangiosarcoma and lung cancer. 
Male and female interim sacrifices exposed to 62.5 ppm of BD were not 
microscopically examined for heart hemangiosarcoma.
    Only observations confirmed by microscopic examination were 
included in the analyses. Among natural deaths for some gender-tissue 
combinations, there were a few animals for which tissues were not 
available. Tissue unavailability was due to autolysis (cell destruction 
post death) and missing tissues due to the delay between accident and 
discovery.

             Table V-11.--Types of Tissues Microscopically Examined by Concentration Dose and Disposition Groups Among Female Mice from NTPa            
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                       Natural death and moribund                                                                                       
          Concentration ppm                    sacrifice                Week 40 sacrifice            Week 65 sacrifice            Terminal sacrifice    
--------------------------------------------------------------------------------------------------------------------------------------------------------
0...................................  lymphoma, heartb, lung,      lymphoma, heart, lung,       lymphoma, heart, lung,       lymphoma, heart, lung,     
                                       ovaries.                     ovaries.                     ovaries.                     ovaries.                  
6.25................................  lymphoma, heart, lung,       nonec......................  lung, ovaries..............  lymphoma, heart, lung,     
                                       ovaries.                                                                               ovaries.                  
20..................................  lymphoma, heart, lung,       none.......................  lung, ovaries..............  lymphoma, heart, lung,     
                                       ovaries.                                                                               ovaries.                  
62.5................................  lymphoma, heart, lung,       lymphoma, lung, ovaries....  lymphoma, heart, lung,       lymphoma, heart, lung,     
                                       ovaries.                                                  ovaries.                     ovaries.                  
200.................................  lymphoma, heart, lung,       lymphoma, heart, lung,       lymphoma, heart, lung,       lymphoma, heart, lung,     
                                       ovaries.                     ovaries.                     ovaries.                     ovaries.                  
--------------------------------------------------------------------------------------------------------------------------------------------------------
a These organs and tissue types are those contained in the OSHA risk assessment and do not reflect all of the types of tissues which were               
  microscopically examined.                                                                                                                             
b Heart, specifically Heart hemangiosarcoma.                                                                                                            
c None of the four tissue types used in the OSHA quantitative risk assessment were microscopically examined.                                            


 Table V-12.--Types of Tissues Microscopically Examined by Concentration Dose and Disposition Groups Among Male 
                                                 Mice from NTPa                                                 
----------------------------------------------------------------------------------------------------------------
                                   Natural death and                                               Terminal     
        Concentration ppm         moribund sacrifice  Week 40  sacrifice  Week 65  sacrifice       sacrifice    
----------------------------------------------------------------------------------------------------------------
0...............................  lymphoma, heart b,  lymphoma, heart,    lymphoma, heart,    lymphoma, heart,  
                                   lung,               lung.               lung.               lung.            
6.25............................  lymphoma, heart,    none c............  none..............  lymphoma, heart,  
                                   lung,                                                       lung.            
20..............................  lymphoma, heart,    none..............  heart, lung.......  lymphoma, heart,  
                                   lung,                                                       lung.            
62.5............................  lymphoma, heart,    lymphoma, lung,...  lymphoma, heart,    lymphoma, heart,  
                                   lung.                                   lung.               lung.            
200.............................  lymphoma, heart,    lymphoma, heart,    lymphoma, heart,    lymphoma, heart,  
                                   lung.               lung.               lung.               lung.            
----------------------------------------------------------------------------------------------------------------
a These organs and tissue types are those contained in the OSHA risk assessment and do not reflect all of the   
  types of tissues which were microscopically examined.                                                         
b Heart, specifically heart, hemangiosarcoma                                                                    
c None of the four tissue types used in the OSHA quantitative risk assessment were microscopically examined.    

2. Measure of Dose
    The mechanism of cancer induction by BD is unknown for both rodents 
and humans. One or more of the metabolites of BD, epoxybutene, 
diolepoxybutane and diepoxybutane, are suspected as being responsible 
for the carcinogenic response in at least some of the cancers. However, 
which of the metabolites may be responsible for how much of the 
carcinogenic response has yet to be determined. Bond suggests that 
epoxybutene and diepoxybutane may be responsible for carcinogenic 
responses. (Ex. 32-28) Dr. Bond wrote:

    If carcinogenic response is elicited by a metabolite, as has 
been suggested, mice because of their higher rate of metabolism, 
might be expected to yield a greater (carcinogenic) response than 
rats. (Ex. 17-21)

    Because there are different theories about which metabolites of BD 
are responsible for the various carcinogenic responses, some risk 
assessments have characterized carcinogenic risk as a result of type of 
dose: External, absorbed, or retained. In the BD proposal (55 FR 
32736), OSHA calculated the 14C-BD equivalents that were retained 
in mice at the conclusion of a 6-hour exposure period and incorrectly 
labeled the level as ``absorbed dose.'' This does not necessarily 
represent all the BD absorbed through inhalation exposure. (Ex. 34-1)

[[Page 56786]]

    The metabolic and pharmacokinetic properties of BD have not been 
fully characterized for either humans or animals. Despite the absence 
of a generally accepted pharmacokinetic model, some metabolic 
information can still be applied to OSHA's QRA. The overall rate of BD 
metabolism in B6C3F1 mice is approximately linear at 
external concentrations up to 200 ppm; BD metabolism increases 
sublinearly as concentrations increase until it is saturated at 625 
ppm. (Ex. 90) Bond reported that epoxybutene is one of the putative 
carcinogenic metabolites for which metabolism in the 
B6C3F1 mouse becomes saturated at 500 ppm; thus, the 
B6C3F1 mouse is unable to eliminate epoxybutene as 
quickly above 500 ppm. Bond suggests that above 500 ppm direct 
quantitative extrapolation of risk from mouse studies may not be 
justified. (Ex. 23-86) Therefore, the 625 ppm exposure group was 
excluded from OSHA's risk assessment. Similarly, NIOSH and Shell did 
not include the 625 ppm exposure group in their best estimates of risks 
using NTP II data. However, NIOSH did include the 625 ppm dose group in 
its sensitivity analyses to see how the inclusion of the data would 
affect the specification (the form and number of dose explanatory 
variables e.g., d, d\2\, d\3\, etc.) of the model and the estimates of 
risk. (Ex. 90)
3. Animal-to-Human Extrapolation
    A QRA based on a mouse bioassay requires setting values for some 
mouse and human variables, including those used in animal-to-human 
extrapolations. The values of these variables were chosen before 
conducting the analyses. In OSHA's quantitative risk assessment, a 
mouse's life span was assumed to be 113 weeks. Mice were 8 weeks old at 
the beginning of the study and were exposed for up to 105 weeks. OSHA 
assumes workers will have an average lifespan of 74 years and an 
occupational lifetime, working 5 days/week, 50 weeks/year, of 45 years. 
In the NTP II study, the average male mouse weighed 40.8 grams and 
female mouse weighed 38.8 grams. (Ex. 90) Mice were assigned breathing 
rates of 0.0245 l/min. Breathing rates of workers (for an 8-hour 
workday) were set at 10 m\3\/8-hr.
    OSHA has chosen to use a straight mg/kg, body weight to the first 
power, (BW)1, intake as the animal-to-human species extrapolation 
factor for dose equivalence. Other BD QRAs employed various 
extrapolation factors such as ppm equivalence, (mg/kg)3/4 
equivalence, BD mono-epoxide blood levels between mice and monkey 
equivalence, and BD total body equivalence in (mg/kg)2/3. OSHA 
believes that the evidence for the use of any of the alternative 
extrapolation factors is persuasive, although the Agency believes that 
body weight extrapolation is appropriate in this case because of the 
systemic nature of the tumors observed in both animal bioassays. This 
conversion of body weight, (BW)\1\ , produces estimates of risk which 
are lower than those derived using (BW)3/4, everything else held 
constant. For example, with a linear, 1-stage model, if OSHA used the 
(BW)3/4 conversion, holding all other elements constant, one would 
expect the estimates of excess risk to humans to be about 6.5 times 
higher than if the (BW) extrapolation factor had been used because of 
the weight of the experimental species (between 38.8 and 40.8 grams), 
and their breathing rate. For the quadratic (2-stage) and cubic (3-
stage) models, the effect of relying on the (BW)3/4 conversion 
rather than the (BW)1, holding all else constant, would be to 
increase the predicted excess human risk more than 6.5 fold. (Ex. 90)
4. Estimation of Occupational Dose
    It is necessary to estimate the development of cancer at a variety 
of occupational doses. This requires occupational doses to be converted 
into units comparable to those used to measure the animal experimental 
dose. As discussed earlier, OSHA first converted animal experimental 
exposures measured in ppm into occupational intake dose measured in 
(mg/kg).
    An exposure of 1 ppm BD is converted into an equivalent exposure 
measured in mg/m\3\ using the equation:
[GRAPHIC] [TIFF OMITTED] TR04NO96.000

    Given a worker weighing 70 kg, breathing 10 m\3\ of air per 8-hour 
day, and exposed to air containing Y ppm BD, the inhaled dose of BD in 
mg/kg is given by:
[GRAPHIC] [TIFF OMITTED] TR04NO96.001

    Using the above formula, one can calculate the estimated equivalent 
inhaled BD exposure among workers based on the exposure concentrations 
for animals (See Table V-13).

  Table V-13.--Estimate of Total Human Inhaled Dose Over a Workday for  
                      Various Exposure Levels of BD                     
------------------------------------------------------------------------
                                                 Estimate of total human
         Exposure concentrations (ppm)              inhaled BD over a   
                                                 workday (mg/kg/8-hours)
------------------------------------------------------------------------
200............................................                     63.2
62.5...........................................                     19.8
20.............................................                      6.3
5..............................................                      1.6
2..............................................                      0.6
1..............................................                      0.3
------------------------------------------------------------------------

5. Selection of Model for Quantitative Risk Assessment
    In the proposal (55 FR 32736), OSHA estimated excess risk using a 
quantal form of the multistage model (in a reparameterized form as 
calculated by GLOBAL83), which based estimates of risk to humans on the 
experience of the group rather than the individual. Three of the later 
risk assessments, Shell, NIOSH, and COHP, used a Weibull time-to-tumor 
form of the multistage model to fit the mouse bioassays. (Exs. 32-27; 
90; 32-16) Time-to-tumor

[[Page 56787]]

models use more of the available information than quantal multistage 
models to characterize time until the development of each observable 
tumor, and extrapolate risks, based on an occupational dosing pattern. 
Since significant increases in tumor incidence occurred at multiple 
sites in the NTP II bioassay and a time-to-tumor model takes these 
competing risks into account, a time-to-tumor method is preferred over 
a quantal model. (Ex. 118-1B)
    Therefore OSHA used a Weibull time-to-tumor form of the multistage 
model to characterize the risks of development of observable tumors, 
using the software package, TOX__RISK Version 3.5 by ICF Kaiser. The 
model predicts the probability, P(t,d), of tumor onset with dose 
pattern d by time t. It adjusts for competing causes of death prior to
time t.
    The Weibull time-to-tumor model is a multistage model based on the 
theory of carcinogenesis developed by Armitage and Doll. This theory of 
carcinogenesis is based on the assumption that a single line of stem 
cells must pass through a certain number of stages sequentially for the 
development of a single tumor cell. In the reparameterized form of the 
model used here, a k stage model is described by a polynomial of degree 
k, with all dose parameters greater than or equal to zero. The number 
of stages necessary for a model to be correctly specified varies by 
type of tumor, animal, and exposure agent, or any combination of the 
three.
    Both the MLE and the 95% upper limit of the risk of developing 
cancer in various tissues per 1,000 workers by time t are calculated. 
The 95% upper bound is the largest value of excess risk that is 
consistent with the observed data with two-sided 95% confidence 
intervals. The 95% upper bound is computed based on the Weibull time-
to-tumor model for which the parameters satisfy:

-2 (Log likelihood-Log likelihoodmax)2.70554

Where: Log likelihoodmax is the maximum value of the log-
likelihood

A 1-stage model is linear in dose; a 2-stage model is quadratic in 
dose; a 3-stage Weibull model is cubic in dose. Below is a mathematical 
representation of a 3-stage Weibull time-to-tumor model:

P(t,d)=1-exp [-(q0 + q1d + q2d2 + q3d3) 
(t-t0z)]

where: t0 designates the time of onset of the tumor, t is the 
variable for time the tumor was observed and is assumed to follow a 
Weibull distribution; d is the dose-metric and is multistage; z is a 
parameter to be estimated, constrained between 1 and 10; the background 
parameter qo and the dose parameters, q1, q2, q3, 
are constrained to be non-negative. Constraining the dose parameters to 
zero or greater is biologically based, since the dose parameters are 
proportional to the mutation rates of the successive stages in the 
development of a tumor cell. The Weibull time-to-tumor model provides 
reasonable fits for about 75% of the tissues in the NTP historical 
control data base, but the precision of the fit to the dose-response 
data depends on the specific agent. (Ex. 90)
    Four forms of the model, one less than the number of exposure 
groups, for each gender-outcome were fit to the data. The correct 
specification of the model, the number of stages, is determined by the 
fit of the model to the data. The likelihood ratio test identifies 
which model is a better fit by determining if the log-likelihood of a 
model is significantly greater than another model's value. The 1-, 2-, 
3- and 4-stage Weibull time-to-tumor models for each gender-outcome 
combination were ordered according to the value of their log-
likelihood. If the log-likelihood of the higher stage model is 
significantly greater than that of the next lower stage model's log-
likelihood, one would reject the null hypothesis (the additional stage 
does not create a model that better characterizes the data) and 
conclude that the higher stage model is a significantly better 
predictor of the estimates of risk in the observed range than is the 
lower stage model.
    The steps of the likelihood ratio test are as follows:
    For example, assuming an alpha of 0.05, and 1 degree of freedom 
(the difference in the number of parameters from 1-stage and 2-stage 
models), the critical value would be 3.84.
    Fail to Reject H0 if:

2 (log likelihood1-stage-log likelihood2-stage)<3.84

    Reject H0 if:

2 (log likelihood1-stage-log likelihood2-
stage)3.84

If two times the difference of the log likelihood values of the nth 
stage model and the nth + 1 stage model was less than 3.84, then the 
additional stage would be deemed unnecessary for goodness of fit; on 
the grounds of parsimony, the lower stage model would be used for the 
risk assessment. Otherwise, the higher stage model would be judged a 
better fit than the lower stage one and the process would continue.
    While the likelihood ratio test is suitable for testing the 
significance of the next higher degree dose parameter, the biologically 
reasonable constraint on the background incidence parameter q0 and 
dose parameters that they be non-negative q1, q2, 
q3>=0,--may impair the log-likelihood ratio test's power to 
determine statistical significance.
    The incidences of lymphoma, heart hemangiosarcoma, lung and ovarian 
tumors are shown in Tables V-14 and V-15 for males and females, 
respectively. The TOXRISK Weibull time-to-tumor model requires that the 
tumor context be described for each observation. Outcomes can be put 
into three context categories: (1) Censored, no tumor; (2) rapidly 
fatal tumor; and (3) observed, tumor incidental to the animal's 
survival. Since OSHA was predicting the time until onset of tumor, 
assuming no lag time between onset and detection of tumor, t0 was 
set to zero. Therefore, estimates of risk to humans based on the 
contribution to the likelihood of either a rapidly fatal or incidental 
tumor are mathematically the same.
    Tables V-16 and V-17 show the Weibull time-to-tumor model estimates 
of log-likelihoods, the shape parameters, intercept and dose 
coefficients for relevant target tissues for male and female mice, 
respectively. The relative performance of various staged models for a 
specific target tissue-gender are enumerated in the log-likelihood 
values. It should be noted that some of the tissue-gender combination's 
log-likelihood values do not vary even though there is a change in the 
number of the stages in the model. For example, the log-likelihood 
values for models of all lymphoma for males and lung tumors for males 
and females are -6.986 E+1, -1.763 E+2, -1.626 E+2, respectively, 
regardless of the specification, number of stages, in the model. OSHA 
concluded that the 1-stage models were preferred.
    As identified in Tables V-16 and V-17, only heart hemangiosarcoma 
models are non-linear. This is consistent with NIOSH's results when 
fitting Weibull time-to-tumor models to these gender-tumor 
combinations. The quadratic (2-stage) model for males and the cubic (3-
stage) model for females better characterized the dose-response 
relationship in modeling time to detection of heart hemangiosarcoma 
than did the linear models. The higher stage model necessary to fit the 
heart hemangiosarcoma data is driven by the absence of cases in the two 
lower exposure groups, shown in Tables V-14 and V-15. Unlike the other 
tissues studied, there were no cases of heart

[[Page 56788]]

hemangiosarcoma in the control and lowest exposure groups for both male 
and female mice. Both male and female mice had similar heart 
hemangiosarcoma tumor rates, almost 30%, among the 200 ppm exposure 
groups. The intercepts, q0, were zero for models of both male and 
female mice based on the dose-response of heart hemangiosarcomas. This 
is consistent with what one would expect, given the absence of 
background incidence rates of heart hemangiosarcomas.

    Table V-14.--Univariate Analysis of Heart, Lung, and All Lymphoma   
   Neoplasms by Exposure Level of 1,3-Butadiene Among NTP II Male Mice  
                  Analyzed in the Time-To-Tumor Models                  
------------------------------------------------------------------------
                                                    Outcome             
                                      ----------------------------------
               Neoplasm                 Tumor n a    Censored c         
                                          (%N b)       n (%N)    Total N
------------------------------------------------------------------------
All lymphoma, 0 ppm..................      4 (5.7)    66 (94.3)       70
All lymphoma, 6.25 ppm...............      3 (6.0)    47 (94.0)       50
All lymphoma, 20 ppm.................     8 (16.0)    42 (84.0)       50
All lymphoma, 62.5 ppm...............    11 (15.9)    58 (84.1)       69
All lymphoma, 200 ppm................     9 (12.9)    61 (87.1)       70
Heart hemangiosarcoma, 0 ppm.........        0 (0)     70 (100)       70
Heart hemangiosarcoma, 6.25 ppm......        0 (0)     49 (100)       49
Heart hemangiosarcoma, 20 ppm........      1 (1.7)    59 (98.3)       60
Heart hemangiosarcoma, 62.5 ppm......      5 (8.6)    53 (91.4)       58
Heart hemangiosarcoma, 200 ppm.......    20 (29.4)    48 (70.6)       68
Lung tumor, 0 ppm....................    22 (31.4)    48 (68.6)       70
Lung tumor, 6.25 ppm.................    23 (46.9)    26 (53.1)       49
Lung tumor, 20 ppm...................    20 (33.3)    40 (66.7)       60
Lung tumor, 62.5 ppm.................    33 (47.8)    36 (52.2)       69
Lung tumor, 200 ppm..................    42 (60.0)    28 (40.0)      70 
------------------------------------------------------------------------
a n is number of microscopically determined outcomes per tumor-context, 
  gender, exposure-group outcome site combination.                      
b N is the total number of gender, exposure-group, outcome site         
  combination which were microscopically examined.                      
c Tumor's context is C (censored); animals were microscopically examined
  and no tumor was found at this site.                                  


    Table V-15.--Univariate Analysis of Heart, Lung, All Lymphoma and   
Ovarian Neoplasms by Exposure Level of 1,3-Butadiene Among NTP II Female
                Mice Analyzed in the Time-To-Tumor Models               
------------------------------------------------------------------------
                                                    Outcome             
                                      ----------------------------------
               Neoplasm                 Tumor  na    Censored c         
                                          (%Nb)        n (%N)    Total N
------------------------------------------------------------------------
All lymphoma, 0 ppm..................    10 (14.3)    60 (85.7)       70
All lymphoma, 6.25 ppm...............    14 (28.0)    36 (72.0)       50
All lymphoma, 20 ppm.................    18 (36.0)    32 (64.0)       50
All lymphoma, 62.5 ppm...............    10 (14.3)    60 (85.7)       70
All lymphoma, 200 ppm................    19 (27.1)    51 (72.9)       70
Heart hemangiosarcoma, 0 ppm.........        0 (0)     70 (100)       70
Heart hemangiosarcoma, 6.25 ppm......        0 (0)     50 (100)       50
Heart hemangiosarcoma, 20 ppm........        0 (0)     50 (100)       50
Heart hemangiosarcoma, 62.5 ppm......      1 (1.7)    58 (98.3)       59
Heart hemangiosarcoma, 200 ppm.......    20 (28.6)    50 (71.4)       70
Lung tumor, 0 ppm....................      4 (5.7)    66 (94.3)       70
Lung tumor, 6.25 ppm.................    15 (25.0)    45 (75.0)       60
Lung tumor, 20 ppm...................    19 (31.7)    41 (68.3)       60
Lung tumor, 62.5 ppm.................    27 (38.6)    43 (61.4)       70
Lung tumor, 200 ppm..................    32 (45.7)    38 (54.3)       70
Ovarian tumor, 0 ppm.................      1 (1.4)    68 (98.6)       69
Ovarian tumor, 6.25 ppm..............        0 (0)     59 (100)       59
Ovarian tumor, 20 ppm................        0 (0)     59 (100)       59
Ovarian tumor, 62.5 ppm..............     9 (12.9)    61 (87.1)       70
Ovarian tumor, 200 ppm...............    11 (15.7)    59 (84.3)      70 
------------------------------------------------------------------------
a n is number of microscopically determined outcomes per tumor-context, 
  gender, exposure-group outcome site combination.                      
b N is the total number of gender, exposure-group, outcome site         
  combination which were microscopically examined.                      
c Tumor's context is C (censored); animals were microscopically examined
  and no tumor was found at this site.                                  


[[Page 56789]]


 Table V-16.--Maximum Likelihood Estimates of Model Coefficients From Various Stages of Weibull Time-To-Tumor Models Using Three Tumor Responses of Male
            Mice in the NTP II Study, Excluding 625 ppm Exposure Group; Selection of Specification of Model is Based on Likelihood Ratio Test           
--------------------------------------------------------------------------------------------------------------------------------------------------------
           Neoplasm             Stage a    Log-likelihood     Z b          q0                q1               q2               q3               q4      
--------------------------------------------------------------------------------------------------------------------------------------------------------
Heart hemangiosarcoma........  W1         -7.061             9.810  0.00              8.306 E-23                                                        
Heart hemangiosarcoma........  c W2       -2.783 E-1            10  0.00              0.00             3.071 E-25                                       
Heart hemangiosarcoma........  W3         -2.712 E-1            10  0.00              1.058 E-24       2.636 E-25       2.057 E-28                      
Heart hemangiosarcoma........  W4         -2.659 E-1            10  0.00              1.119 E-24       2.664 E-25       0.00             9.626 E-31     
All lymphoma.................  c W1       -6.986 E+1         4.743  2.709 E-11        6.136 E-13                                                        
All lymphoma.................  W2         -6.986 E+1         4.743  2.709 E-11        6.136 E-13       0.00                                             
All lymphoma.................  W3         -6.986 E+1         4.743  2.709 E-11        6.136 E-13       0.00             6.540 E-33                      
All lymphoma.................  W4         -6.986 E+1         4.743  2.709 E-11        6.136 E-13       0.00             0.00             0.00           
Lung tumor...................  c W1       -1.763 E+2         3.318  1.132 E-7         2.636 E-9                                                         
Lung tumor...................  W2         -1.760 E+2         3.413  7.674 E-8         1.253 E-9        3.134 E-12                                       
Lung tumor...................  W3         -1.760 E+2         3.143  7.674 E-8         1.253 E-9        3.134 E-12       0.00                            
Lung tumor...................  W4         -1.760 E+2         3.413  7.674 E-8         1.253 E-9        3.139 E-12       0.00             0.00           
--------------------------------------------------------------------------------------------------------------------------------------------------------
a Stage of time-to-tumor model; W1, Weibull 1-stage time-to-tumor model; W2, Weibull 2-stage time-to-tumor model; W3, Weibull 3-stage time-to-tumor     
  model; W4, Weibull 4-stage time-to-tumor model.                                                                                                       
b Z is the shape parameter; it is bounded, (1<=z<=10).                                                                                                  
c Selected Model.                                                                                                                                       


Table V-17.--Maximum Likelihood Estimates of Model Coefficients From Various Stages of Weibull Time-To-Tumor Models Using Four Tumor Responses of Female
            Mice in the NTP II Study, Excluding 625 ppm Exposure Group; Selection of Specification of Model is Based on Likelihood Ratio Test           
--------------------------------------------------------------------------------------------------------------------------------------------------------
           Neoplasm              Stagea    Log-likelihood     Zb           q0                q1               q2               q3               q4      
--------------------------------------------------------------------------------------------------------------------------------------------------------
Heart hemangiosarcoma........  W1         -2.097 E+1         4.957  0.00              4.356 E-13                                                        
Heart hemangiosarcoma........  W2         -8.745             6.126  0.00              0.00             2.222 E-17                                       
Heart hemangiosarcoma........  W3c        -4.866             6.770  0.00              0.00             0.00             8.088 E-21                      
Heart hemangiosarcoma........  W4         -4.267             7.011  0.00              0.00             0.00             2.637 E-22       1.368 E-3      
Ovarian tumor................  W1c        -6.140 E+1         2.857  1.407 E-8         .031 E-9                                                          
Ovarian tumor................  W2         -6.069 E+1         4.079  5.397 E-11        7.075 E-12       1.399 E-13                                       
Ovarian tumor................  W3         -6.069 E+1         4.079  5.397 E-11        7.075 E-12       1.399 E-13       0.00                            
Ovarian tumor................  W4         -6.069 E+1         4.079  5.397 E-11        7.075 E-12       1.399 E-13       0.00             0.00           
All lymphoma.................  W1c        -5.724 E+1         6.857  3.453 E-15        1.338 E-16                                                        
All lymphoma.................  W2         -5.501 E+1         7.143  1.18 E-15         2.577 E-18       2.453 E-19                                       
All lymphoma.................  W3         -5.426 E+1         7.230  7.758 E-16        6.847 E-18       0.00             7.809 E-22                      
All lymphoma.................  W4         -5.401 E+1         7.258  7.360 E-18        7.359 E-18       0.00             0.00             3.387 E-24     
Lung tumor...................  W1c        -1.626 E+2         3.416  2.096 E-8         2.096 E-9                                                         
Lung tumor...................  W2         -1.626 E+2         3.416  2.090 E-8         2.090 E--9       0.00                                             
Lung tumor...................  W3         -1.626 E+2         3.416  2.090 E-8         2.096 E-9        0.00             0.00                            
Lung tumor...................  W4         -1.626 E+2         3.416  2.090 E-8         2.096 E-9        0.00             0.00             0.00           
--------------------------------------------------------------------------------------------------------------------------------------------------------
a Stage of time-to-tumor model; W1, Weibull 1-stage time-to-tumor model; W2, Weibull 2-stage time-to-tumor model; W3, Weibull 3-stage time-to-tumor     
  model; W4, Weibull 4-stage time-to-tumor model.                                                                                                       
b Z is the shape parameter; it is bounded, (1<=z<=10).                                                                                                  
c Selected Model.                                                                                                                                       

OSHA's Estimates of Risk

    The estimates from OSHA's quantitative risk assessment based an 8-
hour TWA, occupational lifetime, working 5 days/week, 50 weeks/year, 
for 45 years, at various BD PELS are shown in Table V-18. The MLEs of 
excess risk of material impairment of health per 1,000 workers for 
cancer, based on tumors of various tissue sites and the 95% upper 
bounds, are presented. Various 8-hour TWA PELS, ranging from 0.1 to 5 
ppm, are presented to provide a context in which to evaluate the OSHA 
final rule PEL of 1 ppm and to explore the feasibility of other PELS, 
including the proposed PEL of 2 ppm. Risks at the former BD 8-hour TWA 
PEL, 1,000 ppm, are not presented in Table V-18. Although risks could 
be estimated for an occupational lifetime exposure to an 8-hour TWA of 
1,000 ppm of BD from the linear models, there is little relevancy to 
estimating the true risk at an 8-hour PEL for BD at 1,000 ppm for an 
occupational lifetime, since

[[Page 56790]]

8-hour TWA BD exposures have been generally far lower than 1,000 ppm.
    Although the estimates of carcinogenic outcomes differ, excess 
risks derived from tumor sites common to both male and female 
B6C3F1 mice had the same relative ranking from lowest to 
highest risk estimates by target tissues (heart hemangiosarcomas < 
lymphomas < lungs) within each gender group. After a lifetime 
occupational exposure to BD at the proposed 8-hour TWA PEL of 2 ppm 
based on the above model fits to these three individual tumor sites, 
one would expect between 2.7 x 10-4 to 16.2 excess cancer cases 
per 1,000 workers, depending on which gender-tumor site dose-response 
relationship is used as the basis for the extrapolation to human 
occupational excess risks. Decreasing the BD 8-hour TWA PEL from 2 to 1 
ppm, results in a reduction of the range of estimates of excess risk of 
cancer to between 3.4 x 10-5 to 8.1 cases per 1,000 workers.
    The estimate of excess cancer risk based on male mouse lymphoma is 
1.3 per 1,000 workers at an 8-hour TWA for an occupational lifetime 
exposure to 1 ppm BD. Extrapolating from female mouse lymphoma data 
results in an estimate of 6.0 extra cancer deaths per 1,000 workers at 
a BD 8-hour TWA PEL of 1 ppm for an occupational lifetime of exposure.
    Extrapolating from the most sensitive site, the female mouse lung, 
based on the 1-stage Weibull time-to-tumor model, with an 8-hour TWA 
PEL of 2 ppm of BD for an occupational lifetime, one would expect 16 
excess cancer cases per 1,000 workers. Lowering the PEL to 1 ppm would 
cut the expected number of excess cancers in half to 8 cases, based on 
the same gender-tumor site. Based on male lung tumors, the estimate of 
excess cancer deaths for an 8-hour TWA exposure to 2 ppm BD over an 
occupational lifetime was 12.8 per 1,000 workers; lowering the 8-hour 
TWA occupational lifetime exposure level to 1 ppm BD decreases the 
estimate of excess cancer risk to 6.4 per 1,000 workers, a reduction of 
6 cancer cases per 1,000 workers.
    OSHA's estimates of premature occupational leukemia deaths based on 
the 1-stage Weibull time-to-tumor models for the following outcome 
sites: All lymphoma, lung tumors, and ovarian tumors, ranged between 
1.3 and 8.1 per 1,000 workers. Similarly, NIOSH's 14 estimates of the 
excess risk of death due to leukemia, based on 1-stage Weibull time-to-
tumor models, as a consequence of exposure to an 8-hour TWA of 1 ppm BD 
over an occupational lifetime, ranged between 0.9 and 30 cases per 
1,000 workers. The preliminary estimate of 8 per 1,000 from the Delzell 
et al. study is concordant with this range of animal-based estimates. 
OSHA acknowledges that there is uncertainty in the Delzell et al. 
estimate, perhaps due to the natural sampling variability present in 
any epidemiologic study plus the possibility of extra-binomial 
uncertainty stemming from exposure misclassification. While this 
uncertainty makes it difficult to say whether quantitative risk 
estimates would be adjusted up or down relative to animal-based 
estimates, this suggestion is far less important than the basic 
conclusion that the Delzell et al. study reinforces earlier estimates. 
Even if refinement of exposures caused the Delzell et al. estimate to 
move up or down by even as much as a factor of 5 or more, it would not 
change this qualitative, and roughly quantitative, agreement.

  Table V-18.--Maximum Likelihood Estimates (MLE) and Ninety-Five Percent Upper Bounds of Lifetime Extra Risk to Develop an Observable Tumor per 1,000  
 Workers Due to an 8-Hour TWA for an Occupational Lifetime a of Exposure to 1,3-Butadiene, Using NTP II Bioassay b and the Best Fitting Weibull Time-To-
                                                                      Tumor Models                                                                      
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                   8-hour time-weighted average concentration c                         
                                                         -----------------------------------------------------------------------------------------------
                                                              0.1 ppm         0.2 ppm         0.5 ppm          1 ppm           2 ppm           5 ppm    
                    Neoplasms                     Stages -----------------------------------------------------------------------------------------------
                                                                    95%             95%             95%             95%             95%             95% 
                                                            MLE    U.B.d    MLE    U.B.     MLE    U.B.     MLE    U.B.     MLE     MLE     MLE    U.B. 
--------------------------------------------------------------------------------------------------------------------------------------------------------
Male mice:                                                                                                                                              
    Heart Hemangiosarcoma.......................       2   e<0.1     0.2   e<0.1     0.4   e<0.1     0.9   e<0.1     1.8  e< 0.1     3.6     0.4     9.1
    All lymphoma................................       1     0.1     0.2     0.3     0.5     0.6     1.1     1.3     2.3     2.5     4.5     6.3    11.2
    Lung tumor..................................       1     0.7     0.1     1.3     2.0     3.2     4.9     6.4     9.8    12.8    19.4    31.7    47.9
Female mice:                                                                                                                                            
    Heart Hemangiosarcoma.......................       3   f<0.1   f<0.1   f<0.1   < 0.1   f<0.1     0.2  f< 0.1     0.5   f<0.1     1.0   f<0.1     2.4
    Ovarian tumor...............................       1     0.1     0.3     0.3     0.5     0.7     1.3     1.4     2.6     2.8     5.2     6.9    13.0
    All lymphoma................................       1     0.6     0.9     1.2     1.8     3.0     4.6     6.0     9.2    12.0    18.3    29.7    45.0
    Lung tumor..................................       1     0.8     1.2     1.6     2.4     4.1     6.1     8.1    12.2    16.2    24.1   40.00   59.4 
--------------------------------------------------------------------------------------------------------------------------------------------------------
a Occupational lifetime, working 5 days/week, 50 weeks/year, for 45 years.                                                                              
b Using data from NTP II for the following exposure groups: 0, 6.25, 20, 62.5 and 200 ppm; the 625 ppm exposure group was excluded.                     
c Estimated lifetime excess risk for cancer assuming: mouse life-span of 113 weeks, male mouse body weight of 40.8g; female mouse body weight of 38.8 g;
  worker's breathing rate is 1.25 m\3\/hr; mouse to human risk extrapolated in mg/kg-day equivalent units.                                              
d 95% U.B., 95% Upper Bounds is the largest value of excess risk that is compatible with the animal response data at a confidence level of 95%.         
e MLEs ranged from 1.510-4 to 6.010-2                                                                                                 
f MLEs ranged from 3.410-8 to 4.310-3                                                                                                 

VII. Significance of Risk

A. Introduction

    In the 1980 ``Benzene Decision,'' the Supreme Court, in its 
discussion of the level of risk that Congress authorized OSHA to 
regulate, indicated its view of the boundaries of acceptable and 
unacceptable risk. The Court stated:

    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. (I.U.D. v. A.P.I., 448 U.S. 607, 655).

    So a risk of \1/1000\ (10-3) is clearly significant. It 
represents the uppermost

[[Page 56791]]

end of the million-fold range suggested by the Court, somewhere below 
which the boundary of acceptable versus unacceptable risk must fall.
    The Court further stated that ``while the Agency must support its 
findings that a certain level of risk exists with substantial evidence, 
we recognize that its determination that a particular level of risk is 
significant will be based largely on policy considerations.'' With 
regard to the methods used to determine the risk level present (as 
opposed to the policy choice of whether that level is ``significant'' 
or not), the Court added that assessment under the OSH Act is ``not a 
mathematical straitjacket,'' and that ``OSHA is not required to support 
its findings with anything approaching scientific certainty.'' The 
Court ruled that ``a reviewing court [is] to give OSHA some leeway 
where its findings must be made on the frontiers of scientific 
knowledge [and that] * * * the 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'' (448 U.S. at 655, 656).
    Nonetheless, OSHA has taken various steps that make it fairly 
confident its risk assessment methodology is not designed to be overly 
``conservative'' (in the sense of erring on the side of 
overprotection). For example, there are several options for 
extrapolating human risks from animal data via interspecies scaling 
factors. The plausible factors range at least as widely as from body 
weight extrapolation at one extreme (risks equivalent at equivalent 
body weights, (mg/kg) \1\) to (body weight) 2/3 (risks equivalent 
at equivalent surface areas) at the other. Intermediate values have 
also been used, and the value of (body weight) 3/4, which is 
supported by physiological theory and empirical evidence, is generally 
considered to be the midpoint of the plausible values. (Body weight) 
2/3 is the most conservative value in this series, while body 
weight extrapolation is the least conservative. OSHA has generally used 
body weight extrapolation in assessing risks from animal data, an 
approach that tends to be significantly less risk conservative than the 
other methodologies and is likely to be less conservative even than the 
central tendency of the plausible values.
    Other steps in OSHA's risk assessment methodology where the Agency 
does not use the most conservative approach are selection of the 
maximum likelihood estimate (MLE) of the parameterized dose-response 
function rather than selection of the upper 95% confidence limit, and 
the use of site-specific tumor incidence, rather than pooled tumor 
response, in determining the dose-response function for a chemical 
agent.
    Other aspects of OSHA's risk assessment methodology reflect more 
conservative choices, including: basing the risk estimate on the more 
sensitive species tested (the mouse); including lung tumors in the 
range of risks presented in the quantitative analysis, even though 
excess deaths from lung cancer have not been observed in any of the 
human studies; and, assuming workers will be exposed to butadiene at 
the maximum permissible level for 45 years. As discussed below, if 
workers are exposed to BD for fewer years, their estimated risks from 
BD will be less than indicated. This caveat, of course, does not 
address lifetime risks taking into account occupational exposure to 
other substances encountered at other jobs. For reasons already 
explained, OSHA believes these choices are appropriate for the BD risk 
assessment. OSHA also recognizes that use of the most conservative 
approach at every step of the risk assessment analysis could produce 
mathematical risk estimates which, because of the additive effect of 
multiple conservative assumptions, may overstate the likely risk. OSHA 
believes its quantitative risk assessment for BD strikes an appropriate 
balance.
    Risk assessment is only one part of the process OSHA uses to 
regulate toxic substances in the workplace. OSHA's overall analytic 
approach to regulating occupational exposure to particular substances 
is a four-step process consistent with judicial interpretations of the 
OSH Act, such as the Benzene Decision, and rational policy formulation. 
In the first step, OSHA quantifies the pertinent health risks, to the 
extent possible, performing quantitative risk assessments. The Agency 
considers a number of factors to determine whether the substance to be 
regulated currently poses a significant risk to workers. These factors 
include the type of risk posed, the quality of the underlying data, the 
plausibility and precision of the risk assessment, the statistical 
significance of the findings and the magnitude of risk. (48 FR 1864, 
January 14, 1983) In the second step, OSHA considers which, if any, of 
the regulatory options being considered will substantially reduce the 
identified risks. In the third step, OSHA looks at the best available 
data to set permissible exposure limits that, to the extent possible, 
both protect employees from significant risks and are also 
technologically and economically feasible. In the fourth and final 
step, OSHA considers the most cost-effective way to fulfill its 
statutory mandate by crafting regulations that allow employers to reach 
the feasible PEL as efficiently as possible.

B. Review of Data Quality and Statistical Significance

    As discussed in the Health Effects section, OSHA has concluded that 
butadiene is a probable human carcinogen. This conclusion is based on a 
body of evidence comprised of animal bioassays, human epidemiological 
investigations, and other experimental studies that together are both 
consistent in their findings and biologically plausible. First, OSHA 
has reviewed four rodent inhalation bioassays, two mouse bioassays 
conducted under the National Toxicology Program (designated NTP I and 
NTP II), a mouse study by Irons et al. in 1989, and a rat study 
sponsored by the IISRP. (Exs. 2-32, 23-1, 32-28D, 90, 96) All three 
mouse studies found a consistently high tumor response in BD-exposed 
mice, relative to control animals. Several target organs were 
identified, particularly by the NTP II study; however, all three 
studies found dose-related increases in the incidences of lymphocytic 
lymphoma and heart hemangiosarcomas associated with exposure to BD. 
Most significantly, the NTP II study reported statistically significant 
increases in tumor incidence among mice exposed to BD well below OSHA's 
current PEL of 1,000 ppm (exposure to as low as 6.25 ppm was associated 
with a statistically significant increase in tumors, e.g., lung tumors 
in female mice). There was also evidence for a dose-rate effect, 
meaning that the observed tumor incidence in mice exposed to high 
concentrations over short periods of time was higher than that observed 
in mice administered an equivalent cumulative concentration over a long 
period of time. The study employing BD-exposed rats also found 
increased incidences of several types of cancer, albeit at lower 
response rates than were observed in the mouse studies. The two major 
epoxide metabolites of BD have also been shown to be carcinogenic in 
rats and mice.
    OSHA has also reviewed a number of human epidemiological studies 
that have examined the mortality experience of styrene-butadiene rubber 
(SBR) workers. These studies have consistently reported an elevated 
relative risk of leukemia-or lymphoma-related death among BD-exposed 
workers. The most recent of these, the study by Delzell et al., updated 
and expanded previous SBR worker mortality studies and found a positive

[[Page 56792]]

and statistically significant dose-response relationship between 
cumulative exposure to BD and increased leukemia mortality, which 
remained statistically significant even after controlling for the 
potential confounder of concurrent styrene exposure. (Ex. 117-1) The 
Delzell et al. study thus provides further and more directly relevant 
evidence that an increased risk of leukemia-related death is associated 
with exposure to BD. Furthermore, other epidemiologic studies have 
reported finding an unusually short latency period (as little as 3 to 4 
years from time of initial exposure to death) for exposure-related 
hematologic malignancies among workers who experienced exposures to BD 
in the past that were higher than exposures that prevail today. (Ex. 2-
26, 3-34 Vol III H-1)
    Evidence for the carcinogenicity of BD is further strengthened by a 
collection of studies showing that the epoxide metabolites of BD are 
mutagenic in a wide variety of in vitro and in vivo test systems. 
Examination of cultured lymphocytes from BD-exposed workers has 
revealed the presence of chromosome aberrations, an elevated frequency 
of chromatid breaks, and various mutations, thereby providing direct 
evidence of genotoxicity in occupationally-exposed humans. (Exs. 118-
2A, 118-2D) Furthermore, the finding of activated K-ras oncogenes in 
tumors of BD-exposed mice provides additional support for a mutagenic 
mode of action; this finding has particular relevance to human risk in 
that K-ras is the most commonly detected oncogene in human cancer. (Ex. 
129)
    The findings from the animal bioassays and human epidemiologic 
studies identify the hematopoietic system as a primary target organ for 
BD-related carcinogenesis. Target organs for toxicity are not 
necessarily those for carcinogenicity. Other experimental findings are 
consistent with these observations. Studies in BD-exposed rodents have 
found concentration-dependent decreases in red blood cell counts, 
hemoglobin concentration, and other indicators of hematopoietic 
suppression. (Exs. 114, 32-38D, 23-12) There is also some suggestive 
evidence that workers exposed to BD at levels well below the current 
1,000 ppm PEL exhibit hematological changes indicative of bone marrow 
depression. (Exs. 23-4, 2-28) Finally, many of the tumor types found in 
BD-exposed mice, including lymphocytic/hematopoietic cancer, lung 
cancer, mammary gland tumors, and possibly hemangiosarcomas, are tumors 
that are often found in association with exposure to other industrial 
chemicals known to cause lymphocytic/hematopoietic cancer in humans. 
Thus, OSHA finds that the body of scientific studies contained in the 
BD record, which includes well-conducted animal bioassays, human 
epidemiologic studies, and other experimental investigations, provides 
convincing evidence that BD is a probable human carcinogen.
    This view is also held by other scientific organizations that have 
examined some or all of the same evidence. EPA considers BD to be a 
probable human carcinogen, and NIOSH regards BD as a potential 
occupational carcinogen and recommends controlling exposures to the 
lowest feasible level. In 1983, based on the findings of the first NTP 
bioassay alone, ACGIH classified BD as an animal carcinogen and, in the 
following year, recommended a new TLV of 10 ppm. In 1992, before the 
Delzell et al. study was released, IARC classified BD as a probable 
human carcinogen (Group 2A).
    As discussed in the Quantitative Risk Assessment section, OSHA has 
selected the NTP II mouse bioassay for quantitative assessment of 
cancer risks for several reasons. Chief among these is that the NTP II 
study was conducted at BD concentrations that are representative of 
current exposure conditions and that the results demonstrated a strong 
dose-response relationship for several cancer sites. In addition, the 
study is of very high quality and pathology results from individual 
animals were available to the Agency, enabling OSHA to use a time-to-
tumor model that could account for the early cancer-related deaths that 
occurred among the test animals (competing risks). OSHA also chose to 
base its risk estimates on the dose-response relationships for three 
cancer types: lung, ovarian, and lymphoma. The incidence of each was 
significantly elevated. It should be noted that pooling the total 
number of animals having any of these tumor types would have yielded 
risk estimates higher than OSHA's final values.
    Because data were available on individual animals, including time 
of death, OSHA chose to use a Weibull time-to tumor form of the 
multistage model based on the biological assumption that cancer is 
induced by carcinogens through a series of events. This model has the 
advantage of accounting for competing risks.
    The multistage model is most frequently used by OSHA; it is also a 
mechanistic model based on the biological assumption that cancer is 
induced by carcinogens through a series of independent stages. The 
model may be conservative, because it assumes no threshold for 
carcinogenesis and because it is approximately linear at low doses, 
although there are other plausible models of carcinogenesis which are 
more conservative. The Agency believes that the multistage model 
conforms most closely to what we know about the etiology of cancer, 
including the fact that linear-at-low-dose behavior is expected for 
exogenous agents, which increases the risk of cancer already posed by 
similar ``background'' processes. There is no evidence that the 
multistage model is biologically incorrect and abundant evidence 
supports its use, especially for genotoxic carcinogens, a category that 
most likely includes BD. OSHA's preference is consistent with the 
position of the Office of Science and Technology Policy of the 
Executive Office of the President, which recommends that ``when data 
and information are limited, and when much uncertainty exists regarding 
the mechanisms of carcinogenic action, models or procedures that 
incorporate low-dose linearity are preferred when compatible with 
limited information.'' (OSTP, Chemical Carcinogens: A Review of the 
Science and Its Associated Principles. Federal Register, March 14, 
1985, p. 10379)
    The BD record contained a great deal of commentary on the possible 
role of the principal epoxide metabolites of BD on the development of 
cancer in test animals, and on whether differences in BD metabolism, 
distribution, and excretion can explain the observed differences in 
cancer responses between BD-exposed mice and rats. In evaluating this 
information, OSHA explored the possibility of using a physiologically-
based pharmacokinetic (PBPK) approach to estimate cancer risk among BD-
exposed workers. In considering the use of PBPK modeling for estimating 
equivalent human dose in its final risk assessment for BD, OSHA 
considered several preselected criteria for judging whether the 
available data was adequate to permit OSHA to rely on a PBPK analysis 
in place of administered exposure levels. These are the same criteria 
that OSHA has recently used to rely on a PBPK-based analysis in its 
risk assessment of methylene chloride. The criteria included the 
following:
    1. The predominant and all relevant minor metabolic pathways must 
be well described in several species, including humans.
    2. The metabolism must be adequately modeled.

[[Page 56793]]

    3. There must be strong empirical support for the putative 
mechanism of carcinogenesis.
    4. The kinetics for the putative carcinogenic metabolic pathway 
must have been measured in test animals in vivo and in vitro and in 
corresponding human tissues at least in vitro.
    5. The putative carcinogenic metabolic pathway must contain 
metabolites that are plausible proximate carcinogens.
    6. The contribution to carcinogenesis via other pathways must be 
adequately modeled or ruled out as a factor.
    7. The dose surrogate in target tissues used in PBPK modeling must 
correlate with tumor responses experienced by test animals.
    8. All biochemical parameters specific to the compound, such as 
blood:air partition coefficients, must have been experimentally and 
reproducibly measured. This must especially be true for those 
parameters to which the PBPK model is sensitive.
    9. The model must adequately describe experimentally measured 
physiological and biochemical phenomena.
    10. The PBPK models must have been validated with other data 
(including human data) that were not used to construct the models.
    11. There must be sufficient data, especially data from a broadly 
representative sample of humans, to assess uncertainty and variability 
in the PBPK modeling.
    For the BD risk assessment, OSHA has chosen to use for animal-to-
human dose equivalency mg/kg-day uptake based on the ppm exposure 
levels in the NTP II mouse study as the dose-metric.7 While the 
body of data in the record leads OSHA to conclude that metabolism of BD 
to active metabolites is probably necessary for carcinogenicity, OSHA 
has chosen total body uptake rather than organ metabolic levels because 
the Agency was unable to determine from the record (a) which of the 
active metabolites are responsible for which observed tumors in the 
mice, (b) what the mouse and human metabolic equivalent doses were, (c) 
whether any of the PBPK models can successfully correlate with the 
tumor responses observed in mice and rats, and (d) whether local 
reactions in the mouse and human bone marrow were more important than 
total body burden. OSHA would have considered using BD metabolite body 
burden based on total human BD metabolites if the human chamber 
concentration data had been available, which would support estimating 
total human BD metabolism. Data of this type were available and used in 
OSHA's PBPK modeling for methylene chloride. In the absence of human 
chamber data or some better estimate of human equivalent dose, OSHA has 
chosen to use mg/kg-day BD uptake from the ppm inhalation exposure 
levels in the NTP II mouse bioassay as suitable for animal-to-human 
equivalency.
---------------------------------------------------------------------------

    \7\ A dose metric is the way in which dose is expressed in 
describing a dose-response relationship. A dose metric may be 
expressed as an applied dose, such as ppm concentration or mg of 
intake per kg body weight, or as an internal dose, such as mg per 
gram wet weight of an organ or mg of total metabolite formed per kg 
body weight.
---------------------------------------------------------------------------

C. Material Impairment of Health

    The 1 ppm 8-hour TWA PEL is designed to reduce cancer risks among 
exposed workers. As mentioned above and in the Health Effects section, 
some epidemiological studies indicate that the increased risk of 
leukemia posed by BD exposure may occur within a short period after 
initial exposure. (This is supported by the NTP mouse bioassays, in 
which there was high early mortality resulting from the development of 
BD-induced cancers, especially lymphomas.) Therefore, OSHA believes 
these hematopoietic cancers are likely to be fatal, will result in 
substantially shortened worker lifespans, and clearly represent 
``material impairment of health'' as defined in the OSH Act and case 
law.
    OSHA has also concluded that exposure to BD is associated with a 
potential risk of adverse reproductive effects in both males and 
females. This conclusion is based on the two NTP animal bioassays, 
which found testicular atrophy in male mice exposed to 625 ppm BD and 
ovarian atrophy in female mice exposed to BD concentrations as low as 
6.25 ppm, as well as other animal studies that have reported dominant 
lethal effects (indicating a genotoxic effect on germ cells) and 
abnormal sperm morphology in BD-exposed male mice. (Exs. 23-74, 23-75, 
117-1) There is also evidence that BD exposure is associated with 
fetotoxicity in mice, and a teratogenic effect indicative of a 
transplacentally induced somatic cell mutation was observed in one 
mouse study. (Exs. 2-32, 23-72, 126) OSHA believes that teratogenic 
effects and gonadal atrophy would also unambiguously constitute 
``material impairment of health.'' Furthermore, although OSHA did not 
quantify reproductive risks that may be associated with exposure to BD, 
OSHA believes that reducing the 8-hour TWA PEL from 1,000 ppm to 1 ppm 
is likely to substantially reduce this risk.

D. Risk Estimates

    OSHA's final estimate of excess cancer risks associated with 
exposure to 5 ppm BD (8-hour TWA) ranges from 11.2 to 59.4 per 1000, 
based on lymphomas, lung tumors and ovarian tumors seen in the NTP II 
mouse study (OSHA did not estimate the risks associated with exposure 
to the current PEL of 1,000 ppm, since workers are rarely, if ever, 
exposed to BD levels of that magnitude). Based on linear models the 
estimated risks at the new PEL of 1 ppm range from 1.3 to 8.1 per 1000, 
which represents a substantial reduction in risk from those associated 
with exposures to 5 ppm or greater.
    OSHA's risk estimates for the 1 ppm PEL are similar in magnitude 
to, or lower than, most of the estimates contained in several risk 
assessments submitted to the BD record, which utilized a variety of 
models and dose metrics. Furthermore, NIOSH's quantitative assessment 
based on the Delzell et al. epidemiologic study of SBR workers yielded 
an estimate of 8 cancer deaths per 1,000 workers exposed to 1 ppm BD, a 
figure that is in close agreement with the upper end of the range of 
risks predicted by OSHA.
    Risks greater than or equal to 10-3 (1 per 1,000) are clearly 
significant and the Agency deems them unacceptably high. OSHA concludes 
that the new BD standard substantially lowers risk but does not reduce 
risk below the level of insignificance. The estimated levels of risk at 
1 ppm are 1.3 to 8.1 per 1000. The ancillary provisions including the 
exposure goal program will further reduce risk from exposure to BD.

E. ``Significant Risk'' Policy Issues

    Further guidance for the Agency in evaluating significant risk and 
narrowing the million-fold range described in the ``Benzene Decision'' 
is provided by an examination of occupational risk rates, legislative 
intent, and the academic literature on ``acceptable risk'' issues. For 
example, in the high risk occupations of mining and quarrying, the 
average risk of death from an occupational injury or an acute 
occupationally-related illness over a lifetime of employment (45 years) 
is 15.1 per 1,000 workers. The typical occupational risk of deaths for 
all manufacturing industries is 1.98 per 1,000. Typical lifetime 
occupational risk of death in an occupation of relatively low risk, 
like retail trade, is 0.82 per 1,000. (These rates are averages derived 
from 1984-1986 Bureau of Labor Statistics data for employers with 11 or 
more employees, adjusted to 45 years of employment, for 50 weeks per 
year).

[[Page 56794]]

    Congress passed the Occupational Safety and Health Act of 1970 
because of a determination that occupational safety and health risks 
were too high. Congress therefore gave OSHA authority to reduce 
significant risks when it is feasible to do so. Within this context, 
OSHA's final estimate of risk from occupational exposure to BD at 
levels of 2 ppm (2.5 to 16.2 deaths per 1,000 workers) or higher is 
substantially higher than other risks that OSHA has concluded are 
significant, is substantially higher than the risk of fatality in some 
high-risk occupations, and is substantially higher than the example 
presented by the Supreme Court in the benzene case. Moreover, a risk in 
the range of 1.3 to 8.1 per 1000 at 1 ppm is also clearly significant; 
therefore, the PEL must be set at least as low as the level of 1 ppm 
documented as feasible across all industries.
    Because of technologic feasibility considerations, OSHA could not 
support promulgating a PEL below 1 ppm. However OSHA has integrated 
other protective provisions into the final standard to further reduce 
the risk of developing cancer among employees exposed to BD.
    Based on OSHA's QRA, employees exposed to BD at the 8-hour TWA PEL 
limit, without the benefit of the supplementary provisions, would 
remain at significant risk of developing adverse health effects, so 
that inclusion of other protective provisions, such as medical 
surveillance and employee training, is both necessary and appropriate. 
The exposure goal program and action level trigger incorporated into 
the standard will encourage employers to lower exposures below 0.5 ppm 
to further reduce significant risk if it is feasible to do so in their 
workplaces. Consequently, the programs triggered by the action level 
will further decrease the incidence of disease beyond the predicted 
reductions attributable merely to a lower PEL.
    As OSHA has explained, numerous issues arise in quantifying 
estimated risk to workers from BD. Such estimates are thus inherently 
uncertain; and, as more information becomes available, some of that 
uncertainty may be addressed and may substantially alter the risk 
estimate. Although OSHA believes the estimates fulfill its legal 
obligation to provide substantial evidence of significant risk the 
estimates should not be interpreted as a precise quantification of the 
cancer risk associated with the new PEL, or as demonstrated evidence of 
actual worker disease caused by BD.
    OSHA's determination of significant risk is predicated, consistent 
with empirical evidence and the legal mandates of the OSHA Act, on 
determining the risk to a worker exposed to BD for a working lifetime 
(45 years) at the PEL. To the extent that future exposures to BD are 
(substantially) lower than 1 ppm, the estimated risks associated with 
those exposures will be (substantially) lower than the range presented 
in OSHA's QRA.
    OSHA believes the final standard will reduce the risks of BD below 
those estimated using the mathematical model. The estimates of risk 
consider only exposures at the PEL, and do not take fully into account 
the other protective provisions of the standard such as medical 
surveillance, hazard communication, training, monitoring, and the 
exposure goal program. The decrease in risk to be achieved by 
additional provisions cannot be adequately quantified beyond a 
determination that they will add to the protection provided by the 
lower PEL alone. OSHA has determined that employers who fulfill the 
provisions of the standard as promulgated will provide protection for 
their employees from the hazards presented by occupational exposure to 
BD well beyond those which would be indicated solely by reduction of 
the PEL.
    Furthermore, as discussed above and in the Health Effects section, 
there is evidence from the NTP bioassays that exposure to periodic high 
concentrations of BD may be associated with a higher cancer risk 
compared to an equivalent cumulative exposure administered over a 
longer time frame. OSHA has included a 5 ppm short-term exposure limit 
(STEL), averaged over 15 minutes, to provide protection to employees 
who are exposed to elevated BD concentrations during brief periods, 
such as in maintenance work.
    As a result, OSHA concludes that its 8-hour TWA PEL of 1 ppm and 
associated action level (0.5 ppm) and STEL (5 ppm) will reduce 
significant risk and that employers who comply with the other 
provisions of the standard will be taking feasible, reasonable, and 
necessary steps to help protect their employees from the hazards of BD.

VIII. Summary of the Final Economic Analysis

    As required by Executive Order 12866 and the Regulatory Flexibility 
Act of 1980 (as amended 1996), OSHA has prepared a Final Economic 
Analysis to accompany the final standard for occupational exposure to 
1,3-butadiene (BD). (The entire analysis, with supporting appendix 
material, has been placed in the BD rulemaking docket. See Exhibit 
137.) The purpose of the final economic analysis is to:
     Describe the need for a standard governing occupational 
exposure to 1,3- butadiene;
     Identify the establishments and industries potentially 
affected by the standard;
     Evaluate the costs, benefits, economic impacts and small 
business impacts of the standard on affected firms;
     Assess the technological and economic feasibility of the 
standard for affected establishments, industries, and small businesses; 
and
     Evaluate the availability of effective non-regulatory 
approaches to the problem of occupational exposure to 1,3-butadiene.

Need for the Standard

    OSHA's final BD standard covers occupational exposures to this 
substance, a high-volume chemical used principally as a monomer in the 
manufacture of a wide range of synthetic rubber and plastic polymers 
and copolymers. In all, about 9,700 employees are estimated to be 
exposed to BD. However, for 2,100 of these employees in the petroleum 
refining industry, BD exposures are below the action level. The largest 
group of exposed workers is found in the BD end-product industry. Other 
BD operations in which workers are exposed are crude BD production, BD 
monomer production, and transportation terminals handling BD monomers 
(stand-alone terminals).
    There is strong evidence that workplace exposure to BD poses an 
increased risk of cancer. Animal bioassays have shown BD to be a source 
of significant risk for tumors at multiple sites (i.e. lung tumors, 
heart hemangiosarcomas, lymphomas and ovarian tumors). BD may also 
potentially cause both male and female reproductive effects. To protect 
all BD-exposed workers from these adverse health effects, the final 
standard lowers the airborne concentration of BD to which workers may 
be exposed from the current permissible exposure limit (PEL) of 1,000 
ppm as an 8-hour time-weighted average (8-hour TWA) to 1 ppm, and adds 
a short term exposure limit (STEL) of 5 ppm, measured over 15 minutes. 
(For a detailed discussion of the risks posed to workers from exposure 
to BD, see the Quantitative Risk Assessment and Significance of Risk 
sections of the preamble, above.)
    OSHA's final BD standard is similar in format and content to other 
health standards issued under Section 6 (b)(5)

[[Page 56795]]

of the Act. In addition to PELs, the standard requires employers to 
monitor the exposures of workers; establish regulated areas when 
exposures may exceed one of these PELs; implement engineering and work 
practice controls to reduce employee exposures to BD; develop an 
exposure goal program; provide respiratory protection to supplement 
engineering controls where such controls are not feasible, are 
insufficient to meet the PELs, are necessary for short infrequent jobs, 
or in emergencies; provide medical screening; train workers about the 
hazards of BD (also required by OSHA's Hazard Communication Standard); 
and keep records relating to the BD standard. Recognizing that workers 
exposed to BD are at significant risk, an industry-labor working group 
joined together to develop joint recommendations for the final standard 
for BD. This group's recommendations form the basis for OSHA's final 
rule. The contents of the standard are explained briefly in Chapter I 
of the final economic analysis and in detail in the Summary and 
Explanation (Section X of the preamble, below).
    Chapter II of the economic analysis describes the uses of BD and 
the industries in which such use occurs. Exposure to 1,3-butadiene 
occurs as a result of exposure to the monomer. Once BD is in polymer 
form, the exposure is minimal to non-existent. In all, OSHA analyzed 5 
types of processes in which BD exposure occurs: crude BD production, 
where the feedstock for BD monomer is produced; BD monomer production, 
in which BD is refined from crude BD to a 99 percent pure monomer; BD 
product manufacture, where BD monomer is converted to various polymer 
products; stand-alone terminals, which receive, store and distribute BD 
monomer; and petroleum refineries, where BD may occur as an unwanted 
byproduct in some types of refining units. Table VIII-1 shows these 
industry operations and the number of workers affected by the final 
rule. A total of 255 facilities are estimated to be potentially 
affected by the standard. These establishments employ 9,700 workers who 
are estimated to be exposed to BD in the course of their work. The 
industry operation with the largest number of directly exposed 
employees is BD product manufacture, which has 6,500 exposed employees 
(over two-thirds of the total).

Table VIII-1.--Industry Operations and Number of Workers Affected by the
                      Final Rule for 1,3-Butadiene                      
------------------------------------------------------------------------
                                                              Number of 
                                                 Number of    facilities
                                                  affected   in industry
                                                  workers         a     
------------------------------------------------------------------------
Crude 1,3-Butadiene Production................          540           27
1,3-Butadiene Monomer Production..............          552           12
1,3-Butadiene Polymer Product Manufacture.....        6,461         c 71
Standard-Alone Terminals......................           50            5
                                               -------------------------
    Subtotal..................................        7,603          115
                                               -------------------------
Petroleum Refining Sector.....................      b 2,100          140
                                               -------------------------
    Total.....................................        9,703          255
------------------------------------------------------------------------
Source: U.S. Department of Labor, OSHA, Office of Regulatory Analysis,  
  1996.                                                                 
a Some facilities may fall under several industry sectors. For example, 
  9 monomer facilities are also crude producing facilities.             
b Potential exposures to 1,3-butadiene are low and of extremely short   
  duration in refining.                                                 
c Represents number of processes and not necessarily plants.            

    Chapter III of the analysis assesses the technological feasibility 
of the final standard's requirements, and particularly its PELs, for 
firms in the 5 industry operations with employee exposure identified in 
the Industry Profile. OSHA finds, based on an analysis of exposure data 
taken on workers performing the BD-related tasks identified for each 
operation, that compliance with the standard is technologically 
feasible for establishments in the industries studied. With few 
exceptions, employers will be able to achieve compliance with both PELs 
through the use of engineering controls and work practices. The few 
exceptions are maintenance activities, such as vessel cleaning, which 
have traditionally often involved the use of respiratory protection.
    The exposure data relied on by OSHA in making its technological 
feasibility determinations were gathered by NIOSH in a series of site 
visits to plants in the affected industries. These data show that many 
facilities in the affected industries have already achieved the 
reductions in employee exposures required by the final rule. At least 
some workers in every job category work in facilities that have already 
achieved the PEL requirements. OSHA's analysis of technological 
feasibility evaluates employee exposures at the operation or task level 
to the extent that such data are available. In other words, the 
analysis identifies relevant exposure data on a job category-by-job 
category basis to permit the Agency to pinpoint those BD-exposed 
workers and job operations that are not yet under good process control 
and will thus need additional controls (including improved 
housekeeping, maintenance procedures, and employee work practices) to 
achieve compliance. Costs are then developed (in Chapter V of the 
economic analysis) for the improved controls needed to reach the new 
levels.
    The benefits that will accrue to BD-exposed employees and their 
employers, and thus to society at large, are substantial and take a 
number of forms. Chapter IV of the analysis describes these benefits, 
both in quantitative and qualitative form. At the current baseline 
exposure levels to BD, the risk model estimates that 76 cancer deaths 
will be averted over a 45-year period. By reducing the total number of 
BD-related cancer deaths from 76 deaths to 17 deaths over 45 years, the 
standard is projected to save an average of 1.3 cancer deaths per year. 
Table VIII-2 shows these risk estimates. In addition to cancer deaths, 
the standard may prevent male and female reproductive effects.

  Table VIII-2.--Worker Exposure to BD and Lung Cancer Risk Over 45 Years At Current Exposure Levels and Levels 
                                           Expected Under the Standard                                          
----------------------------------------------------------------------------------------------------------------
                                                           8-hour time weighted average (ppm)                   
                                       -------------------------------------------------------------------------
                                         0-0.5   0.5-1.0     1     1.0-2.0  2.0-5.0   5.0-10.0    10+c    Total 
----------------------------------------------------------------------------------------------------------------
Lifetime Excess Cancer Risk (per                                                                                
 thousand workers)a...................     2.05      6.1      8.1    12.15     28.1         60      480  .......
Baseline Number of Workers Exposed....     5697      354      156      598      320        440       38     7603
Estimated Excess Deaths in Baseline                                                                             
 (Existing PEL)b......................       12        2        1        7        9         27       18       76
Predicted Number of Workers Exposed at                                                                          
 New PEL..............................     7177      426        0        0        0          0        0     7603

[[Page 56796]]

                                                                                                                
Predicted Excess Deaths at New PELb...       14        3        0        0        0          0        0       17
----------------------------------------------------------------------------------------------------------------
a Based on OSHA 1-stage Weibull time-to-tumor model for lung tumors.                                            
b Computed as level of lifetime risk times the number of exposed workers.                                       
c Based on a median exposure for these workers of 60 ppm.                                                       
Source: Office of Regulatory Analysis, OSHA; Department of Labor.                                               

    The costs employers in the affected industries are estimated to 
incur to comply with the standard total $2.9 million in 1996 dollars. 
These costs, which are presented in Chapter V, the full economic 
analysis, are annualized over a 10-year horizon at a discount rate of 7 
percent. Table VIII-3 shows annualized costs by provision of the 
standard; the most costly provisions are those requiring engineering 
controls ($1.6 million per year) and respiratory protection ($0.7 
million per year). Table VIII-4 analyzes compliance costs by operation 
and shows that BD products manufacture will incur over two-thirds of 
the standard's costs of compliance.

     Table VIII-3.--Annual Costs of the Final Butadiene Standard, by    
                                Provision                               
------------------------------------------------------------------------
                                                              Annualized
                         Provision                              costs   
------------------------------------------------------------------------
Engineering Controls.......................................   $1,551,000
Exposure Goal Program......................................      104,000
Respirators................................................      685,000
Exposure Monitoring........................................      364,000
Objective Data.............................................        3,000
Medical Surveillance.......................................       72,000
Leak and Spill Detection...................................       27,000
Regulated Areas............................................        4,000
Information and Training...................................       12,000
Recordkeeping..............................................       29,000
                                                            ------------
  Total....................................................    2,851,000
------------------------------------------------------------------------


Table VIII-4.--Annual Costs of the Final Butadiene Standard, by Industry
                                 Sector                                 
------------------------------------------------------------------------
                                                              Annualized
                      Industry sector                           costs   
------------------------------------------------------------------------
Crude Production...........................................     $333,000
Monomer....................................................      210,000
BD Products................................................    2,252,000
Stand-Alone Terminals......................................       53,000
Petroleum Refining.........................................        3,000
                                                            ------------
    Total..................................................    2,851,000
------------------------------------------------------------------------

    Chapter VI of the economic analysis analyzes the impacts of 
compliance costs on firms in affected operations. The final rule is 
clearly economically feasible: annualized compliance costs are less 
than 0.5 percent of estimated sales in every industry and are less than 
4 percent of profits in every industry (see Table VIII-5). Costs of 
this magnitude will not affect the viability even of marginal firms.

        Table VIII-5.-- Estimated Sales and Profits of Establishments Affected by the 1,3-Butadiene Rule        
----------------------------------------------------------------------------------------------------------------
                                                             Pre-tax                                            
                                             Sales per      profit per     Annualized     Cost as      Cost as  
                                    SIC       average        average        cost per     percentage   percetage 
                                           establishment  establishment  establishment    of sales    of profit 
                                               ($000)         in SIC                                            
----------------------------------------------------------------------------------------------------------------
Crude 1,3-Butadiene Production..     2869       $53,998     $5,645,237        $12,341          0.02         0.22
1,3-Butadiene Monomer Production     2869        53,998      5,645,237         17,502          0.03         0.31
1,3-Butadiene Product                                                                                           
 Production:                                                                                                    
  --ABS Resins, Butadiene                                                                                       
   Copolymers (<50% butadiene)..     2821        38,000      2,015,155         31,724          0.08         1.57
  --Butadiene Copolymers (.50%                                                                                  
   butadiene), Neoprene, Nitrile                                                                                
   Rubber, Chloroprene Rubbers,                                                                                 
   EPDM Polymers, Styrene-                                                                                      
   Butadiene Rubber (SBR Latex),                                                                                
   Polybutadiene................     2822        16,243      1,328,956         31,724          0.20         2.39
  --Adipontrile/Hexamethylene...     2869        53,998      5,645,237         31,724          0.06         0.56
  --Fungicides..................     2879        42,694      1,681,885         31,724          0.07         1.89
Petroleum Refining..............     2911       525,273     19,100,851             22    Negligible   Negligible
Stand-Alone Terminals...........     4226         2,400        287,273         10,556          0.44        3.67 
----------------------------------------------------------------------------------------------------------------
Source: US Department of Labor, OSHA, Office of Regulatory Analysis, 1996.                                      
Negligible denotes less than 0.005 percent.                                                                     

    Under the Regulatory Flexibility Act, OSHA is required to determine 
whether its regulations have a significant impact on a substantial 
number of small entities. The small firm standards established by the 
U.S. Small Business Administration (SBA) for industries using 1,3-
butadiene are as follows: 1,500 employees for firms in SIC 2911 
(petroleum refining); 1,000 employees for firms in SICs 2869 
(industrial organic chemicals, which includes BD crude and monomer 
producers) and 2822 (synthetic rubber); 750 employees for firms in SIC 
2821 (plastic Table VIII-5 materials and resins); 500 employees for 
firms in SIC 2879 (agricultural chemicals, which includes some 
producers of BD products); and annual receipts of $18.5 million for 
firms in SIC 4226 (special warehousing and storage, which includes 
stand-alone terminals). Using these definitions, OSHA identified two 
small firms among crude

[[Page 56797]]

BD producers, one small firm among monomer producers, 10 small firms 
among BD product manufacturers, and no small firms among stand-alone 
terminals. Because the ownership of one stand-alone terminal could not 
be identified, OSHA assumed that there would be one small stand-alone 
terminal. For each of these industries, OSHA estimated revenues and 
costs for small firms based on the average size of the small firms 
using BD. The typical petroleum refining establishment has fewer than 
1,500 employees. However, because OSHA did not have data on the number 
of firms with fewer than 1,500 employees, the Agency relied on 
establishment data to examine possible impacts on small petroleum 
refineries.
    Table VIII-6 presents the results of the regulatory flexibility 
screening analysis and shows estimated compliance costs and economic 
impacts relative to revenues and pre-tax income for affected small 
businesses at the four-digit SIC code level. This approach reflects 
extreme case impacts because the impacts on small firms are analyzed 
using average per-establishment compliance costs. As shown in the 
table, compliance costs as a percentage of industry revenues never 
reach one percent; they range from less than 0.005 percent to 0.44 
percent for establishments in all affected industries. Estimates of 
compliance costs as a percentage of profits range from less than 0.005 
percent to 3.67 percent. Such impacts are not large enough to be 
significant. In addition, the impacts reflected in the table are likely 
to be overestimated because Table VIII-6 they are based on extreme-case 
costs.

                             Table VIII-6.--Estimated Sales and Profits of Establishments Affected by the 1,3-Butadiene Rule                            
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                     Pre-tax                                            
                                                                                   Average sales    profit per     Annualized     Cost as      Cost as  
                                              SIC     Definition of small entity     per small        small         cost per     percentage   percentage
                                                             per the SBA           establishment  establishment  establishment    of sales    of profit 
                                                                                     ($million)       in SIC                                            
--------------------------------------------------------------------------------------------------------------------------------------------------------
Crude 1,3-Butadiene production............    2869  1,000 employees..............         51.30      $5,363,182       $12,341          0.02         0.23
1,3-Butadiene Monomer production..........    2869  1,000 employees..............         10.60       1,108,182        17,502          0.17         1.58
1,3-Butadiene product production:                                                                                                                       
    ABS Resins, Butadiene Copolymers (<50%    2821  750 employees................         50.00       2,651,515        31,724          0.06         1.20
     butadiene).                                                                                                                                        
    Butadiene Copolymers (.50% butadiene),    2822  1,000 employees..............         24.00       1,963,636        31,724          0.13         1.62
     Neoprene, Nitrile Rubber, Chloroprene                                                                                                              
     Rubbers, EPDM Polymers Styrene-                                                                                                                    
     Butadiene Rubber (SBR Latex),                                                                                                                      
     Polybutadiene.                                                                                                                                     
    Adiponitrile/Hexamethylenediamine.....    2869  1,000 employees..............         10.60       1,108,182        31,724          0.30         2.86
Fungicides................................    2879  500 employees................         30.40       1,197,578        31,724          0.10         2.65
Petroleum refining........................    2911  1,500 employees..............         45.80       1,655,455            22    Negligible   Negligible
Stand-alone terminals.....................    4226  $18.5 million (receipts).....          2.40         287,273        10,556          0.44        3.67 
--------------------------------------------------------------------------------------------------------------------------------------------------------
Source: US Department of Labor, OSHA, Office of Regulatory Analysis, 1996.                                                                              
Negligible denotes less than 0.005 percent.                                                                                                             

    Thus, because this standard will not have a significant impact 
either on the smallest establishments (as defined by the SBA) or on the 
typical establishment in this industry, OSHA certifies that this final 
standard will not have a significant economic impact on a substantial 
number of small entities.
    OSHA also examined the impact of this standard on increased 
expenditures by State, local or tribal governments. OSHA found that 
none of the affected employers were State, local, or tribal 
governments. Further, since the total costs of the standard are $2.8 
million, the stand will not increase expenditures for the private 
sector by more than $100 million. As a result, OSHA certifies that, for 
the purposes of the Unfunded Mandates Reform Act of 1995, as well as 
E.O. 12875, this rule does not include any federal mandate that may 
result in increased expenditures by State, local and tribal 
governments, or increased expenditures by the private sector of more 
than $100 million.

IX. Environmental Impacts

    In accordance with the National Environmental Policy Act (NEPA), 
OSHA has reviewed this standard for occupational exposure to BD and 
determined that this action will have no significant impact on the 
external environment. The new standard can be achieved through a 
combination of engineering controls, work practices, and respirator use 
in maintenance situations. OSHA reviewed the extent to which any of the 
engineering controls or work practices might have an environmental 
impact. OSHA found that these controls will have no significant adverse 
impact on the eternal environment because no additional solid waste 
would be contaminated with BD and that any new releases to the external 
atmosphere would constitute an insignificant increase in emissions. 
Indeed, most of the recommended controls would prove advantageous from 
an environmental viewpoint. For example, such controls as replacing 
slip-tube gauges with magnetic gauges, use of closed loop sampling 
systems, and the use of dual mechanical seals all serve to reduce both 
worker exposures and emissions to the environment. Other controls, such 
as exhaust ventilation in laboratories, leave environmental emissions 
unchanged.
    Based on its review, OSHA concludes that there will be no 
significant impact on the environment external to the work place as a 
result of the promulgation of this standard.

X. Summary and Explanation of the Final Standard

    OSHA has determined that the requirements set forth in this final 
standard are those which, based on currently available data, are 
necessary and appropriate to provide adequate protection to employees 
exposed to BD. In the development of this standard, OSHA carefully 
considered the comments received in the docket in response to the 
proposed rule as well as information received in the BD docket by OSHA 
since initiation of this

[[Page 56798]]

rulemaking. OSHA believes that these provisions are, in large part, 
similar to the requirements recommended by the labor/industry group in 
the recent reopening of the BD rulemaking record. (Ex. 118-12A)

A. Scope and Application

    The final rule covers all occupational exposure to 1,3-butadiene, 
with certain exceptions which are described below. OSHA does not 
believe there are any impacts in construction or maritime employment, 
but, consistent with OSHA's policy, the standard is being made 
applicable to these sectors to avoid gaps in coverage and to protect 
workers in unusual circumstances. Coverage in longshoring and marine 
terminals would only be triggered if BD is present outside sealed 
intact containers.
    The final rule contains three exemptions from the scope and 
application; all three exemptions are typically included in OSHA 
chemical-specific health standards. These exemptions address situations 
in which the Agency has concluded that the likelihood of significant 
exposure is quite low. The final rule's exemptions are as follows:

    (a)(2)(i) Except for the recordkeeping provisions in paragraph 
(m)(1), this section does not apply to processing, use, or handling 
of products containing BD or to other work operations and streams in 
which BD is present where objective data are reasonably relied upon 
that demonstrate that the work operation or the product or the group 
of products or operations to which it belongs may not reasonably be 
foreseen to release BD in airborne concentrations at or above the 
action level or in excess of the STEL under either the expected 
conditions of processing, use, or handling that will cause the 
greatest possible release or in any plausible accident.
    (a)(2)(ii) This section also does not apply to work operations, 
products or streams where the only exposure to BD is from liquid 
mixtures containing 0.1% or less of BD by volume or the vapors 
released from such liquids, unless objective data become available 
that show that airborne concentrations can exceed the action level 
or STEL under reasonably predictable conditions of processing, use 
or handling that will cause the greatest possible release.
    (a)(2)(iii) Except for labeling requirements and requirements 
for emergency response, this section also does not apply to storage, 
transportation, distribution or sale of BD or liquid mixtures in 
intact containers or in transportation pipelines sealed in such a 
manner as to fully contain BD vapors or liquid.

    The language of this section, with a single exception, reflects the 
joint recommendations of the labor-industry group. The exception 
relates to the suggested language in the labor/industry agreement ``or 
in any credible accident'' at the end of paragraph (a)(2)(i).8 
(Ex. 118-12A) OSHA believes that this phrase lacks clarity and has 
chosen to use the word ``plausible'' instead of ``credible'' to better 
convey the Agency's intent. Dow Chemical Company, which reviewed a 
draft of the Agreement, objected to the use of the phrase ``credible 
accident'' because Dow personnel were unsure of its meaning. (Ex. 118-
16, p. 3) Additionally, OSHA has modified the definition of objective 
data to more clearly delineate its intended source and use.
---------------------------------------------------------------------------

    \8\ This section does not apply to processing, use, or handling 
of products containing BD or to other work operations and streams in 
which BD is present where objective data are reasonably relied upon 
that demonstrate that the work operation or the product or the group 
of products or operations to which it belongs may no reasonably be 
foreseen to release BD in airborne concentrations at or above the 
action level or in excess of the STEL under either the expected 
conditions of processing, use, or handling that will cause the 
greatest possible release or in any credible accident.
---------------------------------------------------------------------------

    Although the agreement itself offered little explanation for each 
of the recommended exemptions, the submission of CMA, a participant in 
the joint discussions, sheds some light on the issue of why the term 
``credible accident'' was included. They felt that the ``focus in 
applying the (objective data) exemption should be on reasonably 
predictable conditions of processing, use or handling associated with 
each product, stream or work operation.'' (Ex. 118-13, p. 3) CMA said 
that the addition of the phrase ``credible accident'' was meant to 
trigger only the emergency response requirements of the standard when 
objective data demonstrate that exposures may reasonably be foreseen to 
exceed the action level or STEL during a ``credible accident.''
    OSHA believes that the phrase ``credible accident'' is unnecessary 
because paragraph (a)(2)(i) already states that objective data may be 
used to address situations that can reasonably be foreseen. However, 
OSHA has decided to include the phrase ``any plausible accident'' to 
stress the point that the objective data criteria are not intended to 
be so circumscribed that it is impossible to meet them. OSHA 
acknowledges that a constellation of unforeseen circumstances can occur 
that might lead to exposure above the action level or STEL even when 
the objective data demonstration has been correctly made, but believes 
that such occurrences will be rare. OSHA further believes that 
compliance with other regulations, such as the Process Safety 
Management standard (29 CFR 1910.119), will provide additional 
assurance that such accidents will not occur.
    OSHA proposed to exempt ``processing, use, or handling of products 
containing BD where objective data are reasonably relied upon that 
demonstrate that the product is not capable of releasing BD in airborne 
concentrations at or above the action level or in excess of the STEL 
under the expected conditions of processing, use, or handling that will 
cause the greatest possible release * * *'' (55 FR 32736 at 32803) The 
proposed regulation also included a requirement that the employer keep 
the data supporting the exemption as long as such data were relied 
upon.
    Roger Daniel of the CMA BD panel objected to the requirement that 
in order to be relied upon as objective data, the data must reflect 
include the ``greatest possible release.'' He argued that ``* * * to 
verify the greatest possible release and thereby obtain an exemption, 
employers could be forced to conduct extensive worst case analyses for 
every product.'' (Ex. 112, p. 133)
    OSHA agrees that a worst-case demonstration for each product is not 
necessary to qualify for this exemption under the ``objective data'' 
provision of the scope and application paragraph of the standard. Due 
to concern that the proposed language might be overly difficult to 
interpret, OSHA has modified the language in the standard to reflect 
this and added a definition of the term ``objective data.'' The 
definition now states that ``objective data means monitoring data, or 
mathematical modelling or calculations based on composition, chemical 
and physical properties of a material, stream or product.'' The 
exemption allows use of objective data, and states that when objective 
data are used to exempt employers from the BD standard, the data must 
demonstrate that the work may not ``reasonably be foreseen'' to release 
BD above the action level or the STEL.
    The objective data may be, at least partially, comprised of 
monitoring results. For example, data collected by a trade association 
from its members that meet the definition of objective data may be 
used. However, a single employer's initial monitoring results would not 
be sufficient to meet the criteria for objective data under this 
standard (see discussion of objective data in Definitions section of 
this preamble). A showing by initial monitoring that the level of BD is 
below the action level does greatly reduce the responsibilities of the 
employer; however, it would not support an

[[Page 56799]]

exemption from the standard. Instead, to qualify as objective data, 
OSHA means employers' reliance on manufacturers' worst case studies, 
laboratory studies, and other research that demonstrate, usually by 
means of exposure data, that meaningful exposures cannot occur. 
Paragraph (a)(3) requires that all such data be maintained by the 
employer as long as they are relied upon to support the exemption.
    In comments received during the recent re-opening of the record, 
Total Petroleum suggested that objective data be kept as long as they 
are relied upon and for 5 years thereafter. (Ex. 118-5) However, OSHA 
believes that keeping these data for as long as they are used is a 
better use of resources, and this requirement is included in the final 
rule.
    OSHA has allowed the use of objective data in past standards to 
exempt employers from initial monitoring requirements and hence, from 
most of the provisions of these standards, e.g., formaldehyde 29 CFR 
1910.1048, asbestos 29 CFR 1926.1101. The American Petroleum Institute 
(API) and others voiced support for this approach. (Ex. 108; 112)
    The objective data definition is discussed more extensively in the 
definition section of this preamble.
    The following paragraphs deal with the comments and testimony 
received during the rulemaking on topics related to the scope and 
application of the standard. Some of these comments would appear to 
address both the objective data exemption and an exemption for 
materials containing less than 0.1% BD. This is due, in part, to the 
fact that the proposal did not contain an exemption for the latter 
materials, and commenters objected to having to make a demonstration 
using objective data that materials containing less than 0.1% BD would 
not release BD at levels in excess of the action level or STEL in order 
to be exempted. OSHA has reexamined the issue and has included the 0.1% 
BD cutoff in the final rule paragraph (a)(2)(ii).
Crude Oil and Refinery Products
    Oil refiners indicated that BD is absent from crude oil, and 
requested that OSHA explicitly exempt oil and gas well drilling, 
production and servicing operations, and transportation of crude oil 
from the standard. (Ex. 108; 109; 91) They also indicated that, 
although BD may be an undesirable intermediate by-product with trace 
quantities in enclosed streams in modern petroleum refinery processes, 
BD is normally destroyed, so it would not be present in refined 
products, such as gasoline, motor fuel, or other fuels. They asked for 
an exemption for those refined products.
    A site visit report was submitted to the rulemaking record by 
OSHA's contractor, Kearney/Centaur, which described the processes at a 
refinery. (Ex. 23-119) The site visit report contained the following 
conclusions:

    The concentrations of 1,3-butadiene in the process streams 
studied rarely if ever exceed 2500 ppm. * * * The contents of the 
streams are released to the atmosphere only in extremely small 
quantities through sampling, or by significant spills, leaks or 
accidents. * * * Employees are rarely in close proximity to the 
sampling points or any other potential release point. * * * 
Monitoring data show that exposures are well below the proposed 
limits, below the actions levels and even below measurable levels in 
most cases. (Ex. 23-119)

Based on these comments and data in the docket, OSHA has included the 
exemption for ``streams'' containing less than 0.1% BD, such as those 
found in refineries, and in the final rule has included streams among 
the items for which an objective data exemption can be claimed.
Polymers
    Duke Power asked OSHA to exempt finished BD polymer from the BD 
standard to be consistent with the vinyl chloride and acrylonitrile 
standards, so that the utility would not need to maintain records of 
objective data. (Ex. 32-12) The Rubber Manufacturers Association (RMA) 
said that ``synthetic rubbers made from polymerized BD are used 
extensively by (their 200 companies) members in manufacturing a wide 
range of these rubber products.'' (Ex. 32-13). In the preamble to the 
proposal, OSHA acknowledged that ``[i]t is likely that in a number of 
products made from, containing or treated with BD, there may be 
insignificant residual BD present to the extent that minimal exposure 
would be expected.'' (55 FR 32736 at 32787) RMA indicated that four 
studies indicated the levels of BD in the samples from their plants 
range from 4 ppb to 0.2 ppm. These values are clearly well below the 
0.1% cutoff in the final rule and the percentage exemption would 
therefore apply.
Intact Containers
    Exxon Chemical Company, a producer of BD, which ships it by several 
modes of transportation (ship, barge, tankcar, tanktruck and pipeline) 
indicated that there is no potential for BD exposure since BD-
containing streams are totally contained in pressurized equipment 
during transportation. (Ex. 32-17) Exxon said: ``The developing and 
maintaining the `objective' data would be very cumbersome (for many 
carriers and shipment points and various kinds of BD-containing 
streams) * * * time-consuming and would not contribute to reduced 
exposure.'' Exxon asked OSHA to provide a general exemption for intact 
transportation containers. The Independent Liquid Terminals Association 
(ILTA), whose members own or lease facilities in which BD is stored, 
asked OSHA to establish a concentration cutoff and to grant reasonable 
exemptions from the standard. (Ex. 32-18) Roger Daniel of the CMA panel 
made a similar request. (Tr. 1/18/91, p. 1174) The labor-industry 
agreement also recommended exemption of intact containers and pipelines 
from the standard except for labeling and emergency provisions. (Ex. 
119)
    OSHA is allowing the exemption of ``storage, transportation, 
distribution or sale of BD or liquid mixtures in intact containers or 
in transportation pipelines sealed in such a manner as to fully contain 
BD vapors or liquid,'' OSHA is not excluding by this exemption, the 
situation where BD-containing material is being transferred to or from 
containers, pipelines, or vehicles. Data have shown that there is a 
potential for significant exposure to BD during these operations. For 
example, exposure data indicate high potential exposure during 
unloading of railcars and tank trucks in both monomer and polymer 
production facilities. (Ex. 30) Such operations are not exempt from the 
standard-they are not considered ``sealed'' for purposes of this 
standard and do not ``fully contain BD vapors or liquid.''
Mixtures of Less Than 0.1% BD
    The final rule contains a specific, though qualified, exemption for 
instances where materials containing less than 0.1% BD are present.
    In the proposal, OSHA discussed the application of the Hazard 
Communication Standard (29 CFR 1910.1200) to materials containing less 
than 0.1% of BD, a carcinogen, but did not specifically include an 
exemption for these materials.
    Jack Hinton of Texaco, representative of API, which represents over 
250 companies involved in all aspects of the petroleum industry, 
indicated that

* * * many petroleum streams and products will have little or no BD 
present (and that) much of the petroleum industry, such as 
production, transportation and marketing operations would qualify 
for these case-by-case exemptions. (Ex. 74; Tr.2/20/91, p.1842-44).

Since the ``objective data'' obligation could impose a burden on their

[[Page 56800]]

industry, Mr. Hinton urged OSHA to expand the exemption to include the 
processing, use and handling of streams containing BD, as well as 
products. (Tr. 2/20/91, pp. 1842-44)
    Similarly, CMA stated, ``* * * facilities that manufacture, process 
or use BD often have very extensive, integrated operations.'' (Ex. 32-
28, p. 108; Ex. 112, p. 134) At these facilities, BD is found at 
quantities below 0.1% not just in the immediate area of BD production, 
but in many other streams and products as well. Under these 
circumstances, the burden of generating ``objective data'' which would 
qualify for the exemption would be ``so enormous as to largely 
eliminate its value.'' (Ex. 112, p. 134).
    Exxon Chemical Company also indicated that ``BD is present in a 
large number of product and intermediate streams throughout chemical 
plants and refineries.'' (Ex. 32-17) According to Exxon, there is very 
little exposure potential at low levels, since precautions are taken to 
contain these flammable materials and its rapid dispersion as a gas at 
ambient condition. Exxon suggested an exemption for product and 
intermediate streams containing less than 0.1 percent BD ``as is used 
in the Hazard Communication Standard and in the Benzene Standard.'' 
They claimed that their resources to develop ``objective data'' could 
be devoted to ``more productive activities aimed at exposure 
reduction.'' Arco Products Company stated that ``potential exposures 
are of extremely short duration in the refining business'' and asked 
for the exemption of ``streams with less than 0.1% as in the benzene 
final standard.'' (Ex. 32-20)
    OSHA has found that, on the basis of the record and comments of 
participants in the rulemaking, as well as the recommendations of the 
labor/industry group, the exemptions as stated above are justified. The 
criteria for each exemption are helpful in assuring that only very low 
exposure to BD is possible when the exemptions apply.
    The exemptions from the scope of the standard closely resemble 
those in the benzene standard. The exclusion of products containing 
less than 0.1 percent BD is consistent with the Hazard Communication 
Standard, which has this as a cutoff for application of certain 
requirements to carcinogens (paragraph (a)(2)(ii)).
    The basis for the exemptions for sealed containers and pipelines 
containing mixtures with more than 0.1 percent BD is that it is 
unlikely for such containers and pipelines to leak sufficient BD to 
expose employees over the action level on a regular basis. Further, 
sealed containers and pipelines with liquids containing more than 0.1 
percent BD are covered by the emergency provisions of the standard 
(e.g., personal protective equipment, medical screening). Sealed 
containers and pipelines are also covered by the Hazard Communication 
Standard, 29 CFR 1910.1200. If the containers or pipelines contain more 
than 0.1 percent BD, employers are required to: label the containers 
and pipelines to indicate that they contain BD, a carcinogen; to have 
employee training specifying what to do if the container was opened or 
broken; and to supply employees with material safety data sheets. 
Labeling and training provisions of the Hazard Communication Standard 
provide protection in normal situations where a container or pipeline 
breaks so that employees will know how to handle and clean up the 
material safely. The emergency provisions of the Hazardous Waste and 
Emergency Response Standard would cover emergency situations caused by 
major releases.
    Further, operations where the containers and pipelines are opened 
or the chemicals contained in them are used are covered because of the 
possibility of exposure above the action level or PELs. It should be 
noted that while the Hazard Communication Standard generally exempts 
materials containing less than 0.1 percent of a carcinogen, any 
material containing BD (defined as a potential carcinogen in this 
standard) that is capable of causing exposure above the action level is 
covered even if the 0.1 percent exemption applies. Specifically this 
provision states:

    If the chemical manufacturer, importer or employer has evidence 
to indicate that a component present in the mixture in 
concentrations of less than one per cent (or in the case of 
carcinogens, less than 0.1 percent) could be released in 
concentrations which would exceed an established OSHA permissible 
exposure limit or ACGIH Threshold Limit Value, or could present a 
health risk to employees in those concentrations, the mixture shall 
be assumed to present the same hazard. (29 CFR 1910.1200(d)(5)(iv))

OSHA also notes that a similar provision is included in the standard 
for DBCP (1,2-dibromo-3-chloropropane). (29 CFR 1910.1044).

B. Definitions

    Action level means airborne concentration of BD of 0.5 ppm 
calculated as an eight (8)-hour time-weighted average (TWA). OSHA has 
determined that the final PEL for BD is 1 ppm and the final action 
level for BD is one half that level, 0.5 ppm. OSHA notes that this is 
the action level recommended in the Labor-Industry Joint 
Recommendations. (Ex. 119)
    Due to the variable nature of employee exposures to airborne 
concentrations of BD, an action level provides a means by which the 
employer may have greater assurance that employees will not be exposed 
to BD over the PEL on days when measurements are not taken.
    The action level also increases the cost-effectiveness and 
performance orientation of the standard while improving employee 
protection. Employers who can, in a cost-effective manner, develop 
innovative methodology to reduce exposures below the action level will 
be encouraged to do so in order to save on the expenses for the 
monitoring and medical surveillance provisions of the standard. Their 
employees will be further protected because their exposures will be 
less than half of the permissible exposure limit. They will also avoid 
the need to implement controls specified under paragraph (g) of this 
section, Exposure Goal Program.
    The statistical basis for using an ``action level'' has been 
discussed in connection with several other OSHA health standards (see, 
for example, acrylonitrile (29 CFR Sec. 1910.1045; 43 FR 45809 (1978)). 
In brief, the standard does not require the employer to monitor 
employee exposure on a daily basis. This would be prohibitively 
expensive. Use of the action level is a method that gives the employer 
confidence that if employees are exposed to less than the action level 
on days when measurements are taken, they are most likely not exposed 
over the PEL on days when no measurements are taken--all other factors 
being equal. Where exposure measurements are above the action level, 
the employer cannot reasonably be confident that the employee may not 
be overexposed. Therefore, requiring periodic employee exposure 
measurements to be made where exposures are at or above the action 
level provides the employer with a reasonable degree of confidence that 
employee exposures have been adequately characterized. (Ex. 23-59)
    Use of the action level concept will result in the necessary 
inclusion of employees under this standard whose exposures are above 
the action level and for whom further protection is warranted. The 
action level mechanism will also greatly limit the percentage of 
workplaces covered under the standard because employers whose employees 
are under the action level will be exempt from most provisions of the 
standard. The action level concept,

[[Page 56801]]

therefore, provides an objective means of tailoring different sections 
of the standard to those employees who are at the greatest risk of 
developing adverse health effects from exposure to BD.
    Unique to the BD standard is paragraph (g), Exposure Goal Program, 
which is also triggered at the action level. This program, which OSHA 
included at the recommendation of the Labor/Industry group, is 
described further in the Summary and Explanation of paragraph (g).
    Assistant Secretary means the Assistant Secretary of Labor for 
Occupational Safety and Health, U.S. Department of Labor, or designee.
    Authorized person means any person specifically authorized by the 
employer whose duties require the person to enter a regulated area, or 
any person entering such an area as a designated representative of 
employees for the purpose of exercising the right to observe monitoring 
and measuring procedures, or any other person authorized by the Act or 
regulations issued under the Act. Due to the highly hazardous nature of 
BD exposure, the number of persons designated as authorized should be 
limited, insofar as possible.
    Business day is newly defined in the final rule as any Monday 
through Friday, except those days designated as federal, state, local 
or company holidays. (Ex. 18-12A) This term is used in the paragraph 
dealing with employee notification of monitoring results, (d)(7), in 
which OSHA had proposed that notification occur within 15 working days 
after the receipt of monitoring results. The joint labor/industry group 
recommended 5 business days instead. In addition, they recommended that 
the notification of the corrective action being taken when monitoring 
results indicate exposures in excess of the PELs be required within 15 
business days, (paragraph (d)(7)(ii)). OSHA has accepted the 
recommendations because it is protective of workers. As a general rule, 
OSHA health standards require notification within 15 days of receipt of 
results. Quicker notification is, of course, desirable, but feasibility 
considerations usually make the 15-day period the shortest practical. 
However, in this case, the parties agreed that 5-day notification is 
feasible and desirable and OSHA wholeheartedly endorses the concept.
    OSHA has also allowed 15 business days between medical evaluations 
and notification of employees of their results. This change was 
recommended by the labor/industry agreement and was not proposed by 
OSHA in 1990. OSHA believes that the requirement of paragraph (j)(7) 
requiring that written notification of the medical opinion be provided 
by the employer within 15 business days of the examination or other 
medical evaluation is reasonable and adequately protective of worker 
health.
    1,3-Butadiene means an organic compound with chemical formula 
CH2=CH-CH=CH2 which has a molecular weight of 54.15 gm/mole. 
Its Chemical Abstracts Registry Number is 106-99-0. The definition was 
needlessly lengthy in the proposal and has been shortened.
    OSHA has added a definition for the complete blood count required 
in the medical screening and surveillance section. Because the 
definition may vary, OSHA believes that a definition which includes 
each component of what the Agency requires to be included in a complete 
blood count is needed. These components (which are laboratory tests 
performed on whole blood specimens) are: White blood cell count (WBC), 
hematocrit (Hct), red blood cell count (RBC), hemoglobin (Hgb), 
differential count of white blood cells, red blood cell morphology, red 
blood cell indices, and platelet count.
    Day means any part of a calendar day. Therefore, if a requirement 
is applicable to an employer whose employee is exposed to BD on 10 days 
in a calendar year, that requirement is applicable if the employee is 
exposed to BD for any part of each of 10 calendar days in a year.
    Director means the Director of the National Institute for 
Occupational Safety and Health (NIOSH), U.S. Department of Health and 
Human Services, or designee. This definition remains unchanged from 
that in the proposal.
    OSHA proposed that Emergency situation would mean an occurrence 
such as, but not limited to, equipment failure, rupture of containers, 
or failure of control equipment that may or does result in a 
substantial release of BD that could cause employee exposures that 
greatly exceed the PELs.
    The provisions that the employer must comply with in case of an 
emergency situation include Respiratory Protection, Medical Screening 
and Surveillance, and Employee Information and Training. As is also the 
case in the benzene standard, OSHA does not intend that every leak will 
automatically constitute an emergency situation. The exposure must be 
high and unexpected. Thus, the nature of the emergency provisions is 
performance-oriented and relies upon judgement, for it is not possible 
to specify detailed circumstances which constitute an emergency.
    In objecting to the proposed definition of emergency, Shell noted 
that ``a release does not necessarily equate to high employee 
exposure.'' (Ex. 32-27) OSHA also sought additional guidance in its 
definition of ``emergency;'' when the record was re-opened for comment 
on the labor/industry draft agreement, OSHA raised the issue by 
presenting a revised definition for comment. This was:

    * * * any occurrence such as, but not limited to, equipment 
failure, rupture of containers, or failure of control equipment that 
may or does result in an uncontrolled significant release of BD.

The revised definition changed the conditions of release to qualify as 
an emergency from ``unexpected'' to ``uncontrolled'' to more clearly 
define what the agency considered to be an emergency situation which 
would trigger specific provisions of the standard (e.g., respirator 
use, limited medical screening and surveillance). OSHA asked whether 
the change provided adequate guidance to the public. Relatively few 
commenters dealt specifically with this issue. However, Bridgestone/
Firestone, Inc. stated that `` * * * a controlled release, even in 
significant quantities, is not an emergency precisely because it can be 
controlled.'' (Ex. 118-14, p. 5) They recommended that OSHA define what 
constitutes a significant release as an ``uncontrolled release of BD 
that presents serious danger to employees in the workplace,'' noting 
that OSHA defined catastrophic release in 29 CFR 1910.119 as one posing 
a ``serious danger to employees.'' Bridgestone/Firestone feared that 
defining emergency as proposed might result in application of it to 
situations which are ``lawful, safe and managed by the standard through 
respirator use.'' (Ex. 118-14, p. 6)
    Dow Chemical Company also submitted comments in support of defining 
emergency in terms of ``uncontrolled significant release of BD'' 
because of its consistency with other standards. (Ex. 118-16, p. 3)
    Akzo Nobel Chemicals, Inc. suggested that the definition of an 
emergency should be:

    An uncontrolled dangerous event due to a combination of 
unforeseen circumstances, such as the spill of significant 
quantities of hazardous substances, fire or explosion, massive 
failure of equipment/personnel or other occurrences which require an 
immediate response by persons not working in the immediate area, 
except maintenance activities and which could result in harmful

[[Page 56802]]

exposures during hazardous activities, fires or explosions. (Ex. 
118-3)

They also expressed the belief that use of the term ``uncontrolled'' is 
essential to the definition of an emergency, and that ``daily, 
foreseeable events are not emergencies.'' Azko Nobel gave, as an 
example, the rupture of a container, which they felt would constitute 
an emergency ``only when a dangerous amount of material escaped.'' Akzo 
Nobel felt that the definition of emergency should also depend on the 
type of responder needed to deal with the situation--that ``if the 
responders are persons outside the work area (other than maintenance 
type personnel) that fact suggests that an emergency is occurring.'' 
Akzo Nobel believes the definition of emergency must be tied to the 
amount of hazardous material released and the exposure resulting from 
it.
    All these comments in general support OSHA's revised definition. 
Therefore, OSHA is adopting the revised definition for the reasons 
stated in the comments.
    Employee exposure means exposure to airborne BD which would occur 
if the employee were not using respiratory protection. This definition 
is intended to apply to all variations of the term ``employee 
exposure'' that have essentially the same meaning, such as ``exposed 
employee'' and ``exposure.'' The definition is consistent with OSHA's 
previous use of the term ``employee exposure'' in other health 
standards (Asbestos, 29 CFR 1910.1001; Benzene, 29 CFR 1910.1028; 
Ethylene Oxide, 29 CFR 1910.1047; Cadmium, 29 CFR 1910.1027).
    Objective data are redefined in the final rule to clarify and 
better define what OSHA believes they entail. Objective data are 
defined as:

monitoring data, or mathematical modelling or calculations based on 
composition, chemical and physical properties of a material, stream 
or product.

    In the proposed rule, the term ``objective data'' was used to 
provide an exemption from the scope and application of the rule and was 
not specifically defined in the definition section.9
---------------------------------------------------------------------------

    \9\ This section does not apply to the processing, use or 
handling of products containing BD where objective data are 
reasonably relied upon that demonstrate that the product is not 
capable of releasing BD in airborne concentrations at or above the 
action level or in excess of the STEL under the expected conditions 
of processing, use, or handling that will cause the greatest 
possible release. (55 FR 32803)
---------------------------------------------------------------------------

    There appeared to be some confusion as to what was meant by 
objective data as presented in the proposal. OSHA has determined that a 
specific definition of objective data is necessary, and it has included 
it in the definition section.
    OSHA believes that objective data may include such data as: (1) 
Information provided by the manufacturer or a determination that air 
concentrations will not exceed the action level or STEL, under 
foreseeable conditions of use, based on the information provided by the 
manufacturer; (2) representative data or collective industry data which 
are relevant to the materials, process streams, and products for which 
the exemption is being documented, under foreseeable conditions of use.
    Charles Adkins, then Director of OSHA's Health Standards Programs 
Directorate, explained at the hearing that ``. . . you are allowed to 
make a calculation to determine whether or not you need to do 
monitoring or not. . . . If you're below the action level, you do not 
need to do anything.'' (Tr. 1/15/91, pp. 29-31) Indeed, to qualify for 
an exemption does not necessarily ``. . . have to be actual data 
collected or experimental data. . . . (The employer) . . . can make . . 
. appropriate calculations, and if he can support his calculation, that 
would be considered part of his objective data.'' (Tr. 1/15/91, p. 30)
    The definition of objective data contained in the final rule adopts 
the one contained in the Labor-Industry Joint Recommendations. (Ex. 
119) OSHA believes that such a definition meets the intent of the 
proposal. While OSHA does not require employers to perform complex 
modeling to avail themselves of the objective data exemption, it should 
be noted that there may be times when it would be difficult or 
inappropriate to attempt to use objective data. This issue was 
discussed in the formaldehyde standard, wherein the Agency stated that 
complex modeling exercises may not be a substitute for employee 
exposure monitoring

. . . in workplaces where many complex factors must be considered to 
use objective data, a high degree of uncertainty will be associated 
with trying to assess employee exposure from objective data. In 
these instances employers should conduct exposure monitoring instead 
of relying on objective data so that they can have confidence that 
they are in compliance with the standard's provisions. (52 FR 46100, 
46255-46256, 12/4/87)

However, if carefully used in appropriate circumstances, OSHA believes 
that objective data may be useful in minimizing needless exposure 
monitoring.
    Permissible Exposure Limits, PELs means either the 8 hour Time 
Weighted Average (8-hr TWA) exposure or the Short-Term Exposure Limit 
(STEL). The two limits are often referred to as PELs in various 
documents and this definition clarifies what is meant by ``PELs.''
    Physician or Other Licensed Health Care Professional has been 
incorporated into the standard's medical screening and surveillance 
provisions to include persons certified, registered, or licensed to 
perform various activities required by the standard. OSHA's authority 
does not supersede a state's right to license, register, or certify 
individuals to perform these tasks. Therefore, in the final rule, OSHA 
has replaced the word ``physician'' with the phrase ``physician or 
other licensed health care professional'' to allow individuals to 
perform duties under the provisions of the standard which they are 
permitted to perform in their jurisdiction through their licensure, 
registration, or certification.
    Regulated area means an area where airborne concentrations of BD 
exceed or can reasonably be expected to exceed the permissible exposure 
limits. The definition of regulated areas in the final rule is the same 
as the proposed definition. Texaco was concerned that the phrase ``can 
reasonably be expected'' is open to varied interpretations or could be 
misunderstood, and recommended that regulated areas be required only 
where exposure monitoring indicates that air concentrations of BD are 
above the PELs. (Ex. 32-26) OSHA believes workers will be better 
protected where a regulated area is required even if one of the PELs is 
not exceeded at all times. The specific requirements for a regulated 
area are discussed in the summary and explanation for paragraph (e) 
below.
    This section is newly defined in the final rule to clarify that 
this term is synonymous with the 1,3-Butadiene Final Rule.

C. Permissible Exposure Limits

    Since 1970, the PEL for 1,3-butadiene has been 1,000 parts per 
million (ppm) as an 8-hour TWA. The final rule reduces the permissible 
exposure limits to 1 ppm as an 8-hour time-weighted average (TWA) and 
to 5 ppm as a 15- minute short-term exposure limit (STEL). As part of 
this rulemaking, OSHA is deleting from Table Z-2 of 29 CFR 1910.1000 
the exposure limit of 1000 ppm as an 8-hour TWA for BD. OSHA has 
determined that the former PEL presented a significant risk of cancer 
to employees exposed to BD and

[[Page 56803]]

that compliance with the new standard will substantially reduce that 
risk. The basis for the 8-hour TWA-PEL and STEL is discussed in the 
sections of this preamble dealing with health effects, risk assessment, 
significance of risk, and in the economic analysis. This section 
briefly summarizes some of that discussion.
    As discussed earlier in the Health Effects section, in the NTP 
bioassays, mice exposed to BD via inhalation developed cancer at 
multiple sites. When these data were used to estimate risk via a 
quantitative risk assessment, the data indicated that risk at the 
former PEL was quite high and should be lowered. In addition, 
epidemiologic studies of BD-exposed worker groups have suggested that 
BD induced leukemia in a dose responsive manner. In the proposal, 
OSHA's preliminary risk assessment found its ``best'' estimate of risk, 
derived from the female mouse heart hemangiosarcoma data using the 
multistage model, predicted 147 excess deaths per 1,000 workers at the 
former PEL of 1,000 ppm.
    In 1990 OSHA proposed a PEL of 2 ppm as an 8-hour TWA and 10 ppm as 
a short-term limit, based in part on its preliminary risk assessment, 
which estimated an excess cancer risk of 5.1 per 1,000 workers at the 
proposed PEL of 2 ppm. As discussed earlier in this preamble, economic 
and technologic feasibility considerations led OSHA to propose a PEL of 
2 ppm, although the preliminary risk assessment estimated that there 
was still significant remaining risk at that level of BD. As discussed 
in the Quantitative Risk Assessment section, OSHA used a more recent 
lower dose NTP mouse study to estimate risk. That estimate using lung 
cancer in female mice, the most sensitive cancer site in the most 
sensitive species, was 8.1 excess cancers per 1,000 workers exposed to 
1 ppm BD over a 45-year working lifetime (the estimate at 2 ppm for 
this site was 16.2 lung cancers per 1,000 workers).
    In light of the need to reduce the significant residual risk 
remaining at a PEL of 2 ppm, OSHA determined that it must reevaluate 
the record evidence to assure that significant risk is reduced to the 
extent feasible. This review, discussed at length earlier in this 
preamble, has led OSHA to conclude that an 8-hour time-weighted average 
permissible exposure limit of 1 ppm is both feasible and is needed to 
further protect worker health.
    Throughout this rulemaking there was consensus that the existing 
PEL adopted by OSHA in 1971, 1,000 ppm, which ACGIH had developed as a 
TLV for BD to prevent irritation and narcosis, was inadequate to 
protect workers from the hazard presented by this chemical (e.g., 
IISRP, Ex. 34-4, CMA Ex. 32-28, American Lung Association, Ex. 32-10). 
However, there was not unanimity as to the appropriate level. OSHA's 
expert witness, Dr. Philip Landrigan, stated the following:

    * * * I was distressed to see that in setting the PEL at two 
parts per million that you decided to accept the occurrence of five 
excess deaths per thousand exposed workers which translates to 5,000 
excess deaths per million exposed workers. It seems to me that this 
is not consistent with optimal practice and if the agency has a 
chance to reconsider that risk assessment and possibly lower the 
standard from the proposed PEL of two parts per million, I certainly 
would like to ask you to reconsider. * * * Five thousand cancer 
deaths seems like a lot to me. (Tr. 1/15/91, p. 204)

    In testimony and submissions to the rulemaking record, NIOSH 
recommended that the permissible exposure level be set at the lowest 
feasible levels and recommended 6 parts per billion on the basis of its 
assessment of risk. (Ex. 32-25, Tr. 1/17/91, p. 681) NIOSH's 
quantitative risk assessment was based on NTP's lower dose mouse study 
and application of a time-to-tumor model (see Quantitative Risk 
Assessment and Ex. 90). Although some of the underlying assumptions 
made by NIOSH in its analysis differ from those OSHA has used in a 
subsequent time-to-tumor analysis, the level of risk estimated by NIOSH 
further contributed to OSHA's concern regarding the level of risk 
estimated to remain at the proposed PEL of 2 ppm.
    Other risk assessments were submitted which yielded lower estimates 
of risk. (Shell Oil Company, Ex. 32-27; CMA, 28-14) Each of the risk 
assessments in the record is discussed in the section of this preamble 
dealing with the quantitative risk assessment.
    At the time of the public hearings, industry representatives 
opposed lowering the PEL below 2 ppm. For example, participants from 
Shell stated that they had already ``set an internal standard at 2 
ppm,'' and felt a lower level would not increase employee protection. 
(Shell, Ex. 32-27, 34-7) This was echoed in the comments of styrene-
butadiene latex manufacturers. (Ex. 34-5) In fact, IISRP felt that a 10 
ppm PEL was low enough to eliminate significant risk. They described 
the difficulties the polymer industry anticipated at lower PELS. (Ex. 
34-4, 32-33)
    Labor representatives, particularly the United Rubber Workers, and 
supporters, among them: Irving Selikoff, Cesare Maltoni, Sheldon 
Samuels, Myron Mehlman, and Louis Beliczky, urged OSHA to adopt a PEL 
of 0.2 ppm. (Ex 32-1, 34-6) Diane Factor, representing the AFL-CIO, 
said that ``OSHA must conduct an analysis that attempts to show 
feasibility below 2 ppm and not stop at the industry acceptable 
level.'' (Tr. 1/17/91, p. 839)
    Dr. Myron Mehlman, Professor of Environmental and Community 
Medicine at UMDNJ, Robert Wood Johnson Medical School, New Jersey, 
testifying on behalf of the United Rubber, Cork, Linoleum and Plastic 
Workers of America, AFL-CIO, and the Sierra Club, stated his opinion 
that a PEL of 2 ppm was ``dangerously high.'' (Ex. 79) He urged OSHA to 
``adopt a 0.05 to 2 ppm PEL and 0.2 to 1 ppm STEL to protect the health 
of workers and the environment. (Tr. 2/20/91, p. 1776) The Department 
of Health Services, State of California, performed a quantitative risk 
assessment using the NTP-I mouse study data and urged OSHA to ``* * * 
consider the feasibility of adopting 1 ppm or a lower level.'' (Ex. 32-
16)
    The issues raised by participants and OSHA's concern about the 
level of risk remaining at the 2 ppm PEL led OSHA to conclude that 
further scrutiny and re-analysis of the record data were necessary and 
prudent to assure that the limit set by the Agency is that which is 
reasonably necessary and appropriate and that reduces significant risk 
to the extent feasible, particularly in view of the high degree of 
carcinogenicity of BD.
Joint Recommendations of Labor/Industry Group Regarding PELs
    The March 1996 industry/labor agreement recommended that OSHA adopt 
a PEL of 1 ppm and a STEL of 5 ppm (also an action level of 0.5 ppm). 
OSHA is pleased that this group of interested parties have reached the 
same conclusion as the Agency in this regard. The joint recommendations 
suggest a STEL of 5 ppm, but questioned whether the record would 
support this STEL. IISRP nonetheless agreed that the PELs included in 
the recommendation are feasible in view of the fact that the final rule 
allows the use of respirators in intermittent, short-duration work. 
OSHA's own analysis also shows that a 1 ppm TWA and 5 ppm STEL are 
technologically and economically feasible and necessary to 
substantially reduce significant risk of material impairment of health. 
(See the extensive discussions in the health effects, risk assessment, 
significant risk and feasibility sections.) Therefore, OSHA is 
promulgating these limits in its final rule for BD.

[[Page 56804]]

Short-Term Exposure Limit (STEL)
    The proposed STEL was five times the proposed PEL, 10 ppm. The 
final rule includes a STEL which is five times the new 8-hour TWA 
limit, or 5 ppm.
    The choice of the level of the STEL was a concern to a number of 
rulemaking participants. The CMA Butadiene Panel did not feel a STEL 
was needed at all and strongly objected to its being lower than 10 ppm. 
(Ex. 32-28) The SB latex manufacturers expressed a similar view. (Ex. 
34-5) CMA alleged that the STEL provision lacked a legal basis and that 
the analyses on which OSHA based its proposed STEL were flawed. (Ex. 
32-28) Others objected to the STEL on the basis that BD lacked acute 
health effects. (Ex. 32-19; 32-26; 32-27; 32-33; 60)
    A major labor participant in the rulemaking, URW, urged OSHA to 
adopt a lower STEL of 1 ppm. (Ex. 34-6) As Kenneth Cross stated in his 
testimony for URW,

``Based on more recent toxicological, medical and epidemiological 
data, some of which was unavailable to OSHA when it sent its 
proposed standard to OMB about two years ago, the URW feels more 
secure with a 0.2 part per million PEL and one part per million 
STEL.'' (Tr. 2/20/91, p. 1750)

    OSHA's expert witness, Dr. Ronald L. Melnick of NTP, presented data 
suggesting that a STEL will reduce risk. He performed a ``stop-
exposure'' study that he described as follows:

Groups of 50 male mice were exposed to one of the following 
regimens: (a) 625 ppm for 13 weeks; (b) 200 ppm for 40 weeks; (c) 
625 for 26 weeks; or (d) 312 ppm for 52 weeks. After the exposures 
were terminated, these groups of animals were placed in control 
chambers for the remainder of the 104 week studies * * * Survival 
was markedly reduced in all of the stop-exposure groups due to the 
development of related malignant tumors. The tumor incidence 
profiles in the * * * groups show that lymphocytic lymphomas, 
hemangiosarcomas of the heart, alveolar-bronchiolar neoplasms, 
forestomach squamous cell neoplasms, Harderian gland neoplasms, and 
preputial gland neoplasms were increased compared with controls even 
after only 13 weeks of exposure to 625 ppm * * * at comparable total 
exposures, the incidence of lymphocytic lymphoma was greater with 
exposure to a higher concentration of 1,3-butadiene for a short time 
compared with exposure to a lower concentration for an extended 
duration. (Ex. 42)

Dr. Melnick concluded as follows:

The stop-exposure studies show that multiple organ site neoplasia 
occurs in mice after only 13 weeks of exposure to 1,3-butadiene. It 
is likely that shorter exposure durations would also produce a 
positive carcinogenic response * * * the stop-exposure studies show 
that the concentration of 1,3-butadiene is a much greater 
contributing factor than is the duration of exposure [emphasis 
added]. (Ex. 42, p. 17)

    Industry representatives objected in particular to using the thymic 
lymphomas induced in the mouse due to the potential role of an 
endogenous retrovirus in eliciting this response, and more generally, 
to the use of this study as the basis for imposing a STEL. (e.g., Exs. 
112, 113) In its post-hearing comments, the CMA 1,3-Butadiene Panel 
stated:

The relevance of these studies to an assessment of the human cancer 
risks from 15-minute exposures to butadiene at levels up to 64 ppm 
(the highest exposure that would be consistent with an 8-hour TWA of 
2 ppm) is highly doubtful. This is particularly the case where: (1) 
A dose-rate effect is evident in mice only for lymphomas and only at 
high exposure concentrations; (2) the MuLV retrovirus is known to be 
a significant factor in BD-induced lymphomas in the 
B6C3F1 mouse; (3) the lymphomas do not appear to play 
a significant role in BD-induced carcinogenicity in the * * * mouse 
at the lower levels of exposure of interest to OSHA * * * (4) there 
is no evidence that concentration is more important than duration of 
exposure for any other tumor type.

NIOSH disagreed, and objected to OSHA's omission of the lymphomas from 
the quantitative risk assessment provided in the proposal. NIOSH 
stated:

    OSHA's justification for eliminating these tumors was that 
lymphomas may be related to the presence of an endogenous leukemia 
virus in the B6C3F1 mouse used in the NTP bioassay. 
The endogenous leukemia virus should have increased the background 
rate of lymphoma in both the control and exposed animals, and thus 
the potential confounding effect of this virus was controlled for in 
OSHA's risk assessment. It is still possible that the increased 
lymphoma incidence observed in the * * * mouse was related to an 
interaction between the virus and 1,3-butadiene. However, OSHA also 
cites evidence that a similar lymphoma response was observed in a 
study of NIH-Swiss mice exposed to BD, and indicated that this 
strain of mice is not known to carry the leukemia virus * * * (Ex. 
32-25, p. 4)

NIOSH also cited evidence that retroviruses may be associated with 
certain leukemias and lymphomas in humans and pointed out that ``even 
if 1,3-butadiene interacts with a leukemia virus, a similar mechanism 
might conceivably be involved in producing tumors'' in exposed workers. 
(Ex. 32-25, p. 5) OSHA agrees with the opinion expressed by NIOSH and 
rejects industry's arguments that the observations in the ``stop-
exposure'' study are irrelevant.
    Some further support for a STEL comes from a recent report 
describing analysis of an epidemiologic study of BD-exposed workers 
entitled ``A Follow-up Study of Synthetic Rubber Workers'' by Delzell 
et al. (Ex.117-1) One part of this study pertains to the risk of 
leukemia in workers exposed to BD in what the authors termed ``peak- 
years.'' Peak years are estimates of the number of times per year a 
worker was exposed above 100 ppm (a peak) during 15 minute periods. 
This estimate was then multiplied by 225, the number of workdays in a 
year. This value was used as a variable in Poisson regression analysis. 
There was an association between peak-years and leukemia risk, even 
after controlling for BD ppm-years (cumulative BD exposure) as well as 
other covariates. The relationship was said to be ``irregular'' since 
the risk ratios were 1.0, 2.6 and 0.8 for BD peak-years categories of 
0, >0-199 and 200+, respectively. The underlying reason for the lack of 
a dose-response is unclear; however, the finding of a statistically 
significant elevation in relative risk for peak exposure, even when 
total cumulative exposure is accounted for, is of concern and appears 
to support the need to control peak exposures.
    OSHA further notes that the basis for adopting a STEL does not rest 
solely on the points raised above; in 1986, the US Court of Appeals for 
DC reviewed OSHA's ethylene oxide standard, which did not contain a 
STEL. (Public Citizen Health Research Group v. Tyson, 796 F2d, D.C. 
Cir., 1986). The reason given by OSHA for not including a short-term 
limit in the ethylene oxide standard was that a dose-rate effect had 
not been demonstrated by record data. The Court held that the OSH Act 
compels the Agency to adopt a short term limit if the rulemaking record 
shows that it would further reduce a significant health risk and is 
feasible to implement regardless of whether the record supports a 
``dose-rate'' effect (796 F. 2nd at 1505). This decision states that

    If in fact a STEL would further reduce a significant health risk 
and is feasible to implement, then the OSH Act compels the agency to 
adopt it (barring alternative avenues to the same result). OSHA 
shall set the standard which most adequately assures, to the extent 
feasible, on the basis of best available evidence, that no employee 
will suffer material impairment of health.'' (29 U.S.C. 655(b)(5) 
(1982)) Since OSHA has found that a significant health hazard 
remains even with the 1 ppm PEL, the agency must find either that a 
STEL would have no effect on that risk or that a STEL is not 
feasible. (796 F.2d 1479 (D.C. Cir. 1986))

    Without a STEL, employees could have exposures to BD as high as 32 
ppm, albeit for short periods (15 minutes). Since many workers 
experience intermittent exposure to BD,

[[Page 56805]]

for example, during sampling, transport and laboratory work, imposing 
an 8-hour limit alone would not control these higher peak exposures. 
The STEL by controlling such peak exposures, will reduce total 
cumulative dose, thereby reducing significant risk further, as stated 
by the Court. In addition, properly installed and maintained 
engineering controls should prevent high variability in exposures 
generally. As a general rule, it is good industrial hygiene policy to 
control excessive variabilities as a STEL will do.
    OSHA has concluded that the adoption of a 5 ppm STEL for BD is 
appropriate to further reduce the significant residual risk of cancer 
that remains from exposure to BD at the revised TWA PEL of 1 ppm. In 
addition, there is some evidence of a dose-rate effect as described 
above. Specifically: (a) The ``stop-exposure'' study of Melnick which 
demonstrated that ``at comparable total exposures, the incidence of 
lymphoma was greater with exposure to a higher concentration of BD for 
a short time compared with exposure to a lower concentration for an 
extended duration'' (Ex. 114, p. 125); (b) although a retrovirus in 
B6C3F1 mice likely played a role in the induction of thymic 
lymphoma, the fact that BD exposure in another strain of mouse that did 
not express the virus also developed the same type of cancer, strongly 
suggests that BD induced this tumor very early after exposure; and, (c) 
the suggestive data from the cohort study of Delzell et al., indicating 
the importance of ``peak-year'' exposure to risk of leukemia.

D. Exposure Monitoring

    Section 6(b)(7) of the OSH Act (29 U.S.C. 655) mandates that any 
standard promulgated under section 6(b) shall, where appropriate, 
``provide for monitoring or measuring of employee exposure at such 
locations and intervals, and in such manner as may be necessary for the 
protection of employees.'' The purposes of requiring air sampling for 
employee exposure to BD include the prevention of overexposure of 
employees; the determination of the extent of exposure at the worksite; 
the identification of the source of exposure to BD; and collection of 
exposure data by which the employer can select the proper control 
methods to be used to reduce exposure and to evaluate the effectiveness 
of the control methods selected. Monitoring helps employers to meet the 
legal obligation of the standard to assure that their employees are not 
exposed to BD in excess of the permissible exposure levels, and to be 
able to notify employees of their exposure levels. In addition, 
collection of exposure monitoring data enables the examining physician 
to be informed of employee exposure levels, which may be useful in 
forming the physician's medical opinion (see paragraph (k)).
    Many provisions of the final rule are quite similar to those 
proposed. However, some felt that clearer or more concise language 
should be used. Thus, the specific language of the exposure monitoring 
provisions varies somewhat from that of the proposal. Moreover, 
additional modifications have been made, as appropriate, in response to 
record information and recommendations contained in the record.
    The final rule does not require that exposure monitoring be 
performed wherever BD is present. Under certain circumstances, outlined 
in the scope and application (paragraph (a) of this section), objective 
data may be used in lieu of the monitoring required by paragraph (d) of 
the final rule.
    In the final rule, as in other standards, various provisions of the 
standard are triggered if an employee is exposed above the action 
level, and are not required if the employee is exposed below the action 
level. Thus the importance of correctly determining employee exposure 
cannot be over emphasized.
    Paragraph (d)(1) requires the employer to determine the exposure 
for each employee exposed to BD. This does not mean that separate 
measurements for each employee must be taken but rather that the rule 
allows this obligation to be fulfilled by determining ``representative 
employee exposure.'' Paragraph (d)(1)(I) requires that samples 
collected to fulfill this requirement be taken within the employee's 
breathing zone (also known as ``personal breathing zone samples'' or 
``personal samples''). (Area sampling is required under the standard 
only following emergencies.) The samples used to determine whether an 
employee is exposed above the action level must represent the 
employee's exposure to airborne concentrations of BD over an eight-hour 
period without regard to the use of respirators (See ``Employee 
exposure'', as defined in the definitions section).
    In certain circumstances sampling each employee's exposure to BD 
may be required for initial monitoring. However, in many cases, the 
employer under paragraph (d)(1) may monitor selected employees to 
determine ``representative employee exposures.'' Representative 
exposure sampling is permitted when there are a number of employees 
performing essentially the same job, with BD exposures of similar 
durations and magnitude, under essentially the same conditions. Where 
there are groups of employees whose job functions are similar, OSHA 
permits the use of representative monitoring to characterize employee 
exposures to enable the employer to design a cost-effective monitoring 
program. In designing a representative monitoring plan, OSHA intends 
that employers select a sufficient number of employees within a group 
of employees who are engaged in similar work for sampling such that 
their exposures adequately characterize the exposures of all employees 
within the group. In addition, the employees who are judged as likely 
to have the highest exposures to BD within the group should be selected 
for monitoring to ensure that exposures of the remaining employees in 
the group are not underestimated. Although the employer is free to use 
formal statistical approaches for characterizing the exposures of a 
group of similarly exposed employees, OSHA does not require such 
approaches be used, and allows the employer to use professional 
judgement to select employees for monitoring and for attributing 
exposure results to employees whose exposures were not measured. The 
rationale for designing the representative monitoring plan and for 
selecting employees whose exposures were monitored can be retained as 
part of the exposure monitoring records required to be maintained by 
the employer under paragraph (l)(2) of the final rule.
    To measure representative 8-hour TWA exposures, at least full-shift 
sampling must be conducted for each job function in each job 
classification, in each work area, and for each shift (paragraph 
(d)(1)(ii)). At least one sample covering the entire shift, or 
consecutive representative samples taken over the duration of the 
shift, must be taken. Representative 15-minute short-term employee 
exposures are to be determined on the basis of one or more samples 
representing 15-minute exposures associated with operations that are 
most likely to produce exposures above the short term exposure limit 
for each shift for each job classification in each work area (paragraph 
(d)(1)(iii)).
    To eliminate unnecessary monitoring and improve the cost-
effectiveness of the standard, paragraph (d)(1)(iv) also allows 
employers who can document that exposure levels are the same for 
similar operations during different work shifts to sample only the 
shift for which the highest exposures are expected to

[[Page 56806]]

occur. The employer must be able to demonstrate that employees on the 
shifts who are not monitored are not likely to have exposures higher 
than those of employees on the shifts monitored.
    Paragraph (d)(2) requires all employers who have a place of 
employment covered under the scope of this standard to perform initial 
monitoring for their employees. In addition, the final standard 
requires that the initial monitoring be conducted within 60 days of the 
effective date of the final standard or the introduction of BD into the 
work place. This effective date provision (proposed paragraph 
(d)(2)(ii)) has been moved to the paragraph containing the other start-
up dates, paragraph (m)(2)(I). Although Dow in a recent submission 
expressed concerns that additional time might be needed to set up an 
exposure monitoring program, OSHA believes that initial monitoring can 
be completed within the allowed period of time. (Ex. 118-16) The 
parties to the labor/industry agreement also recommended a start-up 
date for the initial monitoring under the standard of 60 days from the 
effective date. (Ex. 118-12A) Additional flexibility is provided in 
paragraph (d)(2)(ii), in that monitoring data collected up to two years 
prior to the effective date may be relied upon as initial monitoring 
data, provided that it has been collected in accordance with the 
requirements of this paragraph.
    The employer is required to perform initial monitoring of employee 
exposures to BD where objective data are not available to satisfy the 
condition for exemption. If the results of initial monitoring indicate 
employee exposures are below the action level, the employer may 
discontinue monitoring for those employees and is relieved of some 
other obligations under the final rule (e.g., medical surveillance, use 
of personal protective equipment, development of an exposure goal 
program, establishment of regulated areas). Thus, the employer can 
focus attention and resources on employees whose exposures are more 
significant. Therefore, even if operations are not specifically 
exempted from the proposal, keeping exposure levels below the 0.5 ppm 
``action level'' will relieve employers from some duties under the 
standard. A similar approach is used in a number of OSHA standards 
(acrylonitrile, 29 CFR 1910.1045; arsenic, 29 CFR 1910.1018; ethylene 
oxide, 29 CFR 1910.1047).
    Paragraph (d)(2)(ii) of the proposal has been modified as shown in 
paragraph (d)(1)(ii) in the final rule to allow monitoring data 
produced within 2 years prior to the effective date of the standard to 
be relied upon to satisfy the initial monitoring requirement. OSHA had 
proposed a one year limit on the use of this grand-fathered monitoring 
data, but at the suggestion of a number of participants in the 
rulemaking and the labor/industry agreement, OSHA has agreed that 
allowing a two year period is reasonable for this standard. (Ex. 112; 
113; 118-12) Dow Chemical Company in comments on a draft of the labor/
industry joint recommendations asked that OSHA allow the use of data 
which are over two years old to serve as initial monitoring data. (Ex. 
118-16) Dow said that such data ``that are consistent with current data 
reflecting no process changes that might have increased exposure over 
the time period of interest'' should be included as initial monitoring 
data. OSHA believes that expanding the period to two years allows 
adequate latitude to the employer in determining the need for initial 
monitoring.
    In addition, the final rule now more clearly states what OSHA means 
by conditions under which historical monitoring data may not be used 
and initial monitoring is required. Rather than stating that historical 
data may be used only if the conditions under which the monitoring was 
conducted ``remain unchanged,'' it now states that the conditions ``* * 
* have not changed in a manner that may result in new or additional 
exposures.'' This language was recommended by the labor/industry group 
and has been found acceptable and OSHA believes that it more clearly 
articulates its intent than the corresponding provision in the 
proposal; therefore it is included in the final rule. (Ex. 118-12A) 
However, OSHA notes that employers will likely wish to monitor 
following installation of controls to determine their effectiveness.
    Paragraph (d)(3) describes the requirement for periodic monitoring 
and its frequency. CMA suggested that the OSHA BD standard should have 
the same monitoring frequency as OSHA's benzene standard. (Ex. 112) The 
initial submission of the labor/industry group recommended that OSHA 
require more extensive sampling than the Agency had proposed to qualify 
as initial monitoring and establish a baseline. Specifically the group 
recommendation stated:

Establish a baseline of at least 8 samples. The samples may be taken 
in a single year, so long as at least one sample is taken in each 
quarter, and no two are taken within 30 days of each other. The 
employer may utilize monitoring data from the previous two years to 
satisfy the initial monitoring requirement as long as process has 
been consistent. (Ex. 119)

The labor/industry group also recommended less frequent periodic 
monitoring than the quarterly monitoring OSHA proposed when exposures 
exceeded the PELs. The labor/industry group recommended:

    After the baseline has been established, monitoring is * * * 
every 6 months if exposure exceeds PEL or STEL * * * Annually if 
exposure is at or above the AL [action level] but below the PEL. 
(Ex. 119)

    In the Federal Register notice re-opening the record, OSHA raised 
its concerns as follows:

OSHA is concerned that the taking of 8 samples to establish a 
baseline may not be an effective use of scarce industrial hygiene 
resources in that the number of samples taken may be far less 
important than the quality of the samples used to characterize the 
exposure of BD employees. Are there other ways to improve OSHA's 
traditional approach of monitoring at least the one most exposed 
employee in each job classification on each shift? (61 FR 9381, 
9383, 3/8/960)

In its submission, Texas Petro Chemicals objected to the 8 sample 
baseline because they said that they do not have BD exposure for four 
quarters of the year and do not monitor in winter due to ``high 
mobility'' of their employees during the winter and the ``strong 
potential for samples to be invalid'' due to problems with the sampling 
devices during bad weather. (Ex. 118-6) Dow Chemical Company objected 
to specification of the number of sampling events and the schedule 
suggested by the agreement. Dow felt this did not allow the employer 
adequate flexibility in evaluating employee exposures. (Ex. 118-16, p. 
4) Hampshire Chemical Corporation felt that it was unclear what was 
meant by the 8 baseline samples described in the notice. (Ex. 118-8) 
The American Petroleum Institute expressed its preference for a more 
performance-oriented approach to exposure monitoring strategies. (Ex. 
118-11)
    In comments of the Chemical Manufacturers Association, who 
participated in the labor/industry discussion resulting in the 
agreement, the following view was expressed:

The parties to the negotiations have revisited the exposure 
monitoring provisions. The agreement's monitoring scheme now would 
follow OSHA's traditional requirement for initial representative 
monitoring to detect job classifications where the action level is 
exceeded * * * It is only the periodic monitoring that is required 
where there are exceedances that could involve the taking of eight 
samples * * * After this periodic monitoring had been completed, 
additional periodic monitoring would occur at the

[[Page 56807]]

frequency proposed * * * sampling could be terminated when there are 
two consecutive low measurements. (Ex. 118-13, p. 4-5)

Similar comments were received from the International Institute of 
Synthetic Rubber Producers, Inc. (Ex. 118-12, p. 4)
    The labor/industry agreement was more fully discussed by the group 
in a submission received during the period when the record was re-
opened for comment. (Ex. 118-12) Numerous modifications to OSHA's 
proposed provisions for an exposure monitoring program for BD were 
endorsed by the group. (Ex. 119) Primarily these dealt with the 
sampling strategy. OSHA has carefully evaluated the suggested changes 
and has, for the most part, included them in the final rule.
    The periodic monitoring paragraphs have been modified upon the 
basis of the record and the recommendations of the labor/industry 
group. Paragraph (d)(3) states that ``If the monitoring required by 
(d)(2) of this section reveals exposure at or above the action level 
but at or below both the 8-hr TWA and the STEL, the employer shall 
repeat the representative monitoring required by paragraph (d)(1) every 
twelve months.'' OSHA proposed that such monitoring be repeated at 
least every six months. However, OSHA believes that the additional 
monitoring 10 required in the final rule for those whose BD levels 
remain above the PELs will compensate for less frequent periodic 
monitoring in situations where the level is likely to remain lower. It 
must be noted here that additional monitoring requirements are 
triggered whenever there is a change in process or personnel which may 
result in new or additional exposures to BD. A similar schedule for 
periodic monitoring is required in the benzene standard. (29 CFR 
1910.1028)
---------------------------------------------------------------------------

    \10\ If the monitoring required by paragraph (d)(2) of this 
section reveals employee exposure to be above the 8-hour TWA (or 
STEL), the employer shall repeat the representative monitoring 
required by paragraph (d)(1)(ii) (or d(1)(iii)) at least every three 
months until the employer has collected two samples per quarter 
(each at least 7 days apart) within a two-year period, after which 
such monitoring must occur at least every six months.
---------------------------------------------------------------------------

    The results of initial monitoring represent the data which will be 
used to determine when further periodic monitoring will be required. If 
the initial monitoring of employees reveals exposures that are between 
the action level and the 8-hour TWA, then the employer must repeat 
monitoring annually (paragraph (d)(3)(I)). While these employees have 
been shown to be exposed to levels of BD below the 8-hour TWA, their 
levels of exposures are not so far below the PELs that monitoring could 
safely be discontinued. Even minor changes in engineering controls or 
work practices could result in exposures increasing to levels above the 
PEL. Remonitoring on an annual basis will enable the employer to be 
confident that the controls are working or, in the event exposures are 
shown to exceed the 8-hour TWA, will alert the employer as to the need 
for additional controls, and for changes to a more frequent monitoring 
program.
    The draft regulatory text submitted by the labor/industry group 
recommended marked changes to paragraph (d)(3) (ii) and (iii) which 
OSHA believes will provide even greater protection to workers than that 
proposed by the Agency in 1990. (Ex. 118-12A)
    The requirements in paragraphs (d)(3) (ii) and (iii) of the final 
rule provide for periodic monitoring in situations in which either the 
8-hr TWA or STEL is exceeded to be carried out quarterly ``until the 
employer has collected two samples per quarter (each at least 7 days 
apart) within a two-year period * * * after which such monitoring must 
occur at least every 6 months.'' However, if the monitoring result 
indicates that exposure is below the action level as indicated by 2 
consecutive samples taken at least 7 days apart, monitoring may cease 
unless the conditions change, (see (d)(5)). A single low sampling 
result is inadequate to allow monitoring to terminate; for various 
reasons, it may be artifactually low perhaps due to process changes 
during the time of sampling. OSHA believes that such differences are 
unlikely to persist for more than a week and has determined that this 
period is minimal to assure that exposures are truly low enough for the 
employer to stop monitoring.
    Paragraph (d)(3)(iv) has also been modified to allow less frequent 
monitoring when the initial monitoring results exceed either PEL, but 
two consecutive subsequent samples taken at least 7 days apart indicate 
that BD levels no longer exceed either PEL but remain above the action 
level. In this situation, monitoring is required annually. OSHA 
proposed that such monitoring take place every six months.
    OSHA believes that although this approach differs from the Agency's 
usual approach to monitoring, it will meet the need for determining the 
level of BD exposure in the workplace and will focus on situations 
having higher exposure potential. The conditions of use of BD in 
production and manufacturing present exposure patterns that are more 
likely to be predicted by initial monitoring than is the case for some 
of the other substances OSHA has regulated, such as asbestos, where 
exposures primarily occur during disturbing or removing the material in 
various forms. OSHA agrees that monitoring carried out as scheduled in 
the agreement is more likely to reflect the ``true'' exposure level in 
a workplace than monitoring at a single point in time. OSHA notes, 
however, as is the case in other standards, the sampling must be 
performed according to provisions of the standard--i.e., they must be 
personal samples, representative of each shift and job, etc.
    If exposures are above the 8-hour TWA limit, then the employer must 
remonitor every six months. If the employee's exposure is above the 
STEL, the employee shall repeat such monitoring at least every six 
months until the employee's exposure falls to or below the STEL. If, in 
subsequent monitoring, results indicate that an employee's exposure, as 
determined by two consecutive measurements taken at least seven days 
apart, falls from above the 8-hour TWA to between the 8-hour TWA and 
the action level, then monitoring need only be done annually, unless 
production changes lead to higher exposures. Similarly, when two 
consecutive measurements indicate that the exposure has dropped below 
the action level, further monitoring can be discontinued.
    Paragraph (d)(4) allows employers to terminate monitoring for those 
employees whose initial monitoring results are below the action level. 
When the two consecutive exposure measurements (paragraph (d)(3)), 
taken at least seven days apart, indicate that exposure has dropped 
below the action level, further monitoring for these employees can be 
discontinued, unless production changes lead to higher exposures. OSHA 
recognizes that monitoring may be a time-consuming, expensive endeavor 
and therefore offers employers the incentive to be allowed to 
discontinue monitoring for employees whose sampling results indicate 
exposures below the action level. The intent of this provision is to 
allow the employer to stop monitoring employees whose exposure to BD 
falls below the action level. OSHA believes that this provision will 
encourage employers to keep exposures to BD below the action level in 
their workplaces, thereby keeping exposures to a minimum and saving 
employers the time and expense of monitoring. Moreover, employers will 
also benefit because most of the other requirements of the standard are 
not triggered when exposures are below the action level.
    Employees will continue to be protected from excess BD exposure,

[[Page 56808]]

even after periodic monitoring has ceased, because of the requirements 
in paragraph (d)(5) (additional monitoring). Additional monitoring is 
required by paragraph (d)(5)(i) when there has been a process or 
production change or a change in control equipment, personnel or work 
practices which may result in new or additional exposures to BD. When 
the employer suspects a change which may result in new or additional BD 
exposure, the employer is obligated to obtain new employee exposure 
measurements. Instead of listing or trying to define every situation 
where the employer must monitor for new or additional exposures to BD, 
OSHA intends by this provision that employers will institute this 
additional monitoring when the employer has any reason to suspect a 
change. It should be noted that since the PEL and action level are 
relatively low, even a small change in production procedures may cause 
employees whose exposures were below the action level to have exposures 
that are above the PELs.
    Paragraph (d)(5)(ii) requires additional monitoring to be conducted 
whenever leaks, ruptures or other breakdowns occur. Such occurrences 
can result in very high exposures. After the clean-up or repair of the 
leak, employers must re-determine airborne exposure levels for those 
employees who may be exposed at their worksites. These additional 
exposure measurements provide a good method of ascertaining that proper 
corrective methods have been effective and employee exposures are not 
significantly altered from what they were prior to the leak or spill.
    In commenting on the requirement to do additional monitoring after 
leaks or breakdowns, BP felt that ``This requirement seems arbitrary 
since BD is volatile and will rapidly dissipate, especially if the leak 
is outdoors.'' (Ex. 32-8 ) CMA suggested OSHA delete the requirement to 
``repeat the monitoring which is required by paragraph (d)(2)(I)'' and 
instead require employers to ``monitor (using personal or area 
monitoring as appropriate) after the clean up of the spill or repair of 
the leak, rupture or other breakdown to insure that exposures have 
returned to the level that existed prior to the incident.'' (Ex. 112) 
The labor/industry group recommended a similar change which OSHA has 
determined to be appropriately protective. Paragraph (d)(5)(ii) of the 
final rule states:

Whenever spills, leaks, ruptures or other breakdowns occur that may 
lead to employee exposure above the 8-hour TWA limit or above the 
STEL, the employer shall monitor (using leak source (e.g., direct 
reading instruments), area or personal monitoring, as appropriate) 
after the cleanup of the spill or repair of the leak, rupture or 
other breakdown to ensure that exposures have returned to the level 
that existed prior to the incident.

OSHA believes that this provision will allow the employer greater 
flexibility in deciding whether additional monitoring is necessary and 
to determine whether the level of BD in the workplace has returned to 
low levels following such incidents. OSHA further notes that since the 
odor threshold for BD is very near the permissible limits, if the odor 
is detected, then a release has occurred and monitoring must take place 
to assure that exposure has returned to a level below the action level. 
OSHA recognizes that not every worker will recognize the odor of BD at 
a specific concentration in air.
    Paragraph (d)(6) requires employers to use monitoring and 
analytical methods which have an accuracy (at a confidence level of 
95%) of not less than plus or minus 25% for airborne concentrations of 
BD above a PEL and within plus or minus 35% for airborne concentrations 
of BD at or above the action level and below the TWA limit of 1 ppm. 
Methods of measurement are presently available to detect BD to this 
accuracy level (25% or 35%) at levels of 0.155 
ppm. One such method is described in Appendix D.
    Sampling and analysis may be performed by portable direct- reading 
instruments, real-time continuous monitoring systems, passive 
dosimeters or other suitable methods. Employers have the obligation to 
select a monitoring method which meets the accuracy and precision 
requirements of the standard under the unique conditions which exist at 
the worksite.
    Paragraph (d)(7)(i) further requires that employers notify each of 
their employees in writing, either individually or by posting in an 
appropriate location accessible to affected employees, the results of 
personal monitoring samples. OSHA proposed that the employer do this 
within 15 working days after the receipt of the results. However, the 
labor/industry agreement recommended a period of 5 business days for 
the notification by the employer to take place. (Exs. 119, 118-12a) 
OSHA agrees that this will provide information to the employee in a 
more expedient way. The quicker notification takes place, the better. 
Evidence indicates that this industry can comply with a shorter, and 
more desirable, time period. (Ex. 118-12A)
    When exposures over the PEL occur, paragraph (d)(7)(ii) requires 
the employer to notify affected employees in writing of what corrective 
action is being taken to lower exposure to BD to below the PEL, and to 
inform the employee of the schedule to complete this action. Such 
notification must be completed within 15 business days of the 
employer's receipt of the sampling results. (See paragraph (b) for the 
definition of ``business day.'') The requirement to inform employees of 
the corrective actions the employer is going to take to reduce the 
exposure level to below the PELs is necessary to assure employees that 
the employer is making efforts to furnish them with a safe and 
healthful work environment, and is required by section 8(c)(3) of the 
Act. Mandating the schedule for the completion of such activities is 
needed so that the employee can be informed when to expect correction 
of the situation and the employee can be assured that corrective action 
will take place in a specified time frame.
    Paragraph (d)(8) requires employers to allow employees or their 
designated representatives an opportunity to observe employee exposure 
monitoring. This provision is also required by section 8(c)(3) of the 
OSH Act. The proposed rule contained this provision in a separate 
paragraph (paragraph (l)), however, in developing the final rule, OSHA 
determined that observation of monitoring more logically belonged in 
the paragraph dealing with exposure monitoring and has included it in 
paragraph (d).

E. Regulated Areas

    Paragraph (e) (1) of the final rule requires employers to designate 
areas in which occupational exposures to BD exceed or can reasonably be 
expected to exceed the PELs as ``regulated areas.'' In response to 
comments, the wording of this requirement was made consistent with the 
definition of ``regulated area'' used in the standard. (Exs. 32-26; 32-
27; 32-28) A similar recommendation was made by the labor/industry 
group. (Ex. 118-12A)
    The purpose of a regulated area is to ensure that employers make 
employees aware of the presence of BD in the workplace at levels above 
either of the PELs, and to limit access to these areas to as few 
employees as possible. The establishment of a regulated area is an 
effective means of limiting the risk of exposure to substances known to 
pose a risk of material impairment of health or functional capacity. 
Because of the serious nature of the outcome of possible exposure to BD 
and the need for persons entering the area to be provided with properly 
fitted respirators, the number of persons given

[[Page 56809]]

access to the area must be limited to the employees needed to perform 
the work in the area.
    Paragraphs (e)(2) and (e)(3) are identical to the proposed 
paragraphs. Paragraph (e)(2) limits access to regulated areas to 
authorized persons. This provision makes clear that exposure over the 
PEL triggers the need for a regulated area, but that inadvertent 
releases which are covered under paragraph (i), Emergency Situations, 
would not trigger the requirement for a regulated area.
    Consistent with the performance orientation of the standard, 
paragraph (e)(3) does not specify how employers are to demarcate their 
regulated areas. Factors that the Agency believes are appropriate for 
employers to consider in determining how to mark their areas include 
consideration of the configuration of the area, whether the regulated 
area is permanent, the airborne BD concentration, the number of 
employees in adjacent areas, and the period of time the area is 
expected to have exposure levels above the PEL. Permitting employers to 
choose how best to identify and limit access to regulated areas is 
consistent with OSHA's belief that employers are in the best position 
to make such determinations, based on their knowledge of the specific 
conditions of their workplaces.
    Paragraph (e)(4) requires that whenever an employer at a multi-
employer worksite establishes a regulated area he or she must 
communicate effectively the location and access restrictions pertaining 
to the regulated area to other employers with work operations at the 
worksite. Such communication will lessen the possibility that 
unauthorized persons will enter the area or that workers not involved 
in BD-related operations will be inadvertently exposed. OSHA requires 
employers whose employees are exposed to BD at concentrations above 
either of the PELs to be responsible for coordinating their work with 
that of other employers whose employees could suffer excessive exposure 
because of their proximity to the source of exposure to BD. Only one 
comment was received on the proposed multi-employer provision. (Ex. 32-
27) That commenter requested OSHA to clarify that this provision 
applies only to employers whose employees are potentially exposed to 
BD. This interpretation is correct: the intent of this provision is to 
ensure that employers who establish regulated areas communicate with 
other employers whose employees could inadvertently enter the area. 
However, in response to this comment and at the suggestion of the 
labor/industry group, OSHA has made clear that the workers who may have 
access to the regulated area must be told where such areas exist and of 
their restricted access to them. Accordingly the phrase ``whose 
employees may have access to these areas'' has been added to paragraph 
(e)(4).
    The regulated area provision underscores OSHA's concern that 
employees at nearby sites be aware of the existence of a BD exposure 
hazard so that they will remain outside the boundaries delineating the 
regulated area. Requiring the employer who establishes a regulated area 
to notify other employers whose employees might be placed at risk by 
the presence of high concentrations of BD is consistent with other OSHA 
standards, e.g., 29 CFR 1910.1048 (Formaldehyde).

F. Methods of Compliance

    The final standard, like the proposed standard, requires employers 
to institute engineering and work practice controls to reduce the 
exposures of employees to or below the permissible exposure limits 
(both the 8-hour TWA limit and the STEL), to the extent feasible. If 
the employer establishes that engineering and work practice controls 
are inadequate to lower exposures sufficiently to or below either of 
the PELs, the employer must nevertheless implement engineering and work 
practice controls to reduce exposures as low as possible and provide 
supplemental protection with respirators selected in accordance with 
paragraph (h). The methods of compliance requirements in the final rule 
are similar to those in all of OSHA's other substance-specific health 
standards.
    The primary reliance on engineering and work practice controls to 
maintain employee exposures to or below the PELs is consistent with 
good industrial hygiene practice and with the Agency's traditional 
adherence to this hierarchy of controls. This hierarchy specifies that, 
in controlling exposures, engineering controls and work practices are 
to be used in preference to respiratory protective equipment. In this 
final rule, respirators may be used by employees only in emergencies; 
where engineering and work practice controls are not feasible, 
adequate, or have not yet been installed; or during intermittent, non-
routine work operations that are limited in duration.
    Engineering controls involve the installation of equipment, such as 
forced air ventilation, or the modification of a process to prevent or 
contain chemical releases. Work practice controls reduce employee 
exposures by altering the manner in which a task is performed. An 
example of a work practice control would be to train a tank car 
unloader to stand upwind rather than downwind of the tank car's hatch 
during the operation.
    Respirators have traditionally been accorded the last position in 
the hierarchy of controls because of the many problems associated with 
their use. For example, the effective use of respirators requires that 
they be individually selected and fitted for each employee, 
conscientiously worn, carefully maintained, and replaced when 
necessary; these conditions may be difficult to achieve and maintain 
consistently in many workplace environments. Furthermore, unlike 
engineering and work practice controls, which permit the employer to 
evaluate their effectiveness directly by air monitoring and other 
means, it is considerably more difficult to directly measure the 
effectiveness of respirators on a regular basis to ensure that 
employees are not unknowingly being overexposed. Finally, in the case 
of butadiene, respirator cartridges and canisters used to purify the 
air inhaled by the employee have limited capacity. Data relied on by 
OSHA to develop the respiratory protection requirements of the final 
rule show that cartridges will not be able to provide adequate 
protection over an entire workshift (see discussion for paragraph (h), 
Respiratory Protection).
    Industry representatives were in agreement that respirators should 
not be relied upon as a first line of defense if feasible engineering 
and work practice controls are available to protect employees from 
exposure to butadiene. (Ex. 34-4; 60; 61; 66A; 113). For example, James 
L. McGraw, representing the IISRP, commented as follows:

It has long been recognized that engineering controls should be the 
primary means of reducing occupational exposures to regulated 
substances. Respirators are useful as supplementary controls to 
protect workers during emergencies, if engineering controls fail or 
break down, while feasible engineering controls or work practices 
are being designed or implemented, or for mobile or short-term work, 
such as some maintenance operations * * *. At ASRC and, as I 
understand, throughout the industry, respirators are generally used 
only for short-duration tasks where the potential for exposure may 
be relatively high, (and) * * * are generally worn by workers for 
only a small fraction of the shift * * *. Moreover, because they 
inhibit worker mobility, obstruct vision and make communication 
among workers difficult, serious safety risks may be posed

[[Page 56810]]

where respirators are used over long periods of time * * *. The 
required use of respirators over extensive periods of time is also 
psychologically stressful, especially for employees not accustomed 
to such use. All of these factors significantly impair worker 
mobility and productivity. (Ex. 34-4, pp. 7-9)

Thus, according to the hierarchy of controls concept, use of installed 
equipment, such as well-designed and maintained local exhaust 
ventilation, is a superior compliance method because its effectiveness 
does not depend to any marked degree on human behavior, and the 
operation of such equipment is not as vulnerable to human error as is 
the use of personal protective equipment. The Agency has also found 
that modified work practices can aid in achieving compliance with the 
PELs without introducing the safety and comfort problems inherent with 
respirator use.
    Based upon the evidence in the rulemaking record and the Economic 
Analysis, OSHA finds that the use of engineering and work practice 
controls will reduce employee exposures to or below the butadiene PELs 
for practically all work situations, without having to rely on 
excessive respirator use. Some of the controls applicable to the 
production of butadiene monomer and polymers include:

--Installation of closed-loop sampling ports for quality-control 
sampling of process streams;
--Use of self-circulating-type sampling cylinders;
--Replacement of pumps equipped with single mechanical seals with those 
having dual seals;
--Use of an on-line chromatographic system to minimize the need for 
manual process sampling;
--Replacement of slip-tube gauges with magnetic level gauges in 
loading/unloading operations;
--Routine venting and purging of transfer lines between loading and 
unloading operations;
--Prohibiting air recirculation in quality-control laboratories (i.e., 
use of 100 percent make-up air);
--Ensuring that samples are removed from sample cylinders within 
enclosed, ventilated cabinets, and implementing closed-systems for 
injection into chromatographs;
--Voiding and purging sample cylinders outside of the laboratory or 
within an exhausted hood; and
--Purging process lines with nitrogen followed by steam or water 
cleaning prior to performing equipment maintenance.

    OSHA recognizes that there may be situations where engineering and 
work practice controls are not feasible due to a unique feature or 
condition. These situations are recognized in paragraph (f)(1) of the 
final rule, which permits the use of approved respiratory protection 
where employers can demonstrate that engineering and work practice 
controls are not feasible. In such situations, the burden of proof is 
appropriately placed on the employer to make and support a claim of 
infeasibility because the employer has better access to information 
specific to the particular operation that is relevant to the issue of 
feasibility.
    Paragraph (f)(2) requires employers whose employees are exposed 
above either of the PELs to establish and implement a written 
compliance plan that describes the methods to be used to reduce 
employee exposures to or below the PELs. The plan must provide for this 
to be accomplished where feasible with engineering and work practice 
controls, which must include surveys for leak detection on a periodic 
basis. The written plan must include a schedule for implementation and 
must be furnished upon request for examination and copying to OSHA, 
NIOSH, and affected employees or their representatives.
    In the preamble to the proposal, OSHA raised concerns about and 
solicited comments on the suggestion in the JACA report that worker 
exposures to BD originating from pump leaks could be controlled more 
cost-effectively with the use of leak detection programs rather than by 
engineering means, such as installation of pumps with dual mechanical 
seals. (Ex. 30) OSHA also questioned whether use of a continuous air 
monitoring system equipped with an alarm might be an equally effective 
alternative control technology (55 FR 32736 at 32791).
    In response, OSHA received many comments indicating that 
implementation of engineering controls is a far superior control 
strategy than primary reliance on leak detection, and these comments 
urged the Agency to retain its original performance-oriented language 
in the methods of compliance paragraph. For example, Michael J. Murphy 
of Monsanto commented as follows:

    It is Monsanto's position that the actual method of maintaining 
the integrity of engineering controls and process equipment should 
not be specified by OSHA. The appropriate utilization of 
preventative maintenance programs, periodic leak detection surveys, 
continuous monitoring systems and an educated workforce should be 
left up to the employer's professional judgment. So long as the 
overall process is maintained in a fashion which minimizes employee 
exposures as determined by personal monitoring, the actual method of 
compliance should not be a specific item. (Ex. 32-19, p. 6)

    In their post-hearing comments, NIOSH indicated that continuous 
monitoring systems might be useful in some situations, but only as an 
``* * * adjunct to engineering containment features * * *.'' (Ex. 101, 
p. 2) Similarly, Dr. Norman Morrow, of Exxon Chemical Company and 
chairman of the CMA Butadiene Panel, commented that use of double seals 
on pumps combined with a good leak detection and repair program would 
provide more protection to workers than would continuous monitoring 
systems. (Ex. 54, p. 7) The feasibility of relying primarily on 
continuous monitoring systems to maintain low worker exposures was also 
questioned by CMA in their post-hearing submission:

    In a monomer or crude facility which is out of doors and spread 
over a large area, a very large number of such analyzers would be 
required to provide any warning of potential high ambient levels. It 
is likely that even a very large and costly system would fail to 
detect butadiene excursions because of changing wind patterns, areas 
not covered, downtimes for maintenance, cycle times between 
measurements, etc. * * * [B]y contrast, engineering controls such as 
dual or tandem pump seals serve as a true primary safeguard against 
worker exposure. * * * Thus, OSHA should expressly recognize that 
continuous analyzers or monitoring systems, although perhaps 
beneficial in certain situations as part of a leak detection 
program, should not supplant engineering controls which directly 
protect workers against butadiene exposures. (Ex. 112, p. 125)

    After reviewing these comments, OSHA is convinced that primary 
reliance on either manual leak detection programs, as suggested by 
JACA, or continuous monitoring systems, would not provide worker 
protection equivalent to that afforded by engineering and work practice 
controls; therefore, OSHA is retaining the performance-oriented 
language originally proposed for the methods of compliance 
requirements, which allows employers to design their own compliance 
programs so long as they adhere to the general principles for the 
hierarchy of controls set forth in paragraph (f)(1).
    Furthermore, in paragraph (f)(2) of the final rule, OSHA specifies 
that the compliance program must include a leak detection program, but 
leaves the specific design of the program up to the employer. OSHA 
believes that leak detection is a vital element of the compliance 
program for butadiene, given the high volatility of the substance, and 
given that leaks, if not

[[Page 56811]]

detected in timely fashion, can be a significant source of employee 
exposure.
    Howard Kusnetz of Shell Oil objected to the proposal's requirement 
that compliance programs include leak detection:

    OSHA should not require the compliance program to include a 
periodic leak detection survey. If this is to be an effective 
performance standard, the facility needs the maximum flexibility to 
develop an effective program. The engineering control or work 
practice that reduces exposure may not need leak detection to be 
effective. This requirement will be a significant drain of resources 
and not result in enhanced employee protection. This is a 
significant departure from other health standards such as benzene 
and is already being addressed by EPA requirements. (Ex. 32-27, p.2)

    Other rulemaking participants identified leak detection as an 
important component of an effective compliance program for butadiene. 
For example, Frank Parker of Environmental Technologies Incorporated, 
testifying for OSHA, stated that use of double seals on pumps combined 
with a good leak detection and repair program would effectively control 
exposures to butadiene (Tr. 1/17/91, p. 534). In post-hearing 
testimony, NIOSH explained that leaks from process equipment were one 
of the major sources of employee exposure:

    NIOSH supports the contention that 1,3-butadiene processing 
involves closed systems and that exposures are the direct result of 
leaks in these systems. There are only relatively few points * * * 
in which the integrity of these closed systems are likely to be 
(intentionally) broken. * * * Prompt repair of leaks can appreciably 
reduce exposures, and techniques such as Hazard and Operability 
Studies * * * should help even more by anticipating and preventing 
the leaks. (Ex. 101, pp. 1-2)

    Similarly, as discussed above, several participants agreed that 
leak detection programs combined with primary reliance on engineering 
controls were the most effective approach for maintaining low employee 
exposures to BD; a routine leak detection program is one of the control 
elements specified in the exposure goal program recommended in the 
joint labor/industry agreement. (Ex. 118-13A) Furthermore, contrary to 
Mr. Kusnetz's assertion, OSHA has required compliance programs to 
contain provision for leak detection in its final rule for another 
highly volatile carcinogen, ethylene oxide (See 29 CFR 
1910.1047(f)(2)(ii)).
    OSHA believes that the language contained in paragraph (f)(2) of 
the final rule gives employers considerable latitude in designing 
effective leak detection programs. OSHA has not specified a minimum 
frequency for performing leak detection, the methods to be used by 
employers for performing leak detection, nor the locations where 
periodic leak detection must be performed. OSHA believes that the 
employer, with his or her knowledge of specific processes and workplace 
conditions, is in the best position to make these decisions. The 
employer must perform leak detection as often as is reasonable, given 
the specific circumstances of the work operation. The intent of the 
provision as worded in the proposal was to ensure that employers 
include a leak detection program as appropriate to their workplace 
within the compliance program, and that this information be available 
to affected employees or their representatives. Because the 
preponderance of professional opinion contained in the record provides 
support that leak detection programs are important supplements to 
engineering control programs, OSHA has accordingly retained this 
requirement in the final rule.
    The paragraph describing the proposed written compliance program 
requirements also contained a cross reference to paragraph (h) of the 
proposed standard dealing with written emergency plans. OSHA has 
deleted this cross reference in the final rule, recognizing that the 
written emergency plan is required regardless of whether the 
requirement for a written compliance program is triggered by exposures 
exceeding the PELs. This deletion was also included in the regulatory 
text from the joint labor/industry agreement.
    Paragraph (f)(2)(iv) prohibits the use of employee rotation as a 
method of reducing exposure to BD to or below the PELs. This 
requirement, which remains unchanged from the proposal, reflects a 
long-standing Agency policy that rotation of employees is an 
unacceptable practice for reducing exposures of employees to potential 
carcinogens. Although this approach may reduce the risk of cancer among 
individual workers who are periodically rotated out of tasks involving 
such exposure, the practice places a larger pool of workers at risk. 
OSHA received no objection to retaining this requirement for the 
butadiene standard, and its inclusion was supported by the joint labor/
industry agreement. OSHA wishes to make clear that other kinds of 
administrative controls are acceptable so long as they do not involve 
exposing employees who would otherwise not be exposed. Acceptable 
practices include methods such as scheduling certain maintenance tasks 
where there is a potential for high exposures during the work shift 
where there are the fewest employees present in the area.
    The text of the joint labor/industry joint recommendations included 
one other change in the language of proposed paragraph (f), clarifying 
that no written compliance program would be required ``if the initial 
(exposure) reading has been reliably determined to have been in 
error.'' (Ex. 118-13A) None of the participants of the joint agreement 
provided a specific rationale explaining the need to include this 
language; however, one rulemaking participant, Richard Olson of Dow 
Chemical, offered an explanation after reviewing a draft of the 
agreement:

Occasionally, one sample may be over a permissible exposure level 
because of some circumstance such as an analytical error or perhaps 
an unusual, unanticipated action taken by the employee. In such 
cases, the situation surrounding the data point should be 
investigated but that individual sample should not necessarily 
instigate a full-blown program as it may not be representative of 
actual average conditions. (Ex. 118-16, p. 6)

For these reasons, Mr. Olson suggested that the language contained in 
the draft regulatory text from the agreement not be limited to 
circumstances involving only analytical error, but also be applied to 
other unusual events.
    In the final rule, OSHA did not include the language regarding 
erroneous sample results that was contained in the labor/industry 
regulatory text. Clearly, no employer action should ever be based on an 
erroneous reading. In addition, OSHA believes such language is 
unnecessary since it has never been the Agency's intent or practice to 
require employers to comply with a provision of a standard based on the 
results of a single sample so long as the employer has adequate 
documentation that the result is unusual and does not reflect typical 
workplace conditions. Conversely, OSHA would not expect an employer to 
discontinue complying with a provision of the standard simply because a 
single sample suggests employees are not exposed above either of the 
PELs, if the weight of information available to the employer indicates 
otherwise. Indeed, OSHA believes it more likely that gross sampling and 
analytical errors will tend to understate rather than overstate 
exposures for a variety of reasons (for example, due to sampling pump 
fault or failure, taking samples under conditions of high humidity or 
where other hydrocarbons are present, sample loss from breakthrough or 
due to improper sample storage or handling, or

[[Page 56812]]

inefficient desorption of the sample from the media).
    OSHA believes that employers should base their compliance actions 
on the totality of information and data available to them about their 
workplaces and employee exposures, and on their best professional 
judgment. If in the employer's best judgment, a sample result is 
obtained that is not credible or is perceived as unlikely, the employer 
should, as Mr. Olson suggests, investigate the probable causes by 
ensuring that process and engineering equipment are functioning 
properly, by talking with affected employees to determine if there were 
any unusual occurrences or practices that may be associated with the 
result, and conduct repeat monitoring to help confirm that the 
questionable result is not representative of typical workplace 
conditions. On the other hand, should the employer instead choose to 
rely on a minimal program to assess employee exposures and a sample 
result indicates that an operation is associated with worker exposures 
above the PELs, OSHA believes it is prudent to presume that the result 
reflects typical exposure conditions and that a plan for implementing 
corrective measures is necessary.

G. Exposure Goal Program

    Paragraph (g) of the final rule contains requirements for the 
employer to establish an exposure goal program where employee exposures 
are above the action level of 0.5 ppm TWA. As part of the exposure goal 
program, which was recommended by the labor/industry agreement, the 
employer must implement the following control measures:

--A leak prevention, detection, and repair program;
--A program for maintaining effectiveness of local exhaust systems;
--Use of technologies that minimize BD emissions from pumps;
--Use of gauging devices designed to limit employee exposures during 
loading operations;
--Use of controls such as vapor return systems to limit exposures 
during unloading operations; and
--A program to maintain BD concentrations below the action level in 
control rooms.

    The employer is not required to implement the controls specified 
above if he or she demonstrates that the controls are not feasible, 
will not be effective in reducing exposures to or below the action 
level, or are not necessary to achieve exposures to or below the action 
level. In addition, nothing in the exposure goal program requires 
employers to use respiratory protective equipment to achieve the action 
level. The exposure goal program must be implemented within three years 
from the effective date of the standard, in accordance with paragraph 
(m); this is one year beyond the date that employers are required to 
have installed engineering and work practice controls to achieve the 
PELs.
    The requirements in this paragraph were not originally included in 
the proposal, but were proposed as part of the joint labor/industry 
agreement for BD. In its supplemental Federal Register notice, OSHA 
requested comments on the exposure goal program. (61 FR 9382) 
Specifically, OSHA was concerned whether including specification-
oriented requirements for engineering controls in the exposure goal 
program would lead to situations where:

--The use of alternative control methods that would be equally or more 
effective in reducing exposures would be discouraged or ignored;
--The employer would be unable to comply because the specified controls 
are not applicable to the operation(s) where exposures exceed the 
action level; or
--The required controls would not be needed because exposures could be 
reduced to or below the action level by work practices alone, thus 
forcing employers to spend capital resources unnecessarily to comply 
with the letter of the requirement.

    Several other participants raised concerns similar to those of 
OSHA's, generally preferring a more performance-oriented approach that 
did not mandate the use of specific control methods. For example, Paul 
Bailey, representing the American Petroleum Institute, submitted the 
following comment:

API has some concerns with the ``Exposure Goal Program'' * * *, 
particularly shifting the burden to employers (to prove that the 
required controls are not feasible or effective) * * *. The listed 
elements of the exposure goal program may be useful tools for 
controlling exposures, but it is important to provide flexibility 
for use of new exposure control technologies that may become 
available. (Ex.118-11)

API recommended that the specific elements of the program be contained 
in a non-mandatory appendix rather than specified in the regulatory 
text; this approach was also supported in Richard Olson's submission on 
behalf of Dow Chemical. (Ex. 118-16) Mr. Olson also stated that the 
exposure goal program would establish the action level as a ``de facto 
PEL,'' and expressed the concern that specifying control measures might 
cause employers to implement controls for operations that do not 
contribute to employee exposures exceeding the action level. However, 
Mr. Olson acknowledged that the language contained in the draft 
agreement would allow employers to exclude specified elements of the 
program where they are not needed to attain the action level. 
Representatives of three refineries or chemical producers submitted 
similar comments (Exs. 118-5, 118-6, 118-8), arguing that the program 
should not include specifically mandated control methods since it would 
``discourage * * * (the use of) process-based controls in favor of 
equipment based controls * * * '' (Ex. 118-5) and would be `` * * 
*counterproductive to innovating new control strategies * * * '' (Ex. 
118-6)
    However, in describing the program further, the CMA Olefins Panel 
commented that the regulatory language contained in the labor/industry 
agreement addressed these concerns. They said:

The program is meant to supplement, not replace, the requirement 
that an employer ``institute engineering controls and work practices 
to reduce and maintain employee exposure to or below'' the PEL * * 
*. Since the program is required only where exposures are above the 
action level, it in fact creates incentives to develop improved 
engineering controls or work practices that achieve greater 
reductions in exposure.
    In addition, under the program, an employer would not need to 
implement the listed components of an exposure goal program if the 
employer could show that the components are not feasible, effective, 
or necessary to reduce exposures to at or below the action level * * 
*. Thus, OSHA's concerns that the program may impose inapplicable or 
unwarranted requirements are unfounded. (Ex. 118-13, p. 6)

The Panel further stated that the program `` * * * is an innovative 
concept aimed at addressing industry feasibility concerns while 
creating incentives to minimize worker exposure by encouraging the use 
of specified engineering controls with which the industry has 
experience.'' According to the Panel, incentives for developing 
improved exposure control methods are brought about because the 
exposure control program would not be required where exposures are at 
or below the action level (Ex.118-13, p. ii).
    The submission by the IISRP explained that the exposure goal 
program is part of a three-pronged framework developed to address 
concerns about minimizing worker exposures in a feasible manner. 
According to IISRP:


[[Page 56813]]


    * * * OSHA's record does not demonstrate that a 2 ppm (TWA) PEL 
or a 10 ppm STEL is feasible in polymer operations. Recognizing, 
however, that union representatives wished to see butadiene 
exposures even lower than 1 ppm, industry worked to develop an 
overall standard that would minimize exposures and still be 
feasible. The result was a three-part framework:
    (1) A PEL of 1 ppm, STEL of 5 ppm, and action level of 0.5 ppm, 
coupled with
    (2) The flexibility to employ respirators to achieve such 
exposures for non-routine intermittent and limited in duration 
activities and
    (3) The exposure goal program.
     * * * [T]he exposure goal program does not raise the concerns 
expressed by OSHA. No goal program need be initiated when exposures 
are already below the action level by whatever engineering controls 
or work practices. Better * * * controls * * * are thus not 
discouraged; they may always be used to achieve (the) action level 
or lower exposures. (Ex. 118-12, pp. 4-5)

    After considering these comments, as well as the actual regulatory 
language recommended in the joint labor/industry agreement, OSHA finds 
that it is both reasonable and appropriate to include the specified 
control measures in the requirement for the exposure goal program. 
First, OSHA finds it reasonable in that the control measures specified 
in the exposure goal program represent those that are readily available 
to industry and have been proven effective to achieve the action level 
in at least some workplaces. OSHA's analysis of the technological 
feasibility of the standard, based largely on the NIOSH study of BD 
plants, identified some of these controls as approaches that have been 
successfully used to achieve exposure levels well below the PELs (see 
the Economic Analysis discussion in this preamble). For example, Shell 
Oil in Deer Park, Texas, achieved median exposure levels of 0.3 ppm 
(TWA) by implementing a collection system to capture emissions from 
loading operations as well as a combination of magnetic and slip-tube 
gauges (Ex. 16-29); use of magnetic gauges for all loading operations 
would likely reduce exposures further. Replacement of pumps having 
single mechanical seals with dual-seal pumps, which is an improved pump 
technology specified under the exposure goal program, has been 
occurring within the BD industry over the past several years (see the 
Technological Feasibility chapter of the Economic Analysis). Other 
elements of the exposure goal program are not equipment-oriented, but 
instead are designed to ensure that process equipment and engineering 
controls are optimally maintained to minimize or capture BD releases; 
these elements include a leak prevention, detection and repair program 
and a program to maintain the effectiveness of local exhaust 
ventilation equipment. Finally, all of the control measures specified 
in the exposure goal program are those that labor and industry 
representatives jointly agreed were reasonable to include. (Ex. 118-
13A)
    OSHA also finds that the exposure goal program requirements are 
appropriate for two reasons. First, OSHA has determined that a 
significant risk of cancer is associated with lifetime exposure to the 
action level of 0.5 ppm; the estimated risk to workers exposed at this 
level is about 4 per 1,000 (see the Quantitative Risk Assessment 
section of this Preamble). OSHA finds that it is appropriate to expect 
employers who have not already done so to implement the commonly used 
approaches detailed in paragraph (g) for controlling exposures to BD in 
an effort to further reduce this risk. Second, OSHA believes it 
appropriate to craft the exposure goal program requirements in 
specification language because to do otherwise would effectively blur 
the distinction between the exposure goal program and the methods of 
compliance requirements of paragraph (f), a distinction that the CMA 
emphasized was critical. (Ex. 118-13, p. 6) OSHA has not made a 
determination that a 0.5 ppm TWA exposure level for BD was generally 
feasible in affected industry sectors; therefore, the burden of proof 
to demonstrate the infeasibility of engineering and work practice 
controls for achieving the 0.5 ppm action level in an operation cannot 
be placed on the employer. If the requirements for the exposure goal 
program were developed in performance-oriented language, even with the 
aid of a non-mandatory appendix to guide employers and OSHA in its 
interpretation, OSHA believes that the requirement would have no real 
meaning in terms of performance measures by which employers, employees, 
and OSHA could judge compliance. In this situation, the action level 
might well be interpreted as a ``de facto PEL'', as suggested by Mr. 
Olson. By including a minimum specification for the content of the 
program, employers and their employees, as well as OSHA, are provided 
with a clear set of performance measures while maintaining a 
distinction between the exposure goal program and methods of compliance 
requirements for the PELs.
    Nevertheless, OSHA believes the final rule's requirement for the 
exposure goal program, as worded, provides employers with considerable 
flexibility in the design of the program. Key to providing this 
flexibility is the 3-year phase-in date for the program. OSHA believes 
that by extending the implementation date for the exposure goal program 
one year beyond the date for which employers must implement controls to 
achieve the PELs, employers will have sufficient time to explore 
whether the use of alternative engineering approaches, process 
modifications, or work practices will permit them to reduce exposures 
to or below the action level.
    OSHA also finds that commenters' concerns about the program's 
supposed lack of flexibility in allowing for the use of alternative 
technologies is unwarranted, since the extended phase-in period for 
implementation of the exposure goal program will provide employers with 
additional flexibility to design their own programs using alternative 
engineering control methods and work practices. The longer phase-in 
period for the exposure goal program is also appropriate because it 
allows employers to focus their initial efforts on reducing employee 
exposures to or below the PELs, as required under paragraph (f).
    However, if the required implementation date of the exposure goal 
program is approaching and employee exposures still remain above the 
action level, either because the alternative controls were not 
sufficiently effective or the employer was not proactive in identifying 
alternatives, OSHA finds it appropriate to require that the employer 
implement, at a minimum, the controls that have been proven effective 
within the BD industry and identified in the exposure goal program, to 
the extent that such controls are feasible and applicable to the 
affected operations, and will be effective in further reducing employee 
exposures to BD.
    The exposure goal program in paragraph (g) of the final rule 
incorporates two modifications from the language contained in 
regulatory text proposed by the joint labor/industry agreement (Ex. 
118-12A). The joint agreement proposed that worker rotation be 
permitted as part of the exposure goal program. OSHA did not include 
this language in the final rule because of the Agency's long-standing 
policy of not allowing worker rotation to be used to control employee 
exposures to a carcinogen. As explained above in the Summary and 
Explanation for paragraph (f) (Methods of Compliance), employee 
rotation places a larger than necessary pool of workers at risk from 
exposure to BD. In other words, it would result in some employees being 
exposed to a cancer hazard to which they might not otherwise be 
exposed.

[[Page 56814]]

Since OSHA has estimated the lifetime cancer risk from exposure to BD 
to be about 4 per 1,000 workers at the action level of 0.5 ppm, use of 
employee rotation to achieve the action level provides no assurance 
that employees who are rotated into jobs with exposures around the 
action level will not be exposed to BD at levels representing a 
significant risk. Therefore, OSHA finds that employee rotation is not 
an appropriate method for achieving the action level. The second change 
involves the addition of clarifying language in the exposure goal 
program. The regulatory text contained in the joint labor/industry 
agreement stated that employers need not apply the control measures 
specified in the exposure goal program if such methods would not be 
``effective.'' OSHA modified this language to make clear that such 
controls need not be implemented if the employer could demonstrate that 
they will ``not be effective in reducing employee exposures.'' OSHA 
believes that this better reflects the intent expressed in the joint 
labor/industry agreement.

H. Respiratory Protection

    The respiratory protection requirements of the final standard for 
BD are in keeping with the requirements for respiratory protection in 
other OSHA health standards (e.g., Occupational Exposure to Lead, 29 
CFR 1910.1025; Occupational Exposure to Benzene, 29 CFR 1910.1028), and 
with recent developments in the field. The provisions contained in the 
final rule have been changed from the proposal in some important 
respects in response to information and comments placed in the record. 
Comments received on the proposed BD respiratory protection provisions 
addressed broad issues of fit testing protocols, protection factors for 
various respirator classes, and other general respiratory protection 
issues. OSHA is currently evaluating these generic issues in the 
context of revising 29 CFR 1910.134, which is expected to be 
promulgated in the near future. The discussion of the appropriate 
respiratory protection for BD exposure that follows will identify those 
areas that are relevant to the broader issues being dealt with in the 
revision of 29 CFR 1910.134. The respiratory protection provisions 
contained in the final rule on BD reflect OSHA's current thinking on 
how some of these respiratory protection issues should be addressed. 
OSHA thus believes that the final rule for BD will be consistent with 
the revision of 29 CFR 1910.134.
    Use of Respiratory Protection. Respirators are necessary as 
supplementary protection to reduce employee exposures when engineering 
and work practice controls cannot achieve the necessary reduction to or 
below the PELs. Paragraph (h)(1) identifies instances where the use of 
respiratory protection is permitted when employee exposures exceed the 
PELs. These are:

    1. During the time interval necessary to install or implement 
feasible engineering and work practice controls;
    2. In work situations where feasible controls are not yet 
sufficient to maintain exposures below the PELs;
    3. During emergency situations; and
    4. During non-routine work operations that are performed 
infrequently and in which exposures are limited in duration.

    The first three instances are identical to those that were 
contained in the proposal. As to the fourth instance, i.e., ``non-
routine work operations,'' OSHA originally proposed that respirators 
would be permitted for non-routine, limited-duration work operations if 
the employer could demonstrate that engineering and work practice 
controls were infeasible. OSHA received numerous comments arguing that 
OSHA should not impose a burden of proof on employers to demonstrate 
the infeasibility of engineering controls during such work operations.
    The CMA Panel expressed support for allowing respirator use 
``during the period necessary to install feasible engineering controls 
and where feasible * * * controls are not yet sufficient to reduce 
exposures below the PEL.'' (Ex. 118-13) However, in this submission and 
preceding ones, they objected to the proposal, which stated that 
respirators shall be used ``In work operations such as maintenance and 
repair activities, vessel cleaning, or other activities for which 
engineering and work practice controls are demonstrated to be 
infeasible, and exposures are intermittent in nature and limited in 
duration.'' (55 FR at 32805, 8/10/90) CMA's concern centered on the 
requirement to demonstrate the infeasibility of engineering controls 
before respirators could be used in short-term, intermittent work. (Ex. 
112, p. 141-145) They felt that there were certain activities for which 
the infeasibility of engineering controls could not be demonstrated in 
``an absolute technological sense,'' but the use of engineering 
controls would nevertheless be ``highly impracticable'' because the 
work activities are performed infrequently and the controls would prove 
to be very expensive. (Ex. 112, p. 142) CMA witness, Mr. Roger Daniel, 
gave the following example of such an activity:

    You may have 300 (pumps) in the plant and no one of those has to 
have any maintenance or cleaning activities to reestablish the 
integrity of the signal to that instrument more frequently than 
every two years. But because of the nature of the material that 
you're handling and the fact that it can slowly accumulate material 
* * * Periodically this has to be dealt with * * * you could put in 
lines to each of these blow-downs and collect from these 200 
instruments just a little bit of liquid that has to be discharged * 
* * but from a practical standpoint, * * * [it] doesn't seem to make 
good sense. (Tr. 1/18/91. p. 1234-5)

    In a pre-hearing submission CMA enumerated some situations where 
they believed engineering controls to be ``highly impracticable.'' Two 
of these were discussed in some detail. (Ex. 32-28) The first, 
``blowing down of meter leads'' to clear instrument lines of 
accumulated debris was described as occurring only once every several 
years per instrument. CMA felt that installation of permanent blow-down 
lines leading to the flare, which would ensure the containment and 
destruction of BD, was not justified in this case. Second, they 
described breaking into and degassing pumps for maintenance as a work 
task that is performed twice weekly and lasts less than 10 minutes per 
occurrence. They felt that although it might be possible to build an 
enclosure around each of the pumps, the high cost of doing so was 
unjustified, due to the short-term nature of the task. (Ex. 32-28)
    During the public hearing, Charles Adkins, then Director of OSHA 
Health Standards Programs, stated that in the context of the BD 
proposal, OSHA did not intend the term ``infeasible'' to mean an 
absolute technological infeasibility in the strictest sense, but that 
the intent was to limit respirator use to intermittent short duration 
situations where engineering controls are impracticable. He said that 
OSHA has:

    * * * always recognized that there [are] some situations that 
you don't consider it feasible. You don't put in an elaborate 
ventilation system to control exposures to some device that may 
break once every five years * * * and you * * * spend 30 minutes 
repairing that device. That's an appropriate time to use personal 
protective equipment. (Tr. 37, 1/15/91)

    OSHA witness Frank Parker, a Professional Engineer and Certified 
Industrial Hygienist, testified that engineering controls were 
generally cost-effective, but that even when engineering controls are 
technologically feasible, respirators are ``going to be the most 
useful, practical approach'' in those situations in which there is 
``sporadic (exposure) under unique conditions.'' (Tr. 1/17/91, p. 546)

[[Page 56815]]

    In several other health standards, including the benzene standard, 
OSHA has specified some examples of activities for which engineering 
controls are not feasible. In the benzene rule respirators are 
required, ``In work operations for which the employer establishes that 
compliance with either the TWA or STEL, through the use of engineering 
and work practice controls are not feasible, such as some maintenance 
and repair activities, vessel cleaning, or other operations where 
engineering and work practice controls are infeasible because exposures 
are intermittent in nature and limited in duration.'' (29 CFR 
1910.1028(g)(1)(ii)).
    In the preamble to the benzene standard OSHA stated that

    * * * engineering controls are often infeasible when exposures are 
intermittent in nature and limited in duration. For the same reason as 
maintenance and repair activities, extensive attempts at engineering 
controls are often not practical where exposures are both brief and 
occasional. It is both difficult to keep operable and a not very 
productive use of valuable industrial hygiene time, as well as often 
very costly, to try to provide engineering controls for very brief, 
intermittent exposures * * * In addition, for such intermittent and 
irregular exposures, employees can wear respirators with less 
difficulty. (52 FR at 34544, 9/11/87)

    The labor/industry group recommended that respirators be 
specifically allowed ``in non-routine work operations which are 
performed infrequently and in which exposures are limited in 
duration.'' (Ex. 118-12A) OSHA considered all available information on 
this issue and has determined that such a provision is justified for 
BD. OSHA has therefore included the above language in the final rule in 
paragraph (h)(1)(ii).
    The intent of this provision is not to allow employers to organize 
their workplace operations such that work is artificially broken down 
into tasks of small increments of time to allow wholesale respirator 
use when engineering controls are clearly practicable and therefore 
feasible under paragraph (f).
    High exposures have been documented for workers performing certain 
activities such as cylinder voiding and sampling. Such activities may 
be performed intermittently and resulting exposures have been shown to 
be of short duration; however, since such operations are performed 
routinely, engineering controls need to be used to control exposures. 
OSHA does not intend that such routine activities be included in the 
paragraph (h)(1)(ii) exemption from the usual preference for 
engineering and work practice controls. Rather, paragraph (h)(1)(ii) 
contemplates that brief incidental maintenance activities be included. 
On the other hand, in the case of cylinder voiding (which would not be 
covered by paragraph (h)(1)(ii)), NIOSH recommended use of a laboratory 
hood or a vacuum exhaust with an enclosure. (Ex. 16-38; 16-39) For 
maintenance activities, NIOSH said ``maintenance technicians should 
follow decontamination procedures when working on process equipment. 
However, if it is not possible to completely decontaminate a process 
prior to the procedures, then respirators with organic vapor cartridges 
should be worn.'' (Ex. 16-38; 16-39)
    In keeping with OSHA's intention to use a performance-oriented 
approach, where appropriate, the Agency has not defined either ``non-
routine,'' ``infrequently,'' nor ``limited in duration'' in the final 
rule. Reasonable interpretations must be made. To qualify for the 
narrow exemption that permits the use of respirators without 
demonstrating the infeasibility of engineering or work practice 
controls, the task must meet all three criteria; it must be non-
routine, infrequent, and of limited duration. OSHA believes that the 
vast majority of such activities qualifying under paragraph (h)(1)(ii) 
will consist of brief, intermittent maintenance operations such as 
those described by CMA (e.g., blowing down meter leads for 5 minutes 
once a year, or opening pumps for maintenance for 1 hour quarterly). 
(Ex. 32-28, p. 116)
    Emergency Situations. Paragraph (h)(1)(iv) requires employers to 
ensure that employees use respiratory protective equipment during 
emergencies. The joint labor/industry agreement suggested changing 
``emergencies'' to ``accidental release emergencies.'' Submissions by 
CMA (Ex. 118-13) and IISRP (Ex. 118-12) provided no explanation 
supporting the need to change the language in paragraph (h)(1)(iv). 
OSHA did not incorporate this change in the final rule since the 
language suggested by the labor/industry agreement may imply to some 
that a release must occur before an emergency is declared and 
respirators would be required. The language that was originally 
proposed and retained in the final rule, along with the definition of 
``emergency'' in paragraph (b), make clear that employers must ensure 
that employees use respiratory protection during an unusual condition 
or occurrence where there is a potential for a release of BD, even if 
an actual release has not occurred. OSHA believes that this reflects 
common practice in the chemical industry. This provision of the final 
rule is consistent with other OSHA health standards and is necessary to 
ensure that employees do not become exposed should an unusual condition 
result in a release.
    Respirator Selection. Paragraph (h)(1) of the final standard 
requires that employers provide respirators to employees when necessary 
and ensure that employees use the respirators properly. As in other 
OSHA standards, employers are to provide the respirators at no cost to 
the employees. OSHA views this allocation of costs as necessary to 
effectuate the purposes of the Act. This requirement makes explicit an 
Agency position which has long been implicit in the promulgation of 
health standards under section 6(b) of the Act.
    Employers must select respirators from those certified as being 
acceptable for protection against BD or organic vapors by the National 
Institute for Occupational Safety and Health (NIOSH), under the 
provisions of 42 CFR part 84.
    Paragraph (h)(2) of the final rule requires employers to select and 
provide respirators in accordance with the criteria specified in Table 
1. In the proposal, OSHA would not have permitted the use of cartridge-
type negative-pressure respirators because of concern that they would 
not be sufficiently protective due to the short breakthrough times 
associated with high BD concentrations. OSHA requested additional data 
and comment on the issue, and asked NIOSH to conduct another 
breakthrough study to provide more information about the effectiveness 
of organic vapor cartridges in atmospheres containing lower BD 
concentrations.
    The respirator selection table in the proposal was the subject of 
numerous comments addressing two principal issues. (Ex. 32-3; 32-4; 32-
7; 32-8; 32-14; 32-20; 32-22; 32-25; 32-27; 32-28; 112; 118-6; 118-12; 
118-16) First, commenters stated that the table should allow the use of 
cartridge type respirators in limited applications, and that the table 
should include other kinds of available respiratory protective 
equipment, such as half-mask supplied air respirators and loose-fitting 
powered air purifying respirators. (Ex. 32-4; 32-22; 32-27; 32-28; 112; 
118-6; 118-12; 118-16) Second, commenters questioned the assigned 
protection factors (APFs) used in the proposal, stating that OSHA 
should use APF's similar to those used in other OSHA health standards 
or those of the ANSI

[[Page 56816]]

Z88.2-1992 standard. (Ex. 32-7; 32-25; 112; 118-6; 118-16) NIOSH stated 
that if respirators other than a self-contained breathing apparatus 
(SCBA) or a supplied air respirator with auxiliary SCBA that NIOSH 
recommended are permitted, OSHA should use the APFs in the 1987 NIOSH 
Respirator Decision Logic. (Ex. 32-25) The ANSI Z88.2-1992 standard and 
NIOSH decision logic apply the same APFs to half-mask, negative-
pressure respirators (10) and PAPRs equipped with a tight-fitting half 
mask (50); for other respirator types, ANSI generally assigns a higher 
APF than does NIOSH.
    OSHA has determined that cartridge-type respirators will provide 
adequate protection for BD, based on new evidence and data on 
breakthrough times at low BD concentrations (described in the 
discussion of Service Life below) and on comments concerning whether BD 
had adequate odor warning properties that would permit employees to 
detect breakthrough well in advance of their being overexposed. (Ex. 
32-25; 32-28; 112) NIOSH stated that BD does not have adequate warning 
properties, citing the paper by Amoore and Hautala (Odor as an aid to 
chemical safety: odor thresholds compared with threshold limit values 
and volatilities for 214 industrial chemicals in air and water 
dilution. J. Appl. Toxicol. 3:272-290) that lists an air odor threshold 
of 1.6 ppm for BD. (Tr. 1/17/91. p. 741) However, this value is a 
geometric average of all the literature survey odor data that Amoore 
and Hautala used in devising their odor threshold tables. On the other 
hand, Tom Nelson, testifying on behalf of CMA, cited the American 
Industrial Hygiene Association (AIHA) report, Odor Thresholds for 
Chemicals with Established Occupational Standards, which lists BD as 
having a geometric mean odor threshold of 0.45 ppm for detection and 
1.1 ppm for recognition. (Ex. 32-28c) According to CMA, the AIHA report 
represents a more recent compendium of odor threshold data for chemical 
agents than does the Amoore and Hautala study. (Ex. 112) Since the mean 
odor threshold identified by this source is about half of the 1 ppm 
PEL, and more than 10-fold below the 5 ppm STEL, OSHA finds that most 
wearers of air purifying respirators should still be able to detect 
breakthrough before a significant overexposure to BD occurs. 
Accordingly, OSHA is permitting the use of air purifying respirators 
equipped with either organic vapor cartridges or canisters in the final 
rule. In addition, OSHA will permit employers to provide single-use, 
half mask respirators equipped with organic vapor cartridges for 
employees working in environments containing up to 10 ppm BD.
    In the final rule, OSHA has used the APFs for the various 
respirator classes contained in the NIOSH Respirator Decision Logic. 
(Ex. 32-25) The ANSI Z88.2-1992 APF values have not been adopted, 
although they were relied on in the recommended standard from the joint 
labor/industry agreement. As discussed earlier in this section of the 
preamble, OSHA is currently engaged in evaluating extensive data and 
evidence on APFs as part of its 29 CFR 1910.134 revision. However, in 
the case of the BD standard, OSHA's decision to rely on the more 
protective NIOSH APFs is based on evidence showing that organic-vapor 
cartridges and canisters have limited capacity for adsorbing BD and may 
have too short a service life when used in environments containing 
greater than 50 ppm BD. This evidence (discussed in detail in the 
section below entitled Service Life of Organic Vapor Cartridges and 
Canisters) consists of laboratory test data showing that organic vapor 
cartridges and canisters have a useful service life of no more than 
about 1.5 hours when challenged with air containing greater than 50 ppm 
BD, and that, at these concentrations, service life declines rapidly 
with increasing BD concentration. Allowing for a reasonable margin of 
protection, and given that test data were available only for a few 
makes of cartridges and canisters, OSHA believes that air-purifying 
devices should not be used for protection against BD present in 
concentrations greater than 50 ppm, or 50 times the 1 ppm PEL. Thus, 
OSHA finds that the ANSI APFs of 100 for full-facepiece, air-purifying 
respirators and 1,000 for PAPRs equipped with tight-fitting facepieces 
are inappropriate for selecting respirators for BD.
    The proposal contained a provision (g)(2)(iii) requiring employers 
to provide employees with the option of using a positive-pressure 
respirator if the employee is unable to use a negative-pressure device. 
John Hale of Respirator Support Services objected to this provision 
since it would take respirator selection, the most critical aspect of a 
respirator program, out of the hands of the program administrator who 
is most knowledgeable about respirators and put it into the hands of 
the worker. (Ex. 32-3) Hale questioned whether the provision's language 
implied that the individual's medical condition would preclude the 
wearing of any respirator, since the breathing resistance of a modern 
negative pressure respirator is not a concern for a healthy worker. Mr. 
Hale also questioned the additional cost of supplying these alternative 
respirators. The International Institute of Synthetic Rubber Producers 
(IISRP) stated that, ``this provision is unwarranted because employees 
who are not medically fit should not be assigned to a job where 
respiratory protection is required.'' (Ex. 34-4)
    OSHA has similar provisions requiring that the employer supply 
alternative respirators, either upon employee request or if the 
employee has difficulty wearing a negative-pressure device, in other 
substance specific standards such as inorganic arsenic (1910.1018), 
lead (1010.1025), cadmium (1910.1027), benzene (1910.1028), 
formaldehyde (1910.1048), and MDA (1910.1050). It has been OSHA's 
experience that this requirement has not proven to be a burden to 
implement and has proved to be a way to improve worker acceptance of 
respirator use. The language used in the BD proposal was the same as 
the language used in the benzene standard, 1910.1028 (g)(2)(iii). 
However, commenters felt the language in question implied that 
medically unfit workers would be allowed to wear PAPRs or supplied air 
respirators in place of a negative pressure respirator. (Ex. 32-3; 34-
4) This is not the intent of this provision. The final provision 
(h)(2)(iii) has been modified to clarify that employers must determine 
that employees are able to use positive-pressure respiratory devices 
before upgrading an employee's respirator from a negative-pressure 
device. OSHA believes that this change in language better reflects the 
Agency's intent that employees who are unable to wear negative-pressure 
respirators be permitted to wear positive-pressure devices only after 
the employer takes appropriate steps to ensure the employee's ability 
to do so safely.
    Some commenters pointed out that Table 1 of the proposal contained 
an error in that it would have permitted the use of PAPRs and self-
contained breathing apparatus operated in a negative-pressure demand 
mode at any BD concentrations exceeding 50 ppm, which could result in a 
potentially dangerous situation since no maximum use concentration for 
these types of respirators was specified. (Ex. 32-28; 32-25; 32-3; 32-
14) OSHA agrees that its proposed respiratory selection table was in 
error and has revised Table 1 of the final rule to reflect the 
appropriate maximum use concentration for PAPRs. OSHA deleted SCBA 
operated in negative-pressure demand mode from Table 1 since this type 
of respirator is not typically used in industrial settings.

[[Page 56817]]

    Respirator Program. The proposal required (paragraph (g)(3)) that 
employers institute a respirator program in accordance with 29 CFR 
1910.134 (b), (d), (e), and (f). It was pointed out by one commenter 
that since 29 CFR 1910.134 is under revision, these references to 
specific paragraphs may change. (Ex. 32-3) The language of this 
provision has been revised to eliminate any reference to specific 
paragraphs in 29 CFR 1910.134, but still retains the requirement that a 
respirator program in accordance with the respiratory protection 
standard be implemented that contains the basic requirements for proper 
selection, fit, use, training of employees, cleaning, and maintenance 
of respirators. For employers to ensure that employees use respirators 
properly, OSHA has found that the employees need to understand the 
respirator's limits and the hazard it is protecting against in order to 
appreciate why specific requirements must be followed when respirators 
are used.

Service Life of Organic Vapor Cartridges and Canisters

    The proposal in paragraph (g)(4)(i) required that the air purifying 
filters be replaced at 90% of the expiration of service life. The 
service life of organic vapor cartridges and canisters relates to the 
amount of time that the charcoal filter effectively purifies the 
breathing air before contaminants break through the filter and enter 
the facepiece. In laboratory testing for service life, air containing a 
known concentration of contaminant is passed through a cartridge or 
canister at a predetermined flow rate. The concentration of contaminant 
is measured in the air exiting the filter element on the other side. 
The time required for the contaminant concentration to reach a target 
level after passing through the filter element is known as the 
breakthrough time, and represents a measure of the service life of the 
filter element when used in atmospheres containing concentrations of 
the contaminant near the challenge concentration.
    OSHA received comments on the proposed provision that would require 
replacement of organic vapor filters at 90% of the service life. The 
joint labor/industry agreement supported the proposed provision and 
recommended its inclusion in the final rule. (Ex. 118-12) However, John 
Hale of Respirator Support Services questioned how anyone could be 
expected to know when an element had reached 90% of its service life, 
or even come close to guessing it, since service life is dependent on 
the filter's inherent capacity (sorbent efficiency, bed depth, and 
other design factors) and even more so on respirator use conditions. 
(Ex. 32-3) Mr. Hale recommended that OSHA simply require filter 
elements to be replaced at the end of each shift.
    In contrast, Tom Nelson, testifying for CMA (Ex. 32-28 C; 107-22), 
recommended that service life be taken into account to permit the use 
of organic vapor cartridges against BD, pointing out that there were 
test data contained in the BD record that would permit employers to 
establish cartridge change schedules suitable for their individual 
workplaces (these test data are discussed below). Specifically, Mr. 
Nelson suggested modifying paragraph (g)(4)(iii) of the proposal to 
permit the use of cartridge style respirators, provided that the 
cartridges have a minimum service life of at least 110% the anticipated 
duration of respirator use. Mr. Nelson also recommended that service 
life be tested under worst-case conditions of use, i.e., at a flow rate 
of 64 lpm at 25 deg.C and at a relative humidity of 85%.
    OSHA agrees with Mr. Nelson that adequate service life data are 
currently available both to support the use of organic vapor cartridges 
for BD and to establish schedules for changing filter elements. For 
example, NIOSH has performed respirator cartridge breakthrough testing 
at various exposure levels. (Ex. 23-83; 90) The BD record also contains 
other reports of service life testing of organic vapor filters, one a 
published report by Mr. Mark Ackley (Chemical cartridge respirator 
performance: 1,3-butadiene. Am. Ind. Hyg. Assoc. J. 48:447-453 in Ex. 
32-28, Vol. II, App. B), and the other an unpublished report prepared 
by Mr. William Myles of Dow Chemical (Ex. 32-28, Vol. II, App.C). A 
summary of service life test data from these reports is presented in 
Table 2. Most of the breakthrough tests conducted for BD used high 
challenge concentrations relative to the PEL (most exceeding 50 ppm). 
In addition, the data from Myles and those from Ackley measured 
breakthrough times for a target concentration of 10 ppm, which was the 
ACGIH TLV at the time testing was conducted. However, after the 
informal hearing, NIOSH conducted breakthrough tests at lower challenge 
(10 to 50 ppm) and target (2 to 10 ppm) concentrations; some of these 
data are also summarized in Table X-1. (Ex. 90)

     Table X-1. Summary of Breakthrough Test Data for Respirator Cartridges and Canisters Challenged Against    
                                                    Butadiene                                                   
----------------------------------------------------------------------------------------------------------------
                         Breakthrough      Temperature, Relative                                                
       Upstream          Concentration   Humidity (RH), Flow Rate    Breakthrough Time          Reference       
 Concentration (ppm)         (ppm)                 (lpm)                   (min)                                
----------------------------------------------------------------------------------------------------------------
                                                   CARTRIDGES                                                   
----------------------------------------------------------------------------------------------------------------
500..................             10     27 deg.C, 85% RH, 64 lpm  36                    Myles (Ex. 32-28C).    
100..................             10     25 deg.C, 50% RH, 64 lpm  132.8, 142.0          Ackley (Ex. 32-28C).   
100..................             10     25 deg.C, 50% RH, 32 lpm  240.7, 245.1, 260.0   Ackley (Ex. 32-28C).   
100..................             10     27 deg.C, 85% RH, 64 lpm  108                   Myles (Ex. 32-28C).    
100..................             10     27 deg.C, 85% RH, 32 lpm  174                   Myles (Ex. 32-28C).    
75...................              0.75  25 deg.C, 85% RH, 64 lpm  55                    NIOSH (Ex. 23-83).     
93...................              0.93  25 deg.C, 85% RH, 64 lpm  92                    NIOSH (Ex. 23-83).     
50...................              2     25 deg.C, 85% RH, 64 lpm  159.1 a               NIOSH (Ex. 90).        
20...................              2     25 deg.C, 85% RH, 64 lpm  201.1 a               NIOSH (Ex. 90)         
10...................              2     25 deg.C, 85% RH, 64 lpm  217.3 a               NIOSH (Ex.90).         
----------------------------------------------------------------------------------------------------------------
                                                    CANISTERS                                                   
----------------------------------------------------------------------------------------------------------------
500..................             10     27 deg.C, 85% RH, 64 lpm  42                    Myles (Ex. 32-28C)     
100..................             10     27 deg.C, 85% RH, 64 lpm  102                   Myles (Ex. 32-28C)     

[[Page 56818]]

                                                                                                                
100..................             10     27 deg.C, 85% RH, 32 lpm  234                   Myles (Ex. 32-28C).    
----------------------------------------------------------------------------------------------------------------
a Mean values reported.                                                                                         

The more recent NIOSH data (Ex. 90) show that organic vapor cartridges, 
when tested in the range of 10 to 20 ppm, can provide about 3 to 3.5 
hours of protection against BD under worst case test conditions (see 
Table X-1). However, at concentrations above 20 ppm, NIOSH test data 
(Ex. 23-83, see Table X-1) show that breakthrough time begins to 
decline rapidly; breakthrough times of about 2.5, 1, and 1.5 hours were 
obtained at test concentrations of 50, 75, and 93 ppm, respectively. 
More limited data on canister performance provided by Myles (see Table 
X-1) suggest that canisters will provide little gain in service life 
compared to cartridges. At a challenge concentration of 100 ppm and a 
target concentration of 10 ppm, breakthrough of organic vapor canisters 
occurred in 102 minutes under worst-case test conditions.
    After reviewing the record evidence and comments on filter service 
life for BD, OSHA has modified its proposal to include a required 
schedule for the replacement of organic vapor cartridges and canisters 
(paragraph (h)(4)(i) and Table 1). Alternatively, employers may use 
other existing data or conduct additional tests to evaluate cartridge 
or canister service life in BD-contaminated atmospheres, and establish 
schedules for filter replacement based on 90% of the service life 
(paragraph ((h)(4)(ii)), as originally proposed. Employers may adopt 
the second approach, rather than use the default schedule in Table 1, 
so long as the written respirator program clearly describes the basis 
for the filter replacement schedule and demonstrates that employees 
will be adequately protected. In conducting this evaluation, employers 
should consider any workplace-specific factors that may affect filter 
service life, such as pattern and intensity of exposure to BD, 
temperature and humidity, and presence of other air contaminants that 
may shorten service life. In addition, where air-purifying respirators 
are used intermittently throughout the day, the filter replacement 
schedule developed by the employer must consider the effects of BD 
migration through the filter element during periods of non-use, and the 
impact of this effect on service life.
    Under the default schedule in the final rule, cartridges and 
canisters for negative- pressure respirators must be replaced every 4 
hours at BD concentrations less than or equal to 5 ppm, every 3 hours 
at concentrations between 5 and 10 ppm, every 2 hours at 10 to 25 ppm, 
and every hour at 25 to 50 ppm (see Table 1 of the final rule). The 
record contained no specific evidence on the performance of PAPR 
cartridges against BD. Therefore, the default change schedule for PAPR 
cartridges is based on that of negative-pressure devices, i.e., PAPR 
cartridges must be replaced every 2 hours or every 1 hour at BD 
concentrations less than or equal to 25 ppm or 50 ppm, respectively. 
Under the default replacement schedule, the maximum service time 
permitted in Table 1 begins from the time that the filter seal is 
broken, regardless of whether the respirator is actually put into 
immediate use, and runs continuously regardless of the pattern of 
respirator use. For example, if the seals of a pair of cartridges for a 
negative-pressure half mask respirator are broken at 8 am and the 
respirator is used in atmospheres not exceeding 5 ppm BD, the 
cartridges must be replaced no later than 12 pm, even if the respirator 
was only used intermittently for a few minutes. OSHA believes that it 
is necessary to define the replacement schedule requirement in this 
manner to account for BD migration throughout the cartridge during 
periods of non-use, and to ensure simplicity in administering the 
respirator program.
    In setting the service lives of air purifying respirators for BD, 
OSHA has taken a conservative approach in evaluating the service life 
testing data. Temperature, humidity, air flow through the filter, the 
work rate, and the presence of other potential interfering chemicals in 
the workplace all can have a serious effect on the service life of an 
air purifying cartridge or canister. High temperature and humidity 
directly impact the performance of the activated carbon in air 
purifying filters. Humidities of 85% and temperatures of 25  deg.C or 
higher are commonly reached in the summer at BD polymer processing 
plants located on the Gulf Coast. An air flow rate of 64 liters per 
minute (lpm) used to test cartridges represents an air flow that may be 
achieved at a moderately high work rate. In addition, filter elements 
from different manufacturers may exhibit different service lives 
depending upon the types and amounts of charcoal used. OSHA realizes 
that lower humidity, temperature, and air flow through the filter would 
increase the estimates of service life. However, OSHA believes that, in 
establishing a default schedule for filter replacement that applies to 
all work situations involving exposure to BD, it is important to base 
the schedule on worst case conditions found in the workplace, since 
this will provide the greatest margin for safety in using air purifying 
respirators with BD. NIOSH in its comments (Ex. 32-25) stated that 
filters should be tested at worst case conditions of temperature, 
humidity, and BD concentration, and in combination with the other gases 
and vapors present in the workplace, since they may drastically affect 
service lives.
    OSHA believes that specifying a schedule for filter changes based 
on service life data, or allowing employers to develop schedules based 
on BD-specific test data, is key to permitting the use of organic vapor 
cartridge respirators for protection against BD, since the service life 
data described above clearly demonstrate that organic vapor cartridges 
will not provide adequate protection if used over an entire work shift. 
In addition, OSHA believes that specifying a default filter change 
schedule for organic vapor cartridges will simplify compliance for 
those employers who do not have access to additional breakthrough data 
for BD.
    Furthermore, OSHA finds that the odor warning properties of BD will 
provide an additional margin of protection in the event that the filter 
replacement schedule contained in Table 1 is not adequate for certain 
work situations. The regulatory text recommended by the joint labor/
industry agreement suggested that OSHA add language in paragraph (h)(4) 
to require that employers replace air-purifying elements as soon as 
possible if an employee detects the odor of BD while using the 
respirator. OSHA agrees that this is an appropriate precaution,

[[Page 56819]]

and has included the language in the final rule.
    Respirator Use. The proposal required (paragraph (g)(4)(i)) that 
canisters be labeled with the date they were put into service. A date 
alone was all that was needed since the proposal would have allowed for 
their use for a full work shift before replacement. However, in the 
final rule, OSHA will now be allowing the use of air purifying 
cartridges for BD exposures, and the service life of these cartridges 
is less than a full work shift. Therefore, the proposed provision has 
been modified in the final rule (paragraph (h)(4)(iii)) to require the 
labeling of air purifying filter elements with both the date and the 
time of the start of use to allow for their prompt replacement once the 
service life listed in Table 1 is reached.
    The final standard (paragraph (h)(4)(v)) permits employees to leave 
the regulated area to readjust the respirator facepiece to their faces 
for proper fit. The respirator wearer who detects the odor of BD or who 
feels eye irritation should leave the area immediately and replace the 
air purifying elements before reentry. It also permits employees 
wearing respirators to leave the regulated area to wash their faces and 
respirator facepieces to avoid potential skin irritation associated 
with respirator use.
    End-of-Service-Life Indicators. End-of-service-life indicators 
(ESLI) for BD do not now exist. The final standard contains a provision 
(paragraph (h)(4)(iv)) that would allow the use of such a NIOSH-
approved ESLI. OSHA originally proposed permitting the use of a NIOSH-
approved ELSI for BD, and inclusion of this requirement was supported 
by the joint labor/industry agreement. This provision is intended to 
encourage respirator manufacturers to develop a reliable ESLI for 
organic vapor cartridges and canisters used to protect against BD. 
Respirator manufacturers have been reluctant to develop filter elements 
with ESLI without an indication from OSHA that it would allow the use 
of an ESLI.
    In its comments on the proposed standard, NIOSH stated that if OSHA 
chooses to allow air purifying respirators for BD, OSHA should require 
the use of an ESLI along with the requirement for doing a service life 
determination based on the worst case BD exposure level expected, at 
high humidity levels and high temperatures encountered at that plant 
location. (Ex. 32-25) Since a NIOSH approved ESLI for BD does not yet 
exist, OSHA cannot make their use a prerequisite for air purifying 
respirator use with BD, since by doing so OSHA would preclude the use 
of air purifying respirators. However, OSHA does encourage employers to 
use ESLIs when they are approved by NIOSH.
    John Hale of Respirator Support Services objected to the practice 
of relying on mechanical end-of-service-life indicators, stating that 
since mechanical devices do fail, it is preferable instead to rely upon 
breakthrough to dictate when to replace air purifying elements. (Ex. 
32-3) However, since the permissible exposure limits for chemicals such 
as BD are being lowered to levels almost at the odor threshold, a 
reliable ESLI would not replace breakthrough detection by the wearer, 
but would instead provide an additional means of ensuring that air 
purifying elements are replaced before their service life expires.
    Air purifying filter elements with end of service life indicators 
(ESLI) may be used until the ESLI indicates that filter replacement is 
necessary. For cartridges and chin style canisters this may mean that 
their service lives with an ESLI would be longer than the conservative 
service lives listed in Table 1. However, the final rule includes a 
requirement to replace the cartridge or canister at the beginning of 
the next work shift, regardless of any residual service life left, due 
to the problem of BD migration through the filter element during the 
time the previously exposed filter element is not in use (e.g., 
overnight).
    Fit Testing. Paragraph (h)(5) of the final BD rule requires 
employers to perform either qualitative (QLFT) or quantitative (QNFT) 
fit testing at the time a tight-fitting negative-pressure respirator is 
first assigned to an employee who is working in atmospheres containing 
10 ppm or less of BD, and annually thereafter. At BD concentrations 
above 10 ppm, employers must use QNFT for full-facepiece, negative-
pressure respirators. In the proposal, employers would have been 
required to perform either QNFT or QLFT on all tight-fitting respirator 
facepieces, including those used for positive-pressure devices. The 
final rule also adds a new paragraph (h)(5)(iii) that requires 
employers to ensure that employees perform a fit check of the 
respirator facepiece before each entry into a BD-contaminated 
atmosphere.
    OSHA received many comments on the proposed fit test requirements 
for BD. The IISRP stated that OSHA should not require QNFT at exposure 
levels above 20 ppm (i.e., an APF of 10), because it is scientifically 
unnecessary and much more expensive than QLFT. (Ex. 34-4) In the 
preamble to the BD proposal (55 FR 32793), OSHA referred to the 
Agency's proposed revision to 29 CFR 1910.134, which in turn discussed 
evidence indicating that QLFT was not reliable in achieving APFs higher 
than 10. (55 FR at 32793) OSHA's standards for cadmium (29 CFR 1910.27) 
and asbestos (29 CFR 1910.1001) require QNFT of full facepiece 
respirators used at APFs higher than 10. Although the Agency will make 
a final determination on the effectiveness of QLFT for achieving APFs 
higher than 10 as part of its revision of 29 CFR 1910.134, OSHA is not 
aware of any data or evidence presented in the BD rulemaking that 
suggest that OSHA should depart from the position expressed in the 
proposal. Therefore, the final rule for BD will require QNFT when 
negative-pressure respirators are to be used in atmospheres containing 
more than 10 ppm BD.
    When tight fitting respirators are used, OSHA requires respirator 
fit testing because proper fit is critical to the performance of tight 
fitting negative pressure, air-purifying respirators. With tight 
fitting air-purifying respirators, a negative pressure is created 
within the facepiece of a properly fitted respirator when the wearer 
inhales. A poorly fitted respirator allows contaminated workplace air 
to enter the facepiece through gaps and leaks in the seal between the 
face and the facepiece instead of passing through the sorbent material.
    The fit testing of positive pressure respirators, both half masks 
and full facepieces, was part of the respirator fit testing provisions 
in the proposal (paragraph (g)(5)(i)), based on a concern that 
employees may ``overbreathe'' while wearing the respirator, thus 
creating a temporary negative pressure within the facepiece and 
increasing the likelihood for leakage. Tom Nelson, testifying for CMA, 
questioned this requirement since the requirement had never appeared in 
previous OSHA standards. (Ex. 112) Mr. Nelson also claimed that 
requiring fit testing of positive-pressure respirators due to the 
potential for ``overbreathing'' was unwarranted for BD since this was 
likely to occur only at extremely high work rates. (Ex. 112) In 
addition, Mr. Nelson stated that, if OSHA does require fit testing of 
positive pressure respirators, then it should adopt the ANSI approach.
    OSHA has previously required fit testing for positive pressure 
respirators in the recent cadmium standard, 29 CFR 1910.1027(g)(4) 
(ii), (iii), and (iv). However, OSHA is currently conducting a 
comprehensive evaluation of the need to require fit testing of 
positive-pressure facepieces as part of its rulemaking to revise 29 CFR 
1910.134. Until this

[[Page 56820]]

evaluation is complete and OSHA has made a final determination, OSHA is 
not including the proposed requirement to fit test positive-pressure 
devices in the final rule for BD.
    Some commenters objected to the requirement contained in Appendix E 
that employers conduct at least three separate quantitative fit tests 
to obtain a fit factor for a respirator, questioning the basis for the 
requirement and arguing that it was too costly. (Exs. 32-3, 32-28, 112, 
118-6) For example, John Hale of Respirator Support Services provided 
the following comment in his pre-hearing submission:

    On what technical basis does OSHA impose this requirement? It is 
widely accepted among the health and safety professionals * * * that 
there is no more confidence gained from three fit test results than 
from one. Indeed, it would take many more than three to provide any 
level of statistical confidence in the actual value arrived at for a 
fit factor. The burden of time and expense imposed by this 
requirement is completely unjustified.* * * (and) there is no 
benefit to the respirator wearer. (Ex. 32-3)

As with other respirator issues raised in the BD record, OSHA is 
currently revising its required protocols for fit testing as part of 
the revision of 29 CFR 1910.134. At this time, OSHA has modified 
Appendix E in the final rule for BD to require a single test when QNFT 
is performed, pending OSHA's final determination for the revised 29 CFR 
1910.134 standard.
    Several commenters stated that the BD standard fit testing 
requirements did not allow the use of the Portacount fit testing device 
since there is no protocol for that method contained in Appendix E. 
(Ex. 32-3; 32-4; 32-8; 32-11; 32-27; 32-28; 112; 118-16) In 1988 OSHA 
issued a compliance memorandum classifying the use of the Portacount 
fit test as a de minimis violation for those OSHA standards that 
contain a mandatory appendix listing quantitative fit test protocols 
and instrumentation. The validation of fit testing methods such as the 
Portacount and appropriate protocols for such methods are to be 
addressed fully in the fit testing section of the 29 CFR 1910.134 
respiratory protection standard revision. Shell Oil Company, in a pre-
hearing submission to the BD record stated:

    In a new standard, it would seem reasonable for OSHA to 
recognize the Portacount system. It is improper for OSHA arbitrarily 
to exclude a proven fit-test system from a standard, but to 
encourage a technical violation by advising industry that it would 
consider Portacount [a de minimis violation] * * * (Ex. 32-27, p. 3)

CMA asked that OSHA allow use of ``any QNFT equipment such as the 
Portacount that can reliably measure a test challenge.'' (Ex. 32-28, p. 
131)
    TSI, Inc. (Ex. 32-11, Att. 1-3) submitted three technical papers to 
the BD record reporting the results of studies comparing the 
``Portacount,'' condensation nuclei counting (CNC) respirator fit-test 
method with the aerosol/photometer method. The first, published in the 
Journal of the International Society for Respiratory Protection, 
described a U.S. Army study comparing fit factors determined by CNC and 
the more traditional corn oil aerosol/photometer determinations. 
Initial tests did not employ human subjects, but rather they used a 
mask/headform assembly enclosed in a plastic hood. Numerous conditions 
of heat and humidity were tested repeatedly.
    The correlation coefficient was calculated to determine the 
strength of the relationship between measurements made in applying the 
two methods.\11\ The correlation coefficients calculated in this study 
ranged from 0.953 to 0.996.
---------------------------------------------------------------------------

    \11\ The correlation coefficient is the proportion of the total 
sum of the squares variation that is explained by the linear 
relationship. Thus, a correlation coefficient of zero indicates the 
two are not related, while a value close to 1 indicates a high 
positive correlation.
---------------------------------------------------------------------------

    The Army study also fit-tested human subjects using both methods. 
Subjects were tested by each method sequentially and the pass-fail 
agreement/disagreements determined for 100 comparison tests. Agreement 
exceeded 95%. The author concluded that ``(CNC) was a suitable 
alternative to conventional photo-meter quantitative fit testing 
systems.'' (Ex. 32-11, Att. 1, p. 8)
    The second study, performed at Shell Oil Company, described 
sequential fit tests of approximately 50 test subjects at each of two 
chemical plants. (Ex. 32-11, Att. 2) Again Portacount/CNC methodology 
was compared with the corn oil aerosol/photometric method. This 
researcher also compared fit test outcomes as pass-fail agreement/
disagreement. The differences in the results obtained from the 
Portacount/CNC method and aerosol/photometric method shoed less than a 
10% discordance and were not statistically distinguishable. The author 
concluded that ``the Portacount would appear to be an acceptable system 
for quantitative fit testing.'' (Ex. 32-11, Att. 2, p. 6)
    The final submission was a paper by Rose et al. that appeared in 
the Journal of Applied Occupational and Environmental Hygiene in 1990. 
(Ex. 32-11, Att. 3) Again, sequential fit-factor measurements using 
both the aerosol/photometer test system and CNC (Portacount) methods 
were compared. They were tested at the same fitting of the respirator 
for each subject. The study involved 24 test subjects. It was found 
that fit factors determined by photometer were lower than the CNC 
determinations in 14 of 24 pairs. However, the correlation coefficient 
was over 0.85, indicating that the two sets of measurements were highly 
correlated. Other statistical tests were applied and no differences 
between the two methods were demonstrated. When pairwise comparisons of 
pass-fail agreement/disagreements were made, the authors concluded 
``there was only one discordant pair in the 48 comparisons at the two 
critical fit factors.'' In reviewing the then-current literature, Rose 
et al. noted that several other studies had shown good agreement 
between the results of the 2 fit factor measurement methods also.
    These findings affirm OSHA's earlier determination based on a study 
by Lawrence Livermore National Laboratory (as described in the above-
mentioned compliance directive) that the CNC/Portacount method of fit 
factor determination is acceptable. Rather than continue to consider 
use of the CNC/Portacount method as a de minimis violation, OSHA is in 
this final rule accepting its use for fit testing for BD exposure and 
has included instructions for performing this fit test in Appendix E. 
These instructions are essentially the same as those of the 
manufacturer.
    In Appendix E of the proposal, the QNFT protocol in section 
C(4)(xi) required that half masks and full facepiece respirators obtain 
a minimum fit factor of 100 during QNFT fit testing. John Hale stated 
that a minimum fit factor of 10 times the APF for that class of 
respirator is needed. (Ex. 32-3) James Kline of Wilson Safety Products 
pointed out that the preamble stated that a minimum fit factor of 100 
for half masks and 500 for full facepieces should be obtained during 
fit testing, while Appendix E mentioned only a fit factor of 100. (Ex. 
32-14) Mr. Kline recommended that the minimum fit factor should be ten 
times the applicable APF or the protection factor needed for the 
application, whichever is lower. NIOSH also recognized the difference 
in fit factor requirements between the preamble of the proposal and 
Appendix E and recommended a fit factor of 100 be used for quarter and 
half mask and that a fit factor of 500 be used for full facepieces. 
(Ex. 32-25) OSHA agrees that the language in the proposed Appendix E 
was in error, and has corrected it in the final rule to require that a 
minimum fit factor of 100 for half

[[Page 56821]]

masks and 500 for full facepieces be obtained during QNFT testing.
    Obtaining a proper fit for each employee may require that the 
employer provide two to three different sizes and types of masks so 
that an employee can select the most comfortable respirator that has a 
facepiece with the least leakage around the face seal. In past 
rulemaking efforts, OSHA has consistently found that this is a 
necessary requirement for fit testing of negative-pressure devices 
since the configuration of each manufacturer's facepiece varies, and it 
is highly unlikely that all employees will be comfortably fitted with 
the facepiece of a single manufacturer, even if different sizes are 
provided.
    However, the requirement in Appendix E to use respirators from 
multiple manufacturers for the fit testing of positive-pressure 
respirators was questioned by CMA since, unlike the case for negative-
pressure facepieces, most people can be adequately fitted with a single 
manufacturer's positive-pressure equipment. (Ex. 112) CMA was also 
concerned that, if employees were assigned different makes and models 
of positive-pressure facepieces, confusion would arise in the workplace 
with the use of different types of hoses specific to each manufacturer, 
increasing the likelihood that incompatible respirator hardware would 
be used, increasing risks to workers. However, as discussed above, OSHA 
is not now requiring fit testing of positive-pressure devices in the 
final rule for BD, deferring judgement until the issue is resolved in 
the rulemaking for 29 CFR 1910.134.
    The CMA submission addressed two additional fit test issues, 
recommending that OSHA delete the protocol for the irritant smoke QLFT 
in Appendix E, due to health concerns, and that the grimace exercise be 
deleted from the QNFT protocols because it tends to yield an 
artificially low fit factor. (Ex. 32-28, Ex. 112) OSHA is evaluating 
both of these issues in the context of the rulemaking for 29 CFR 
1910.134. At the present time, OSHA is retaining in Appendix E the 
irritant smoke QLFT, should employers wish to continue using it. Should 
OSHA determine upon promulgation of a final revision of 29 CFR 1910.134 
that use of irritant smoke QLFT poses excessive risks to employees, 
OSHA will make appropriate changes to its final rule for BD.
    Regarding the issue of the grimace test, this exercise is to 
determine whether the facepiece being tested will reseat itself on the 
face after the respirator seal is broken. In quantitative fit testing, 
the test instrument should show a rise in challenge agent concentration 
within the mask during the grimace exercise, followed by a drop once 
the respirator reseats itself. If the respirator fails to reseat, 
subsequent test exercises will show excessive leakage, resulting in a 
failed test. Since even a properly fitting mask may show increased 
penetration during the grimace exercise, the penetration observed 
during the exercise is not to be used in calculating the overall fit 
factor. OSHA has revised Appendix E in the final rule to clarify this 
aspect of determining fit factors for respirator facepieces.
    The preamble to the proposal contained a discussion of the need to 
perform a facepiece fit check prior to entry into a BD exposed work 
area. (55 FR 32736 at 32793) The purpose of performing such a negative 
pressure or positive pressure fit check is to meet the objective of 
demonstrating that a proper facepiece seal is being obtained each time 
the respirator is donned. Appendix E, Section II contains descriptions 
of the recommended positive and negative fit check methods. This test 
can be either a positive pressure fit check, in which the exhalation 
valve is closed and the wearer exhales into the facepiece to produce a 
positive pressure, or a negative pressure fit check, in which the inlet 
is closed and the wearer inhales so that the facepiece collapses 
slightly. Not all tight fitting respirators can be fit checked by using 
one or the other of these methods, since the wearer must be able to 
block off either the inlet or exhalation valves. Where the fit cannot 
be checked using one of the above methods, the wearer shall use the fit 
check method recommended by the manufacturer of the respirator being 
used. Language has been added to the respirator fit testing section of 
the final BD standard at paragraph (h)(5)(iii) that contains this 
requirement.

I. Personal Protective Equipment

    This paragraph, which in the proposed rule was included in the 
Respiratory Protection paragraph, has been separated into a separate 
paragraph to facilitate compliance. Paragraph (i)(6) (paragraph (g)(6) 
of the proposed rule) requires that personal protective equipment must 
be worn where appropriate to prevent eye contact and limit dermal 
exposure to liquefied BD and solutions containing BD. Furthermore, it 
must be provided by the employer at no cost to the employee and the 
employer shall ensure its use where appropriate. OSHA believes that 
this performance oriented approach affords employers the flexibility to 
provide in a given situation only the protective clothing and equipment 
necessary to protect employees without specifying the exact nature of 
protective equipment to be used. This paragraph is sufficiently 
performance-oriented to allow the employer adequate flexibility to 
provide only the personal protective equipment necessary to protect 
employees in each particular work operation from the BD exposure 
encountered. Therefore, compliance can be tailored to fit the hazards 
posed on a day-to-day basis.
    OSHA further notes that the generic requirements for Personal 
Protective Equipment (PPE) (Part 1910, Subpart I) apply for BD except 
where a specific provisions of the BD standard would provide otherwise.

J. Emergency Situations

    Under paragraph (b) of this section, OSHA defines an emergency 
situation to be any occurrence such as, but not limited to, equipment 
failure, rupture of containers, or failure of control equipment that 
may or does result in an uncontrolled significant release of BD.
    Paragraph (j) requires that employers develop new written plans for 
emergency situations or modify an existing plan to contain applicable 
elements of 29 CFR 1910.38, Employee Emergency Plans and Fire 
Prevention Plans, and of 29 CFR 1910.120, Hazardous Waste Operations 
and Emergency Responses and how the cause of the emergency is to 
addressed.
    Both the above-mentioned standards require written plans for 
emergency responses and set out their content and use; however, it is 
noted that paragraph (q)(1) of 1910.120 states the following:

An emergency response plan shall be developed and implemented to 
handle anticipated emergencies prior to the commencement of 
emergency response operations. The plan shall be in writing and 
available for inspection and copying by employees, their 
representatives and OSHA personnel. Employers who will evacuate 
their employees from the danger area when an emergency occurs, and 
who do not permit any of their employees to assist in handling the 
emergency, are exempt from the requirements of this paragraph is 
they provide an emergency action plan in accordance with (29 CFR) 
1910.38(a) of this part.

Thus, only one of the two standards, either 1910.38 or 1910.120, would 
likely apply in a single facility. OSHA believes that it is likely that 
smaller facilities will comply with the provisions of 29 CFR 1910.38, 
while employers whose facilities are large enough to have specific 
emergency response personnel available will comply with 29 CFR 
1910.120.

[[Page 56822]]

    OSHA recognizes that all sudden releases of BD do not constitute an 
emergency. For example, the accidental breaking of a sampling syringe 
containing a minute amount of BD would not normally constitute an 
emergency. On the other hand, failure of a valve on a reaction vessel, 
a flange, or a safety relief valve would likely constitute an 
emergency. OSHA believes that compliance with these requirements will 
ensure that affected employees are effectively protected during a BD 
emergency.
    In the limited reopening of the BD record in March 1996, OSHA 
stated that it proposed to define ``Emergency'' as:

* * * any occurrence such as, but not limited to, equipment failure, 
rupture of containers, or failure of control equipment that may or 
does result in an unexpected significant release of BD.

The agency said that it was considering limiting the emergency releases 
to those that are uncontrolled, so that the last phrase of the 
definition would read: ``* * * that may or does result in an 
uncontrolled significant release of BD.'' It then asked whether this 
addition adequately clarifies what situations OSHA considers to be 
emergencies, and whether the term ``significant release'' gives 
adequate guidance to employers as to how much BD must be released in 
order to constitute an emergency?
    Some comment was received on this issue and it is discussed in the 
paragraph dealing with the definition of the term emergency situation 
in the definition section (b) of the Summary and Explanation.
    OSHA has chosen to use the term uncontrolled occurrence because it 
is more descriptive and is consistent with the Hazard Communication 
Standard (29 CFR 1910.1200) and Hazardous Waste Operations and 
Emergency Response Standard (29 CFR 1920.120).
    In the proposed rule, OSHA included provisions for respiratory use 
and for alerting employees during emergencies. These have been omitted 
from this section as redundant. Paragraph (j)(1)(iv) sets out the 
requirement for respirator use during emergencies. Paragraph (k)(4)(ii) 
sets out medical screening requirements for those exposed to 
significant releases of BD.

K. Medical Screening and Surveillance

    Where appropriate, medical screening and surveillance programs are 
required by section 6(b)(7) of the OSH Act to be included in OSHA 
health standards to aid in determining whether the health of workers is 
adversely affected by exposure to toxic substances. The relationship 
between medical screening and medical surveillance was clarified in 
posthearing comments by Dr. William Halperin, NIOSH. (Ex. 90, p.4) 
According to Dr. Halperin:

The term ``medical'' surveillance is often used to encompass two 
distinct activities: (1) Medical screening: the search for early 
disease and (2) medical surveillance: the ongoing collection, 
analysis and dissemination of health related information that can be 
applied to the promotion of health and the prevention of adverse 
health effects (Ex. 90, p. 4).

Paragraph (k) of this rule clarifies OSHA's intention to include both 
activities in a program to identify and prevent BD-related 
disease.12
---------------------------------------------------------------------------

     12 Nothing in this standards changes the meaning of the term 
``medical surveillance'' as it has been used in previous standards, 
such as the asbestos standards, 29 CFR 1910.1001 and 1926.110.
---------------------------------------------------------------------------

    Health hazards that have been shown to be associated with 
occupational exposure to BD include leukemia, non-Hodgkins lymphoma, 
and anemia. Additionally, adverse reproductive and developmental 
outcomes have been observed in toxicologic studies of male and female 
mice. The medical screening and surveillance program specified in 
paragraph (k) has the following goals:
    1. To prevent occupational diseases related to BD exposure;
    2. To detect and treat BD-related disease before a worker would 
routinely seek medical care; and
    3. To provide information on the adequacy of the PELs for BD.
    Although most of the medical screening and surveillance provisions 
remain the same as in the proposal, several changes have been made. 
These changes include:
    (1) Physical examinations are required once every three years, 
rather than annually;
    (2) An annual health questionnaire for workers exposed to BD has 
been added;
    (3) An annual complete blood count including differential and 
platelet count (CBC) is required;
    (4) Medical evaluation of employees required to wear respirators, 
including assessment of cardiopulmonary function, is no longer required 
in this rule, and employers are referred to 29 CFR 1910.134;
    (5) Employees with past BD exposures that meet specific criteria 
must be offered continued participation in medical screening and 
surveillance programs;
    (6) Activities pertaining to medical screening and medical 
surveillance have been more clearly delineated; and
    (7) Responsibility for the program has been expanded to include 
other licensed health care professionals, as well as physicians.
    Paragraph (k)(1) specifies the circumstances under which employers 
must provide medical screening and surveillance for employees exposed 
to BD. Under paragraph (k)(1)(i) this program must be offered to each 
employee with exposure to BD at concentrations at or above the action 
level on at least 30 days a year. Additionally, it must be made 
available to those employees who have or may have exposure to BD at or 
above the PELs on at least 10 days per year.
    This provision remains the same as that contained in the proposed 
rule. An alternative set of criteria for employee coverage was 
suggested in the joint labor-management agreement submitted to OSHA by 
the USWA and the IISRP. (Exs. 118-12; 119) This agreement would have 
raised the threshold of employee exposure to BD concentrations at or 
above the action level for at least 60 days per year, and at or above 
the PELs for at least 30 days per year. OSHA's review of the record did 
not produce evidence of controversy for the trigger levels as 
originally proposed. In fact, Shell Oil Company provided written 
comments which stated in part,

This is a reasonable definition of who should be covered, with a 
time factor (30 days a year) for exposures at or above the action 
level * * * and a shorter time factor (10 days a year) for exposures 
at or above the PEL * * * or STEL * * * (Ex. 32-27)

    Additionally, designation of trigger levels for medical screening 
and surveillance at or above the action level for 30 days and at or 
above the PELs for 10 days per year is consistent with past OSHA 
policy. For example, in the rulemaking for occupational exposure to 
coke oven emissions OSHA determined that a specific time period is the 
most effective and administratively feasible method to adopt in order 
to exclude workers with very limited exposures, e.g., temporary 
assignments during vacation periods. (41 FR 46777) At the same time, 
OSHA was concerned that the selected time period be sufficiently 
inclusive, and chose a cut-off point of 30 days. (41 FR 46777) The 
rulemaking for occupational exposure to inorganic arsenic followed the 
same policy. (43 FR 19620) Subsequently, the health standard for 
occupational exposure to benzene and the proposed rule for methylene 
chloride used the 30/10 triggers for inclusion in the medical 
surveillance program. (29 CFR 1910.1028; 56 FR 57036)
    This overall approach to employee selection for coverage by the 
medical screening and surveillance program is based, in part, on the 
theory that cancers

[[Page 56823]]

associated with BD exposure are likely to be dose-related. Thus, 
employees exposed for only a few days a year may be at lower risk of 
developing BD-related disease. This approach allows employers to 
concentrate valuable medical screening and surveillance resources on 
higher risk employees.
    Another change in the coverage of the medical screening and 
surveillance program is the elimination of coverage based only on 
required respirator use. The proposal specified that each employee 
whose exposure to BD requires the use of a respirator, regardless of 
the duration of exposure, be covered by the program. In the final rule, 
employees using respirators will be part of the medical screening 
program if they are over the action level or PELs for the amount of 
time stated in the medical screening provisions (on least 30 or more 
days for the action level and on 10 or more days for the PELs). This 
change is consistent with the recommendations contained in the labor-
management agreement, and with OSHA's intention to clearly delineate 
medical screening requirements for employees with chemical specific 
exposures and those who must wear respirators, irrespective of the 
specific hazard. (Ex. 118-12; 29 CFR 1910.134) OSHA believes that the 
medical screening requirements for respirator users must be consistent 
with the provisions contained in 29 CFR 1910.134. Support for this 
approach was received from several industry representatives. (Exs. 118-
11; 118-13; 118-14)
    The proposed rule also included a provision for medical evaluation 
of cardiopulmonary function for all employees whose exposures require 
them to use respirators. This evaluation was supported by Dr. Philip 
Landrigan of the Mount Sinai Medical Center. He stated that,

* * * the cardiorespiratory testing for people that are going to be 
wearing respirators is very much indicated, that wearing a 
respirator increases the work of breathing. It is important to know 
that a person has sufficient cardiorespiratory capacity to be able 
safely and healthfully to be able to work with the respirator on. 
(Tr.1/15/91, p. 200)

    However OSHA received several comments, including ones from Shell, 
CMA, and Dr. James A. Saunders, that disagreed with this provision. 
(Exs. 32-27; 112; Tr. 1/18/91, p. 1213-1214) According to CMA,

    All employees who wear respirators should not receive an 
evaluation of cardiopulmonary function. As in the benzene standard, 
a pulmonary function test should be performed every three years on 
employees who wear respirators for at least 30 days per year. The 
cardiopulmonary function of these employees should also be evaluated 
but no specific test should be required except as directed by the 
examining physician. (Ex. 112, pp. 127-128)

The testimony of Dr. Saunders, who testified on behalf of the CMA BD 
panel, supported the CMA position on this issue. (Tr. 1/18/91, pp. 
1213-1214) Shell offered the following opinion,

    This is not a reasonable definition of who should be evaluated. 
* * * To promulgate slightly different requirements for respirator 
user evaluation in different individual chemical exposure standards 
only creates confusion and nonuniformity. OSHA needs to finalize a 
respirator standard rather than putting different details in each 
standard. * * * (Ex. 32-27, attachment II, p. 3)

    In the final rule, OSHA has clarified its position on medical 
screening and surveillance for employees whose exposure to BD requires 
them to use a respirator. Determinations regarding an employee's 
physical ability to perform the work and use the equipment should be 
made pursuant to 29 CFR 1910.134. Accordingly, paragraph (k)(4)(iii) 
has been added to refer employers to the standard on respiratory 
protection, and the requirement for evaluation of cardiopulmonary 
function has been deleted from this standard. Comments that support 
these changes have also been received from labor and industry 
representatives in response to the limited reopening of the rulemaking 
record. (Exs. 118-11; 118-13; 118-14; 118-16)
    The concept for paragraph (k)(1)(ii) was recommended in the labor-
management agreement submitted to OSHA by the USWA and the IISRP. It 
requires that employers continue medical screening and surveillance for 
employees after they have transferred to a job without potential 
exposure to BD when their work histories meet specified criteria. (Ex. 
118-12) These criteria are: (1) Exposure at or above the 8-hour TWA 
limit or STEL on 30 or more days a year for 10 or more years; (2) 
exposure at or above the Action level on 60 days a year for 10 or more 
years; or (3) exposure above 10 ppm for 30 days in any past year. (Ex. 
118-12) This would also include employees who transfer to low exposure 
BD jobs, provided that their work histories meet the specified 
criteria. OSHA welcomes this new provision to the final rule because of 
the additional protection it affords to workers with a history of 
occupational exposure to BD. The relatively short latency periods 
associated with BD-related diseases, which range from 4-9 years to 15-
20 years, provide supporting rationale for this provision.
    Objections to this provision were made by Texas Petrochemicals 
Corporation and Hampshire Chemical Corporation on the grounds of 
unreliable past exposure measurements and recordkeeping. (Exs. 118-6; 
118-8) The Air Transport Association objected to this provision on the 
grounds that including ``employees whose past exposure was over a 
period of 10 years seems extreme.'' (Ex. 118-18B) Instead, they 
suggested a ``period of 5 or 3 years'' as a selection criterion. In 
response to these concerns, OSHA believes that the epidemiologic 
evidence suggests that these workers may be at increased risk of BD-
related disease. This provision narrows the coverage of previously 
exposed workers to those with the greatest risk. It is OSHA's opinion 
that this approach errs on the side of caution for this group of 
workers. Support for this requirement, together with the provisions of 
paragraph (k)(1)(i), was offered by CMA in their statement that, ``this 
eligibility standard is appropriate for the medical surveillance 
program and will effectively protect employees most at risk.'' (Ex. 
118-13) OSHA is of the opinion that, when taken in conjunction with the 
entire labor-management agreement, the requirement to include employees 
with historical BD exposure will be protective for high risk employees 
and provide valuable data for the medical surveillance portion of this 
section, paragraph (k)(8)(i).
    Paragraph (k)(1)(iii) requires that coverage in the medical 
screening and surveillance program must be extended to each employee 
exposed to BD following an emergency situation regardless of the 
airborne concentrations of BD normally present in the workplace. Where 
very large amounts of BD are maintained in a sealed system, routine 
exposure may be essentially zero. However, system failure might result 
in catastrophic exposures. Thus, employers who have identified 
operations where there is potential for an emergency involving BD must 
take the necessary action to implement an emergency plan, as required 
in 29 CFR 1910.38. Additionally, employers must ensure that emergency 
medical care is available to exposed employees, and that such care is 
rendered by physicians or other licensed health care professionals with 
knowledge of the acute and chronic toxicity of BD.
    Paragraph (k)(2) addresses program administration. Specifically, 
this provision requires that the medical screening and surveillance 
program be provided without cost to the employee, without loss of pay, 
and at a reasonable time and place. It is OSHA's opinion

[[Page 56824]]

that this provision is necessary to encourage employee participation. 
This same requirement was contained in the proposal. Furthermore, it is 
consistent with other OSHA health standards as well as with provisions 
contained in the OSH Act.
    Additionally, paragraph (k)(2)(ii) requires that all physical 
examinations, medical procedures, and health questionnaires be 
administered by a ``physician or other licensed health care 
professional,'' defined as an individual whose legally permitted scope 
of practice (i.e., license, registration, or certification) allows him 
or her to independently provide or be delegated the responsibility to 
provide some or all of the health care services required by paragraph 
(k) of this section. The proposal required that all medical procedures 
be performed by or under the supervision of a licensed physician.
    However, OSHA has long been considering the issue of whether and 
how to specify the particular professionals who are to perform medical 
surveillance in all of its standards. The Agency has determined that 
other professionals who are licensed under state laws to provide 
medical screening and surveillance services would also be appropriate 
providers of such services for the purposes of the BD standard. The 
Agency recognizes that the personnel able to provide the required 
medical screening and surveillance may vary from state-to-state 
depending on the state's licensing laws. Under the final rule, an 
employer, after becoming familiar with state laws delineating scope of 
practice for various licensed health care professionals, has the 
flexibility to retain the services of a range of qualified licensed 
health care professionals, thus potentially reducing cost and 
inconvenience for employers, and easing compliance burdens.
    In the future, OSHA may attempt, with the cooperation of interested 
stakeholders, to specify which health care professionals are the most 
appropriate to perform each of a variety of diagnostic, therapeutic, 
medical management and other services. The more generic approach 
contained in this standard does, however, signal OSHA's belief that 
employees should have access to, and that employers should retain, when 
feasible, those professionals with the greatest level of expertise in 
discriminating between medical problems associated with occupational or 
environmental exposures and those associated with organic conditions 
unrelated to exposure. While the limited numbers of occupational 
physicians and occupational health nurses available to perform these 
services is increasing, such expertise does not necessarily correlate 
with any particular credential.
    The final program administration requirement, paragraph 
(k)(2)(iii), is for all laboratory tests to be conducted by an 
accredited laboratory. This provision is consistent with other health 
standards, including benzene (29 CFR 1910.1028), bloodborne pathogens 
(29 CFR 1910. 1030), and lead (29 CFR 1910.1025). Furthermore, OSHA 
believes that this requirement is a necessary element for quality 
control in the medical screening and surveillance program.
    The required frequency of medical screening activities is shown in 
paragraph (k)(3). For each employee covered under paragraphs (k)(1)(i)-
(ii), a health questionnaire and CBC are required every year. 
Additionally, physical examinations must be provided at specified 
intervals: (1) An initial physical examination if twelve months or more 
have elapsed since the last physical examination conducted as part of a 
medical screening program for BD exposure; (2) a preplacement 
examination before assumption of duties by the employee in a job with 
BD exposure; (3) every three years after the initial or preplacement 
physical examination; (4) at the discretion of the physician or other 
licensed health care professional; (5) a termination of exposure 
examination at the time of employee reassignment to an area where 
exposure to BD is below the Action level, if the employee's past 
exposure history does not meet the criteria of paragraph (k)(1)(ii) for 
continued participation in the program, and if twelve months or more 
have elapsed since the last physical examination; and (6) at 
termination of employment, if twelve months or more have elapsed since 
the last physical examination.
    There are several differences between the proposed and final rules 
regarding the type and frequency of medical screening activities. 
First, the initial physical examination provided under this section 
must be provided only ``if twelve months or more have elapsed since the 
last physical examination conducted as part of a medical screening 
program for BD exposure.'' This addition to the proposal language was 
made to prevent unnecessary extra physical examinations when the 
medical screening and surveillance portion of the final rule becomes 
effective. It is OSHA's opinion that, if an employee has received a 
physical examination as part of a medical screening program for BD 
within the past year, a repeated physical examination conducted just to 
coincide with the promulgation of this rule would be unnecessary and 
costly to the employer and burdensome for the employee. However, 
evaluation of the data for the entire group of BD exposed workers would 
still need to be done to comply with the surveillance portion of this 
paragraph.
    Second, the requirement for preplacement evaluations has been 
changed from ``before the time of initial assignment of the employee'' 
to ``before assumption of duties by the employee.'' This change 
reflects comments received from Shell, which stated,

* * * before the time of initial assignment of the employee is not 
effective. OSHA should make clear that what is meant is at the time 
of initial assignment or transfer into a job meeting the entry 
criteria, and preferable before assumption of duties in such an 
assignment. (Ex. 32-27, attachment II, p. 4)

    OSHA agrees that this wording more clearly reflects the intention 
behind this requirement for preplacement examinations. Such 
examinations are intended to evaluate an employee's ability to work in 
a safe and healthful manner in a specific work environment. 
Additionally, they establish a baseline of information against which 
future health status changes can be compared.
    Third, the frequency of physical examinations has been changed from 
once a year to every three years following the initial or preplacement 
examination. Several comments were received that addressed the 
frequency of these examinations. For example, CMA offered the opinion 
that, ``requiring a complete physical examination each year is 
unreasonable and excessively burdensome.'' (Ex. 112, p. 131) Dr. 
Saunders, testifying on behalf of the CMA BD panel, also objected to 
annual physical examinations, stating that they are ``unreasonable and 
wasteful of limited medical resources.'' (Tr. 1/18/91, p. 1210) OSHA 
agrees that an annual physical examination is not the most effective 
medical screening activity to detect BD-related disease, and thus has 
changed this requirement. However, OSHA does not agree with CMA that 
physical examinations should only be provided ``where warranted by 
symptoms of adverse health effects that might be related to butadiene 
exposure.'' (Ex. 112, p. 127) Such an approach would ignore principles 
of medical screening and surveillance, i.e., early identification of 
disease before medical care would routinely be sought. Most recently, 
support has been expressed by both labor and industry representatives 
for this frequency schedule. (Exs. 118-12; 118-13)

[[Page 56825]]

    Fourth, under the final rule employees covered by the medical 
screening and surveillance program must be offered an annual health 
questionnaire and a CBC. It is OSHA's opinion that these medical 
evaluation activities will be effective in detecting signs and symptoms 
of BD-related disease that occur in the interval between physical 
examinations. Furthermore, they allow for greater efficiency of medical 
resource utilization. Support for this approach to medical screening 
has been shown in the labor-management agreement submitted to OSHA. 
(Ex. 118-12; 118-13)
    Fifth, to allow for the application of professional judgement in 
the care of employees exposed to BD, physical examinations are to be 
provided at the discretion of the physician or other licensed health 
care professional reviewing the annual health questionnaire and blood 
test results. This provision not only creates a mechanism for immediate 
response to abnormal questionnaire responses or laboratory results, but 
provides flexibility by eliminating the requirement for unnecessary 
physical examinations and requiring physical examinations when they are 
indicated.
    The sixth difference between the NPRM and the final rule pertaining 
to the frequency of physical examinations concerns those that occur at 
termination of employment or at the time of employee reassignment to an 
area where exposure to BD is below the action level, if the employee 
has not been exposed over the action level or the PELs for the 
requisite period of time and if twelve months or more have elapsed 
since the last physical examination. The NPRM required a termination 
physical examination ``if three months or more have elapsed since (the) 
last annual medical examination.'' The final rule extends this time 
interval to a lapse of one year or more.
    The frequency of medical evaluations for employees exposed to BD 
following an emergency situation is specified in paragraph (k)(3)(ii). 
Medical screening in this situation is required to be conducted as 
quickly as possible, but no later than 48 hours after the event. This 
requirement is supported in part by the labor-management agreement that 
recommended these medical evaluations to ``be performed as quickly as 
possible.'' (Ex. 118-12, p.16) OSHA has added the stipulation ``but not 
later than 48 hours after the exposure'' to ensure that a baseline CBC 
is obtained within that time period. An accurate CBC baseline reading 
is vital for comparison with subsequent CBC values in order to detect 
significant deviations from normal.
    Finally, paragraph (k)(3)(iii) addresses medical evaluations for 
employees who must wear a respirator by referring employers to 29 CFR 
1910.134. This change from the NPRM is consistent with comments 
received from Shell,

* * * Respirator user medical evaluation should have some 
uniformity, regardless of the exposure. To promulgate slightly 
different requirements for respirator user evaluation in different 
individual chemical exposure standards only creates confusion and 
nonuniformity. OSHA needs to finalize a respirator standard rather 
than putting different details in each standard. * * * (Ex. 32-27, 
attachment II, p. 3)

This approach further clarifies OSHA's intention to distinguish between 
health-related issues of employees who wear respirators and those who 
are exposed to BD. Support for the separation of these issues was 
provided by both labor and industry representatives. (Ex. 118-12; 118-
13; 118-11; 118-14; 119)
    Paragraph (k)(4) covers the required content of medical screening. 
One of the required components is a comprehensive occupational and 
health history that is updated annually. This history must place 
particular emphasis on the hematopoietic and reticuloendothelial 
systems, including exposure to chemicals, in addition to BD, that may 
have an adverse effect on these systems, the presence of signs and 
symptoms that might be related to disorders of these systems, and any 
other information determined by the physician or other licensed health 
care professional to be necessary. OSHA has restated the intended focus 
of the occupational and health history to more clearly reflect current 
knowledge of BD epidemiology. While OSHA is not specifying the format 
of the questionnaire, samples provided in Appendix F indicate the 
minimum information that must be obtained through the use of any 
questionnaire to comply with the requirements of this paragraph.
    A complete occupational and health history is one part of a 
thorough medical evaluation. More specifically, however, for workers 
who are exposed to BD this history has several focused goals. First, 
the initial history may identify workers who are potentially at 
increased risk of adverse health effects from exposure to BD. For 
example, as suggested by Dr. William Halperin of NIOSH on cross 
examination, ``[i]t may be reasonable to advise workers with a previous 
history of leukemia or lymphoma to avoid exposure to [BD] * * *'' (Tr. 
1/17/91, p. 705) Personal risk factors, such as existing hematologic 
abnormalities, that also place a worker at increased risk of BD-related 
disease, may also be identified through the health history. 
Additionally, predisposition to lymphomas is associated with immune 
deficiency syndromes.
    Second, the initial and updated occupational and health history 
will have a training effect on workers by educating them about the 
potential adverse health effects from exposure to BD. Over time OSHA 
believes that informed workers will be more likely to seek medial 
attention for signs and symptoms that may be associated with BD 
exposure. Third, the initial history will provide a critical baseline 
of health status against which any changes can be compared. Finally, 
the health questionnaire might also suggest to the physician or other 
licensed health care professional additional medical tests or 
procedures that would be prudent to offer to the employee.
    Another required component of medical screening for BD is a 
complete physical examination, with special emphasis on the spleen, 
liver, lymph nodes and skin. The physical examination for BD exposed 
employees provides an opportunity for direct observation and palpation 
of target organs such as the lymph nodes, liver, and spleen. 
Specifically, the physician or other licensed health care professional 
would be looking for signs of lymphadenopathy (enlarged lymph nodes), 
splenomegaly (enlarged spleen), or hepatomegaly (enlarged liver). 
Although lymphadenopathy is not specific for either lymphoma or 
leukemia, the physical examination provides an opportunity to detect 
this finding before symptoms develop. This rationale was rejected by 
Dr. Saunders in his testimony. (Tr. 1/18/91, p. 1211-1212) However, 
according to Dr. Halperin of NIOSH, ``[s]ome individuals may benefit by 
receiving treatment at this earlier point in the course of their 
disease.'' (Ex. 90, p. 5) Dr. Dennis D. Weisenburger, an expert witness 
for OSHA, also offered testimony that supported this basis for periodic 
physical examination of BD exposed employees. (Tr. 1/16/91, pp. 275-
276)
    The final required medical screening activity is a complete blood 
count (CBC). A CBC consists of a white blood cell (WBC) count, 
hematocrit, hemoglobin, differential WBC count, platelet count, red 
blood cell (RBC) count, and WBC and RBC morphology. (Ex. 23-55) It is 
an important component of the medical screening program because acute 
leukemia may, in some cases, be diagnosed with the aid of a CBC prior 
to the onset of symptoms. Additionally, the CBC is an effective test

[[Page 56826]]

for the detection of anemia, which may result from BD exposure. (Tr. 1/
17/91, p. 784)
    Animal evidence suggests that BD affects the bone marrow, resulting 
in anemia. In mice, inhalation of BD at 1,250 ppm resulted in a 
decrease in circulating erythrocytes, total hemoglobin and hematocrit, 
an increase in mean corpuscular volume, and leukopenia (a decrease in 
the WBC count), due mainly to a decrease in segmented neutrophils. (Ex. 
23-12) These findings are consistent with a diagnosis of macrocytic 
megaloblastic anemia, suggesting that a CBC with a leukocyte count 
might yield information on overexposure to BD.
    Additionally, changes in hemoglobin level, thrombocyte (platelet) 
count, and leukocyte count occur in the presence of leukemia. However, 
the detection of leukemia at a pre-clinical phase, i.e., prior to onset 
of symptoms, may not lead to improved treatment outcomes. The value of 
early disease detection, in this case, is that it provides an 
opportunity to terminate further potential exposure to BD. An employee 
who already has hematologic abnormalities due to leukemia should avoid 
exposure to BD and any other chemicals that could accelerate or worsen 
cytopenias and blood cell dysfunction.
    Abnormality in blood counts is found in only 37 percent of patients 
with bone marrow infiltration. The correlation between peripheral blood 
counts and marrow involvement by lymphoma is poor. However, examination 
of the peripheral smear in patients with non-Hodgkins lymphoma may 
yield evidence of malignant cells in about 15 percent of patients. (Ex. 
23-52, p. 1,357)
    A CBC would also be a valuable screening tool for disorders other 
than leukemia and lymphoma. According to testimony offered by OSHA's 
expert witness Dr. Dennis D. Weisenburger,

    * * * the occurrence of other diseases of the blood and blood 
forming organs should also be critically examined in workers with BD 
exposure, particularly blood cytopenias, bone marrow failure, 
aplastic anemia, and the myelodysplastic (pre-leukemic) syndromes, 
which have also been associated with other chemical agents. (Ex. 39, 
p. 11)

Because the latency period for development of lymphohematopoietic 
disorders and cancers is relatively short, e.g., death from leukemia 
may occur in as little as 3-4 years after initial exposure, a CBC 
performed annually is reasonable and prudent. (Ex. 39, p. 9)
    The combination of an annual CBC and a physical examination every 
three years balances both the need to diagnose leukemias (CBC) and 
lymphomas (physical examination) at an early stage, and the limited 
number of cases likely to be identified through the screening program. 
OSHA believes that waiting for sentinel cases to be identified would 
place other employees at risk of chronic BD-related illnesses, such as 
leukemias and lymphomas. The more quickly such illnesses are 
recognized, the sooner workplace modifications may be instituted to 
protect the health of other employees. An annual CBC, in addition to a 
health questionnaire, is an efficient means of using medical screening 
resources to detect early leukemia or anemia in individuals, while 
simultaneously providing data that can be used to protect the whole 
population of exposed employees. A medical screening strategy that 
includes an annual CBC and health questionnaire with physical 
examinations provided every three years has received support from both 
labor and industry representatives. (Exs. 118-12; 118-13)
    To allow for individual differences among covered employees, as 
well as professional judgement, provision is made for inclusion of any 
other test which the examining physician or other licensed health care 
professional deems necessary. This requirement is provided to ensure 
that adequate flexibility is incorporated into the standard, so that 
any occupational diseases due to BD exposure are adequately diagnosed 
and treated. Furthermore, this provision is consistent with previously 
promulgated health standards.
    Medical screening requirements for employees exposed to BD in an 
emergency situation focus on the acute effects of BD exposure. These 
effects include: Irritation of the eyes, nose, throat, lungs, or skin; 
blurred vision; coughing; drowsiness; nausea; and headache. At a 
minimum, the required medical screening components include: A CBC 
within 48 hours of the exposure and then monthly for three months; and 
a physical examination if the employee reports symptoms related to any 
of the acute effects. Employee participation in the medical screening 
and surveillance program, subsequent to a BD exposure from an emergency 
situation, need not continue for the duration of employment. This 
limitation on employee inclusion after emergency exposure is supported 
in comments received from Shell. (Ex. 32-27, Att. II, pp. 3-4) However, 
to accommodate management of individual cases, continued employee 
participation in the medical screening and surveillance program, beyond 
the minimum requirements, is left to the discretion of the physician or 
other health care professional.
    Additionally, the time frame for the collection of the blood 
specimen has been extended from immediately after the emergency to 
``within 48 hours of the exposure and then monthly for three months.'' 
Again, support for this approach was provided by Shell,

    ``Immediately'' after every emergency may not be possible or 
even reasonable. We suggest ``as soon as possible'' after a 
significant exposure from an emergency event and at least within 48 
hours. * * * (Ex. 32-27, attachment II, p.4)

Further support for this medical screening strategy following an 
emergency situation was provided by Dr. William Halperin, NIOSH,

    The life span of a red blood cell is approximately 120 days. 
Thus, the results of a medical examination shortly after a high 
exposure may be normal despite severely compromised blood-producing 
capacity. If an exposure is high enough to warrant a medical 
examination, then it would be reasonable to obtain a baseline 
hematologic examination at the time of exposure, followed by 
reexaminations at 30, 60, and 90 days. (Ex. 90)

    A physical examination is required only if the employee reports 
symptoms related to the acute effects after exposure to BD in an 
emergency situation. Comments submitted by Shell support the idea that 
not every exposure in an emergency situation necessitates a physical 
examination. (Ex. 32-27, attachment II, p. 4) It is OSHA's opinion that 
this approach provides flexibility, as suggested by Dr. Saunders. (Tr. 
1/18/91, p. 1214-1213) Contrary to the suggestion by CMA, it does not 
leave the need and frequency for medical examinations following an 
emergency situation completely to the judgement of the physician. (Ex. 
112, p. 128) Thus, OSHA believes the final rule adopts a moderate, yet 
protective, approach for medical evaluation requirements for employees 
exposed to BD in an emergency situation.
    Paragraph (k)(5) addresses additional medical evaluations and 
referrals. Whenever the results of medical screening indicate 
abnormalities of the hematopoietic or reticuloendothelial systems, for 
which a non-occupational cause is not readily apparent to the health 
care professional, the employee shall be referred to an appropriate 
specialist, e.g., hematologist, for further evaluation. The content of 
the evaluation is left to the professional judgement of the specialist 
to whom the employee is referred. This provision is essential to ensure 
that employees receive prompt diagnosis at the earliest stage possible, 
when treatment is most likely to be effective.

[[Page 56827]]

    In the NPRM, the paragraph on additional examinations and referrals 
contained a provision for the content of the medical examinations or 
consultations to include, ``evaluation of fertility and other tests, if 
requested by the employee and deemed appropriate by the physician.'' 
(55 FR 32736 at 32806) After evaluation of all factors presented in the 
rulemaking, the Agency has deleted the provision for fertility testing 
from the final rule. However, given the observations in experimental 
animals, the medical screening and surveillance program provided by the 
employer should address the potential reproductive and developmental 
problems of workers exposed to BD. (The reader is referred to the 
Health Effects section of this preamble.) The sample health 
questionnaires provided in Appendix F include examples of questions 
that address reproductive and developmental health concerns.
    Information that the employer must provide to the examining 
physician or other licensed health care provider is listed in paragraph 
(k)(6). Specifically, that information includes: (1) A copy of the BD 
standard; (2) a description of the employee's duties as they relate to 
BD exposure; (3) the employee's actual or representative BD exposure 
level; (4) a description of required pertinent personal protective 
equipment; and (5) information from previous employment-related medical 
evaluations which the physician or other licensed health care 
professional may not otherwise have available. The purpose of this 
requirement is to provide information necessary for the physician or 
other licensed health care professional to make an informed 
determination regarding whether the employee may be at increased risk 
from exposure to BD.
    Paragraph (k)(7) requires employers to ensure that the physician or 
other licensed health care professional produces a written opinion of 
the evaluation results and provides a copy to the employer and employee 
within 15 business days of the medical evaluation. OSHA rejected 
Shell's suggestion of extending the time frame for provision of the 
written opinion to the employee from 15 to 30 days. (Ex. 32-27) In 
OSHA's opinion 30 days is too long to wait to inform employees of the 
results of the medical evaluation. However, OSHA agrees with the 
recommendation made in the labor-management agreement to specify 
``business days.'' (Ex. 118-12, p.18) It is OSHA's opinion that this 
recommendation does not adversely impact the health of employees in the 
medical screening and surveillance program and, yet, it provides a more 
practical time frame for the communication of this information.
    The written opinion must contain the results of the medical 
evaluation that are pertinent to BD exposure, an opinion concerning 
whether the employee has any detected medical conditions which would 
place the employee's health at increased risk of material impairment 
from exposure to BD, and any recommended limitations on the employee's 
exposure to BD. This opinion must be developed with consideration given 
to a comparison of all available medical evaluation results for 
occupational exposure to BD. OSHA recommends that the physician or 
other licensed health care professional use a flow sheet to chart 
temporal changes in the CBC. The occurrence of temporal changes in the 
CBC indices, even if the actual results remain within normal limits, 
should be considered when evaluating risk of material impairment to 
health, as well as the overall medical opinion.
    Additionally, the written opinion must include a statement that the 
employee has been informed of the medical evaluation results and any 
conditions resulting from BD exposure that require further explanation 
or treatment. This written opinion shall not contain any information 
that is not related to the employee's ability to work with BD. In 
rendering this opinion, the physician or other licensed health care 
professional must rely on the results obtained from the medical 
evaluation. This provision does not negate the ethical obligation of 
the physician or other health care professional to transmit any other 
adverse findings directly to the employee.
    Medical surveillance requirements are specified in paragraph 
(k)(8). This provision requires the employer to ensure periodic review 
of information obtained from the medical screening program activities 
to determine whether the health of the employee population of that 
employer is adversely affected by exposure to BD. This requirement is 
meant to clarify OSHA's longstanding policy that individual data 
collected during medical screening activities should be examined in the 
aggregate, with personal identifiers removed, so that population trends 
or patterns can be observed and appropriately managed. This medical 
surveillance provision does not require employers to conduct 
epidemiologic or any other type of research studies, although such 
studies are certainly not precluded.
    It is OSHA's opinion that this information review will provide 
employers with supplemental evidence of the effectiveness of their 
exposure control strategies. The employer's obligations regarding 
medical surveillance may be limited to a determination that all medical 
evaluation results are within normal limits and temporal changes in 
these results have not occurred. However, should a pattern of abnormal 
findings be identified, the employer may have an opportunity for 
primary prevention of BD-related disease. Information learned from 
medical surveillance activities must be disseminated to employees 
covered by the medical screening and surveillance program provision, as 
defined in paragraph (k)(1).

L. Hazard Communication

    The requirements for hazard communication have been moved from 
proposed paragraph (j), redesignated and promulgated as paragraph (l) 
of the final rule. The paragraph addressing hazard communication in the 
final BD rule is consistent with the requirements of OSHA's Hazard 
Communication Standard (HCS). The HCS requires all employers to provide 
information concerning the hazards of workplace chemicals to their 
employees. The transmittal of hazard information to employees is to be 
accomplished by such means as container labeling and other forms of 
warning, material safety data sheets, and employee training.
Signs and Labels
    Since the HCS is ``intended to address comprehensively the issue of 
evaluating the potential hazard of chemicals and communicating 
information concerning hazards and appropriate protective measures to 
employees,'' OSHA is including paragraph (l)(1) only to reference HCS 
requirements for labels and material safety data sheets. Employers who 
have already met their longstanding requirements to comply with the HCS 
will have no additional duties with regard to labels and MSDSs under 
the BD rule.
    The warning sign and labels for BD which OSHA proposed in 1990 have 
been deleted from the final rule in response to the recommendation of 
various commenters, including the labor/industry group, who suggested 
that no requirements were needed beyond those already listed in the 
HCS. (Tr. 1/18/91, p. 1169; Tr. 1/22/91, pp. 1348-1249; Ex. 112, 32-17, 
32-19, 32-22, 32-27, 108, 118-12A) Therefore, the final rule now 
references the HCS.
Employee Information and Training
    OSHA is also referencing the HCS for employee information and 
training, but is specifying additional provisions applicable when 
employee exposures

[[Page 56828]]

are likely to exceed the action level or STEL. Paragraph (l)(2) 
reiterates that training must be afforded employees in accordance with 
the HCS and contains various provisions which apply when exposure 
limits are exceeded. The first of these is the requirement that a 
training program be instituted and that employee participation in it be 
assured by the employer (paragraph (l)(2)(i)).
    OSHA believes that training is not a passive process. The 
information provided employees in training requires their comprehension 
of the material and subsequent use of what they have learned while 
performing their duties in the workplace. There are many different ways 
to accomplish training effectively, but it cannot be a mechanical 
transfer of information such as giving someone a written document. 
OSHA's voluntary guidelines, which are found in OSHA publication No. 
2252, are available to provide employers with additional guidance in 
setting up and implementing an appropriate employee training program. 
An effective training program is a critical component of any safety and 
health program in the workplace. Workers who are fully informed and 
engaged in the protective measures established by the employer will 
play a significant role in the prevention of adverse health effects. 
Ineffective training will not serve the purpose of making workers full 
participants in the program, and the likelihood of a successful program 
for safety and health in the absence of an effectively-trained 
workforce is remote.
    OSHA expects that employers will ensure that the information and 
training is effective. Although not specifically required in the 
standard, any good training program should include an evaluation 
component to help ensure effectiveness. The voluntary training 
guidelines previously recommended can provide additional guidance in 
this respect.
    Paragraph (l)(2)(ii) requires employers to provide the required 
information and training prior to or at the time of initial assignment 
to work with BD. This paragraph also requires that such training be 
repeated annually when employees are exposed over the action level or 
STEL ((l)(2)(iii)). OSHA notes that annual training for workers exposed 
above an action level is also required in other standards e.g., benzene 
(29 CFR 1910.1028), asbestos (29 CFR 1910.1001), cadmium (29 CFR 
1910.1027), formaldehyde (29 CFR 1910.1048).
    CMA requested that OSHA correct the final rule to require annual 
training only when the employee is assigned to a job where the 
potential exposure is above the action level or STEL. OSHA has included 
this provision in paragraph (l)(2)(iii). (Ex. 112, p. 116) OSHA notes, 
however that all employees potentially exposed to BD must receive 
training at least once as provided by the HCS. Those employees whose 
tasks place them at risk of higher exposure (above the action level or 
STEL) need training at least annually to review the nature of the 
hazards of BD exposure and the methods to be used to minimize exposure 
and to maintain a continuing awareness of the potential dangers 
associated with exposure.
    In its submission, CMA also requested that OSHA specify in the 
final rule that where the BD standard does not apply because objective 
data are used to exempt a material or process from the standard, the 
hazard communication requirements would come from the HCS. (Ex. 112, p. 
178) OSHA does not believe this is necessary and that it might lead to 
greater confusion. Clearly, exemption from the BD standard does not 
imply exemption from the HCS.
    OSHA notes that materials containing less than 0.1% BD are exempt 
from the BD standard unless there is evidence which indicates that the 
action level or STEL can reasonably be expected to be exceeded during 
the job. On the other hand, the HCS contains no exemption from employee 
information and training provisions for materials containing less than 
0.1% of a carcinogen (BD).
    Paragraph (l)(2)(iv) indicates that employers must ensure that the 
information and training is presented in a manner that is 
understandable to employees, and lists topics which must be included in 
the training program.
    The labor/industry agreement recommended deletion of the proposed 
requirement that: ``The training program shall be conducted in a manner 
that the employee is able to understand.'' (Ex. 118-12A) No explanation 
for this suggestion was offered in submissions to the record. OSHA 
believes that it is essential that training be understood by the 
employee. Thus, OSHA has not deleted the requirement from the standard.
    Paragraph (l)(2)(iv) also addresses the items upon which employees 
are to be trained and includes training regarding specific measures 
employees can take to protect themselves from the effects of BD 
exposure. Paragraphs (l)(2)(iv)(A) through (F) set forth the basic 
topics to be covered during the requisite training program. CMA asked 
that OSHA delete most of this list of training topics. (Ex. 112, p. 
177) CMA felt that the HCS provisions were adequate. However, the 
labor/industry group did not make a similar recommendation, and the 
final rule contains basic guidance to employers establishing an 
employee training program as to what subjects must be included. OSHA 
believes that these requirements build upon the HCS and provide BD-
specific information needed by the employee to reduce exposure to BD, 
and therefore prevent adverse health effects from occurring.
    Upon recommendation of the labor/industry group, OSHA has 
consolidated some of the training topics and made them more concise and 
clearer. (Ex. 118-12A) The labor/industry group recommended deletion of 
proposed paragraph (k)(4)(iii)(D), which stated that the training must 
cover

The measure employees can take to protect themselves from exposure 
to BD, including a review of their habits, such as smoking and 
personal hygiene; and specific procedures the employer has 
implemented to protect employees from exposure to BD, such as 
appropriate work practices, emergency procedures, and personal 
protective equipment. (55 FR 32736 at 32807)

OSHA agrees that most of this material is to be covered under the other 
topics listed in the final rule, but has determined that the training 
must include information regarding what employees themselves can do to 
assist in protecting themselves from exposure to BD. Additionally, as 
recommended in the labor/industry agreement, reference to personal 
habits and hygiene has been deleted. (Ex. 118-12A) OSHA has concluded 
that there is little data regarding the relationship of personal habits 
to the hazards associated with BD exposure to justify the inclusion of 
this provision in the final rule. Therefore this subject is not 
included among those required in the training program.
    Paragraph (l)(3)(i) requires the employer to give copies of the BD 
standard in its entirety, including all appendices, to employees. In 
response to the labor/industry group recommendation, OSHA has included 
in the provision that the standard must also be provided by the 
employer to persons designated as employee representative(s). (Ex. 118-
12A) Further, the copy must be provided at no cost to the employee.
    In paragraph (l)(3)(ii) OSHA has indicated that the Assistant 
Secretary or the Director may access all materials relating to employee 
information and training in the workplace. This would be done in 
conjunction with an inspection to ascertain compliance with the rule, 
or in the event of a NIOSH health hazard evaluation. Review of the 
available materials regarding information and training will help 
evaluate whether the program has been properly conducted, as well as 
ascertain

[[Page 56829]]

what could be improved if employees do not appear to be effectively 
trained. As in previous paragraph (l)(3)(i), and at the suggestion of 
the labor/industry group, designated employee representatives are to be 
provided all materials relating to information and training. (Ex. 118-
12A) This will be useful to them in helping to assure that their 
members are benefitting from all the protection the BD standard 
affords.
    The training provisions of this final rule are performance-oriented 
because employees may be exposed to BD in a variety of circumstances. 
Thus, the standard lists the topics of information to be transmitted to 
the employees, but does not specify the ways in which it is to be 
transmitted.

M. Recordkeeping

    Section 8(c)(3) of the Act provides for the promulgation of 
``regulations requiring employers to maintain accurate records of 
employee exposures to potentially toxic materials or harmful physical 
agents which are required to be monitored or measured under section 
6.'' All employers with BD in their workplace must do initial 
monitoring or reasonably rely on objective data that show that 
workplace exposures to BD are at or below the action level. Paragraph 
(m)(1) of the final rule requires employers who are relying on 
objective data (under paragraph (d)(2)) to avoid the initial monitoring 
requirements of the final rule, to maintain records that show the basis 
for their reliance and the reasoning used in reaching the conclusion 
that such monitoring is not necessary.
    The objective data must provide the same degree of assurance that 
employees are not being significantly exposed to butadiene as 
monitoring would. Thus, such data should include information about the 
materials, product, activity, or process tested and found to qualify 
for exemptions; the source (e.g., manufacturer, testing laboratory, 
research study) of the objective data; the protocol used to obtain the 
results; a description of the product(s), materials(s), activities, or 
processes to which the relied upon data applies and an explanation of 
why such data are worthy of being relied upon; and any other data the 
employer believes are relevant to the exemption. This documentation is 
intended to demonstrate the appropriateness of the employer's reliance 
on objective data in lieu of the initial monitoring of employee 
exposure to BD.
    The Agency has made a determination that significant employee 
exposures to BD should be closely monitored. Therefore it is 
appropriate to require the employer to carefully document and keep 
records of the data that are being relied upon in lieu of actual 
monitoring.
    At the suggestion of the labor/industry group and for consistency 
with other provisions of the standard, the word ``streams'' has been 
included in paragraph (m)(1), since it is part of the exemptions in 
paragraph (a)(2) of this section.13 (Ex. 118-12A)
---------------------------------------------------------------------------

    \13\ Paragraph (m)(1)(i) now reads in pertinent part: ``Where 
the processing, use, or handling of products or streams made from or 
containing BD * * *
---------------------------------------------------------------------------

     Paragraph (m)(1)(iii) requires the employer to keep records of the 
objective data relied upon for as long as the employer continues to 
rely on such data.
    Paragraph (m)(2) requires that employers keep records of all 
exposure monitoring required by the final rule. The provisions in this 
paragraph are consistent with those of 29 CFR 1910.1020, OSHA's Access 
to Employee Exposure and Medical Records standard. Paragraph (m)(2) 
specifies what information related to employee exposure monitoring must 
be kept. For example, it requires retention of information on the 
sampling and analytical methods, as well as information about the 
employee(s) sampled and their use of protective equipment. At the 
recommendation of the labor/industry group, records must also be 
maintained on written corrective action to be taken when monitoring 
indicates exposures over the PEL. (Ex. 118-12A) In addition, OSHA has 
also included a requirement that the schedule for completing the 
corrective action also be maintained.
    A new paragraph, (m)(3), has been added to the final rule, which 
requires that records of respirator fit tests be maintained by the 
employer until the next fit test is administered to the employee. In 
the proposal, this provision was included in the mandatory appendix for 
respirator fit testing. OSHA believes that it will be more convenient 
for those using the standard to have all recordkeeping provisions 
together in the standard. Therefore recordkeeping provisions from other 
parts of the standard are being moved to paragraph (m) of the final 
rule.
    Paragraph (m)(4) requires that the employer keep accurate medical 
records for each employee subject to medical screening and surveillance 
under the standard. Section 8(c) of the Act authorizes the promulgation 
of regulations requiring an employer to keep necessary and appropriate 
records regarding activities to permit the enforcement of the Act or to 
develop information regarding the causes and prevention of occupational 
illnesses. OSHA has determined that, in this context, requiring 
employers to maintain both medical and exposure measurement records is 
necessary and appropriate, and paragraph (m)(3) simply details what 
information must be kept.
    Paragraph (m)(5)(i) states that all records required to be 
maintained by the standard must be made available to the Assistant 
Secretary and Director of NIOSH for examination and copying if such 
records are requested in writing. Access to these records is necessary 
for compliance monitoring. These records also contain information that 
the agencies may need to carry out other statutory responsibilities.
    Paragraph (m)(5)(ii) provides that employees, former employees, and 
their designated representatives have access upon request to all 
exposure and medical records required by the standard. This provision 
is consistent with 29 CFR 1910.1020 (e). Section 8(c)(3) and other 
provisions of the Act make clear that employees and their 
representatives are expected to have an active and meaningful role in 
workplace safety and health. Employees and their representatives need 
information about employee exposures to toxic substances and their 
potential effects on health and safety if they are to benefit fully 
from these statutorily created rights.
    OSHA's generic rule (29 CFR 1910.1020) permitting access to 
employee exposure and medical records was issued on May 23, 1980. (45 
FR 35212) This rule applies to records created pursuant to specific 
standards and to records that are voluntarily created by employers. 
OSHA retains unrestricted access to medical and exposure records, but 
the Agency's access to personally identifiable records is subject to 
the Agency's rules of practice and procedure concerning OSHA access to 
employee medical records, which are codified at 29 CFR 1913.10.
    Paragraph (m)(6) of the final rule addresses transfer of records. 
Under paragraph (m)(6)(i), when an employer ceases to do business, the 
employer must transfer records required by this section to the 
successor employer, who shall receive and maintain such records. If 
there is no successor employer, the employer shall notify the Director 
of NIOSH at least three months prior to anticipated disposal of the 
records, and shall transmit the records to the Director, if so 
requested. Under paragraph (m)(6)(ii), the employer is required to 
transfer medical and exposure records in accordance with

[[Page 56830]]

requirements set forth in 29 CFR 1910.1020(h).
    The Agency believes it is necessary to keep certain records for 
extended periods of time because of the long latency periods commonly 
observed for the induction of cancer caused by exposures to 
carcinogens. Cancer often is not detected until 20 or more years after 
onset of exposure. The extended record retention period required by 29 
CFR 1910.1020 therefore is needed for two purposes. First, possession 
of past and present exposure data and medical records aids in the 
diagnosis of workers' disease and determination of work-relatedness. In 
addition, retaining records for extended periods make possible future 
review to determine the effectiveness and adequacy of OSHA's final 
rules.
    The time periods required for retention of exposure records and 
medical records are thirty years and the period of employment plus 
thirty years, respectively. These retention requirements are consistent 
with those in the OSHA exposure and medical records access standard.

N. Dates

    This paragraph establishes the effective date of the final rule for 
butadiene and sets out start-up dates for various provisions of the 
standard. The final rule becomes effective 90 days following 
publication in the Federal Register. This period enables employers to 
familiarize themselves with the final rule. In addition, individual 
provisions, where appropriate, have delayed start-up dates. In 
addition, the Agency has established delayed start-up dates for several 
provisions of the final rule, based on evidence submitted to the record 
demonstrating that compliance with some provisions may require longer 
times than compliance with other provisions. These dates are based on 
the record in this rulemaking and on the Agency's experience with other 
standards concerning the amount of time required for employers to 
perform initial employee monitoring, institute medical surveillance 
programs, implement emergency procedures, etc.
    The effective date, in conjunction with the start-up dates, will 
allow sufficient time for employers to achieve compliance with the 
substantive requirements of the final rule.
    Paragraph (n)(2)(i) requires that initial monitoring shall be 
completed within sixty days of the effective date of the standard or 
within 60 days of the introduction of BD into the workplace. In the 
proposed rule, this paragraph was designated as paragraph (d)(2)(ii); 
it has been moved to paragraph (n) in the final rule to consolidate all 
effective date information in one section.
    Dow Chemical Company objected to the 60 day start-up date for 
initial monitoring as being inadequate to set up such a program. (Ex. 
118-16) OSHA believes that 60 days after the effective date of the 
standard is sufficient time to carry out initial monitoring. OSHA 
believes that much of the required monitoring may have already been 
performed by employers.
    Final rule paragraph (n)(2)(iii) requires that the feasible 
engineering controls required by paragraph (f)(1) be implemented within 
two years after the effective date of the standard. This represents an 
extension of 12 months beyond that proposed for engineering controls. 
In testimony, the CMA Panel Chair, Dr. Norman Morrow, said that it was 
necessary to extend the one year start-up date to two years because of 
the time needed to identify those areas needing control, to determine 
the appropriate control measure to use, and to procure and install the 
equipment. (Tr. 1/18/91, p. 1168)
    Other submissions contained similar requests for extension of the 
period to comply with controls. (Ex. 28-32; 112) OSHA agrees that 
additional time may be needed to come into full compliance and thus the 
final rule permits a full 24 months for compliance with the engineering 
controls provision of the final rule. During the period in which 
employers are implementing these controls, additional respirator use 
may be required to comply with the new exposure limits.
    Paragraph (n)(2)(iii) also has a start-up date of within three 
years of the effective date of the standard to implement the exposure 
goal program (paragraph (g)). This is the length of time agreed upon by 
the labor/industry group who developed the provisions for the exposure 
goal program and submitted them to OSHA. (Ex. 118-12A) OSHA believes 
that this will provide ample time for employers to install or otherwise 
comply with the provisions in the program.
    Final rule paragraph (n)(2)(ii), which covers start-up dates for 
paragraphs (c) through (m), including those for feasible work practice 
controls but not for the engineering controls specified in the 
paragraph (f)(1), requires that employers attain compliance within 180 
days of the effective date of the BD standard. This provision is 
identical to proposed paragraph (n)(2)(i).
    The rest of the provisions of the standard must be implemented 
within 180 days of the effective date.

O. Appendices

    Six appendices have been included at the end of this standard. 
Appendices A, B, C, D, and F are included primarily for purposes of 
information and compliance assistance and should not be construed as 
establishing a mandatory requirement not otherwise imposed by the 
standard, or as detracting from an obligation which the standard does 
impose. However, the protocols for respiratory fit testing in Appendix 
E are binding.
    The appendices have been updated from the proposal to reflect the 
final rule. Additionally, a number of technical and typographical 
corrections have been made in them. Appendix A contains information 
briefly describing the properties of BD and its hazards, and describes 
in general terms the provisions of the standard. Further, it contains 
the procedures to be used during emergencies, fires, and other 
situations in which there is potential for BD exposure.
    Appendix B describes more fully the chemical and physical 
properties of BD and gives procedures to use when leaks or spills 
occur. Correct disposal is also outlined. Additional information is 
given on ways to safely handle BD.
    Appendix C provides medical screening and surveillance guidelines 
for BD. The appendix describes the effects of BD exposure on the body 
and gives an overview of the medical screening and surveillance 
provisions of the standard. In general terms, it provides the physician 
or other licensed healthcare professional with an outline of the 
requirements of the rule.
    Appendix D contains the sampling method developed and validated by 
the OSHA laboratory for use with BD. This is a non-mandatory appendix--
the use of other measurement methods is allowed when accuracy levels 
required in the standard are met. Paragraph (d)(6) states that 
monitoring shall be accurate, at a confidence level of 95 percent, to 
within plus or minus 25 percent for airborne concentrations of BD at or 
above the 1 ppm TWA limit and to within plus or minus 35 percent for 
airborne concentrations of BD at or above the action level of 0.5 ppm 
and below the 1 ppm TWA limit. In addition, paragraph (m)(2)(ii)(C) 
requires that the exposure measurement record include sampling and 
analytical methods used and evidence of their accuracy.
    Supplementary data used by the OSHA laboratory in developing the 
analytical method were included in the proposal, but have been deleted 
from the final rule. (55 FR 32736 at 32814.)

[[Page 56831]]

    Basically, the OSHA method is a charcoal tube (CT)-gas 
chromatography (GC)-mass spectrometry (MS) (CT-GC-MS) method. It 
involves the use of charcoal tubes and sampling pumps, followed by 
analysis of the samples by gas chromatography and a confirmation of GC 
peak by MS when it is necessary. The charcoal is coated with 4-tert-
butylcatechol to inhibit the polymerization of BD, in order to increase 
the stability of the sample. (Ex. 118-9) Since BD often is present in a 
complex mixture which may make it difficult to adequately evaluate due 
to interferences, MS is used in GC-MS combination to identify the GC 
chemical peak and to make sure that there is no interferences and to 
identify any interferences that occur.
    OSHA agrees with API that no single CT-GC-MS method can be used as 
a ``cookbook'' for all situations. (Ex. 118-11) The American Petroleum 
Institute (API) developed a method to ``resolve interferences for 
complex mixtures found in the petroleum industry'' in 1991 and refined 
the method in 1996. (Exs. 108 and 118-11) The API method uses a long 
length of capillary column with different configurations for a greater 
separation ability from other isomers/interferences found in the 
petroleum industry. API asked OSHA's acceptance of the API BD 
monitoring method. (Ex. 118-11) OSHA believes that the API method, as 
well as other methods which may be developed that accurately measure BD 
levels in the breathing zone of exposed workers, are acceptable.
    Since many of the duties relating to employee exposure are 
dependent on the results of measurement procedures, employers must 
assure that the evaluation of employee exposure is performed by a 
technically qualified person.
    Appendix E is the only mandatory appendix to the BD rule. This 
appendix has been revised somewhat from the proposal throughout, 
primarily for clarity. However, it now contains a protocol for using 
ambient aerosol condensation nuclei counter (CNC) quantitative fit 
testing, which was not included in the proposal.
    Appendix F contains sample questionnaires for use in medical 
screening and surveillance. The appendix contains two sample 
questionnaires, one for the initial medical evaluation and the other 
for the annual updating of the medical evaluations. These are included 
to provide medical personnel information to assist them in complying 
with the standard.
Authority and Signature
    This document was prepared under the direction of Joseph A. Dear, 
Assistant Secretary of Labor for Occupational Safety and Health, U.S. 
Department of Labor, 200 Constitution Avenue, N.W., Washington, D.C. 
20210
    Pursuant to sections 4, 6(b), 8(c) and 8(g) of the Occupational 
Safety and Health Action (29 U.S.C. 653, 655, 657), section 107 of the 
Contract Work Hours and Safety Standards Act (the Construction Safety 
Act) (40 U.S.C. 333); the Longshore and Harbor Workers' Compensation 
Act (33 U.S.C. 941); the Secretary of Labor's Order No. 1-90 (55 FR 
9033); and 29 CFR part 1911; 29 CFR parts 1910, 1915 and 1926 are 
amended as set forth below.

List of Subjects in 29 CFR Parts 1910, 1915 and 1926

    1,3-Butadiene, Cancer, Chemicals, Health risk-assessment, 
Occupational safety and health.

    Signed at Washington, DC, this 24th day of October 1996.
Joseph A. Dear,
Assistant Secretary of Labor.

PART 1910--[AMENDED]

    Part 1910 of Title 29 of the Code of Federal Regulations is hereby 
amended as follows:

Subpart B--[Amended]

    1. The authority citation for subpart B of Part 1910 is revised to 
read as follows:

    Authority: Secs. 4, 6 and 8 of the Occupational Safety and 
Health Act, 29 U.S.C. 653, 655; 657; Walsh-Healey Act, 41 U.S.C. 35 
et seq; Service Contract Act of 1965, 41 U.S.C. 351 et seq; sec. 
107, Contract Work Hours and Safety Standards Act (Construction 
Safety Act), 40 U.S.C. 333; sec. 41, Longshore and Harbor Workers' 
Compensation Act, 33 U.S.C. 941; National Foundation of Arts and 
Humanities Act, 20 U.S.C. 951 et seq.; Secretary of Labor's Order 
No. 12-71 (36 FR 8754); 8-76 (41 FR 25059); 9-83 (48 FR 35736) or 1-
90 (55 FR 9033), as applicable; and 29 CFR part 1911.

    2. A new paragraph (l) is added to Sec. 1910.19 to read as follows:


Sec. 1910.19  Special provisions for air contaminants.

* * * * *
    (l) 1,3-Butadiene (BD): Section 1910.1051 shall apply to the 
exposure of every employee to BD in every employment and place of 
employment covered by Secs. 1910.12, 1910.13, 1910.14, 1910.15, or 
Sec. 1910.16, in lieu of any different standard on exposure to BD which 
would otherwise be applicable by virtue of those sections.

Subpart Z--Toxic and Hazardous Substances--[Amended]

    3. The authority citation for subpart Z of part 1910 continues to 
read as follows:
    Authority: Secs. 4, 6, and 8 of the Occupational Safety and 
Health Act of 1970 (29 U.S.C. 653, 655, and 657); Secretary of 
Labor's Order No. 12-71 (36 FR 8754), 8-76 (41 FR 25059), 9-83 (48 
FR 35736), of 1-90 (55 FR 9033) as applicable; and 29 CFR part 1911.
    Section 1910.1000, Tables Z-1, Z-2, and Z-3 also issued under 5 
U.S.C. 553. Section 1910.1000, Tables Z-1, Z-2, and Z-3 not issued 
under 29 CFR Part 1911 except for the arsenic (organic compounds), 
benzene, cotton dust, and 1,3-butadiene listings.
    Section 1910.1001 also issued under section 107 of the Contract 
Work Hours and Safety Standards Act (40 U.S.C. 333) and 5 U.S.C. 
553.
    Section 1910.1002 not issued under 29 U.S.C. 655 or 29 CFR 1911; 
also issued under 5 U.S.C. 553.
    Section 1910.1200 also issued under 5 U.S.C. 553.


Sec. 1910.1000  [Amended]

    4. The entry in Table Z-1 of Sec. 1910.1000, ``Butadiene (1,3-
Butadiene)'' is amended as follows: remove the ``1000'' and ``2200'' 
from the columns entitled ppm(a)1 and mg/m3 (b)1 
respectively, add ``1 ppm/5 ppm STEL'' in the ppm (a)1 column; and 
add the following to the butadiene entry ``; See 29 CFR 1910.1051; 29 
CFR 1910.19(l)'' so that the entry reads as follows: ``Butadiene (1,3-
Butadiene); See 29 CFR 1910.1051; 29 CFR 1910.19(l).''
    5. A new 1910.1051 is added to read as follows:


Sec. 1910.1051 1,3-Butadiene.

    (a) Scope and application. (1) This section applies to all 
occupational exposures to 1,3-Butadiene (BD), Chemical Abstracts 
Service Registry No. 106-99-0, except as provided in paragraph (a)(2) 
of this section.
    (2)(i) Except for the recordkeeping provisions in paragraph (m)(1) 
of this section, this section does not apply to the processing, use, or 
handling of products containing BD or to other work operations and 
streams in which BD is present where objective data are reasonably 
relied upon that demonstrate the work operation or the product or the 
group of products or operations to which it belongs may not reasonably 
be foreseen to release BD in airborne concentrations at or above the 
action level or in excess of the STEL under the expected conditions of 
processing, use, or handling that will cause the greatest possible 
release or in any plausible accident.

[[Page 56832]]

    (ii) This section also does not apply to work operations, products 
or streams where the only exposure to BD is from liquid mixtures 
containing 0.1% or less of BD by volume or the vapors released from 
such liquids, unless objective data become available that show that 
airborne concentrations generated by such mixtures can exceed the 
action level or STEL under reasonably predictable conditions of 
processing, use or handling that will cause the greatest possible 
release.
    (iii) Except for labeling requirements and requirements for 
emergency response, this section does not apply to the storage, 
transportation, distribution or sale of BD or liquid mixtures in intact 
containers or in transportation pipelines sealed in such a manner as to 
fully contain BD vapors or liquid.
    (3) Where products or processes containing BD are exempted under 
paragraph (a)(2) of this section, the employer shall maintain records 
of the objective data supporting that exemption and the basis for the 
employer's reliance on the data, as provided in paragraph (m)(1) of 
this section.
    (b) Definitions: For the purpose of this section, the following 
definitions shall apply:
    Action level means a concentration of airborne BD of 0.5 ppm 
calculated as an eight (8)-hour time-weighted average.
    Assistant Secretary means the Assistant Secretary of Labor for 
Occupational Safety and Health, U.S. Department of Labor, or designee.
    Authorized person means any person specifically designated by the 
employer, whose duties require entrance into a regulated area, or a 
person entering such an area as a designated representative of 
employees to exercise the right to observe monitoring and measuring 
procedures under paragraph (d)(8) of this section, or a person 
designated under the Act or regulations issued under the Act to enter a 
regulated area.
    1,3-Butadiene means an organic compound with chemical formula 
CH2=CH-CH=CH2 that has a molecular weight of approximately 
54.15 gm/mole.
    Business day means any Monday through Friday, except those days 
designated as federal, state, local or company specific holidays.
    Complete Blood Count (CBC) means laboratory tests performed on 
whole blood specimens and includes the following: White blood cell 
count (WBC), hematocrit (Hct), red blood cell count (RBC), hemoglobin 
(Hgb), differential count of white blood cells, red blood cell 
morphology, red blood cell indices, and platelet count.
    Day means any part of a calendar day.
    Director means the Director of the National Institute for 
Occupational Safety and Health (NIOSH), U.S. Department of Health and 
Human Services, or designee.
    Emergency situation means any occurrence such as, but not limited 
to, equipment failure, rupture of containers, or failure of control 
equipment that may or does result in an uncontrolled significant 
release of BD.
    Employee exposure means exposure of a worker to airborne 
concentrations of BD which would occur if the employee were not using 
respiratory protective equipment.
    Objective data means monitoring data, or mathematical modelling or 
calculations based on composition, chemical and physical properties of 
a material, stream or product.
    Permissible Exposure Limits, PELs means either the 8 hour Time 
Weighted Average (8-hr TWA) exposure or the Short-Term Exposure Limit 
(STEL).
    Physician or other licensed health care professional is an 
individual whose legally permitted scope of practice (i.e., license, 
registration, or certification) allows him or her to independently 
provide or be delegated the responsibility to provide one or more of 
the specific health care services required by paragraph (k) of this 
section.
    Regulated area means any area where airborne concentrations of BD 
exceed or can reasonably be expected to exceed the 8-hour time weighted 
average (8-hr TWA) exposure of 1 ppm or the short-term exposure limit 
(STEL) of 5 ppm for 15 minutes.
    This section means this 1,3-butadiene standard.
    (c) Permissible exposure limits (PELs).--(1) Time-weighted average 
(TWA) limit. The employer shall ensure that no employee is exposed to 
an airborne concentration of BD in excess of one (1) part BD per 
million parts of air (ppm) measured as an eight (8)-hour time-weighted 
average.
    (2) Short-term exposure limit (STEL). The employer shall ensure 
that no employee is exposed to an airborne concentration of BD in 
excess of five parts of BD per million parts of air (5 ppm) as 
determined over a sampling period of fifteen (15) minutes.
    (d) Exposure monitoring--(1) General. (i) Determinations of 
employee exposure shall be made from breathing zone air samples that 
are representative of the 8-hour TWA and 15-minute short-term exposures 
of each employee.
    (ii) Representative 8-hour TWA employee exposure shall be 
determined on the basis of one or more samples representing full-shift 
exposure for each shift and for each job classification in each work 
area.
    (iii) Representative 15-minute short-term employee exposures shall 
be determined on the basis of one or more samples representing 15-
minute exposures associated with operations that are most likely to 
produce exposures above the STEL for each shift and for each job 
classification in each work area.
    (iv) Except for the initial monitoring required under paragraph 
(d)(2) of this section, where the employer can document that exposure 
levels are equivalent for similar operations on different work shifts, 
the employer need only determine representative employee exposure for 
that operation from the shift during which the highest exposure is 
expected.
    (2) Initial monitoring. (i) Each employer who has a workplace or 
work operation covered by this section, shall perform initial 
monitoring to determine accurately the airborne concentrations of BD to 
which employees may be exposed, or shall rely on objective data 
pursuant to paragraph (a)(2)(i) of this section to fulfill this 
requirement.
    (ii) Where the employer has monitored within two years prior to the 
effective date of this section and the monitoring satisfies all other 
requirements of this section, the employer may rely on such earlier 
monitoring results to satisfy the requirements of paragraph (d)(2)(i) 
of this section, provided that the conditions under which the initial 
monitoring was conducted have not changed in a manner that may result 
in new or additional exposures.
    (3) Periodic monitoring and its frequency. (i) If the initial 
monitoring required by paragraph (d)(2) of this section reveals 
employee exposure to be at or above the action level but at or below 
both the 8-hour TWA limit and the STEL, the employer shall repeat the 
representative monitoring required by paragraph (d)(1) of this section 
every twelve months.
    (ii) If the initial monitoring required by paragraph (d)(2) of this 
section reveals employee exposure to be above the 8-hour TWA limit, the 
employer shall repeat the representative monitoring required by 
paragraph (d)(1)(ii) of this section at least every three months until 
the employer has collected two samples per quarter (each at least 7 
days apart) within a two-year period, after which such monitoring must 
occur at least every six months.
    (iii) If the initial monitoring required by paragraph (d)(2) of 
this section reveals employee exposure to be above the STEL, the 
employer shall repeat the

[[Page 56833]]

representative monitoring required by paragraph (d)(1)(iii) of this 
section at least every three months until the employer has collected 
two samples per quarter (each at least 7 days apart) within a two-year 
period, after which such monitoring must occur at least every six 
months.
    (iv) The employer may alter the monitoring schedule from every six 
months to annually for any required representative monitoring for which 
two consecutive measurements taken at least 7 days apart indicate that 
employee exposure has decreased to or below the 8-hour TWA, but is at 
or above the action level.
    (4) Termination of monitoring. (i) If the initial monitoring 
required by paragraph (d)(2) of this section reveals employee exposure 
to be below the action level and at or below the STEL, the employer may 
discontinue the monitoring for employees whose exposures are 
represented by the initial monitoring.
    (ii) If the periodic monitoring required by paragraph (d)(3) of 
this section reveals that employee exposures, as indicated by at least 
two consecutive measurements taken at least 7 days apart, are below the 
action level and at or below the STEL, the employer may discontinue the 
monitoring for those employees who are represented by such monitoring.
    (5) Additional monitoring. (i) The employer shall institute the 
exposure monitoring required under paragraph (d) of this section 
whenever there has been a change in the production, process, control 
equipment, personnel or work practices that may result in new or 
additional exposures to BD or when the employer has any reason to 
suspect that a change may result in new or additional exposures.
    (ii) Whenever spills, leaks, ruptures or other breakdowns occur 
that may lead to employee exposure above the 8-hr TWA limit or above 
the STEL, the employer shall monitor [using leak source, such as direct 
reading instruments, area or personal monitoring], after the cleanup of 
the spill or repair of the leak, rupture or other breakdown, to ensure 
that exposures have returned to the level that existed prior to the 
incident.
    (6) Accuracy of monitoring. Monitoring shall be accurate, at a 
confidence level of 95 percent, to within plus or minus 25 percent for 
airborne concentrations of BD at or above the 1 ppm TWA limit and to 
within plus or minus 35 percent for airborne concentrations of BD at or 
above the action level of 0.5 ppm and below the 1 ppm TWA limit.
    (7) Employee notification of monitoring results. (i) The employer 
shall, within 5 business days after the receipt of the results of any 
monitoring performed under this section, notify the affected employees 
of these results in writing either individually or by posting of 
results in an appropriate location that is accessible to affected 
employees.
    (ii) The employer shall, within 15 business days after receipt of 
any monitoring performed under this section indicating the 8-hour TWA 
or STEL has been exceeded, provide the affected employees, in writing, 
with information on the corrective action being taken by the employer 
to reduce employee exposure to or below the 8-hour TWA or STEL and the 
schedule for completion of this action.
    (8) Observation of monitoring.--(i) Employee observation. The 
employer shall provide affected employees or their designated 
representatives an opportunity to observe any monitoring of employee 
exposure to BD conducted in accordance with paragraph (d) of this 
section.
    (ii) Observation procedures. When observation of the monitoring of 
employee exposure to BD requires entry into an area where the use of 
protective clothing or equipment is required, the employer shall 
provide the observer at no cost with protective clothing and equipment, 
and shall ensure that the observer uses this equipment and complies 
with all other applicable safety and health procedures.
    (e) Regulated areas. (1) The employer shall establish a regulated 
area wherever occupational exposures to airborne concentrations of BD 
exceed or can reasonably be expected to exceed the permissible exposure 
limits, either the 8-hr TWA or the STEL.
    (2) Access to regulated areas shall be limited to authorized 
persons.
    (3) Regulated areas shall be demarcated from the rest of the 
workplace in any manner that minimizes the number of employees exposed 
to BD within the regulated area.
    (4) An employer at a multi-employer worksite who establishes a 
regulated area shall communicate the access restrictions and locations 
of these areas to other employers with work operations at that worksite 
whose employees may have access to these areas.
    (f) Methods of compliance.--(1) Engineering controls and work 
practices. (i) The employer shall institute engineering controls and 
work practices to reduce and maintain employee exposure to or below the 
PELs, except to the extent that the employer can establish that these 
controls are not feasible or where paragraph (h)(1)(i) of this section 
applies.
    (ii) Wherever the feasible engineering controls and work practices 
which can be instituted are not sufficient to reduce employee exposure 
to or below the 8-hour TWA or STEL, the employer shall use them to 
reduce employee exposure to the lowest levels achievable by these 
controls and shall supplement them by the use of respiratory protection 
that complies with the requirements of paragraph (h) of this section.
    (2) Compliance plan. (i) Where any exposures are over the PELs, the 
employer shall establish and implement a written plan to reduce 
employee exposure to or below the PELs primarily by means of 
engineering and work practice controls, as required by paragraph (f)(1) 
of this section, and by the use of respiratory protection where 
required or permitted under this section. No compliance plan is 
required if all exposures are under the PELs.
    (ii) The written compliance plan shall include a schedule for the 
development and implementation of the engineering controls and work 
practice controls including periodic leak detection surveys.
    (iii) Copies of the compliance plan required in paragraph (f)(2) of 
this section shall be furnished upon request for examination and 
copying to the Assistant Secretary, the Director, affected employees 
and designated employee representatives. Such plans shall be reviewed 
at least every 12 months, and shall be updated as necessary to reflect 
significant changes in the status of the employer's compliance program.
    (iv) The employer shall not implement a schedule of employee 
rotation as a means of compliance with the PELs.
    (g) Exposure Goal Program. (1) For those operations and job 
classifications where employee exposures are greater than the action 
level, in addition to compliance with the PELs, the employer shall have 
an exposure goal program that is intended to limit employee exposures 
to below the action level during normal operations.
    (2) Written plans for the exposure goal program shall be furnished 
upon request for examination and copying to the Assistant Secretary, 
the Director, affected employees and designated employee 
representatives.
    (3) Such plans shall be updated as necessary to reflect significant 
changes in the status of the exposure goal program.
    (4) Respirator use is not required in the exposure goal program.

[[Page 56834]]

    (5) The exposure goal program shall include the following items 
unless the employer can demonstrate that the item is not feasible, will 
have no significant effect in reducing employee exposures, or is not 
necessary to achieve exposures below the action level:
    (i) A leak prevention, detection, and repair program.
    (ii) A program for maintaining the effectiveness of local exhaust 
ventilation systems.
    (iii) The use of pump exposure control technology such as, but not 
limited to, mechanical double-sealed or seal-less pumps.
    (iv) Gauging devices designed to limit employee exposure, such as 
magnetic gauges on rail cars.
    (v) Unloading devices designed to limit employee exposure, such as 
a vapor return system.
    (vi) A program to maintain BD concentration below the action level 
in control rooms by use of engineering controls.
    (h) Respiratory protection.--(1) General. The employer shall 
provide respirators that comply with the requirements of this 
paragraph, at no cost to each affected employee, and ensure that each 
affected employee uses such respirator where required by this section. 
Respirators shall be used in the following circumstances:
    (i) During the time interval necessary to install or implement 
feasible engineering and work practice controls;
    (ii) In non-routine work operations which are performed 
infrequently and in which exposures are limited in duration.
    (iii) In work situations where feasible engineering controls and 
work practice controls are not yet sufficient to reduce exposures to or 
below the PELs; or
    (iv) In emergencies.
    (2) Respirator selection. (i) Where respirators are required, the 
employer shall select and provide the appropriate respirator as 
specified in Table 1 in paragraph (h)(5)(ii) of this section, and 
ensure its use.
    (ii) The employer shall select respirators from among those 
approved by the National Institute for Occupational Safety and Health 
(NIOSH) under the provisions of 42 CFR Part 84, ``Respiratory 
Protective Devices.'' Air purifying respirators shall have filter 
element(s) approved by NIOSH for organic vapors or BD.
    (iii) If an employee whose job requires the use of a respirator 
cannot use a negative pressure respirator, the employee must be 
provided with a respirator having less breathing resistance, such as a 
powered air-purifying respirator or supplied air respirator, if the 
employee is able to use it and if it will provide adequate protection.
    (3) Respirator program. Where respiratory protection is required, 
the employer shall institute a respirator program in accordance with 29 
CFR 1910.134.
    (4) Respirator use. (i) Where air-purifying respirators are used, 
the employer shall replace the air purifying filter element(s) 
according to the replacement life interval set for the class of 
respirator listed in Table 1 in paragraph (h)(5) of this section and at 
the beginning of each work shift.
    (ii) In lieu of the replacement intervals listed in Table 1, the 
employer may replace cartridges or canisters at 90% of the expiration 
of service life, provided the employer can demonstrate that employees 
will be adequately protected. BD breakthrough data relied upon by the 
employer must derive from tests conducted under worst case conditions 
of humidity, temperature, and air flow rate through the filter element. 
The employer shall describe the data supporting the cartridge/canister 
change schedule and the basis for reliance on the data in the 
employer's respirator program.
    (iii) A label shall be attached to the filter element(s) to 
indicate the date and time it is first installed on the respirator. If 
an employee detects the odor of BD, the employer shall replace the air-
purifying element(s) immediately.
    (iv) If a NIOSH-approved end of service life indicator (ESLI) for 
BD becomes available for an air-purifying filter element, the element 
may be used until such time as the indicator shows no further useful 
service life or until replaced at the beginning of the next work shift, 
whichever comes first. If an employee detects the odor of BD, the 
employer shall replace the air-purifying element(s) immediately.
    (v) The employer shall permit employees who wear respirators to 
leave the regulated area to wash their faces and respirator facepieces 
as necessary in order to prevent skin irritation associated with 
respirator use or to change the filter elements of air-purifying 
respirators whenever they detect a change in breathing resistance or 
whenever the odor of BD is detected.
    (5) Respirator fit testing. (i) The employer shall perform either 
qualitative fit testing (QLFT) or quantitative fit testing (QNFT), as 
required in Appendix E to this section, at the time of initial fitting 
and at least annually thereafter for employees who wear tight-fitting 
negative pressure respirators. Fit testing shall be used to select a 
respirator facepiece which exhibits minimum leakage and provides the 
required protection as prescribed in Table 1 in paragraph (h)(5)(ii) of 
this section.
    (ii) For each employee wearing a tight-fitting full facepiece 
negative pressure respirator who is exposed to airborne concentrations 
of BD that exceed 10 times the TWA PEL (10 ppm), the employer shall 
perform quantitative fit testing as required in Appendix E to this 
section, at the time of initial fitting and at least annually 
thereafter.

 Table 1.--Minimum Requirements for Respiratory Protection for Airborne 
                                   BD                                   
------------------------------------------------------------------------
Concentration of airborne BD (ppm)                                      
        or condition of use              Minimum required respirator    
------------------------------------------------------------------------
Less than or equal to 5 ppm (5      (a) Air-purifying half mask or full 
 times PEL).                         facepiece respirator equipped with 
                                     approved BD or organic vapor       
                                     cartridges or canisters. Cartridges
                                     or canisters shall be replaced     
                                     every 4 hours.                     
Less than or equal to 10 ppm (10    (a) Air-purifying half mask or full 
 times PEL).                         facepiece respirator equipped with 
                                     approved BD or organic vapor       
                                     cartridges or canisters. Cartridges
                                     or canisters shall be replaced     
                                     every 3 hours.                     
Less than or equal to 25 ppm (25    (a) Air-purifying full facepiece    
 times PEL).                         respirator equipped with approved  
                                     BD or organic vapor cartridges or  
                                     canisters. Cartridges or canisters 
                                     shall be replaced every 2 hours.   
                                    (b) Any powered air-purifying       
                                     respirator equipped with approved  
                                     BD or organic vapor cartridges.    
                                     PAPR cartridges shall be replaced  
                                     every 2 hours.                     
                                    (c) Continuous flow supplied air    
                                     respirator equipped with a hood or 
                                     helmet.                            
Less than or equal to 50 ppm (50    (a) Air-purifying full facepiece    
 times PEL).                         respirator equipped with approved  
                                     BD or organic vapor cartridges or  
                                     canisters. Cartridges or canisters 
                                     shall be replaced every (1) hour.  
                                    (b) Powered air-purifying respirator
                                     equipped with a tight-fitting      
                                     facepiece and an approved BD or    
                                     organic vapor cartridges. PAPR     
                                     cartridges shall be replaced every 
                                     (1) hour.                          

[[Page 56835]]

                                                                        
Less than or equal to 1,000 ppm     (a) Supplied air respirator equipped
 (1,000 times PEL).                  with a half mask of full facepiece 
                                     and operated in a pressure demand  
                                     or other positive pressure mode.   
Greater than 1000 ppm.............  (a) Self-contained breathing unknown
                                     concentration, or apparatus        
                                     equipped with a firefighting full  
                                     facepiece and operated in a        
                                     pressure demand or other positive  
                                     pressure mode.                     
                                    (b) Any supplied air respirator     
                                     equipped with a full facepiece and 
                                     operated in a pressure demand or   
                                     other positive pressure mode in    
                                     combination with an auxiliary self-
                                     contained breathing apparatus      
                                     operated in a pressure demand or   
                                     other positive pressure mode.      
Escape from IDLH conditions.......  (a) Any positive pressure self-     
                                     contained breathing apparatus with 
                                     an appropriate service life.       
                                    (b) A air-purifying full facepiece  
                                     respirator equipped with a front or
                                     back mounted BD or organic vapor   
                                     canister.                          
------------------------------------------------------------------------
Notes: Respirators approved for use in higher concentrations are        
  permitted to be used in lower concentrations. Full facepiece is       
  required when eye irritation is anticipated.                          

    (iii) The employer shall ensure that employees wearing tight 
fitting respirators perform a facepiece seal fit check to ensure that a 
proper facepiece seal is obtained prior to entry into a BD atmosphere. 
The recommended positive or negative pressure fit check procedures 
listed in Appendix E to this section or the respirator manufacturer's 
recommended fit check procedure shall be used.
    (i) Protective clothing and equipment. Where appropriate to prevent 
eye contact and limit dermal exposure to BD, the employer shall provide 
protective clothing and equipment at no cost to the employee and shall 
ensure its use. Eye and face protection shall meet the requirements of 
29 CFR 1910.133.
    (j) Emergency situations. Written plan. A written plan for 
emergency situations shall be developed, or an existing plan shall be 
modified, to contain the applicable elements specified in 29 CFR 
1910.38, ``Employee Emergency Plans and Fire Prevention Plans,'' and in 
29 CFR 1910.120 ``Hazardous Waste Operations and Emergency Responses,'' 
for each workplace where there is a possibility of an emergency.
    (k) Medical screening and surveillance.--(1) Employees covered. The 
employer shall institute a medical screening and surveillance program 
as specified in this paragraph for:
    (i) Each employee with exposure to BD at concentrations at or above 
the action level on 30 or more days or for employees who have or may 
have exposure to BD at or above the PELs on 10 or more days a year;
    (ii) Employers (including successor owners) shall continue to 
provide medical screening and surveillance for employees, even after 
transfer to a non-BD exposed job and regardless of when the employee is 
transferred, whose work histories suggest exposure to BD:
    (A) At or above the PELs on 30 or more days a year for 10 or more 
years;
    (B) At or above the action level on 60 or more days a year for 10 
or more years; or
    (C) Above 10 ppm on 30 or more days in any past year; and
    (iii) Each employee exposed to BD following an emergency situation.
    (2) Program administration. (i) The employer shall ensure that the 
health questionnaire, physical examination and medical procedures are 
provided without cost to the employee, without loss of pay, and at a 
reasonable time and place.
    (ii) Physical examinations, health questionnaires, and medical 
procedures shall be performed or administered by a physician or other 
licensed health care professional.
    (iii) Laboratory tests shall be conducted by an accredited 
laboratory.
    (3) Frequency of medical screening activities. The employer shall 
make medical screening available on the following schedule:
    (i) For each employee covered under paragraphs (j)(1) (i)-(ii) of 
this section, a health questionnaire and complete blood count with 
differential and platelet count (CBC) every year, and a physical 
examination as specified below:
    (A) An initial physical examination that meets the requirements of 
this rule, if twelve months or more have elapsed since the last 
physical examination conducted as part of a medical screening program 
for BD exposure;
    (B) Before assumption of duties by the employee in a job with BD 
exposure;
    (C) Every 3 years after the initial physical examination;
    (D) At the discretion of the physician or other licensed health 
care professional reviewing the annual health questionnaire and CBC;
    (E) At the time of employee reassignment to an area where exposure 
to BD is below the action level, if the employee's past exposure 
history does not meet the criteria of paragraph (j)(1)(ii) of this 
section for continued coverage in the screening and surveillance 
program, and if twelve months or more have elapsed since the last 
physical examination; and
    (F) At termination of employment if twelve months or more have 
elapsed since the last physical examination.
    (ii) Following an emergency situation, medical screening shall be 
conducted as quickly as possible, but not later than 48 hours after the 
exposure.
    (iii) For each employee who must wear a respirator, physical 
ability to perform the work and use the respirator must be determined 
as required by 29 CFR 1910.134.
    (4) Content of medical screening. (i) Medical screening for 
employees covered by paragraphs (j)(1) (i)-(ii) of this section shall 
include:
    (A) A baseline health questionnaire that includes a comprehensive 
occupational and health history and is updated annually. Particular 
emphasis shall be placed on the hematopoietic and reticuloendothelial 
systems, including exposure to chemicals, in addition to BD, that may 
have an adverse effect on these systems, the presence of signs and 
symptoms that might be related to disorders of these systems, and any 
other information determined by the examining physician or other 
licensed health care professional to be necessary to evaluate whether 
the employee is at increased risk of material impairment of health from 
BD exposure. Health questionnaires shall consist of the sample forms in 
Appendix C to this section, or be equivalent to those samples;
    (B) A complete physical examination, with special emphasis on the 
liver, spleen, lymph nodes, and skin;
    (C) A CBC; and
    (D) Any other test which the examining physician or other licensed 
health care professional deems necessary to evaluate whether the

[[Page 56836]]

employee may be at increased risk from exposure to BD.
    (ii) Medical screening for employees exposed to BD in an emergency 
situation shall focus on the acute effects of BD exposure and at a 
minimum include: A CBC within 48 hours of the exposure and then monthly 
for three months; and a physical examination if the employee reports 
irritation of the eyes, nose throat, lungs, or skin, blurred vision, 
coughing, drowsiness, nausea, or headache. Continued employee 
participation in the medical screening and surveillance program, beyond 
these minimum requirements, shall be at the discretion of the physician 
or other licensed health care professional.
    (5) Additional medical evaluations and referrals. (i) Where the 
results of medical screening indicate abnormalities of the 
hematopoietic or reticuloendothelial systems, for which a non-
occupational cause is not readily apparent, the examining physician or 
other licensed health care professional shall refer the employee to an 
appropriate specialist for further evaluation and shall make available 
to the specialist the results of the medical screening.
    (ii) The specialist to whom the employee is referred under this 
paragraph shall determine the appropriate content for the medical 
evaluation, e.g., examinations, diagnostic tests and procedures, etc.
    (6) Information provided to the physician or other licensed health 
care professional. The employer shall provide the following information 
to the examining physician or other licensed health care professional 
involved in the evaluation:
    (i) A copy of this section including its appendices;
    (ii) A description of the affected employee's duties as they relate 
to the employee's BD exposure;
    (iii) The employee's actual or representative BD exposure level 
during employment tenure, including exposure incurred in an emergency 
situation;
    (iv) A description of pertinent personal protective equipment used 
or to be used; and
    (v) Information, when available, from previous employment-related 
medical evaluations of the affected employee which is not otherwise 
available to the physician or other licensed health care professional 
or the specialist.
    (7) The written medical opinion. (i) For each medical evaluation 
required by this section, the employer shall ensure that the physician 
or other licensed health care professional produces a written opinion 
and provides a copy to the employer and the employee within 15 business 
days of the evaluation. The written opinion shall be limited to the 
following information:
    (A) The occupationally pertinent results of the medical evaluation;
    (B) A medical opinion concerning whether the employee has any 
detected medical conditions which would place the employee's health at 
increased risk of material impairment from exposure to BD;
    (C) Any recommended limitations upon the employee's exposure to BD; 
and
    (D) A statement that the employee has been informed of the results 
of the medical evaluation and any medical conditions resulting from BD 
exposure that require further explanation or treatment.
    (ii) The written medical opinion provided to the employer shall not 
reveal specific records, findings, and diagnoses that have no bearing 
on the employee's ability to work with BD.

    Note: However, this provision does not negate the ethical 
obligation of the physician or other licensed health care 
professional to transmit any other adverse findings directly to the 
employee.

    (8) Medical surveillance. (i) The employer shall ensure that 
information obtained from the medical screening program activities is 
aggregated (with all personal identifiers removed) and periodically 
reviewed, to ascertain whether the health of the employee population of 
that employer is adversely affected by exposure to BD.
    (ii) Information learned from medical surveillance activities must 
be disseminated to covered employees, as defined in paragraph (k)(1) of 
this section, in a manner that ensures the confidentiality of 
individual medical information.
    (l) Communication of BD hazards to employees.--(1) Hazard 
communication. The employer shall communicate the hazards associated 
with BD exposure in accordance with the requirements of the Hazard 
Communication Standard, 29 CFR 1910.1200, 29 CFR 1915.1200, and 29 CFR 
1926.59.
    (2) Employee information and training. (i) The employer shall 
provide all employees exposed to BD with information and training in 
accordance with the requirements of the Hazard Communication Standard, 
29 CFR 1910.1200, 29 CFR 1915.1200, and 29 CFR 1926.59.
    (ii) The employer shall institute a training program for all 
employees who are potentially exposed to BD at or above the action 
level or the STEL, ensure employee participation in the program and 
maintain a record of the contents of such program.
    (iii) Training shall be provided prior to or at the time of initial 
assignment to a job potentially involving exposure to BD at or above 
the action level or STEL and at least annually thereafter.
    (iv) The training program shall be conducted in a manner that the 
employee is able to understand. The employee shall ensure that each 
employee exposed to BD over the action level or STEL is informed of the 
following:
    (A) The health hazards associated with BD exposure, and the purpose 
and a description of the medical screening and surveillance program 
required by this section;
    (B) The quantity, location, manner of use, release, and storage of 
BD and the specific operations that could result in exposure to BD, 
especially exposures above the PEL or STEL;
    (C) The engineering controls and work practices associated with the 
employee's job assignment, and emergency procedures and personal 
protective equipment;
    (D) The measures employees can take to protect themselves from 
exposure to BD.
    (E) The contents of this standard and its appendices, and
    (F) The right of each employee exposed to BD at or above the action 
level or STEL to obtain:
    (1) medical examinations as required by paragraph (j) of this 
section at no cost to the employee;
    (2) the employee's medical records required to be maintained by 
paragraph (m)(4) of this section; and
    (3) all air monitoring results representing the employee's exposure 
to BD and required to be kept by paragraph (m)(2) of this section.
    (3) Access to information and training materials. (i) The employer 
shall make a copy of this standard and its appendices readily available 
without cost to all affected employees and their designated 
representatives and shall provide a copy if requested.
    (ii) The employer shall provide to the Assistant Secretary or the 
Director, or the designated employee representatives, upon request, all 
materials relating to the employee information and the training 
program.
    (m) Recordkeeping.--(1) Objective data for exemption from initial 
monitoring. (i) Where the processing, use, or handling of products or 
streams made from or containing BD are exempted from other requirements 
of this section under paragraph (a)(2) of this section, or where 
objective data have been relied on in lieu of initial

[[Page 56837]]

monitoring under paragraph (d)(2)(ii) of this section, the employer 
shall establish and maintain a record of the objective data reasonably 
relied upon in support of the exemption.
    (ii) This record shall include at least the following information:
    (A) The product or activity qualifying for exemption;
    (B) The source of the objective data;
    (C) The testing protocol, results of testing, and analysis of the 
material for the release of BD;
    (D) A description of the operation exempted and how the data 
support the exemption; and
    (E) Other data relevant to the operations, materials, processing, 
or employee exposures covered by the exemption.
    (iii) The employer shall maintain this record for the duration of 
the employer's reliance upon such objective data.
    (2) Exposure measurements. (i) The employer shall establish and 
maintain an accurate record of all measurements taken to monitor 
employee exposure to BD as prescribed in paragraph (d) of this section.
    (ii) The record shall include at least the following information:
    (A) The date of measurement;
    (B) The operation involving exposure to BD which is being 
monitored;
    (C) Sampling and analytical methods used and evidence of their 
accuracy;
    (D) Number, duration, and results of samples taken;
    (E) Type of protective devices worn, if any; and
    (F) Name, social security number and exposure of the employees 
whose exposures are represented.
    (G) The written corrective action and the schedule for completion 
of this action required by paragraph (d)(7)(ii) of this section.
    (iii) The employer shall maintain this record for at least 30 years 
in accordance with 29 CFR 1910.20.
    (3) Respirator Fit-test. (i) The employer shall establish a record 
of the fit tests administered to an employee including:
    (A) The name of the employee,
    (B) Type of respirator,
    (C) Brand and size of respirator,
    (D) Date of test, and
    (E) Where QNFT is used, the fit factor, strip chart recording or 
other recording of the results of the test.
    (ii) Fit test records shall be maintained for respirator users 
until the next fit test is administered.
    (4) Medical screening and surveillance. (i) The employer shall 
establish and maintain an accurate record for each employee subject to 
medical screening and surveillance under this section.
    (ii) The record shall include at least the following information:
    (A) The name and social security number of the employee;
    (B) Physician's or other licensed health care professional's 
written opinions as described in paragraph (k)(7) of this section;
    (C) A copy of the information provided to the physician or other 
licensed health care professional as required by paragraphs (k)(7)(ii)-
(iv) of this section.
    (iii) Medical screening and surveillance records shall be 
maintained for each employee for the duration of employment plus 30 
years, in accordance with 29 CFR 1910.20.
    (5) Availability. (i) The employer, upon written request, shall 
make all records required to be maintained by this section available 
for examination and copying to the Assistant Secretary and the 
Director.
    (ii) Access to records required to be maintained by paragraphs 
(l)(1)-(3) of this section shall be granted in accordance with 29 CFR 
1910.20(e).
    (6) Transfer of records. (i) Whenever the employer ceases to do 
business, the employer shall transfer records required by this section 
to the successor employer. The successor employer shall receive and 
maintain these records. If there is no successor employer, the employer 
shall notify the Director, at least three (3) months prior to disposal, 
and transmit them to the Director if requested by the Director within 
that period.
    (ii) The employer shall transfer medical and exposure records as 
set forth in 29 CFR 1910.20(h).
    (n) Dates.--(1) Effective date. This section shall become effective 
ninety (90) days after the date of publication in the Federal Register.
    (2) Start-up dates. (i) The initial monitoring required under 
paragraph (d)(2) of this section shall be completed within sixty (60) 
days of the effective date of this standard or the introduction of BD 
into the workplace.
    (ii) The requirements of paragraphs (c) through (m) of this 
section, including feasible work practice controls but not including 
engineering controls specified in paragraph (f)(1) of this section, 
shall be complied with within one-hundred and eighty (180) days after 
the effective date of this section.
    (iii) Engineering controls specified by paragraph (f)(1) of this 
section shall be implemented within two (2) years after the effective 
date of this section, and the exposure goal program specified in 
paragraph (g) of this section shall be implemented within three (3) 
years after the effective date of this section.
    (o) Appendices. (1) Appendix E to this section is mandatory.
    (2) Appendices A, B, C, D, and F to this section are informational 
and are not intended to create any additional obligations not otherwise 
imposed or to detract from any existing obligations.

Appendix A. Substance Safety Data Sheet For 1,3-Butadiene (Non-
Mandatory)

I. Substance Identification

    A. Substance: 1,3-Butadiene (CH2CH-
CHCH2).
    B. Synonyms: 1,3-Butadiene (BD); butadiene; biethylene; bi-
vinyl; divinyl; butadiene-1,3; buta-1,3-diene; erythrene; NCI-
C50602; CAS-106-99-0.
    C. BD can be found as a gas or liquid.
    D. BD is used in production of styrene-butadiene rubber and 
polybutadiene rubber for the tire industry. Other uses include 
copolymer latexes for carpet backing and paper coating, as well as 
resins and polymers for pipes and automobile and appliance parts. It 
is also used as an intermediate in the production of such chemicals 
as fungicides.
    E. Appearance and odor: BD is a colorless, non-corrosive, 
flammable gas with a mild aromatic odor at standard ambient 
temperature and pressure.
    F. Permissible exposure: Exposure may not exceed 1 part BD per 
million parts of air averaged over the 8-hour workday, nor may 
short-term exposure exceed 5 parts of BD per million parts of air 
averaged over any 15-minute period in the 8-hour workday.

II. Health Hazard Data

    A. BD can affect the body if the gas is inhaled or if the liquid 
form, which is very cold (cryogenic), comes in contact with the eyes 
or skin.
    B. Effects of overexposure: Breathing very high levels of BD for 
a short time can cause central nervous system effects, blurred 
vision, nausea, fatigue, headache, decreased blood pressure and 
pulse rate, and unconsciousness. There are no recorded cases of 
accidental exposures at high levels that have caused death in 
humans, but this could occur. Breathing lower levels of BD may cause 
irritation of the eyes, nose, and throat. Skin contact with 
liquefied BD can cause irritation and frostbite.
    C. Long-term (chronic) exposure: BD has been found to be a 
potent carcinogen in rodents, inducing neoplastic lesions at 
multiple target sites in mice and rats. A recent study of BD-exposed 
workers showed that exposed workers have an increased risk of 
developing leukemia. The risk of leukemia increases with increased 
exposure to BD. OSHA has concluded that there is strong evidence 
that workplace exposure to BD poses an increased risk of death from 
cancers of the lymphohematopoietic system.
    D. Reporting signs and symptoms: You should inform your 
supervisor if you develop any of these signs or symptoms and suspect 
that they are caused by exposure to BD.

III. Emergency First Aid Procedures

    In the event of an emergency, follow the emergency plan and 
procedures designated for your work area. If you have been trained

[[Page 56838]]

in first aid procedures, provide the necessary first aid measures. 
If necessary, call for additional assistance from co-workers and 
emergency medical personnel.
    A. Eye and Skin Exposures: If there is a potential that 
liquefied BD can come in contact with eye or skin, face shields and 
skin protective equipment must be provided and used. If liquefied BD 
comes in contact with the eye, immediately flush the eyes with large 
amounts of water, occasionally lifting the lower and the upper lids. 
Flush repeatedly. Get medical attention immediately. Contact lenses 
should not be worn when working with this chemical. In the event of 
skin contact, which can cause frostbite, remove any contaminated 
clothing and flush the affected area repeatedly with large amounts 
of tepid water.
    B. Breathing: If a person breathes in large amounts of BD, move 
the exposed person to fresh air at once. If breathing has stopped, 
begin cardiopulmonary resuscitation (CPR) if you have been trained 
in this procedure. Keep the affected person warm and at rest. Get 
medical attention immediately.
    C. Rescue: Move the affected person from the hazardous exposure. 
If the exposed person has been overcome, call for help and begin 
emergency rescue procedures. Use extreme caution so that you do not 
become a casualty. Understand the plant's emergency rescue 
procedures and know the locations of rescue equipment before the 
need arises.

IV. Respirators and Protective Clothing

    A. Respirators: Good industrial hygiene practices recommend that 
engineering and work practice controls be used to reduce 
environmental concentrations to the permissible exposure level. 
However, there are some exceptions where respirators may be used to 
control exposure. Respirators may be used when engineering and work 
practice controls are not technically feasible, when such controls 
are in the process of being installed, or when these controls fail 
and need to be supplemented or during brief, non-routine, 
intermittent exposure. Respirators may also be used in situations 
involving non-routine work operations which are performed 
infrequently and in which exposures are limited in duration, and in 
emergency situations. In some instances cartridge respirator use is 
allowed, but only with strict time constraints. For example, at 
exposure below 5 ppm BD, a cartridge (or canister) respirator, 
either full or half face, may be used, but the cartridge must be 
replaced at least every 4 hours, and it must be replaced every 3 
hours when the exposure is between 5 and 10 ppm. If the use of 
respirators is necessary, the only respirators permitted are those 
that have been approved by the National Institute for Occupational 
Safety and Health (NIOSH). In addition to respirator selection, a 
complete respiratory protection program must be instituted which 
includes regular training, maintenance, fit testing, inspection, 
cleaning, and evaluation of respirators. If you can smell BD while 
wearing a respirator, proceed immediately to fresh air, and change 
cartridge (or canister) before re-entering an area where there is BD 
exposure. If you experience difficulty in breathing while wearing a 
respirator, tell your supervisor.
    B. Protective Clothing: Employees should be provided with and 
required to use impervious clothing, gloves, face shields (eight-
inch minimum), and other appropriate protective clothing necessary 
to prevent the skin from becoming frozen by contact with liquefied 
BD (or a vessel containing liquid BD).
    Employees should be provided with and required to use splash-
proof safety goggles where liquefied BD may contact the eyes.

V. Precautions for Safe Use, Handling, and Storage

    A. Fire and Explosion Hazards: BD is a flammable gas and can 
easily form explosive mixtures in air. It has a lower explosive 
limit of 2%, and an upper explosive limit of 11.5%. It has an 
autoignition temperature of 420 deg. C (788 deg. F). Its vapor is 
heavier than air (vapor density, 1.9) and may travel a considerable 
distance to a source of ignition and flash back. Usually it contains 
inhibitors to prevent self-polymerization (which is accompanied by 
evolution of heat) and to prevent formation of explosive peroxides. 
At elevated temperatures, such as in fire conditions, polymerization 
may take place. If the polymerization takes place in a container, 
there is a possibility of violent rupture of the container.
    B. Hazard: Slightly toxic. Slight respiratory irritant. Direct 
contact of liquefied BD on skin may cause freeze burns and 
frostbite.
    C. Storage: Protect against physical damage to BD containers. 
Outside or detached storage of BD containers is preferred. Inside 
storage should be in a cool, dry, well-ventilated, noncombustible 
location, away from all possible sources of ignition. Store 
cylinders vertically and do not stack. Do not store with oxidizing 
material.
    D. Usual Shipping Containers: Liquefied BD is contained in steel 
pressure apparatus.
    E. Electrical Equipment: Electrical installations in Class I 
hazardous locations, as defined in Article 500 of the National 
Electrical Code, should be in accordance with Article 501 of the 
Code. If explosion-proof electrical equipment is necessary, it shall 
be suitable for use in Group B. Group D equipment may be used if 
such equipment is isolated in accordance with Section 501-5(a) by 
sealing all conduit \1/2\- inch size or larger. See Venting of 
Deflagrations (NFPA No. 68, 1994), National Electrical Code (NFPA 
No. 70, 1996 ), Static Electricity (NFPA No. 77, 1993), Lightning 
Protection Systems (NFPA No. 780, 1995), and Fire Hazard Properties 
of Flammable Liquids, Gases and Volatile Solids (NFPA No. 325, 
1994).
    F. Fire Fighting: Stop flow of gas. Use water to keep fire-
exposed containers cool. Fire extinguishers and quick drenching 
facilities must be readily available, and you should know where they 
are and how to operate them.
    G. Spill and Leak: Persons not wearing protective equipment and 
clothing should be restricted from areas of spills or leaks until 
clean-up has been completed. If BD is spilled or leaked, the 
following steps should be taken:
    1. Eliminate all ignition sources.
    2. Ventilate area of spill or leak.
    3. If in liquid form, for small quantities, allow to evaporate 
in a safe manner.
    4. Stop or control the leak if this can be done without risk. If 
source of leak is a cylinder and the leak cannot be stopped in 
place, remove the leaking cylinder to a safe place and repair the 
leak or allow the cylinder to empty.
    H. Disposal: This substance, when discarded or disposed of, is a 
hazardous waste according to Federal regulations (40 CFR part 261). 
It is listed as hazardous waste number D001 due to its ignitability. 
The transportation, storage, treatment, and disposal of this waste 
material must be conducted in compliance with 40 CFR parts 262, 263, 
264, 268 and 270. Disposal can occur only in properly permitted 
facilities. Check state and local regulation of any additional 
requirements as these may be more restrictive than federal laws and 
regulation.
    I. You should not keep food, beverages, or smoking materials in 
areas where there is BD exposure, nor should you eat or drink in 
such areas.
    J. Ask your supervisor where BD is used in your work area and 
ask for any additional plant safety and health rules.

VI. Medical Requirements

    Your employer is required to offer you the opportunity to 
participate in a medical screening and surveillance program if you 
are exposed to BD at concentrations exceeding the action level (0.5 
ppm BD as an 8-hour TWA) on 30 days or more a year, or at or above 
the 8 hr TWA (1 ppm) or STEL (5 ppm for 15 minutes) on 10 days or 
more a year. Exposure for any part of a day counts. If you have had 
exposure to BD in the past, but have been transferred to another 
job, you may still be eligible to participate in the medical 
screening and surveillance program. The OSHA rule specifies the past 
exposures that would qualify you for participation in the program. 
These past exposure are work histories that suggest the following: 
(1) That you have been exposed at or above the PELs on 30 days a 
year for 10 or more years; (2) that you have been exposed at or 
above the action level on 60 days a year for 10 or more years; or 
(3) that you have been exposed above 10 ppm on 30 days in any past 
year. Additionally, if you are exposed to BD in an emergency 
situation, you are eligible for a medical examination within 48 
hours. The basic medical screening program includes a health 
questionnaire, physical examination, and blood test. These medical 
evaluations must be offered to you at a reasonable time and place, 
and without cost or loss of pay.

VII. Observation of Monitoring

    Your employer is required to perform measurements that are 
representative of your exposure to BD and you or your designated 
representative are entitled to observe the monitoring procedure. You 
are entitled to observe the steps taken in the measurement 
procedure, and to record the results obtained. When the monitoring 
procedure is taking place in an area where respirators or personal 
protective clothing and equipment are required to be worn, you or 
your representative must also be provided with,

[[Page 56839]]

and must wear, the protective clothing and equipment.

VIII. Access to Information

    A. Each year, your employer is required to inform you of the 
information contained in this appendix. In addition, your employer 
must instruct you in the proper work practices for using BD, 
emergency procedures, and the correct use of protective equipment.
    B. Your employer is required to determine whether you are being 
exposed to BD. You or your representative has the right to observe 
employee measurements and to record the results obtained. Your 
employer is required to inform you of your exposure. If your 
employer determines that you are being overexposed, he or she is 
required to inform you of the actions which are being taken to 
reduce your exposure to within permissible exposure limits and of 
the schedule to implement these actions.
    C. Your employer is required to keep records of your exposures 
and medical examinations. These records must be kept by the employer 
for at least thirty (30) years.
    D. Your employer is required to release your exposure and 
medical records to you or your representative upon your request.

Appendix B. Substance Technical Guidelines for 1,3-Butadiene (Non-
Mandatory)

I. Physical and Chemical Data

    A. Substance identification:
    1. Synonyms: 1,3-Butadiene (BD); butadiene; biethylene; bivinyl; 
divinyl; butadiene-1,3; buta-1,3-diene; erythrene; NCI-C50620; CAS-
106-99-0.
    2. Formula: CH2CH-CHCH2.
    3. Molecular weight: 54.1.
    B. Physical data:
    1. Boiling point (760 mm Hg): -4.7  deg.C (23.5  deg.F).
    2. Specific gravity (water=1): 0.62 at 20  deg.C (68  deg.F).
    3. Vapor density (air=1 at boiling point of BD): 1.87.
    4. Vapor pressure at 20  deg.C (68  deg.F): 910 mm Hg.
    5. Solubility in water, g/100 g water at 20  deg.C (68  deg.F): 
0.05.
    6. Appearance and odor: Colorless, flammable gas with a mildly 
aromatic odor. Liquefied BD is a colorless liquid with a mildly 
aromatic odor.

II. Fire, Explosion, and Reactivity Hazard Data

    A. Fire:
    1. Flash point: -76  deg.C (-105  deg.F) for take out; liquefied 
BD; Not applicable to BD gas.
    2. Stability: A stabilizer is added to the monomer to inhibit 
formation of polymer during storage. Forms explosive peroxides in 
air in absence of inhibitor.
    3. Flammable limits in air, percent by volume: Lower: 2.0; 
Upper: 11.5.
    4. Extinguishing media: Carbon dioxide for small fires, polymer 
or alcohol foams for large fires.
    5. Special fire fighting procedures: Fight fire from protected 
location or maximum possible distance. Stop flow of gas before 
extinguishing fire. Use water spray to keep fire-exposed cylinders 
cool.
    6. Unusual fire and explosion hazards: BD vapors are heavier 
than air and may travel to a source of ignition and flash back. 
Closed containers may rupture violently when heated.
    7. For purposes of compliance with the requirements of 29 CFR 
1910.106, BD is classified as a flammable gas. For example, 7,500 
ppm, approximately one-fourth of the lower flammable limit, would be 
considered to pose a potential fire and explosion hazard.
    8. For purposes of compliance with 29 CFR 1910.155, BD is 
classified as a Class B fire hazard.
    9. For purposes of compliance with 29 CFR 1910.307, locations 
classified as hazardous due to the presence of BD shall be Class I.
    B. Reactivity:
    1. Conditions contributing to instability: Heat. Peroxides are 
formed when inhibitor concentration is not maintained at proper 
level. At elevated temperatures, such as in fire conditions, 
polymerization may take place.
    2. Incompatibilities: Contact with strong oxidizing agents may 
cause fires and explosions. The contacting of crude BD (not BD 
monomer) with copper and copper alloys may cause formations of 
explosive copper compounds.
    3. Hazardous decomposition products: Toxic gases (such as carbon 
monoxide) may be released in a fire involving BD.
    4. Special precautions: BD will attack some forms of plastics, 
rubber, and coatings. BD in storage should be checked for proper 
inhibitor content, for self-polymerization, and for formation of 
peroxides when in contact with air and iron. Piping carrying BD may 
become plugged by formation of rubbery polymer.
    C. Warning Properties:
    1. Odor Threshold: An odor threshold of 0.45 ppm has been 
reported in The American Industrial Hygiene Association (AIHA) 
Report, Odor Thresholds for Chemicals with Established Occupational 
Health Standards. (Ex. 32-28C)
    2. Eye Irritation Level: Workers exposed to vapors of BD 
(concentration or purity unspecified) have complained of irritation 
of eyes, nasal passages, throat, and lungs. Dogs and rabbits exposed 
experimentally to as much as 6700 ppm for 7\1/2\ hours a day for 8 
months have developed no histologically demonstrable abnormality of 
the eyes.
    3. Evaluation of Warning Properties: Since the mean odor 
threshold is about half of the 1 ppm PEL, and more than 10-fold 
below the 5 ppm STEL, most wearers of air purifying respirators 
should still be able to detect breakthrough before a significant 
overexposure to BD occurs.

III. Spill, Leak, and Disposal Procedures

    A. Persons not wearing protective equipment and clothing should 
be restricted from areas of spills or leaks until cleanup has been 
completed. If BD is spilled or leaked, the following steps should be 
taken:
    1. Eliminate all ignition sources.
    2. Ventilate areas of spill or leak.
    3. If in liquid form, for small quantities, allow to evaporate 
in a safe manner.
    4. Stop or control the leak if this can be done without risk. If 
source of leak is a cylinder and the leak cannot be stopped in 
place, remove the leaking cylinder to a safe place and repair the 
leak or allow the cylinder to empty.
    B. Disposal: This substance, when discarded or disposed of, is a 
hazardous waste according to Federal regulations (40 CFR part 261). 
It is listed by the EPA as hazardous waste number D001 due to its 
ignitability. The transportation, storage, treatment, and disposal 
of this waste material must be conducted in compliance with 40 CFR 
parts 262, 263, 264, 268 and 270. Disposal can occur only in 
properly permitted facilities. Check state and local regulations for 
any additional requirements because these may be more restrictive 
than federal laws and regulations.

IV. Monitoring and Measurement Procedures

    A. Exposure above the Permissible Exposure Limit (8-hr TWA) or 
Short-Term Exposure Limit (STEL):
    1. 8-hr TWA exposure evaluation: Measurements taken for the 
purpose of determining employee exposure under this standard are 
best taken with consecutive samples covering the full shift. Air 
samples must be taken in the employee's breathing zone (air that 
would most nearly represent that inhaled by the employee).
    2. STEL exposure evaluation: Measurements must represent 15 
minute exposures associated with operations most likely to exceed 
the STEL in each job and on each shift.
    3. Monitoring frequencies: Table 1 gives various exposure 
scenarios and their required monitoring frequencies, as required by 
the final standard for occupational exposure to butadiene.

    Table 1.--Five Exposure Scenarios and Their Associated Monitoring   
                               Frequencies                              
------------------------------------------------------------------------
 Action    8-hr                                                         
  level     TWA    STEL            Required monitoring activity         
------------------------------------------------------------------------
-*......      -       -   No 8-hr TWA or STEL monitoring required.      
+*......      -       -   No STEL monitoring required. Monitor 8-hr TWA 
                           annually.                                    
+.......      +       -   No STEL monitoring required. Periodic         
                           monitoring 8-hr TWA, in accordance with      
                           (d)(3)(ii).**                                
+.......      +       +   Periodic monitoring 8-hr TWA, in accordance   
                           with (d)(3)(ii)**. Periodic monitoring STEL, 
                           in accordance with (d)(3)(iii).              

[[Page 56840]]

                                                                        
+.......      -       +   Periodic monitoring STEL, in accordance with  
                           (d)(3)(iii). Monitor 8-hr TWA, annually.     
------------------------------------------------------------------------
* Exposure Scenario, Limit Exceeded: + = Yes, -= No.                    
** The employer may decrease the frequency of exposure monitoring to    
  annually when at least 2 consecutive measurements taken at least 7    
  days apart show exposures to be below the 8 hr TWA, but at or above   
  the action level.                                                     

    4. Monitoring techniques: Appendix D describes the validated 
method of sampling and analysis which has been tested by OSHA for 
use with BD. The employer has the obligation of selecting a 
monitoring method which meets the accuracy and precision 
requirements of the standard under his or her unique field 
conditions. The standard requires that the method of monitoring must 
be accurate, to a 95 percent confidence level, to plus or minus 25 
percent for concentrations of BD at or above 1 ppm, and to plus or 
minus 35 percent for concentrations below 1 ppm.

V. Personal Protective Equipment

    A. Employees should be provided with and required to use 
impervious clothing, gloves, face shields (eight-inch minimum), and 
other appropriate protective clothing necessary to prevent the skin 
from becoming frozen from contact with liquid BD.
    B. Any clothing which becomes wet with liquid BD should be 
removed immediately and not re-worn until the butadiene has 
evaporated.
    C. Employees should be provided with and required to use splash 
proof safety goggles where liquid BD may contact the eyes.

VI. Housekeeping and Hygiene Facilities

    For purposes of complying with 29 CFR 1910.141, the following 
items should be emphasized:
    A. The workplace should be kept clean, orderly, and in a 
sanitary condition.
    B. Adequate washing facilities with hot and cold water are to be 
provided and maintained in a sanitary condition.

VII. Additional Precautions

    A. Store BD in tightly closed containers in a cool, well-
ventilated area and take all necessary precautions to avoid any 
explosion hazard.
    B. Non-sparking tools must be used to open and close metal 
containers. These containers must be effectively grounded.
    C. Do not incinerate BD cartridges, tanks or other containers.
    D. Employers must advise employees of all areas and operations 
where exposure to BD might occur.

Appendix C. Medical Screening and Surveillance for 1,3-Butadiene (Non-
Mandatory)

I. Basis for Medical Screening and Surveillance Requirements

A. Route of Entry Inhalation

B. Toxicology

    Inhalation of BD has been linked to an increased risk of cancer, 
damage to the reproductive organs, and fetotoxicity. Butadiene can 
be converted via oxidation to epoxybutene and diepoxybutane, two 
genotoxic metabolites that may play a role in the expression of BD's 
toxic effects.
    BD has been tested for carcinogenicity in mice and rats. Both 
species responded to BD exposure by developing cancer at multiple 
primary organ sites. Early deaths in mice were caused by malignant 
lymphomas, primarily lymphocytic type, originating in the thymus.
    Mice exposed to BD have developed ovarian or testicular atrophy. 
Sperm head morphology tests also revealed abnormal sperm in mice 
exposed to BD; lethal mutations were found in a dominant lethal 
test. In light of these results in animals, the possibility that BD 
may adversely affect the reproductive systems of male and female 
workers must be considered.
    Additionally, anemia has been observed in animals exposed to 
butadiene. In some cases, this anemia appeared to be a primary 
response to exposure; in other cases, it may have been secondary to 
a neoplastic response.

C. Epidemiology

    Epidemiologic evidence demonstrates that BD exposure poses an 
increased risk of leukemia. Mild alterations of hematologic 
parameters have also been observed in synthetic rubber workers 
exposed to BD.

II. Potential Adverse Health Effects

A. Acute

    Skin contact with liquid BD causes characteristic burns or 
frostbite. BD is gaseous form can irritate the eyes, nasal passages, 
throat, and lungs. Blurred vision, coughing, and drowsiness may also 
occur. Effects are mild at 2,000 ppm and pronounced at 8,000 ppm for 
exposures occurring over the full workshift.
    At very high concentrations in air, BD is an anesthetic, causing 
narcosis, respiratory paralysis, unconsciousness, and death. Such 
concentrations are unlikely, however, except in an extreme emergency 
because BD poses an explosion hazard at these levels.

B. Chronic

    The principal adverse health effects of concern are BD-induced 
lymphoma, leukemia and potential reproductive toxicity. Anemia and 
other changes in the peripheral blood cells may be indicators of 
excessive exposure to BD.

C. Reproductive

    Workers may be concerned about the possibility that their BD 
exposure may be affecting their ability to procreate a healthy 
child. For workers with high exposures to BD, especially those who 
have experienced difficulties in conceiving, miscarriages, or 
stillbirths, appropriate medical and laboratory evaluation of 
fertility may be necessary to determine if BD is having any adverse 
effect on the reproductive system or on the health of the fetus.

III. Medical Screening Components At-A-Glance

A. Health Questionnaire

    The most important goal of the health questionnaire is to elicit 
information from the worker regarding potential signs or symptoms 
generally related to leukemia or other blood abnormalities. 
Therefore, physicians or other licensed health care professionals 
should be aware of the presenting symptoms and signs of 
lymphohematopoietic disorders and cancers, as well as the procedures 
necessary to confirm or exclude such diagnoses. Additionally, the 
health questionnaire will assist with the identification of workers 
at greatest risk of developing leukemia or adverse reproductive 
effects from their exposures to BD.
    Workers with a history of reproductive difficulties or a 
personal or family history of immune deficiency syndromes, blood 
dyscrasias, lymphoma, or leukemia, and those who are or have been 
exposed to medicinal drugs or chemicals known to affect the 
hematopoietic or lymphatic systems may be at higher risk from their 
exposure to BD. After the initial administration, the health 
questionnaire must be updated annually.

B. Complete Blood Count (CBC)

    The medical screening and surveillance program requires an 
annual CBC, with differential and platelet count, to be provided for 
each employee with BD exposure. This test is to be performed on a 
blood sample obtained by phlebotomy of the venous system or, if 
technically feasible, from a fingerstick sample of capillary blood. 
The sample is to be analyzed by an accredited laboratory.
    Abnormalities in a CBC may be due to a number of different 
etiologies. The concern for workers exposed to BD includes, but is 
not limited to, timely identification of lymphohematopoietic 
cancers, such as leukemia and non-Hodgkin's lymphoma. Abnormalities 
of portions of the CBC are identified by comparing an individual's 
results to those of an established range of normal values for males 
and females. A substantial change in any individual employee's CBC 
may also be viewed as ``abnormal'' for that individual even if all 
measurements fall within the population-based range of normal 
values. It is suggested that a flowsheet for laboratory values be 
included in each employee's medical record so that comparisons and 
trends in annual CBCs can be easily made.
    A determination of the clinical significance of an abnormal CBC 
shall be the responsibility of the examining physician, other 
licensed health care professional, or medical specialist to whom the 
employee is referred. Ideally, an abnormal CBC should be compared to 
previous CBC measurements for the same employee, when available. 
Clinical common sense may dictate that a CBC value

[[Page 56841]]

that is very slightly outside the normal range does not warrant 
medical concern. A CBC abnormality may also be the result of a 
temporary physical stressor, such as a transient viral illness, 
blood donation, or menorrhagia, or laboratory error. In these cases, 
the CBC should be repeated in a timely fashion, i.e., within 6 
weeks, to verify that return to the normal range has occurred. A 
clinically significant abnormal CBC should result in removal of the 
employee from further exposure to BD. Transfer of the employee to 
other work duties in a BD-free environment would be the preferred 
recommendation.

C. Physical Examination

    The medical screening and surveillance program requires an 
initial physical examination for workers exposed to BD; this 
examination is repeated once every three years. The initial physical 
examination should assess each worker's baseline general health and 
rule out clinical signs of medical conditions that may be caused by 
or aggravated by occupational BD exposure. The physical examination 
should be directed at identification of signs of lymphohematopoietic 
disorders, including lymph node enlargement, splenomegaly, and 
hepatomegaly.
    Repeated physical examinations should update objective clinical 
findings that could be indicative of interim development of a 
lymphohematopoietic disorder, such as lymphoma, leukemia, or other 
blood abnormality. Physical examinations may also be provided on an 
as needed basis in order to follow up on a positive answer on the 
health questionnaire, or in response to an abnormal CBC. Physical 
examination of workers who will no longer be working in jobs with BD 
exposure are intended to rule out lymphohematopoietic disorders.
    The need for physical examinations for workers concerned about 
adverse reproductive effects from their exposure to BD should be 
identified by the physician or other licensed health care 
professional and provided accordingly. For these workers, such 
consultations and examinations may relate to developmental toxicity 
and reproductive capacity.
    Physical examination of workers acutely exposed to significant 
levels of BD should be especially directed at the respiratory 
system, eyes, sinuses, skin, nervous system, and any region 
associated with particular complaints. If the worker has received a 
severe acute exposure, hospitalization may be required to assure 
proper medical management. Since this type of exposure may place 
workers at greater risk of blood abnormalities, a CBC must be 
obtained within 48 hours and repeated at one, two, and three months.

Appendix D: Sampling and Analytical Method for 1,3-Butadiene (Non-
Mandatory)

    OSHA Method No.: 56.
    Matrix:  Air.
    Target concentration:  1 ppm (2.21 mg/m\3\)
    Procedure: Air samples are collected by drawing known volumes of 
air through sampling tubes containing charcoal adsorbent which has 
been coated with 4-tert-butylcatechol. The samples are desorbed with 
carbon disulfide and then analyzed by gas chromatography using a 
flame ionization detector.
    Recommended sampling rate and air volume: 0.05 L/min and 3 L.
    Detection limit of the overall procedure: 90 ppb (200 ug/m \3\) 
(based on 3 L air volume).
    Reliable quantitation limit: 155 ppb (343 ug/m \3\) (based on 3 
L air volume).
    Standard error of estimate at the target concentration: 6.5%.
    Special requirements: The sampling tubes must be coated with 4-
tert-butylcatechol. Collected samples should be stored in a freezer.
    Status of method: A sampling and analytical method has been 
subjected to the established evaluation procedures of the Organic 
Methods Evaluation Branch, OSHA Analytical Laboratory, Salt Lake 
City, Utah 84165.

1.  Background

    This work was undertaken to develop a sampling and analytical 
procedure for BD at 1 ppm. The current method recommended by OSHA 
for collecting BD uses activated coconut shell charcoal as the 
sampling medium (Ref. 5.2). This method was found to be inadequate 
for use at low BD levels because of sample instability.
    The stability of samples has been significantly improved through 
the use of a specially cleaned charcoal which is coated with 4-tert-
butylcatechol (TBC). TBC is a polymerization inhibitor for BD (Ref. 
5.3).

1.1.1  Toxic effects

    Symptoms of human exposure to BD include irritation of the eyes, 
nose and throat. It can also cause coughing, drowsiness and fatigue. 
Dermatitis and frostbite can result from skin exposure to liquid BD. 
(Ref. 5.1)
    NIOSH recommends that BD be handled in the workplace as a 
potential occupational carcinogen. This recommendation is based on 
two inhalation studies that resulted in cancers at multiple sites in 
rats and in mice. BD has also demonstrated mutagenic activity in the 
presence of a liver microsomal activating system. It has also been 
reported to have adverse reproductive effects. (Ref. 5.1)

1.1.2.  Potential workplace exposure

    About 90% of the annual production of BD is used to manufacture 
styrene-butadiene rubber and Polybutadiene rubber. Other uses 
include: Polychloroprene rubber, acrylonitrile butadiene-stryene 
resins, nylon intermediates, styrene-butadiene latexes, butadiene 
polymers, thermoplastic elastomers, nitrile resins, methyl 
methacrylate-butadiene styrene resins and chemical intermediates. 
(Ref. 5.1)

1.1.3.  Physical properties (Ref. 5.1)

    CAS No.: 106-99-0
    Molecular weight: 54.1
    Appearance: Colorless gas
    Boiling point: -4.41  deg.C (760 mm Hg)
    Freezing point: -108.9  deg.C
    Vapor pressure: 2 atm @ 15.3  deg.C; 5 atm @ 47  deg.C
    Explosive limits: 2 to 11.5% (by volume in air)
    Odor threshold: 0.45 ppm
    Structural formula: H2C:CHCH:CH2
    Synonyms: BD; biethylene; bivinyl; butadiene; divinyl; buta-1,3-
diene; alpha-gamma-butadiene; erythrene; NCI-C50602; pyrrolylene; 
vinylethylene.

1.2.  Limit defining parameters

    The analyte air concentrations listed throughout this method are 
based on an air volume of 3 L and a desorption volume of 1 mL. Air 
concentrations listed in ppm are referenced to 25  deg.C and 760 mm 
Hg.

1.2.1.  Detection limit of the analytical procedure

    The detection limit of the analytical procedure was 304 pg per 
injection. This was the amount of BD which gave a response relative 
to the interferences present in a standard.

1.2.2.  Detection limit of the overall procedure

    The detection limit of the overall procedure was 0.60 g 
per sample (90 ppb or 200 g/m3). This amount was 
determined graphically. It was the amount of analyte which, when 
spiked on the sampling device, would allow recovery approximately 
equal to the detection limit of the analytical procedure.

1.2.3.  Reliable quantitation limit

    The reliable quantitation limit was 1.03 g per sample 
(155 ppb or 343 g/m3). This was the smallest amount of 
analyte which could be quantitated within the limits of a recovery 
of at least 75% and a precision (1.96 SD) of 
25% or better.

1.2.4.  Sensitivity 1
---------------------------------------------------------------------------

    \1\ The reliable quantitation limit and detection limits 
reported in the method are based upon optimization of the instrument 
for the smallest possible amount of analyte. When the target 
concentration of an analyte is exceptionally higher than these 
limits, they may not be attainable at the routine operation 
parameters.
---------------------------------------------------------------------------

    The sensitivity of the analytical procedure over a concentration 
range representing 0.6 to 2 times the target concentration, based on 
the recommended air volume, was 387 area units per g/mL. 
This value was determined from the slope of the calibration curve. 
The sensitivity may vary with the particular instrument used in the 
analysis.

1.2.5.  Recovery

    The recovery of BD from samples used in storage tests remained 
above 77% when the samples were stored at ambient temperature and 
above 94% when the samples were stored at refrigerated temperature. 
These values were determined from regression lines which were 
calculated from the storage data. The recovery of the analyte from 
the collection device must be at least 75% following storage.

1.2.6.  Precision (analytical method only)

    The pooled coefficient of variation obtained from replicate 
determinations of analytical standards over the range of 0.6 to 2 
times the target concentration was 0.011.

1.2.7.  Precision (overall procedure)

    The precision at the 95% confidence level for the refrigerated 
temperature storage test

[[Page 56842]]

was 12.7%. This value includes an additional 
5% for sampling error. The overall procedure must 
provide results at the target concentrations that are 
25% at the 95% confidence level.

1.2.8.  Reproducibility

    Samples collected from a controlled test atmosphere and a draft 
copy of this procedure were given to a chemist unassociated with 
this evaluation. The average recovery was 97.2% and the standard 
deviation was 6.2%.

2. Sampling procedure

2.1.  Apparatus

    2.1.1.  Samples are collected by use of a personal sampling pump 
that can be calibrated to within 5% of the recommended 
0.05 L/min sampling rate with the sampling tube in line.
    2.1.2.  Samples are collected with laboratory prepared sampling 
tubes. The sampling tube is constructed of silane-treated glass and 
is about 5-cm long. The ID is 4 mm and the OD is 6 mm. One end of 
the tube is tapered so that a glass wool end plug will hold the 
contents of the tube in place during sampling. The opening in the 
tapered end of the sampling tube is at least one-half the ID of the 
tube (2 mm). The other end of the sampling tube is open to its full 
4-mm ID to facilitate packing of the tube. Both ends of the tube are 
fire-polished for safety. The tube is packed with 2 sections of 
pretreated charcoal which has been coated with TBC. The tube is 
packed with a 50-mg backup section, located nearest the tapered end, 
and with a 100-mg sampling section of charcoal. The two sections of 
coated adsorbent are separated and retained with small plugs of 
silanized glass wool. Following packing, the sampling tubes are 
sealed with two \7/32\ inch OD plastic end caps. Instructions for 
the pretreatment and coating of the charcoal are presented in 
Section 4.1 of this method.

2.2.  Reagents

    None required.

2.3.  Technique

    2.3.1.  Properly label the sampling tube before sampling and 
then remove the plastic end caps.
    2.3.2.  Attach the sampling tube to the pump using a section of 
flexible plastic tubing such that the larger front section of the 
sampling tube is exposed directly to the atmosphere. Do not place 
any tubing ahead of the sampling tube. The sampling tube should be 
attached in the worker's breathing zone in a vertical manner such 
that it does not impede work performance.
    2.3.3.  After sampling for the appropriate time, remove the 
sampling tube from the pump and then seal the tube with plastic end 
caps. Wrap the tube lengthwise.
    2.3.4.  Include at least one blank for each sampling set. The 
blank should be handled in the same manner as the samples with the 
exception that air is not drawn through it.
    2.3.5.  List any potential interferences on the sample data 
sheet.
    2.3.6.  The samples require no special shipping precautions 
under normal conditions. The samples should be refrigerated if they 
are to be exposed to higher than normal ambient temperatures. If the 
samples are to be stored before they are shipped to the laboratory, 
they should be kept in a freezer. The samples should be placed in a 
freezer upon receipt at the laboratory.

2.4.  Breakthrough

    (Breakthrough was defined as the relative amount of analyte 
found on the backup section of the tube in relation to the total 
amount of analyte collected on the sampling tube. Five-percent 
breakthrough occurred after sampling a test atmosphere containing 
2.0 ppm BD for 90 min at 0.05 L/min. At the end of this time 4.5 L 
of air had been sampled and 20.1 g of the analyte was 
collected. The relative humidity of the sampled air was 80% at 23 
deg.C.)
    Breakthrough studies have shown that the recommended sampling 
procedure can be used at air concentrations higher than the target 
concentration. The sampling time, however, should be reduced to 45 
min if both the expected BD level and the relative humidity of the 
sampled air are high.

2.5.  Desorption efficiency

    The average desorption efficiency for BD from TBC coated 
charcoal over the range from 0.6 to 2 times the target concentration 
was 96.4%. The efficiency was essentially constant over the range 
studied.

2.6.  Recommended air volume and sampling rate

    2.6.1.  The recommended air volume is 3L.
    2.6.2.  The recommended sampling rate is 0.05 L/min for 1 hour.

2.7.  Interferences

    There are no known interferences to the sampling method.

2.8.  Safety precautions

    2.8.1.  Attach the sampling equipment to the worker in such a 
manner that it will not interfere with work performance or safety.
    2.8.2.  Follow all safety practices that apply to the work area 
being sampled.

3.  Analytical procedure

3.1.  Apparatus

    3.1.1.  A gas chromatograph (GC), equipped with a flame 
ionization detector (FID).2
---------------------------------------------------------------------------

    \2\ A Hewlett-Packard Model 5840A GC was used for this 
evaluation. Injections were performed using a Hewlett-Packard Model 
7671A automatic sampler.
---------------------------------------------------------------------------

    3.1.2.  A GC column capable of resolving the analytes from any 
interference.3
---------------------------------------------------------------------------

    \3\ A 20-ft x \1/8\-inch OD stainless steel GC column containing 
20% FFAP on 80/100 mesh Chromabsorb W-AW-DMCS was used for this 
evaluation.
---------------------------------------------------------------------------

    3.1.3.  Vials, glass 2-mL with Teflon-lined caps.
    3.1.4.  Disposable Pasteur-type pipets, volumetric flasks, 
pipets and syringes for preparing samples and standards, making 
dilutions and performing injections.

3.2.  Reagents

    3.2.1.  Carbon disulfide.4
---------------------------------------------------------------------------

    \4\ Fisher Scientific Company A.C.S. Reagent Grade solvent was 
used in this evaluation.
---------------------------------------------------------------------------

    The benzene contaminant that was present in the carbon disulfide 
was used as an internal standard (ISTD) in this evaluation.
    3.2.2.  Nitrogen, hydrogen and air, GC grade.
    3.2.3.  BD of known high purity.5
---------------------------------------------------------------------------

    \5\ Matheson Gas Products, CP Grade 1,3-butadiene was used in 
this study.
---------------------------------------------------------------------------

3.3.  Standard preparation

    3.3.1.  Prepare standards by diluting known volumes of BD gas 
with carbon disulfide. This can be accomplished by injecting the 
appropriate volume of BD into the headspace above the 1-mL of carbon 
disulfide contained in sealed 2-mL vial. Shake the vial after the 
needle is removed from the septum.6
---------------------------------------------------------------------------

    \6\ A standard containing 7.71 g/mL (at ambient 
temperature and pressure) was prepared by diluting 4 L of 
the gas with 1-mL of carbon disulfide.
---------------------------------------------------------------------------

    3.3.2.  The mass of BD gas used to prepare standards can be 
determined by use of the following equations:

MV=(760/BP)(273+t)/(273)(22.41)

Where:

MV=ambient molar volume
BP=ambient barometric pressure
T=ambient temperature
g/L=54.09/MV
g/standard=(g/L)(L) BD used to 
prepare the standard

3.4.  Sample preparation

    3.4.1.  Transfer the 100-mg section of the sampling tube to a 2-
mL vial. Place the 50-mg section in a separate vial. If the glass 
wool plugs contain a significant amount of charcoal, place them with 
the appropriate sampling tube section.
    3.4.2.  Add 1-mL of carbon disulfide to each vial.
    3.4.3.  Seal the vials with Teflon-lined caps and then allow 
them to desorb for one hour. Shake the vials by hand vigorously 
several times during the desorption period.
    3.4.4.  If it is not possible to analyze the samples within 4 
hours, separate the carbon disulfide from the charcoal, using a 
disposable Pasteur-type pipet, following the one hour. This 
separation will improve the stability of desorbed samples.
    3.4.5.  Save the used sampling tubes to be cleaned and repacked 
with fresh adsorbent.

3.5.  Analysis

    3.5.1.  GC Conditions
    Column temperature: 95  deg.C
    Injector temperature: 180  deg.C
    Detector temperature: 275  deg.C
    Carrier gas flow rate: 30 mL/min
    Injection volume: 0.80 L
    GC column: 20-ft x \1/8\-in OD stainless steel GC column 
containing 20%
    FFAP on 80/100 Chromabsorb W-AW-DMCS.
    3.5.2.  Chromatogram. See Section 4.2.
    3.5.3.  Use a suitable method, such as electronic or peak 
heights, to measure detector response.

[[Page 56843]]

    3.5.4.  Prepare a calibration curve using several standard 
solutions of different concentrations. Prepare the calibration curve 
daily. Program the integrator to report the results in g/
mL.
    3.5.5.  Bracket sample concentrations with standards.

3.6.  Interferences (analytical)

    3.6.1.  Any compound with the same general retention time as the 
analyte and which also gives a detector response is a potential 
interference. Possible interferences should be reported by the 
industrial hygienist to the laboratory with submitted samples.
    3.6.2.  GC parameters (temperature, column, etc.) may be changed 
to circumvent interferences.
    3.6.3.  A useful means of structure designation is GC/MS. It is 
recommended that this procedure be used to confirm samples whenever 
possible.

3.7.  Calculations

    3.7.1.  Results are obtained by use of calibration curves. 
Calibration curves are prepared by plotting detector response 
against concentration for each standard. The best line through the 
data points is determined by curve fitting.
    3.7.2.  The concentration, in ug/mL, for a particular sample is 
determined by comparing its detector response to the calibration 
curve. If any analyte is found on the backup section, this amount is 
added to the amount found on the front section. Blank corrections 
should be performed before adding the results together.
    3.7.3.  The BD air concentration can be expressed using the 
following equation:

mg/m \3\=(A)(B)/(C)(D)

Where:

A=g/mL from Section 3.7.2
B=volume
C=L of air sampled
D=efficiency

    3.7.4.  The following equation can be used to convert results in 
mg/m \3\ to ppm:
ppm=(mg/m \3\)(24.46)/54.09

Where:

mg/m \3\=result from Section 3.7.3.
24.46=molar volume of an ideal gas at 760 mm Hg and 25 deg.C.

3.8.  Safety precautions (analytical)

    3.8.1.  Avoid skin contact and inhalation of all chemicals.
    3.8.2.  Restrict the use of all chemicals to a fume hood 
whenever possible.
    3.8.3.  Wear safety glasses and a lab coat in all laboratory 
areas.

4.  Additional Information

4.1.  A procedure to prepare specially cleaned charcoal coated with 
TBC

    4.1.1.  Apparatus.
    4.1.1.1.  Magnetic stirrer and stir bar.
    4.1.1.2.  Tube furnace capable of maintaining a temperature of 
700 deg.C and equipped with a quartz tube that can hold 30 g of 
charcoal.8
---------------------------------------------------------------------------

     8 A Lindberg Type 55035 Tube furnace was used in this 
evaluation.
---------------------------------------------------------------------------

    4.1.1.3.  A means to purge nitrogen gas through the charcoal 
inside the quartz tube.
    4.1.1.4.  Water bath capable of maintaining a temperature of 
60 deg.C.
    4.1.1.5.  Miscellaneous laboratory equipment: One-liter vacuum 
flask, 1-L Erlenmeyer flask, 350-M1 Buchner funnel with a coarse 
fitted disc, 4-oz brown bottle, rubber stopper, Teflon tape etc.

4.1.2.  Reagents

    4.1.2.1.  Phosphoric acid, 10% by weight, in water.9
---------------------------------------------------------------------------

     9  Baker Analyzed'' Reagent grade was diluted with water for 
use in this evaluation.
---------------------------------------------------------------------------

    4.1.2.2.  4-tert-Butylcatechol (TBC).10
---------------------------------------------------------------------------

     10  The Aldrich Chemical Company 99% grade was used in this 
evaluation.
---------------------------------------------------------------------------

    4.1.2.3.  Specially cleaned coconut shell charcoal, 20/40 
mesh.11
---------------------------------------------------------------------------

     11  Specially cleaned charcoal was obtained from Supelco, Inc. 
for use in this evaluation. The cleaning process used by Supelco is 
proprietary.
---------------------------------------------------------------------------

    4.1.2.4.  Nitrogen gas, GC grade.
    4.1.3.  Procedure.
    Weigh 30g of charcoal into a 500-mL Erlenmeyer flask. Add about 
250 mL of 10% phosphoric acid to the flask and then swirl the 
mixture. Stir the mixture for 1 hour using a magnetic stirrer. 
Filter the mixture using a fitted Buchner funnel. Wash the charcoal 
several times with 250-mL portions of deionized water to remove all 
traces of the acid. Transfer the washed charcoal to the tube furnace 
quartz tube. Place the quartz tube in the furnace and then connect 
the nitrogen gas purge to the tube. Fire the charcoal to 700  deg.C. 
Maintain that temperature for at least 1 hour. After the charcoal 
has cooled to room temperature, transfer it to a tared beaker. 
Determine the weight of the charcoal and then add an amount of TBC 
which is 10% of the charcoal, by weight.
    CAUTION-TBC is toxic and should only be handled in a fume hood 
while wearing gloves.
    Carefully mix the contents of the beaker and then transfer the 
mixture to a 4-oz bottle. Stopper the bottle with a clean rubber 
stopper which has been wrapped with Teflon tape. Clamp the bottle in 
a water bath so that the water level is above the charcoal level. 
Gently heat the bath to 60  deg.C and then maintain that temperature 
for 1 hour. Cool the charcoal to room temperature and then transfer 
the coated charcoal to a suitable container.
    The coated charcoal is now ready to be packed into sampling 
tubes. The sampling tubes should be stored in a sealed container to 
prevent contamination. Sampling tubes should be stored in the dark 
at room temperature. The sampling tubes should be segregated by 
coated adsorbent lot number.

4.2 Chromatograms

    The chromatograms were obtained using the recommended analytical 
method. The chart speed was set at 1 cm/min for the first three min 
and then at 0.2 cm/min for the time remaining in the analysis.
    The peak which elutes just before BD is a reaction product 
between an impurity on the charcoal and TBC. This peak is always 
present, but it is easily resolved from the analyte. The peak which 
elutes immediately before benzene is an oxidation product of TBC.

5. References

    5.1.  ``Current Intelligence Bulletin 41, 1,3-Butadiene'', U.S. 
Dept. of Health and Human Services, Public Health Service, Center 
for Disease Control, NIOSH.
    5.2.  ``NIOSH Manual of Analytical Methods'', 2nd ed; U.S. Dept. 
of Health Education and Welfare, National Institute for Occupational 
Safety and Health: Cincinnati, OH. 1977, Vol. 2, Method No. S91 DHEW 
(NIOSH) Publ. (US), No. 77-157-B.
    5.3.  Hawley, G.C., Ed. ``The Condensed Chemical Dictionary'', 
8th ed.; Van Nostrand Rienhold Company: New York, 1971; 139.5.4. 
Chem. Eng. News (June 10, 1985), (63), 22-66.

Appendix E: Respirator Fit Testing Procedures (Mandatory)

A. The Employer Shall Conduct Fit Testing Using the Following 
Procedures

    These provisions apply to both QLFT and QNFT
    1. The test subject shall be allowed to pick the most 
comfortable respirator from a selection of respirators of various 
sizes and models.
    2. Prior to the selection process, the test subject shall be 
shown how to put on a respirator, how it should be positioned on the 
face, how to set strap tension and how to determine a comfortable 
fit. A mirror shall be available to assist the subject in evaluating 
the fit and positioning the respirator. This instruction may not 
constitute the subject's formal training on respirator use, because 
it is only a review.
    3. The test subject shall be informed that he/she is being asked 
to select the respirator which provides the most comfortable fit. 
Each respirator represents a different size and shape, and if fitted 
and used properly, will provide adequate protection.
    4. The test subject shall be instructed to hold each chosen 
facepiece up to the face and eliminate those which obviously do not 
give a comfortable fit.
    5. The more comfortable facepieces are noted; the most 
comfortable mask is donned and worn at least five minutes to assess 
comfort. Assistance in assessing comfort can be given by discussing 
the points in item 6 below. If the test subject is not familiar with 
using a particular respirator, the test subject shall be directed to 
don the mask several times and to adjust the straps each time to 
become adept at setting proper tension on the straps.
    6. Assessment of comfort shall include reviewing the following 
points with the test subject and allowing the test subject adequate 
time to determine the comfort of the respirator:
    (a) Position of the mask on the nose.
    (b) Room for eye protection.
    (c) Room to talk.
    (d) Position of mask on face and cheeks.
    7. The following criteria shall be used to help determine the 
adequacy of the respirator fit:
    (a) Chin properly placed;
    (b) Adequate strap tension, not overly tightened;

[[Page 56844]]

    (c) Fit across nose bridge;
    (d) Respirator of proper size to span distance from nose to 
chin;
    (e) Tendency of respirator to slip;
    (f) Self-observation in mirror to evaluate fit and respirator 
position.
    8. The test subject shall conduct the negative and positive 
pressure fit checks using procedures in Appendix A or those 
recommended by the respirator manufacturer. Before conducting the 
negative or positive pressure fit checks, the subject shall be told 
to seat the mask on the face by moving the head from side-to-side 
and up and down slowly while taking in a few slow deep breaths. 
Another facepiece shall be selected and retested if the test subject 
fails the fit check tests.
    9. The test shall not be conducted if there is any hair growth 
between the skin and the facepiece sealing surface, such as stubble 
beard growth, beard, or sideburns which cross the respirator sealing 
surface. Any type of apparel which interferes with a satisfactory 
fit shall be altered or removed.
    10. If a test subject exhibits difficulty in breathing during 
the tests, she or he shall be referred to a physician to determine 
whether the test subject can wear a respirator while performing her 
or his duties.
    11. If the employee finds the fit of the respirator 
unacceptable, the test subject shall be given the opportunity to 
select a different respirator and to be retested.
    12. Exercise regimen. Prior to the commencement of the fit test, 
the test subject shall be given a description of the fit test and 
the test subject's responsibilities during the test procedure. The 
description of the process shall include a description of the test 
exercises that the subject will be performing. The respirator to be 
tested shall be worn for at least 5 minutes before the start of the 
fit test.
    13. Test Exercises. The test subject shall perform exercises, in 
the test environment, while wearing any applicable safety equipment 
that may be worn during actual respirator use which could interfere 
with fit, in the manner described below:
    (a) Normal breathing. In a normal standing position, without 
talking, the subject shall breathe normally.
    (b) Deep breathing. In a normal standing position, the subject 
shall breathe slowly and deeply, taking caution so as to not 
hyperventilate.
    (c) Turning head side to side. Standing in place, the subject 
shall slowly turn his/her head from side to side between the extreme 
positions on each side. The head shall be held at each extreme 
momentarily so the subject can inhale at each side.
    (d) Moving head up and down. Standing in place, the subject 
shall slowly move his/her head up and down. The subject shall be 
instructed to inhale in the up position (i.e., when looking toward 
the ceiling).
    (e) Talking. The subject shall talk out loud slowly and loud 
enough so as to be heard clearly by the test conductor. The subject 
can read from a prepared text such as the Rainbow Passage, count 
backward from 100, or recite a memorized poem or song.

Rainbow Passage

When the sunlight strikes raindrops in the air, they act like a 
prism and form a rainbow. The rainbow is a division of white light 
into many beautiful colors. These take the shape of a long round 
arch, with its path high above, and its two ends apparently beyond 
the horizon. There is, according to legend, a boiling pot of gold at 
one end. People look, but no one ever finds it. When a man looks for 
something beyond reach, his friends say he is looking for the pot of 
gold at the end of the rainbow.

    (f) Grimace. The test subject shall grimace by smiling or 
frowning. (Only for QNFT testing, not performed for QLFT)
    (g) Bending over. The test subject shall bend at the waist as if 
he/she were to touch his/her toes. Jogging in place shall be 
substituted for this exercise in those test environments such as 
shroud type QNFT units which prohibit bending at the waist.
    (h) Normal breathing. Same as exercise (a). Each test exercise 
shall be performed for one minute except for the grimace exercise 
which shall be performed for 15 seconds.
    The test subject shall be questioned by the test conductor 
regarding the comfort of the respirator upon completion of the 
protocol. If it has become uncomfortable, another model of 
respirator shall be tried.

B. Qualitative Fit Test (QLFT) Protocols

1. General

    (a) The employer shall assign specific individuals who shall 
assume full responsibility for implementing the respirator 
qualitative fit test program.
    (b) The employer shall ensure that persons administering QLFT 
are able to prepare test solutions, calibrate equipment and perform 
tests properly, recognize invalid tests, and assure that test 
equipment is in proper working order.
    (c) The employer shall assure that QLFT equipment is kept clean 
and well maintained so as to operate within the parameters for which 
it was designed.

2. Isoamyl Acetate Protocol

    (a) Odor threshold screening.
    The odor threshold screening test, performed without wearing a 
respirator, is intended to determine if the individual tested can 
detect the odor of isoamyl acetate.
    (1) Three 1 liter glass jars with metal lids are required.
    (2) Odor free water (e.g. distilled or spring water) at 
approximately 25 degrees C shall be used for the solutions.
    (3) The isoamyl acetate (IAA) (also known at isopentyl acetate) 
stock solution is prepared by adding 1 cc of pure IAA to 800 cc of 
odor free water in a 1 liter jar and shaking for 30 seconds. A new 
solution shall be prepared at least weekly.
    (4) The screening test shall be conducted in a room separate 
from the room used for actual fit testing. The two rooms shall be 
well ventilated to prevent the odor of IAA from becoming evident in 
the general room air where testing takes place.
    (5) The odor test solution is prepared in a second jar by 
placing 0.4 cc of the stock solution into 500 cc of odor free water 
using a clean dropper or pipette. The solution shall be shaken for 
30 seconds and allowed to stand for two to three minutes so that the 
IAA concentration above the liquid may reach equilibrium. This 
solution shall be used for only one day.
    (6) A test blank shall be prepared in a third jar by adding 500 
cc of odor free water.
    (7) The odor test and test blank jars shall be labeled 1 and 2 
for jar identification. Labels shall be placed on the lids so they 
can be periodically peeled off and switched to maintain the 
integrity of the test.
    (8) The following instruction shall be typed on a card and 
placed on the table in front of the two test jars (i.e., 1 and 2): 
``The purpose of this test is to determine if you can smell banana 
oil at a low concentration. The two bottles in front of you contain 
water. One of these bottles also contains a small amount of banana 
oil. Be sure the covers are on tight, then shake each bottle for two 
seconds. Unscrew the lid of each bottle, one at a time, and sniff at 
the mouth of the bottle. Indicate to the test conductor which bottle 
contains banana oil.''
    (9) The mixtures used in the IAA odor detection test shall be 
prepared in an area separate from where the test is performed, in 
order to prevent olfactory fatigue in the subject.
    (10) If the test subject is unable to correctly identify the jar 
containing the odor test solution, the IAA qualitative fit test 
shall not be performed.
    (11) If the test subject correctly identifies the jar containing 
the odor test solution, the test subject may proceed to respirator 
selection and fit testing.
    (b) Isoamyl acetate fit test
    (1) The fit test chamber shall be similar to a clear 55-gallon 
drum liner suspended inverted over a 2-foot diameter frame so that 
the top of the chamber is about 6 inches above the test subject's 
head. The inside top center of the chamber shall have a small hook 
attached.
    (2) Each respirator used for the fitting and fit testing shall 
be equipped with organic vapor cartridges or offer protection 
against organic vapors.
    (3) After selecting, donning, and properly adjusting a 
respirator, the test subject shall wear it to the fit testing room. 
This room shall be separate from the room used for odor threshold 
screening and respirator selection, and shall be well ventilated, as 
by an exhaust fan or lab hood, to prevent general room 
contamination.
    (4) A copy of the test exercises and any prepared text from 
which the subject is to read shall be taped to the inside of the 
test chamber.
    (5) Upon entering the test chamber, the test subject shall be 
given a 6-inch by 5-inch piece of paper towel, or other porous, 
absorbent, single-ply material, folded in half and wetted with 0.75 
cc of pure IAA. The test subject shall hang the wet towel on the 
hook at the top of the chamber.
    (6) Allow two minutes for the IAA test concentration to 
stabilize before starting the fit test exercises. This would be an 
appropriate time to talk with the test subject; to explain the fit 
test, the importance of his/her cooperation, and the purpose for the 
test

[[Page 56845]]

exercises; or to demonstrate some of the exercises.
    (7) If at any time during the test, the subject detects the 
banana like odor of IAA, the test is failed. The subject shall 
quickly exit from the test chamber and leave the test area to avoid 
olfactory fatigue.
    (8) If the test is failed, the subject shall return to the 
selection room and remove the respirator. The test subject shall 
repeat the odor sensitivity test, select and put on another 
respirator, return to the test area and again begin the fit test 
procedure described in (1) through (7) above. The process continues 
until a respirator that fits well has been found. Should the odor 
sensitivity test be failed, the subject shall wait about 5 minutes 
before retesting. Odor sensitivity will usually have returned by 
this time.
    (9) When the subject wearing the respirator passes the test, its 
efficiency shall be demonstrated for the subject by having the 
subject break the face seal and take a breath before exiting the 
chamber.
    (10) When the test subject leaves the chamber, the subject shall 
remove the saturated towel and return it to the person conducting 
the test, so there is no significant IAA concentration buildup in 
the chamber during subsequent tests. The used towels shall be kept 
in a self sealing bag to keep the test area from being contaminated.

3. Saccharin Solution Aerosol Protocol

    The entire screening and testing procedure shall be explained to 
the test subject prior to the conduct of the screening test.
    (a) Taste threshold screening. The saccharin taste threshold 
screening, performed without wearing a respirator, is intended to 
determine whether the individual being tested can detect the taste 
of saccharin.
    (1) During threshold screening as well as during fit testing, 
subjects shall wear an enclosure about the head and shoulders that 
is approximately 12 inches in diameter by 14 inches tall with at 
least the front portion clear and that allows free movements of the 
head when a respirator is worn. An enclosure substantially similar 
to the 3M hood assembly, parts # FT 14 and # FT 15 combined, is 
adequate.
    (2) The test enclosure shall have a \3/4\-inch hole in front of 
the test subject's nose and mouth area to accommodate the nebulizer 
nozzle.
    (3) The test subject shall don the test enclosure. Throughout 
the threshold screening test, the test subject shall breathe through 
his/her slightly open mouth with tongue extended.
    (4) Using a DeVilbiss Model 40 Inhalation Medication Nebulizer 
or equivalent the test conductor shall spray the threshold check 
solution into the enclosure. This nebulizer shall be clearly marked 
to distinguish it from the fit test solution nebulizer.
    (5) The threshold check solution consists of 0.83 grams of 
sodium saccharin USP in 100 ml of warm water. It can be prepared by 
putting 1 ml of the fit test solution (see (b)(5) below) in 100 ml 
of distilled water.
    (6) To produce the aerosol, the nebulizer bulb is firmly 
squeezed so that it collapses completely, then released and allowed 
to fully expand.
    (7) Ten squeezes are repeated rapidly and then the test subject 
is asked whether the saccharin can be tasted.
    (8) If the first response is negative, ten more squeezes are 
repeated rapidly and the test subject is again asked whether the 
saccharin is tasted.
    (9) If the second response is negative, ten more squeezes are 
repeated rapidly and the test subject is again asked whether the 
saccharin is tasted.
    (10) The test conductor will take note of the number of squeezes 
required to solicit a taste response.
    (11) If the saccharin is not tasted after 30 squeezes (step 10), 
the test subject may not perform the saccharin fit test.
    (12) If a taste response is elicited, the test subject shall be 
asked to take note of the taste for reference in the fit test.
    (13) Correct use of the nebulizer means that approximately 1 ml 
of liquid is used at a time in the nebulizer body.
    (14) The nebulizer shall be thoroughly rinsed in water, shaken 
dry, and refilled at least each morning and afternoon or at least 
every four hours.
    (b) Saccharin solution aerosol fit test procedure
    (1) The test subject may not eat, drink (except plain water), 
smoke, or chew gum for 15 minutes before the test.
    (2) The fit test uses the same enclosure described in (a) above.
    (3) The test subject shall don the enclosure while wearing the 
respirator selected in section (a) above. The respirator shall be 
properly adjusted and equipped with a particulate filter(s).
    (4) A second DeVilbiss Model 40 Inhalation Medication Nebulizer 
or equivalent is used to spray the fit test solution into the 
enclosure. This nebulizer shall be clearly marked to distinguish it 
from the screening test solution nebulizer.
    (5) The fit test solution is prepared by adding 83 grams of 
sodium saccharin to 100 ml of warm water.
    (6) As before, the test subject shall breathe through the 
slightly open mouth with tongue extended.
    (7) The nebulizer is inserted into the hole in the front of the 
enclosure and the fit test solution is sprayed into the enclosure 
using the same number of squeezes required to elicit a taste 
response in the screening test. A minimum of 10 squeezes is 
required.
    (8) After generating the aerosol the test subject shall be 
instructed to perform the exercises in section I. A. 13 above.
    (9) Every 30 seconds the aerosol concentration shall be 
replenished using one half the number of squeezes as initially.
    (10) The test subject shall indicate to the test conductor if at 
any time during the fit test the taste of saccharin is detected.
    (11) If the taste of saccharin is detected, the fit is deemed 
unsatisfactory and a different respirator shall be tried.

4. Irritant Fume Protocol

    (a) The respirator to be tested shall be equipped with high-
efficiency particulate air (HEPA) filters.
    (b) No form of test enclosure or hood for the test subject shall 
be used.
    (c) The test subject shall be allowed to smell a weak 
concentration of the irritant smoke before the respirator is donned 
to become familiar with its irritating properties.
    (d) Break both ends of a ventilation smoke tube containing 
stannic chloride. Attach one end of the smoke tube to an aspirator 
squeeze bulb and cover the other end with a short piece of tubing to 
prevent potential injury from the jagged end of the smoke tube.
    (d) Advise the test subject that the smoke can be irritating to 
the eyes and instruct the subject to keep his/her eyes closed while 
the test is performed.
    (e) The test conductor shall direct the stream of irritant smoke 
from the smoke tube towards the face seal area of the test subject. 
He/She shall begin at least 12 inches from the facepiece and 
gradually move to within one inch, moving around the whole perimeter 
of the mask.
    (f) The exercises identified in section I. A. 13 above shall be 
performed by the test subject while the respirator seal is being 
challenged by the smoke.
    (g) Each test subject passing the smoke test without evidence of 
a response (involuntary cough) shall be given a sensitivity check of 
the smoke from the same tube once the respirator has been removed to 
determine whether he/she reacts to the smoke. Failure to evoke a 
response shall void the fit test.
    (h) The fit test shall be performed in a location with exhaust 
ventilation sufficient to prevent general contamination of the 
testing area by the test agent.

C. Quantitative Fit Test (QNFT) Protocols

    The following quantitative fit testing procedures have been 
demonstrated to be acceptable.
    (1) Quantitative fit testing using a non-hazardous challenge 
aerosol (such as corn oil or sodium chloride) generated in a test 
chamber, and employing instrumentation to quantify the fit of the 
respirator.
    (2) Quantitative fit testing using ambient aerosol as the 
challenge agent and appropriate instrumentation (condensation nuclei 
counter) to quantify the respirator fit.
    (3) Quantitative fit testing using controlled negative pressure 
and appropriate instrumentation to measure the volumetric leak rate 
of a facepiece to quantify the respirator fit.

1. General

    (a) The employer shall assign specific individuals who shall 
assume full responsibility for implementing the respirator 
quantitative fit test program.
    (b) The employer shall ensure that persons administering QNFT 
are able to calibrate equipment and perform tests properly, 
recognize invalid tests, calculate fit factors properly and assure 
that test equipment is in proper working order.
    (c) The employer shall assure that QNFT equipment is kept clean, 
maintained and calibrated according to the manufacturer's 
instructions so as to operate at the parameters for which it was 
designed.

[[Page 56846]]

2. Generated aerosol quantitative fit testing protocol

Apparatus

    (a) Instrumentation. Aerosol generation, dilution, and 
measurement systems using particulates (corn oil or sodium chloride) 
or gases or vapors as test aerosols shall be used for quantitative 
fit testing.
    (b) Test chamber. The test chamber shall be large enough to 
permit all test subjects to perform freely all required exercises 
without disturbing the challenge agent concentration or the 
measurement apparatus. The test chamber shall be equipped and 
constructed so that the challenge agent is effectively isolated from 
the ambient air, yet uniform in concentration throughout the 
chamber.
    (c) When testing air-purifying respirators, the normal filter or 
cartridge element shall be replaced with a high-efficiency 
particulate air (HEPA) filter supplied by the same manufacturer in 
the case of particulate QNFT aerosols or a sorbent offering 
contaminant penetration protection equivalent to high-efficiency 
filters where the QNFT test agent is a gas or vapor.
    (d) The sampling instrument shall be selected so that a computer 
record or strip chart record may be made of the test showing the 
rise and fall of the challenge agent concentration with each 
inspiration and expiration at fit factors of at least 2,000. 
Integrators or computers which integrate the amount of test agent 
penetration leakage into the respirator for each exercise may be 
used provided a record of the readings is made.
    (e) The combination of substitute air-purifying elements, 
challenge agent and challenge agent concentration shall be such that 
the test subject is not exposed in excess of an established exposure 
limit for the challenge agent at any time during the testing process 
based upon the length of the exposure and the exposure limit 
duration.
    (f) The sampling port on the test specimen respirator shall be 
placed and constructed so that no leakage occurs around the port 
(e.g. where the respirator is probed), a free air flow is allowed 
into the sampling line at all times and so that there is no 
interference with the fit or performance of the respirator. The in-
mask sampling device (probe) shall be designed and used so that the 
air sample is drawn from the breathing zone of the test subject, 
midway between the nose and mouth and with the probe extending into 
the facepiece cavity at least \1/4\ inch.
    (g) The test set up shall permit the person administering the 
test to observe the test subject inside the chamber during the test.
    (h) The equipment generating the challenge atmosphere shall 
maintain the concentration of challenge agent constant to within a 
10 percent variation for the duration of the test.
    (I) The time lag (interval between an event and the recording of 
the event on the strip chart or computer or integrator) shall be 
kept to a minimum. There shall be a clear association between the 
occurrence of an event and its being recorded.
    (j) The sampling line tubing for the test chamber atmosphere and 
for the respirator sampling port shall be of equal diameter and of 
the same material. The length of the two lines shall be equal.
    (k) The exhaust flow from the test chamber shall pass through a 
high-efficiency filter before release.
    (l) When sodium chloride aerosol is used, the relative humidity 
inside the test chamber shall not exceed 50 percent.

    (m) The limitations of instrument detection shall be taken into 
account when determining the fit factor.
    (n) Test respirators shall be maintained in proper working order 
and inspected for deficiencies such as cracks, missing valves and 
gaskets, etc.

4. Procedural Requirements

    (a) When performing the initial positive or negative pressure 
fit check the sampling line shall be crimped closed in order to 
avoid air pressure leakage during either of these fit checks.
    (b) The use of an abbreviated screening QLFT test is optional 
and may be utilized in order to quickly identify poor fitting 
respirators which passed the positive and/or negative pressure test 
and thus reduce the amount of QNFT time. The use of the CNC QNFT 
instrument in the count mode is another optional method to use to 
obtain a quick estimate of fit and eliminate poor fitting 
respirators before going on to perform a full QNFT.
    (c) A reasonably stable challenge agent concentration shall be 
measured in the test chamber prior to testing. For canopy or shower 
curtain type of test units the determination of the challenge agent 
stability may be established after the test subject has entered the 
test environment.
    (d) Immediately after the subject enters the test chamber, the 
challenge agent concentration inside the respirator shall be 
measured to ensure that the peak penetration does not exceed 5 
percent for a half mask or 1 percent for a full facepiece 
respirator.
    (e) A stable challenge concentration shall be obtained prior to 
the actual start of testing.
    (f) Respirator restraining straps shall not be over tightened 
for testing. The straps shall be adjusted by the wearer without 
assistance from other persons to give a reasonably comfortable fit 
typical of normal use.
    (g) The test shall be terminated whenever any single peak 
penetration exceeds 5 percent for half masks and 1 percent for full 
facepiece respirators. The test subject shall be refitted and 
retested.
    (I) Calculation of fit factors.
    (1) The fit factor shall be determined for the quantitative fit 
test by taking the ratio of the average chamber concentration to the 
concentration measured inside the respirator for each test exercise 
except the grimace exercise.
    (2) The average test chamber concentration shall be calculated 
as the arithmetic average of the concentration measured before and 
after each test (i.e. 8 exercises) or the arithmetic average of the 
concentration measured before and after each exercise or the true 
average measured continuously during the respirator sample.
    (3) The concentration of the challenge agent inside the 
respirator shall be determined by one of the following methods:
    (i) Average peak penetration method means the method of 
determining test agent penetration into the respirator utilizing a 
strip chart recorder, integrator, or computer. The agent penetration 
is determined by an average of the peak heights on the graph or by 
computer integration, for each exercise except the grimace exercise. 
Integrators or computers which calculate the actual test agent 
penetration into the respirator for each exercise will also be 
considered to meet the requirements of the average peak penetration 
method. .
    (ii) Maximum peak penetration method means the method of 
determining test agent penetration in the respirator as determined 
by strip chart recordings of the test. The highest peak penetration 
for a given exercise is taken to be representative of average 
penetration into the respirator for that exercise.
    (iii) Integration by calculation of the area under the 
individual peak for each exercise except the grimace exercise. This 
includes computerized integration.
    (iv) The calculation of the overall fit factor using individual 
exercise fit factors involves first converting the exercise fit 
factors to penetration values, determining the average, and then 
converting that result back to a fit factor. This procedure is 
described in the following equation:
[GRAPHIC] [TIFF OMITTED] TR04NO96.002

Where ff1, ff2, ff3, etc. are the fit factors for 
exercise 1,2,3, etc. [Results of the grimace exercise (7) are not 
used in this calculation.]

    (j) The test subject shall not be permitted to wear a half mask 
or quarter facepiece respirator unless a minimum fit factor of 100 
is obtained, or a full facepiece respirator unless a minimum fit 
factor of 500 is obtained.
    (k) Filters used for quantitative fit testing shall be replaced 
whenever increased breathing resistance is encountered, or when the 
test agent has altered the integrity of the filter media. Organic 
vapor cartridges/canisters shall be replaced if there is any 
indication of breakthrough by a test agent.

2. Ambient aerosol condensation nuclei counter (CNC) quantitative fit 
testing protocol

    The ambient aerosol condensation nuclei counter (CNC) 
quantitative fit testing

[[Page 56847]]

(PortacountTM) protocol quantitatively fit tests respirators 
with the use of a probe. The probed respirator is only used for 
quantitative fit tests. A probed respirator has a special sampling 
device, installed on the respirator, that allows the probe to sample 
the air from inside the mask. A probed respirator is required for 
each make, model, and size in which your company requires and can be 
obtained from the respirator manufacturer or distributor. The CNC 
instrument manufacturer Dynatech Nevada also provides probe 
attachments (TSI sampling adapters) that permits fit testing in an 
employee's own respirator. A fit factor pass level of 100 is 
necessary for a half-mask respirator and a fit factor of at least 10 
times greater than the assigned protection factor for any other 
negative pressure respirator. The Agency does not recommend the use 
of homemade sampling adapters. The entire screening and testing 
procedure shall be explained to the test subject prior to the 
conduct of the screening test.
    (a) Portacount Fit Test Requirements.
    (1) Check the respirator to make sure the respirator is fitted 
with a high efficiency filter and that the sampling probe and line 
are properly attached to the facepiece.
    (2) Instruct the person to be tested to don the respirator 
several minutes before the fit test starts. This purges the 
particles inside the respirator and permits the wearer to make 
certain the respirator is comfortable. This individual should have 
already been trained on how to wear the respirator properly.
    (3) Check the following conditions for the adequacy of the 
respirator fit: Chin properly placed; Adequate strap tension, not 
overly tightened; Fit across nose bridge; Respirator of proper size 
to span distance from nose to chin; Tendencies for the respirator to 
slip, Self-observation in a mirror to evaluate fit and respirator 
position.
    (4) Have the person wearing the respirator do a fit check. If 
leakage is detected, determine the cause. If leakage is from a 
poorly fitting facepiece, try another size of the same type of 
respirator.
    (5) Follow the instructions for operating the Portacount and 
proceed with the test.
    (b) Portacount Test Exercises.
    (1) Normal breathing. In a normal standing position, without 
talking, the subject shall breathe normally for 1 minute.
    (2) Deep breathing. In a normal standing position, the subject 
shall breathe slowly and deeply for 1 minute, taking caution so as 
too not hyperventilate.
    (3) Turning head side to side. Standing in place, the subject 
shall slowly turn his or her head from side to side between the 
extreme positions on each side for 1 minute. The head shall be held 
at each extreme momentarily so the subject can inhale at each side.
    (4) Moving head up and down. Standing in place, the subject 
shall slowly move his or her head up and down for 1 minute. The 
subject shall be instructed to inhale in the up position (i.e., when 
looking toward the ceiling).
    (5) Talking. The subject shall talk out loud slowly and loud 
enough so as to be heard clearly by the test conductor. The subject 
can read from a prepared text such as the Rainbow Passage, count 
backward from 100, or recite a memorized poem or song for 1 minute.
    (6) Grimace. The test subject shall grimace by smiling or 
frowning for 15 seconds.
    (7) Bending Over. The test subject shall bend at the waist as if 
he or she were to touch his or her toes for 1 minute. Jogging in 
place shall be substituted for this exercise in those test 
environments such as shroud type QNFT units which prohibit bending 
at the waist.
    (8) Normal Breathing. Remove and re-don the respirator within a 
one-minute period. Then, in a normal standing position, without 
talking, the subject shall breathe normally for 1 minute.
    After the test exercises, the test subject shall be questioned 
by the test conductor regarding the comfort of the respirator upon 
completion of the protocol. If it has become uncomfortable, another 
model of respirator shall be tried.
    (c) Portacount Test Instrument.
    (1) The Portacount will automatically stop and calculate the 
overall fit factor for the entire set of exercises. The overall fit 
factor is what counts. The Pass or Fail message will indicate 
whether or not the test was successful. If the test was a Pass, the 
fit test is over.
    (2) A record of the test needs to be kept on file assuming the 
fit test was successful. The record must contain the test subject's 
name; overall fit factor; make, model and size of respirator used, 
and date tested.

BILLING CODE 4510-26-P

[[Page 56848]]

[GRAPHIC] [TIFF OMITTED] TR04NO96.003



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[GRAPHIC] [TIFF OMITTED] TR04NO96.004



[[Page 56850]]

[GRAPHIC] [TIFF OMITTED] TR04NO96.005



[[Page 56851]]

[GRAPHIC] [TIFF OMITTED] TR04NO96.006



[[Page 56852]]

[GRAPHIC] [TIFF OMITTED] TR04NO96.007



[[Page 56853]]

[GRAPHIC] [TIFF OMITTED] TR04NO96.008



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[GRAPHIC] [TIFF OMITTED] TR04NO96.009



[[Page 56855]]

[GRAPHIC] [TIFF OMITTED] TR04NO96.010



BILLING CODE 4510-26-C

[[Page 56856]]

PART 1915--[AMENDED]

    Part 1915 of 29 CFR is hereby amended as follows:
    1. The authority citation for 29 CFR part 1915 continues to read as 
follows:

    Authority: Sec. 41, Longshore and Harbor Workers Compensation 
Act (33 U.S.C. 941); secs. 4, 6, and 8 of the Occupational Safety 
and Health Act of 1970 (29 U.S.C. 653, 655, and 657); sec. 4 of the 
Administrative Procedure Act (5 U.S.C. 553); Secretary of Labor's 
Order No. 12-71 (36 FR 8754), 8-76 (41 FR 25059), 9-83 (48 FR 
35736), or 1-90 (55 FR 9033), as applicable; 29 CFR part 1911.


Sec. 1915.1000  [Amended]

    2. The entry in Table Z-1 of Section 1915.1000, for ``Butadiene 
(1,3-Butadiene)'' is amended as follows: remove the ``1000'' and 
``2200'' from the columns entitled ppm a* and mg/m3 b* 
respectively; add ``1 ppm/5 ppm STEL'' in the ppm a* column; and 
add the following to the butadiene entry: ``; See 29 CFR 1910.1051; 29 
CFR 1910.19(l)'' so that the entry reads as follows: ``Butadiene (1,3-
Butadiene); See 29 CFR 1910.1051; 29 CFR 1910.19(l).''

PART 1926--[AMENDED]

    Part 1926 of 29 CFR is hereby amended as set forth below:

Subpart Z--[Amended]

    1. The authority citation for Subpart Z of 29 CFR part 1926 is 
revised to read as follows:

    Authority: Sec. 107, Contract Work Hours and Safety Standards 
Act (40 U.S.C. 333); secs. 4, 6, 8, Occupational Safety and Health 
Act of 1970 (29 U.S.C. 653, 655, 657); Secretary of Labor's Order 
No. 12-71 (36 FR 8754), 8-76 (41 FR 25059) 9-83 (48 FR 35736) or 1-
90 (55 FR 9033), as applicable; 29 CFR part 1911.


Appendix A to Sec. 1926.55   [Amended]

    2. The entry in Appendix A to Sec. 1926.55 for ``Butadiene (1,3-
Butadiene)'' is amended as follows: remove the ``1000'' and ``2200'' 
from the columns entitled ppma and mg/m3 b respectively; add ``1 
ppm/5 ppm STEL'' in the ppma column; and add the following to the 
butadiene entry; ``; See 29 CFR 1910.1051; 29 CFR 1910.19(l)'' so that 
the entry reads as follows: ``Butadiene (1,3-Butadiene); See 29 CFR 
1910.1051; 29 CFR 1910.19(1).''

[FR Doc. 96-27791 Filed 11-1-96; 8:45 am]
BILLING CODE 4510-26-P