[Federal Register Volume 65, Number 122 (Friday, June 23, 2000)]
[Notices]
[Pages 39264-39277]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-15916]



[[Page 39263]]

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Part V





Environmental Protection Agency





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National Advisory Committee for Acute Exposure Guideline Levels (AEGLs) 
for Hazardous Substances, Proposed AEGL Values; Notice

  Federal Register / Vol. 65, No. 122 / Friday, June 23, 2000 / 
Notices  

[[Page 39264]]


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ENVIRONMENTAL PROTECTION AGENCY

[OPPTS-00293; FRL-6591-2]


National Advisory Committee for Acute Exposure Guideline Levels 
(AEGLs) for Hazardous Substances; Proposed AEGL Values

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: The National Advisory Committee for Acute Exposure Guideline 
Levels for Hazardous Substances (NAC/AEGL Committee) is developing 
AEGLs on an ongoing basis to provide Federal, State, and local agencies 
with information on short-term exposures to hazardous chemicals. This 
notice provides AEGL values and Executive Summaries for 14 chemicals 
for public review and comment. Comments are welcome on both the AEGL 
values in this notice and the Technical Support Documents placed in the 
public version of the official docket for these 14 chemicals.

DATES: Comments, identified by the docket control number OPPTS-00293, 
must be received by EPA on or before July 24, 2000.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I. of the ``SUPPLEMENTARY INFORMATION.'' To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number OPPTS-00293 in the subject line on the first page of 
your response.

FOR FURTHER INFORMATION CONTACT: For general information contact: 
Barbara Cunningham, Director, Office of Program Management and 
Evaluation, Office of Pollution Prevention and Toxics (7401), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (202) 554-1404; e-mail address: 
[email protected].
    For technical information contact: Paul S. Tobin, Designated 
Federal Officer (DFO), Office of Prevention, Pesticides and Toxic 
Substances (7406), 1200 Pennsylvania Ave., NW., Washington, DC 20460; 
telephone number: (202) 260-1736; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:   

I. General Information

A. Does this Action Apply to Me?

    This action is directed to the general public to provide an 
opportunity for review and comment on ``Proposed'' AEGL values and 
their supporting scientific rationale. This action may be of particular 
interest to anyone who may be affected if the AEGL values are adopted 
by government agencies for emergency planning, prevention, or response 
programs, such as EPA's Risk Management Program under the Clean Air Act 
(CAA) and Amendments Section 112r. It is possible that other Federal 
agencies besides EPA, as well as State and Local agencies and private 
organizations, may adopt the AEGL values for their programs. As such, 
the Agency has not attempted to describe all the specific entities that 
may be affected by this action. If you have any questions regarding the 
applicability of this action to a particular entity, consult the 
technical person listed under ``FOR FURTHER INFORMATION CONTACT.''

B. How Can I Get Additional Information, Including Copies of this 
Document or Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations'' and then look up the entry for this document under the 
``Federal Register--Environmental Documents.'' You can also go directly 
to the Federal Register listings at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket control number OPPTS-00293. The official 
record consists of the documents specifically referenced in this 
action, any public comments received during an applicable comment 
period, and other information related to this action, including any 
information claimed as Confidential Business Information (CBI). This 
official record includes the documents that are physically located in 
the docket, as well as the documents that are referenced in those 
documents. The public version of the official record does not include 
any information claimed as CBI. The public version of the official 
record, which includes printed, paper versions of any electronic 
comments submitted during an applicable comment period, is available 
for inspection in the TSCA Nonconfidential Information Center, North 
East Mall Rm. B-607, Waterside Mall, 401 M St., SW., Washington, DC. 
The Center is open from noon to 4 p.m., Monday through Friday, 
excluding legal holidays. The telephone number of the Center is (202) 
260-7099.
    3. Fax-on-Demand. You may request to receive a faxed copy of the 
document(s) by using a faxphone to call (202) 401-0527 and select the 
item number 4800 for an index of the items available by fax-on-demand 
in this category, or select the item number for the document related to 
the chemical(s) identified in this document as listed in the chemical 
table in Unit III. You may also follow the automated menu.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number OPPTS-00293 in the subject line on 
the first page of your response.
    1. By mail. Submit your comments to: OPPT Document Control Office 
(7407), Office of Pollution Prevention and Toxics (OPPT), Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460. 
For express delivery, use the address in Unit I.C.2.
    2. In person or by courier. Deliver your comments to: OPPT Document 
Control Office (DCO) in East Tower Rm. G-099, Waterside Mall, 401 M 
St., SW., Washington, DC. The DCO is open from 8 a.m. to 4 p.m., Monday 
through Friday, excluding legal holidays. The telephone number for the 
DCO is (202) 260-7093.
    3. Electronically. You may submit your comments electronically by 
e-mail to: ``[email protected],'' or mail your computer disk to the 
address identified above. Do not submit any information electronically 
that you consider to be CBI. Electronic comments must be submitted as 
an ASCII file avoiding the use of special characters and any form of 
encryption. Comments and data will also be accepted on standard disks 
in WordPerfect 6.1/8.0 or ASCII file format. All comments in electronic 
form must be identified by docket control numbers OPPTS-00293. 
Electronic comments may also be filed online at many Federal Depository 
Libraries.

D. How Should I Handle CBI that I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI by marking any part or all of that information as 
CBI. Information so marked will not be disclosed except in accordance 
with procedures set forth in 40 CFR part 2. In addition to one complete 
version of the comment that includes any

[[Page 39265]]

information claimed as CBI, a copy of the comment that does not contain 
the information claimed as CBI must be submitted for inclusion in the 
public version of the official record. Information not marked 
confidential will be included in the public version of the official 
record without official notice. If you have any questions about CBI or 
the procedures for claiming CBI, please consult the technical person 
listed under ``FOR FURTHER INFORMATION CONTACT.''

E. What Should I Consider as I Prepare My Comments for EPA?

    You may find the following suggestions helpful for preparing your 
comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data that you 
used that support your views.
    4. If you estimate potential burden or costs, explain how you 
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Offer alternative ways to improve the proposed notice.
    7. Make sure to submit your comments by the deadline in this 
document.
    8. To ensure proper receipt by EPA, be sure to identify the docket 
control number assigned to this action in the subject line on the first 
page of your response. You may also provide the name, date, and Federal 
Register citation.

II. Background

A. Introduction

    EPA's Office of Prevention, Pesticides and Toxic Substances (OPPTS) 
provided notice in the Federal Register of October 31, 1995 (60 FR 
55376) (FRL-4987-3) of the establishment of the NAC/AEGL Committee with 
the stated charter objective as ``the efficient and effective 
development of Acute Exposure Guideline Levels (AEGLs) and the 
preparation of supplementary qualitative information on the hazardous 
substances for federal, state, and local agencies and organizations in 
the private sector concerned with [chemical] emergency planning, 
prevention, and response.'' The NAC/AEGL Committee is a discretionary 
Federal advisory committee formed with the intent to develop AEGLs for 
chemicals through the combined efforts of stakeholder members from both 
the public and private sectors in a cost-effective approach that avoids 
duplication of efforts and provides uniform values, while employing the 
most scientifically sound methods available. An initial priority list 
of 85 chemicals for AEGL development was published in the Federal 
Register of May 21, 1997 (62 FR 27734) (FRL-5718-9). This list is 
intended for expansion and modification as priorities of the 
stakeholder member organizations are further developed. While the 
development of AEGLs for chemicals are currently not statutorily based, 
at lease one rulemaking references their planned adoption. The CAA and 
Amendments Section 112(r) Risk Management Program states, ``EPA 
recognizes potential limitations associated with the Emergency Response 
Planning Guidelines and Level of Concern and is working with other 
agencies to develop AEGLs. When these values have been developed and 
peer-reviewed, EPA intends to adopt them, through rulemaking, as the 
toxic endpoint for substances under this rule (see 61 FR 31685).'' It 
is believed that other Federal and State agencies and private 
organizations will also adopt AEGLs for chemical emergency programs in 
the future.

B. Characterization of the AEGLs

    The AEGLs represent threshold exposure limits for the general 
public and are applicable to emergency exposure periods ranging from 10 
mins. to 8 hrs. AEGL-2 and AEGL-3 levels, and AEGL-1 levels as 
appropriate, will be developed for each of five exposure periods (10 
and 30 mins., 1 hr., 4 hrs., and 8 hrs.) and will be distinguished by 
varying degrees of severity of toxic effects. It is believed that the 
recommended exposure levels are applicable to the general population 
including infants and children, and other individuals who may be 
sensitive and susceptible. The AEGLs have been defined as follows:
    AEGL-1 is the airborne concentration (expressed as parts per 
million (ppm) or milligrams/meter cubed (mg/m3) of a 
substance above which it is predicted that the general population, 
including susceptible individuals, could experience notable discomfort, 
irritation, or certain asymptomatic, non-sensory effects. However, the 
effects are not disabling and are transient and reversible upon 
cessation of exposure.
    AEGL-2 is the airborne concentration (expressed as ppm or mg/
m3) of a substance above which it is predicted that the 
general population, including susceptible individuals, could experience 
irreversible or other serious, long-lasting adverse health effects or 
impaired ability to escape.
    AEGL-3 is the airborne concentration (expressed as ppm or mg/
m3) of a substance above which it is predicted that the 
general population, including susceptible individuals, could experience 
life-threatening effects or death.
    Airborne concentrations below the AEGL-1 represent exposure levels 
that could produce mild and progressively increasing odor, taste, and 
sensory irritation, or certain non-symptomatic, non-sensory effects. 
With increasing airborne concentrations above each AEGL level, there is 
a progressive increase in the likelihood of occurrence and the severity 
of effects described for each corresponding AEGL level. Although the 
AEGL values represent threshold levels for the general public, 
including sensitive subpopulations, it is recognized that certain 
individuals, subject to unique or idiosyncratic responses, could 
experience the effects described at concentrations below the 
corresponding AEGL level.

C. Development of the AEGLs

    The NAC/AEGL Committee develops the AEGL values on a chemical-by-
chemical basis. Relevant data and information are gathered from all 
known sources including published scientific literature, State and 
Federal agency publications, private industry, public databases and 
individual experts in both the public and private sectors. All key data 
and information are summarized for the NAC/AEGL Committee in draft form 
by Oak Ridge National Laboratories together with ``draft'' AEGL values 
prepared in conjunction with NAC/AEGL Committee members. Both the 
``draft'' AEGLs and ``draft'' Technical Support Documents are reviewed 
and revised as necessary by the NAC/AEGL Committee members prior to 
formal NAC/AEGL Committee meetings. Following deliberations on the AEGL 
values and the relevant data and information for each chemical, the 
NAC/AEGL Committee attempts to reach a concensus . Once the NAC/AEGL 
Committee reaches a concensus, the values are considered ``Proposed'' 
AEGLs. The Proposed AEGL values and the accompanying scientific 
rationale for their development are the subject of this notice.
    In this document the NAC/AEGL Committee is publishing proposed AEGL 
values and the accompanying scientific rationale for their development 
for 14 hazardous substances. These values represent the third set of 
exposure levels proposed and published by the NAC/AEGL

[[Page 39266]]

Committee. EPA published the first ``Proposed'' AEGLs for 12 chemicals 
from the initial priority list in the Federal Register of October 30, 
1997 (62 FR 58840-58851) (FRL-5737-3) and for 10 chemicals in the 
Federal Register of March 15, 2000 (65 FR 14186-14196) (FRL-6492-4) in 
order to provide an opportunity for public review and comment. In 
developing the proposed AEGL values, the NAC/AEGL Committee has 
followed the methodology guidance Guidelines for Developing Community 
Emergency Exposure Levels for Hazardous Substances, published by the 
National Research Council of the National Academy of Sciences (NSC/NAS) 
in 1993. The term Community Emergency Exposure Levels (CEELs) is 
synonymous with AEGLs in every way. The NAC/AEGL Committee has adopted 
the term Acute Exposure Guideline Levels to better connote the broad 
application of the values to the population defined by the NAS and 
addressed by the NAC/AEGL Committee. The NAC/AEGL Committee invites 
public comment on the proposed AEGL values and the scientific rationale 
used as the basis for their development.
    Following public review and comment, the NAC/AEGL Committee will 
reconvene to consider relevant comments, data, and information that may 
have an impact on the NAC/AEGL Committee's position and will again seek 
concensus for the establishment of interim AEGL values. Although the 
interim AEGL values will be available to Federal, State, and local 
agencies and to organizations in the private sector as biological 
reference values, it is intended to have them reviewed by a 
subcommittee of the NAS. The NAS subcommittee will serve as a peer 
review of the interim AEGLs and as the final arbitor in the resolution 
of issues regarding the AEGL values, and the data and basic methodology 
used for setting AEGLs. Following concurrence, ``Final'' AEGL values 
will be published under the auspices of the NAS.

III. Fax-On-Demand Item Number for Chemicals Listed in this 
Document

    On behalf of the NAC/AEGL Committee, EPA is providing an 
opportunity for public comment on the AEGLs for the 14 chemicals 
identified in the following table. This table also provides the fax-on-
demand item number for the chemical specific documents, which may be 
obtained as described in Unit ?????.

 
------------------------------------------------------------------------
                                                      Fax-On-Demand Item
            CAS No.                 Chemical name             No.
------------------------------------------------------------------------
75-78-5                          Dimethyldichlorosil  4867
                                  ane
75-79-6                          Methyltrichlorosila  4868
                                  ne
91-08-7 and 584-84-9             2,4- and 2,6-        4873
                                  Toluene
                                  diisocyanate
107-11-9                         Allylamine           4876
107-15-3                         Ethylenediamine      4878
108-91-8                         Cyclohexylamine      4883
123-73-9 (4170-30-3)             trans-               4903
                                  Crotonaldehyde
                                  (cis/trans
                                  Crotonaldehyde
                                  mixture)
624-83-9                         Methyl isocyanate    4898
7647-01-0                        Hydrogen chloride    4907
7803-51-2                        Phosphine            4923
13463-39-3                       Nickel carbonyl      4929
13463-40-6                       Iron pentacarbonyl   4930
------------------------------------------------------------------------

IV. Executive Summaries

    The following are executive summaries from the chemical specific 
Technical Support Documents (which may be obtained as described in Unit 
I.B.1 and III.) that support the NAC/AEGL Committee's development of 
AEGL values for each chemical substance. This information provides the 
following information: A general description of each chemical, 
including its properties and principle uses; a summary of the rationale 
supporting the AEGL-1, 2, and 3 concentration levels; a summary table 
of the AEGL values; and a listing of key references that were used to 
develop the AEGL values. More extensive toxicological information and 
additional references for each chemical may be found in the complete 
Technical Support Documents. Risk managers may be interested to review 
the complete Technical Support Document for a chemical when deciding 
issues related to use of the AEGL values within various programs.

A. Dimethyldichlorosilane

    1. Description. Dimethyldichlorosilane is an alkyl-substituted 
silicon tetrahydride existing as a clear liquid with a sharp acrid odor 
that is similar to hydrogen chloride (HCl) (HSDB, 1996). 
Dimethyldichlorosilane is used as a high-purity derivation reagent for 
gas chromatography (HSDB, 1996) and as an intermediate in the 
production of silicones that are used as lubricating fluids, resins, 
and plastic copolymers (Bisesi, 1994). It reacts vigorously with water 
and decomposes to form HCl and other hydrolysis products (AIHA, 1996). 
Complete hydrolysis of one mole of dimethyldichlorosilane would yield a 
maximum of two moles of HCl. Hydrogen chloride is a known respiratory 
irritant. Data on dimethyldichlorosilane are limited to LC50 
studies in rats.
    In the absence of appropriate chemical-specific data for 
dimethyldichlorosilane, a modification of the AEGL-1 values for HCl was 
utilized to derive AEGL-1 values for dimethyldichlorosilane. The use of 
HCl as a surrogate for dimethyldichlorosilane was deemed appropriate 
since it is believed that it is the hydrolysis product, HCl, that is 
responsible for the adverse effect. The HCl AEGL-1 values were based on 
a no-adverse-effect-level (NOAEL) in exercising asthmatics (Stevens et 
al., 1992). Since two moles of HCl are produced for every mole of 
dimethyldichlorosilane hydrolyzed, a modifying factor of 2 was applied 
to the HCl AEGL-1 values to approximate AEGL-1 values for 
dimethyldichlorosilane. The AEGL-1 values were held constant for all 
specified exposure periods since mild irritant effects represent 
threshold effects and generally do not vary over time.
    The AEGL-2 was based on corneal opacity, and grey spots on the 
lungs of rats exposed to 1,309 ppm dimethyldichlorosilane for 1 hr. 
(Dow

[[Page 39267]]

Corning, 1997a). This level was considered to be the threshold for 
impairment of escape and the onset of serious long-term effects. An 
uncertainty factor of 10 was applied to account for interspecies 
variability since data for dimethyldichlorosilane were available for 
only one species and an uncertainty factor of 3 was applied to account 
for sensitive human subpopulations since the irritant effects observed 
are not likely to vary greatly among individuals. A modifying factor of 
3 was applied to account for the sparse database for effects as defined 
by AEGL-2. Thus, the total uncertainty/modifying factor is 100. The 
concentration-exposure time relationship for many irritant and 
systemically acting vapors and gases may be described by Cn 
x t = k, where the exponent, n, ranges from 0.8 to 3.5 (Ten Berge et 
al., 1986). Much of the acute toxicity of dimethyldichlorosilane 
appears to be due to HCl and the value of n reported for HCl is 1 (Ten 
Berge et al., 1986). Therefore, the exponent n = 1 was used for scaling 
of the AEGL values for dimethyldichlorosilane across time.
    The AEGL-3 was based on the calculated LC01 of 1,590 ppm 
in rats exposed to dimethyldichlorosilane for 1 hr. (Dow Corning, 
1997a). An uncertainty factor of 10 was applied to account for 
interspecies variability since data for dimethyldichlorosilane were 
available for only one species and an uncertainty factor of 3 was 
applied to account for sensitive human subpopulations since the 
irritant effects observed are not likely to vary greatly among 
individuals. Thus, the total uncertainty factor is 30. The 
concentration-exposure time relation-ship for many irritant and 
systemically acting vapors and gases may be described by Cn 
x t = k, where the exponent, n, ranges from 0.8 to 3.5 (Ten Berge et 
al., 1986). Much of the acute toxicity of dimethyldichlorosilane 
appears to be due to HCl, the dimethyldichlorosilane hydrolysis 
product, and the value of n for HCl is 1 (Ten Berge et al., 1986). 
Therefore, the exponent n = 1 was used for scaling of the AEGL values 
for dimethyldichlorosilane across time.
    The calculated values are listed in the table below.

                                        Summary of Proposed AEGL Values For Dimethyldichlorosilane [ppm (mg/m3)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10 mins.            30 mins.              1 hr.              4 hrs.              8 hrs.            (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)            0.90 (4.8)          0.90 (4.8)          0.90 (4.8)          0.90 (4.8)          0.90 (4.8)          Modification of HCl
                                                                                                                                      AEGL-1 values
                                                                                                                                      (USEPA, 1997)
AEGL-2 (Disabling)               78 (410)            26 (140)            13 (69)             3.3 (17)            1.6 (8.5)           Corneal opacity,
                                                                                                                                      gray spots on
                                                                                                                                      lungs in rats (Dow
                                                                                                                                      Corning, 1997a)
AEGL-3 (Lethality)               320 (1700)          110 (560)           53 (280)            13 (69)             6.6 (35)            1 hr. LC01 in rats
                                                                                                                                      (Dow Corning,
                                                                                                                                      1997a)
--------------------------------------------------------------------------------------------------------------------------------------------------------

    2. References--i. AIHA (American Industrial Hygiene Association). 
1996. Emergency Response Planning Guidelines. Dimethyldichlorosilane. 
AIHA, Fairfax, VA.
    ii. Bisesi, M.S. 1994. Organic Silicon Esters. Patty's Industrial 
Hygiene and Toxicology. Fourth Ed. Vol. II, Part D. G.D. Clayton and 
F.E. Clayton, Eds. pp. 3096-3101.
    iii. Dow Corning. 1997a. An acute whole body inhalation toxicity 
study of dimethyldichlorosilane in Fischer 344 rats. Report No. 1997-
I0000-43381. Study No. 8487. Dow Corning Corporation. Health and 
Environmental Sciences. Midland, MI.
    iv. HSDB (Hazardous Substances Data Bank). 1996. 
Dimethyldichlorosilane. Retrieved online 7-22-96.
    v. Stevens, B., Koenig, J.Q., Rebolledo, V., Hanley, Q.S., and 
Covert, D.S. 1992. Respiratory effects from the inhalation of hydrogen 
chloride in young adult asthmatics. Journal of Occupational Medicine. 
34:923-929.
    vi. Ten Berge, W.F., Zwart, A., and Appleman, L.M. 1986. 
Concentration-time mortality response relationship of irritant and 
systemically acting vapours and gases. Journal of Hazardous Materials. 
13:301-309.
    vii. USEPA (United States Environmental Protection Agency). 1997. 
Acute exposure guideline levels (AEGLs) for hydrogen chloride (NAC/PRO 
Draft 3:7/97).

B. Methyltrichlorosilane

    1. Description. Methyltrichlorosilane is an alkyl-substituted 
silicon tetrahydride existing as a clear liquid with a sharp acrid odor 
that is similar to HCl (HSDB, 1997). Methyltrichlorosilane is used as 
an intermediate in the production of silicones that are used as 
lubricating fluids, resins, and plastic copolymers (Bisesi, 1994). It 
reacts vigorously with water and may decompose to form three moles of 
HCl for every mole of methyltrichlorosilane (AIHA, 1996). Hydrogen 
chloride is a known respiratory irritant. Data on methyltrichlorosilane 
are limited to 1-hr. and 4-hr. LC50 studies in rats.
    In the absence of relevant chemical-specific data for 
methyltrichlorosilane, AEGL a modification of the AEGL-1 values for HCl 
was utilized to derive AEGL-1 values for methyltrichlorosilane. The use 
of HCl as a surrogate for methyltrichlorosilane was deemed appropriate 
since it is believed that it is the hydrolysis product, HCl, that is 
responsible for the adverse effect. The HCl AEGL-1 values were based on 
a NOAEL in exercising asthmatics (Stevens et al., 1992). Since three 
moles of HCl are produced for every mole of methyltrichlorosilane 
hydrolyzed, a modifying factor of 3 was applied to the HCl AEGL-1 
values to approximate AEGL-1 values for methyltrichlorosilane. The 
AEGL-1 values were held constant for all specified exposure periods 
since mild irritant effects represent threshold effects and generally 
do not vary over time.
    The AEGL-2 was based on ocular opacity, clear fluid around the 
eyes, nose, and mouth, nasal staining, and hunched posture observed in 
rats exposed to 622 ppm methyltrichlorosilane for 1 hr. (Dow Corning, 
1997a). This level was considered to be the threshold for impairment of 
escape and the onset of serious long-term effects. An uncertainty 
factor of 10 was applied to these data to account for interspecies 
variability since data for methyltrichlorosilane were available for 
only one species and an uncertainty factor of 3 was applied to account 
for sensitive human subpopulations since the irritant effects observed 
are not likely to vary greatly among individuals. A modifying factor of 
3 was applied to account for the sparse database for effects as defined 
by AEGL-2. Thus, the total uncertainty/modifying factor is 100. The 
concentration-exposure time relationship for many irritant and 
systemically acting vapors and gases may be described by Cn 
x t = k, where the exponent, n, ranges from 0.8 to 3.5 (Ten Berge et 
al., 1986). Much of the acute toxicity of methyltrichlorosilane appears 
to be due to HCl and the value

[[Page 39268]]

of n reported for HCl is 1 (Ten Berge et al., 1986). Therefore, the 
exponent n = 1 was used for scaling of the AEGL values for 
methyltrichlorosilane across time.
    The AEGL-3 was based on the calculated LC01 of 844 ppm 
in rats exposed to methyltrichlorosilane for 1 hr. (Dow Corning, 
1997a). An uncertainty factor of 10 was applied to account for 
interspecies variability since data were available for only one species 
and an uncertainty factor of 3 was applied to account for sensitive 
human subpopulations since the irritant effects observed are not likely 
to vary greatly among individuals. Thus, the total uncertainty/ 
modifying factor is 30. The concentration-exposure time relationship 
for many irritant and systemically acting vapors and gases may be 
described by Cn x t = k, where the exponent, n, ranges from 
0.8 to 3.5 (Ten Berge et al., 1986). Much of the acute toxicity of 
methyltrichlorosilane appears to be due to HCl and the value of n 
reported for HCl is 1 (Ten Berge et al., 1986). Therefore, the exponent 
n = 1 was used for scaling of the AEGL values for methyltrichlorosilane 
across time.
    The calculated values are listed in the following table.

                                              Proposed AEGL Values for Methyltrichlorosilane [ppm (mg/m3)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10 mins.            30 mins.              1 hr.              4 hrs.              8 hrs.            (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)            0.60 (3.7)          0.60 (3.7)          0.60 (3.7)          0.60 (3.7)          0.60 (3.7)          Modification of HCl
                                                                                                                                      AEGL-1 values
                                                                                                                                      (USEPA, 1997)
AEGL-2 (Disabling)               37 (230)            12 (73)             6.2 (38)            1.6 (9.8)           0.78 (4.8)          Ocular opacity,
                                                                                                                                      irritation and
                                                                                                                                      hunched posture in
                                                                                                                                      rats (Dow Corning,
                                                                                                                                      1997a)
AEGL-3 (Lethality)               170 (1000)          56 (340)            28 (170)            7.0 (43)            3.5 (21)            1 hr. LC01 in rats
                                                                                                                                      (Dow Corning,
                                                                                                                                      1997a)
--------------------------------------------------------------------------------------------------------------------------------------------------------

    2. References--i. AIHA. 1996. Emergency Response Planning 
Guidelines. Methyltrichlorosilane. AIHA, Fairfax, VA,
    ii. Bisesi, M.S. 1994. Organic Silicon Esters. Patty's Industrial 
Hygiene and Toxicology. Fourth Ed. Vol II, Part D. G.D. Clayton and 
F.E. Clayton, Eds. pp. 3096-3101.
    iii. Dow Corning. 1997a. An acute whole body inhalation toxicity 
study of methyltrichlorosilane in Fischer 344 rats. Report No. 1997-
I0000-43537. Study No. 8602. Dow Corning Corporation. Health and 
Environmental Sciences. Midland, MI.
    iv. HSDB. 1997. Methyltrichlorosilane. Retrieved online 10-10-97.
    v. Stevens, B., Koenig, J.Q., Rebolledo, V., Hanley, Q.S., Covert, 
D.S. 1992. Respiratory effects from the inhalation of hydrogen chloride 
in young adult asthmatics. Journal of Occupational Medicine. 34:923-
929.
    vi. Ten Berge, W.F. et al. 1986. Concentration-time mortality 
response relationship of irritant and systemically acting vapours and 
gases. Journal of Hazardous Materials. 13:301-309.
    vii. USEPA. 1997. Acute exposure guideline levels (AEGLs) for 
hydrogen chloride (NAC/PRO Draft 3:7/97).

C. and D. 2,4- and 2,6-Toluene Diisocyanate (TDI)

    1. Description. Toluene diisocyanate (TDI) is among a group of 
chemicals, the isocyanates, that are highly reactive compounds 
containing an -NCO group. Toluene diisocyanate exists as both the 2,4- 
and 2,6- isomers which are available commercially usually in ratios of 
65:35 or 80:20 (Karol, 1986; WHO, 1987). Toluene diisocyanate is used 
extensively in the manufacture of polyurethane foam products as well as 
paints, varnishes, elastomers, and coatings (WHO, 1987).
    Toxicological effects from inhaled TDI consist of irritation and 
sensitization of the respiratory tract. Sensitization may occur from 
either repeated exposure over a relatively long period of time (i.e., 
years), or, it may consist of an induction phase precipitated by a 
relatively high concentration followed by a challenge phase in which 
sensitized individuals react to a low concentration of TDI. Because 
repeated exposures are required for sensitization, only irritation 
effects were considered in establishing AEGL values.
    Human data were available for derivation of AEGL-1 and -2. 
Asthmatics were exposed to 0.01 ppm (0.071 mg/m3) TDI for 1 
hr., then after a rest of 45 mins., to 0.02 ppm (0.142 mg/
m3) TDI for 1 hr. Controls were exposed to 0.02 ppm (0.142 
mg/m3) TDI for 2 hrs. (Baur, 1985). Although no 
statistically significant differences in lung function parameters were 
observed among asthmatics during or after exposure, non-pathological 
bronchial obstruction was indicated in several individuals. In the 
control group, there was a significant increase in airway resistance 
immediately and 30 mins. after the beginning of exposure but none of 
the subjects developed bronchial obstruction. Both groups reported 
symptoms of eye and throat irritation, cough, chest tightness, 
rhinitis, dyspnea, and/or headache but time to onset of symptoms was 
not given. There was also no indication whether the effects were worse 
in asthmatics with 0.01 or 0.02 ppm. Therefore, the concentration of 
0.02 ppm (0.142 mg/m3) was chosen as the basis for the 10-
mins., 30-mins., and 1-hr. AEGL-1 values and the concentration of 0.01 
ppm (0.071 mg/m3) was chosen as the 4- and 8-hr. AEGL-1 
values. Extrapolations were not performed.
    Derivation of AEGL-2 was based on human data. Exposure of 
volunteers to 0.5 ppm (3.56 mg/m3) for 30 mins. resulted in 
severe eye and throat irritation and lacrimation (Henschler et al., 
1962). A higher-exposure concentration was intolerable. Extrapolations 
were made using the equation Cn x t = k, where n ranges from 
0.8 to 3.5 (Ten Berge et al., 1986). In the absence of an empirically 
derived, chemical-specific exponent, to obtain conservative and 
protective AEGL-2 values, scaling was performed using n = 3 for 
extrapolating to the 10-min. time point and n = 1 for the 1- and 4-hr. 
time points. The 4-hr. value is also proposed for the 8-hr. value since 
extrapolation to 8 hrs. resulted in a concentration similar to that 
shown to be tolerated for >7 hrs. with only mild effects. An 
uncertainty factor of 3 was applied to account for sensitive 
individuals because the mechanism of action of an irritant gas is not 
expected to differ among individuals.
    No human data were available for derivation of AEGL-3 values. 
Reports of human fatalities occurred under unusual circumstances and 
exposure concentrations were not measured. Deaths were attributed to 
chemical pneumonitis. Therefore, animal data were used to derive AEGL-3 
values. Based on LC50 values, the mouse is the most 
sensitive species to the effects of TDI. The 4-hr. mouse 
LC50 of 9.7 ppm (69.1 mg/m3) (Duncan et al., 
1962) was divided by 3 to estimate a threshold of lethality. This 
estimated 4-hr. lethality threshold was used to extrapolate to the 30-
min. and 1- and 8-hr. AEGL-3 time

[[Page 39269]]

points. Values were scaled using the equation Cn x t = k, 
where n ranges from 0.8 to 3.5 (Ten Berge et al., 1986). In the absence 
of an empirically derived, chemical-specific exponent, to obtain 
conservative and protective AEGL-2 values, scaling was performed using 
n = 3 for extrapolating to the 30-min. and 1-hr. time points and n = 1 
for the 8-hr. time point. A total uncertainty factor of 10 was applied 
which includes 3 to account for sensitive individuals and 3 for 
interspecies extrapolation (the mechanism of action of an irritant gas 
is not expected to vary greatly between or among species). The 10-min. 
values were not extrapolated from 4 hrs. because the NAC/AEGL Committee 
determined that extrapolating from greater than or equal to 4 hrs. to 
10 mins. is associated with unacceptably large inherent uncertainty, 
and the 30-min. values were adopted for 10 min. to be protective of 
human health. Therefore, the 10-min. AEGL-3 value was flatlined from 
the 30-min. value. The NAC/AEGL Committee recognizes that individuals 
pre-sensitized to TDI may exist in the general population, but that 
this rate of sensitization cannot be predicted. If the rate of 
sensitization to TDI in the general population were quantifiable, the 
NAC/AEGL Committee might have considered lower values for AEGL-3. At 
the proposed AEGL-3 levels, there may be individuals who have a strong 
reaction to TDI and these individuals may not be protected.

                                     Summary of Proposed AEGL Values for 2,4-/2,6-Toluene Diisocyanate [ppm (mg/m3)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10 mins.            30 mins.              1 hr.              4 hrs.              8 hrs.            (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)            0.020 (0.14)        0.020 (0.14)        0.020 (0.14)        0.010 (0.07)        0.010 (0.07)        Chest tightness,
                                                                                                                                      eye and throat
                                                                                                                                      irritation (Baur,
                                                                                                                                      1985)
AEGL-2 (Disabling)               0.24 (1.71)         0.17 (1.21)         0.083 (0.59)        0.021 (0.15)        0.021 (0.15)        Severe eye and
                                                                                                                                      throat irritation,
                                                                                                                                      lacrimation
                                                                                                                                      (Henschler et al.,
                                                                                                                                      1962)
AEGL-3 (Lethal)                  0.65 (4.6)          0.65 (4.6)          0.51 (3.6)          0.32 (2.3)          0.16 (0.93)         4-hrs. LC50 in the
                                                                                                                                      mouse (Duncan et
                                                                                                                                      al., 1962)
--------------------------------------------------------------------------------------------------------------------------------------------------------

    2. References--i. Baur, X. 1985. Isocyanate hypersensitivity. Final 
Report to the International Isocyanate Institute. III File No. 10349; 
III Project: E-AB-19.
    ii. Duncan, B., Scheel, L.D., Fairchild, E.J., Killens, R., and 
Graham, S. 1962. Toluene diisocyanate inhalation toxicity: Pathology 
and mortality. American Industry Hygiene Association Journal. 23:447-
456.
    iii. Henschler, D., Assman, W., and Meyer, K. O. 1962. On the 
Toxicology of Toluenediisocyanate [in German]. Archivs fur Toxikologie 
19:364-387.
    iv. Karol, M.H. 1986. Respiratory effects of inhaled isocyanates. 
CRC Critical Reviews in Toxicology. Vol. 16. CRC Press.
    v. Ten Berge, W.F., Zwart, A., and Appelman, L. M. 1986. 
Concentration-time mortality response relationship of irritant and 
systemically acting vapours and gases. Journal of Hazardous Materials. 
13:301-309.
    vi. WHO (World Health Organization). 1987. Toluene diisocyanates. 
Environmental Health Criteria 75. WHO, Geneva. pp.72.

E. Allylamine

    1. Description. Allylamine is a colorless or yellowish volatile 
liquid with a very sharp ammonia-like odor that is irritating to mucous 
membranes. It is highly flammable and moderately reactive with 
oxidizing materials. Industrially, it is used in the vulcanization of 
rubber and in the synthesis of pharmaceuticals. In addition to being a 
severe respiratory, eye, and skin irritant, allylamine is a 
cardiovascular toxin when administered at high doses orally, by 
injection or by inhalation. Allylamine cardiotoxicity is proposed to be 
related to its metabolism to acrolein and hydrogen peroxide. Allylamine 
acute inhalation toxicity has been studied in rats and mice; the 
response in human volunteers briefly exposed to irritating levels has 
been reported.
    AEGL-1 values were based on an occupational study in which exposure 
to 0.2 ppm allylamine for 3-4 hrs. a day was not associated with worker 
detection or complaints, but exposure to higher but undefined 
concentrations caused mucous membrane irritation (Shell Oil Co., 1992). 
The same AEGL-1 value is proposed for 10 mins. to 8 hrs. (i.e., ``flat-
line'') because 0.2 ppm is expected to produce no or mild irritation, 
which does not generally vary greatly with time. No uncertainty factors 
were applied because 0.2 ppm was a no-effect-level (NOEL) for mucous 
membrane irritation in humans exposed repeatedly.
    The AEGL-2 was based on a rat study in which exposure to 60 ppm for 
14 hrs. caused heart lesions including scattered myofibril fragments 
with loss of striation, perivascular edema, and cellular infiltration 
(Guzman et al., 1961). Extrapolation to 30, 60, 240, and 480 mins. was 
performed using the equation Cn x t = k, where n = 1.71 
(calculated from a linear regression of rat cardiotoxicity data of 
Guzman et al., 1961). The 10-min. value was not extrapolated from 16 
hrs. because the NAC has determined that extrapolating from 4 hrs. to 
10 mins. is associated with unacceptably large inherent uncertainty, 
and the 30-min. value was adopted for 10 mins. to be protective of 
human health. An interspecies uncertainty factor of 10 was applied to 
account for the lack of acute toxicity studies and toxicokinetic and 
metabolism data from other species. An intraspecies uncertainty factor 
of 10 was applied because significant intraspecies variation occurred 
in the rat cardiotoxic responses in the key study, and there were no 
data to determine the human variability of allylamine-induced 
cardiotoxicity.
    The AEGL-3 values were derived from a rat inhalation 
LC50 study where exposure was for 1, 4, or 8 hrs. (Hine et 
al., 1960). The threshold for lethality, as represented by 
LC01 values calculated using probit analysis, was the AEGL-3 
toxicity endpoint. The 1, 4, and 8-hr. AEGL-3 values were based on 
their respective LC01 values, and the 10- and 30-min. AEGL-3 
values were extrapolated from the 1-hr. LC01 using the 
equation Cn x t = k, where n = 0.8458 (calculated from a 
linear regression of the Hine et al., 1960 data). An uncertainty factor 
of 30 was applied: 10 to account for interspecies variability (to 
account for the lack of acute toxicity studies and toxicokinetic and 
metabolism data from other species) and 3 for human variability 
(lethality, as an endpoint associated with severe pulmonary edema, is 
not likely to vary greatly among humans). Similar AEGL-3 values were 
obtained from other rat studies that used fewer animals and exposure 
concentrations.

[[Page 39270]]



                                              Summary of Proposed AEGL Values for Allylamine [ppm (mg/m3)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10 mins.            30 mins.              1 hr.              4 hrs.              8 hrs.            (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1                           0.2 (0.47)          0.2 (0.47)          0.2 (0.47)          0.2 (0.47)          0.2 (0.47)          NOAEL for human
                                                                                                                                      mucous membrane
                                                                                                                                      irritation (Shell
                                                                                                                                      Oil Co., 1992)
AEGL-2                           4.2 (9.8)           4.2 (9.8)           2.8 (6.5)           1.2 (2.8)           0.83 (1.9)          Heart lesions in
                                                                                                                                      rats (Guzman et
                                                                                                                                      al., 1961)
AEGL-3                           140 (330)           40 (94)             18 (42)             3.5 (8.1)           2.3 (5.4)           Lethality threshold
                                                                                                                                      in rats (Hine et
                                                                                                                                      al., 1960)
--------------------------------------------------------------------------------------------------------------------------------------------------------

    2. References--i. Guzman, R.J., Loquvam, G.S., Kodama, J.K., and 
Hine, C.H. 1961. Myocarditis produced by allylamines. Archives of 
Environmental Health. 2:62-73.
    ii. Hine, C.H., Kodama, J.K., Guzman, R.J., and Loquvam, G.S. 1960. 
The toxicity of allylamines. Archives of Environmental Health. 1:343-
352.
    iii. Shell Oil Co. 1992. Initial submission: Letter submitting 
enclosed information on exposure of workers to mono-allylamine, di-
allylamine, and tri-allylamine. EPA/OTS Doc. #88-920002051.
    iv. Ten Berge, W.F., Zwart, A., and Appelman, L.M. 1986. 
Concentration-time mortality response relationship of irritant and 
systemically acting vapors and gases. Journal of Hazardous Materials. 
13:302-309.

F. Ethylenediamine (EDA)

    1. Description. Ethylenediamine (EDA) is a basic, hygroscopic, 
flammable liquid that is an eye, mucous membrane, and respiratory 
irritant and a known respiratory and skin sensitizer. Occupational 
inhalation exposure has resulted in an asthmatic response including 
rhinitis, coughing, wheezing, shortness of breath, and bronchospasm. 
EDA is used to stabilize rubber latex, as an inhibitor in antifreeze 
solutions, and in the preparation of dyes, insecticides, and 
fungicides.
    The values developed for AEGL-2 and AEGL-3 level were based on 
studies in which toxicity endpoints occurred that were within the scope 
of the definition for that level. However, persons previously 
sensitized to EDA may experience more severe effects, the extent of 
which cannot be predicted from the available information. No data were 
available to determine the concentration-time relationship for EDA 
toxic effects. The concentration-time relationship for many irritant 
and systemically acting vapors and gases may be described by 
Cn x t = k, where the exponent n ranges from 0.8 to 3.5 (Ten 
Berge et al., 1986). To obtain conservative and protective AEGL-2 and 
AEGL-3 values, scaling across time was performed using n = 3 to 
extrapolate to exposure times 8 hrs., except for the 10-min. values. 
The NAC determined that extrapolating from 4 hrs. to 10 mins. is 
associated with unacceptably large inherent uncertainty, and the 30-
min. values were adopted for 10 mins. to be protective of human health. 
AEGL-1 values were not recommended due to insufficient data.
    AEGL-2 values were based on a study in which rats and guinea pigs 
(6/group) exposed for 8 hrs. to 484 ppm EDA (1,000 ppm 
nominal) had bronchiolar edema of unspecified severity and ``light 
cloudy swelling of the kidney'' but none died (Carpenter et al., 1948). 
An uncertainty factor of 100 was used: 10 for intraspecies variability 
(mechanism of toxicity and variability of the toxic response among 
humans is uncertain) and 10 for interspecies variability (key study 
tested only one EDA concentration and reported few experimental 
details, not providing a clear picture of species variability). The 
derived AEGL-2 values are supported by a study in which rats (15/sex) 
exposed to 132 ppm 7 hours/day for 30 days had a slight increase in the 
incidence (i.e., 1/26 vs. 0/27 for controls) of unspecified ``major'' 
histopathological lesions (Pozzani and Carpenter, 1954).
    The AEGL-3 values were derived from a range-finding test in which 
0/6 rats died from exposure for 8 hrs. to 1,000 ppm (2,000 
ppm nominal) but 6/6 died from 8-hr. exposure to 2,000 ppm 
(4,000 ppm nominal) (Smyth et al., 1951). Toxic effects (other than 
death) were not described; 1,000 ppm was considered to be the estimated 
lethality threshold. An uncertainty factor of 100 was applied: 10 for 
intraspecies variability (cause of death was not defined in key study 
and variability of the toxic response among humans cannot be predicted) 
and 10 for interspecies extrapolation (only one EDA concentration was 
tested, the cause of death was not defined in the key study, and there 
were no data from other species). The AEGL-3 values are supported by a 
study in which rats (15/sex) exposed to 225 ppm 7 hours/day for 30 days 
had fractional mortality (first two deaths were on exposure day 4), and 
most rats had cloudy swelling of the liver and kidney convoluted 
tubules (Pozzani and Carpenter, 1954).

                                                Summary of AEGL Values For Ethylenediamine [ppm (mg/m3)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification                10 mins.             30 min.              1 hr.              4 hrs.              8 hrs.            (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1                            Not recommended     Not recommended     Not recommended     Not recommended     Not recommended     Not recommended
AEGL-2                            12 (30)             12 (30)             9.7 (24)            6.1 (19)            4.8 (13)            Bronchiolar edema,
                                                                                                                                       kidney swelling
                                                                                                                                       (Carpenter et
                                                                                                                                       al., 1948)
AEGL-3                            25 (62)             25 (62)             20 (49)             13 (31)             10 (26)             Lethality
                                                                                                                                       threshold; no
                                                                                                                                       stated toxic
                                                                                                                                       effects (Smyth et
                                                                                                                                       al., 1951)
--------------------------------------------------------------------------------------------------------------------------------------------------------

    2. References--i. Carpenter, C.P., Smyth, Jr., H.F., and Shaffer, 
C.B. 1948. The acute toxicity of ethylene imine to small animals. 
Journal of Industrial Hygiene and Toxicology. 30:2-6.
    ii. Pozzani, U.C. and Carpenter, C.P. 1954. Response of rats to 
repeated inhalation of ethylenediamine vapors. AMA Archives of 
Industrial Hygiene and Occupational Medicine. 9:223-226.
    iii. Smyth, H.F., C.P. Carpenter, and C.S. Weil. 1951. Range-
finding toxicity data: List IV. AMA Archives of Industrial Hygiene and 
Occupational Medicine. 4:119-122.

[[Page 39271]]

    iv. Ten Berge, W.F., Zwart, A., and Appelman, L.M. 1986. 
Concentration-time mortality response relationship of irritant and 
systemically acting vapors and gases. Journal of Hazardous Materials. 
13:302-309.

G. Cylohexylamine

    1. Description. Cyclohexylamine is a respiratory, eye, and skin 
irritant, as well as a strong base (pKa = 10.7) with a 
fishy, amine odor that has only recently been found naturally. It is 
used primarily for boiler water treatment (corrosion inhibition) as 
well as organic synthesis of rubber and agricultural chemicals. 
Occupational exposures to cyclohexylamine caused headache, nausea, 
dizziness, vomiting, eye, nose and throat irritation, and rapid and 
irregular heartbeats in some individuals. Acute exposure in animals 
resulted in extreme mucous membrane irritation, gasping, CNS effects 
(tremors, clonic muscular spasms), lung hemorrhage, opaque corneas, 
vascular lesions, and hemolysis.
    No data were available to determine the concentration-time 
relationship for cyclohexylamine toxicity. The concentration-time 
relationship for many irritant and systemically acting vapors and gases 
may be described by Cn x t = k, where the exponent n ranges 
from 0.8 to 3.5 (Ten Berge et al., 1986). To obtain conservative and 
protective AEGL-2 and AEGL-3 values, scaling across time was performed 
using n = 3 to extrapolate to shorter exposure times and n = 1 to 
extrapolate to longer exposure times for 30 min. through 8-hr. values 
(scaling was not performed for AEGL-1 derivation). The 10-min. values 
were not extrapolated from 4 hrs. because the NAC determined that 
extrapolating from 4 hrs. to 10 mins. is associated with unacceptably 
large inherent uncertainty, and the 30-min. values were adopted for 10 
mins. to be protective of human health.
    AEGL-1, AEGL-2, and AEGL-3 values were derived from a study in 
which Sprague-Dawley rats (5/sex/dose) were exposed for 4 hrs. to 54.2 
ppm or 567 ppm cyclohexylamine vapor, or to a vapor/aerosol combination 
containing 542 ppm vapor and 612 mg/m3 aerosol (Bio/
dynamics, Inc., 1990). At 54.2 ppm, rats had labored breathing, 
partially closed eyes, and red nasal discharge; rats exposed to the two 
higher doses additionally had rales, gasping, dried red facial 
material, tremors, weight loss, irreversible ocular lesions, and two 
rats exposed to the aerosol-containing atmosphere died. AEGL-1 values 
were obtained by dividing the lowest-observed-adverse-effect-level 
(LOAEL) of 54.2 ppm by 3 to estimate a NOAEL, which may be associated 
with mild or no respiratory and ocular irritation. An uncertainty 
factor of 10 was applied: 3 to account for sensitive humans and 3 for 
interspecies variability, because mild sensory irritation from a 
surface-contact, basic irritant gas is not likely to vary greatly among 
humans or animals. The same AEGL value was adopted for 10 mins., 30 
mins., 1, 4, and 8 hrs.; flat-lining across time was considered 
appropriate since mild irritant effects generally do not vary greatly 
over time.
    AEGL-2 values were based on exposure for 4 hrs. to 54.2 ppm, at 
which concentration the rats had moderate respiratory effects and 
ocular irritation, and which was a NOAEL for irreversible ocular 
lesions. An uncertainty factor of 10 was used: 3 for interspecies 
variability and 3 for intraspecies variability (moderate respiratory 
and ocular irritation from a surface-contact, basic irritant gas is not 
likely to vary greatly among humans or animals).
    The AEGL-3 values were based on exposure for 4 hrs. to 567 ppm, 
which caused severe respiratory effects and irreversible ocular lesions 
and was regarded as an estimate of the lethality threshold because 2/10 
animals died at the next higher concentration tested. An uncertainty 
factor of 30 was applied: 3 to account for intraspecies variability 
(lethality response resulting from a basic irritant gas is not likely 
to vary greatly among humans) and 10 for extrapolation from animals to 
humans (significant variation was seen among species for the exposure 
causing lethality, and the data were insufficient to determine that 
rats were the most sensitive species).

                                            Summary of Proposed AEGL Values for Cyclohexylamine [ppm(mg/m3)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10 mins.            30 mins.              1 hr.              4 hrs.              8 hrs.            (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1                           1.8 (7.3)           1.8 (7.3)           1.8 (7.3)           1.8 (7.3)           1.8 (7.3)           NOAEL for
                                                                                                                                      respiratory and
                                                                                                                                      ocular irritation;
                                                                                                                                      may cause mild or
                                                                                                                                      no sensory
                                                                                                                                      irritation (Bio/
                                                                                                                                      dynamics, Inc.,
                                                                                                                                      1990)
AEGL-2                           11 (44)             11 (44)             8.6 (35)            5.4 (22)            2.7 (11)            Moderate
                                                                                                                                      respiratory
                                                                                                                                      effects, ocular
                                                                                                                                      irritation; NOAEL
                                                                                                                                      for irreversible
                                                                                                                                      ocular lesions
                                                                                                                                      (Bio/dynamics,
                                                                                                                                      Inc., 1990).
AEGL-3                           38 (150)            38 (150)            30 (120)            19 (77)             9.4 (38)            Lethality
                                                                                                                                      threshold, severe
                                                                                                                                      respiratory
                                                                                                                                      effects, and
                                                                                                                                      irreversible
                                                                                                                                      ocular lesions
                                                                                                                                      (Bio/dynamics,
                                                                                                                                      Inc., 1990).
--------------------------------------------------------------------------------------------------------------------------------------------------------

    2. References--i. Bio/dynamics, Inc. 1990. An acute inhalation 
toxicity study of C-1388 in the rat. Final Report. Project No. 89-8214. 
December 4, 1990.
    ii. Ten Berge, W.F., Zwart, A., and Appelman, L.M. 1986. 
Concentration-time mortality response relationship of irritant and 
systemically acting vapors and gases. Journal of Hazardous Materials. 
13:302-309.

H. and I. Cis- and Trans-Crotonaldehyde

    1. Description. Crotonaldehyde is a colorless, flammable liquid and 
an extreme eye, skin, and respiratory irritant. It causes a burning 
sensation in the nasal and upper respiratory tract, lacrimation, 
coughing, bronchoconstriction, pulmonary edema, and deep lung damage. 
Crotonaldehyde is used primarily for the manufacture of sorbic acid and 
other organic chemicals. It is found in tobacco smoke and is a 
combustion product of diesel engines and wood, but also occurs 
naturally in meat, fish, and many fruits and vegetables.
    Crotonaldehyde can exist as either the cis or the trans isomer; 
commercial crotonaldehyde is a mixture of the two isomers consisting of 
>95% trans isomer. Because virtually no physical or chemical data or in 
vivo exposure studies were located for the cis or trans isomers 
individually (information was for the commercial mixture), and because 
OSHA, NIOSH, and the ACGIH have adopted the same occupational exposure 
limits for both isomers, the AEGL values prepared in this report will 
apply to both trans-crotonaldehyde (123-73-9) and to the cis/trans 
mixture (4170-30-3), which contains predominantly the trans isomer.
    AEGL-1 values were derived from a Health Hazard Evaluation 
conducted by NIOSH where workers exposed to about

[[Page 39272]]

0.56 ppm crotonaldehyde for >8 hrs. reported occasional minor eye 
irritation (Fannick, 1982). Exponential scaling across time was not 
performed because results from another study suggested that the 
concentration-time relationship determined from the rat LC50 
study of Rinehart (1967) was not appropriate for predicting human 
sensory irritation (i.e., irritation was much greater for shorter 
exposure durations than for longer exposure durations yielding 
comparable concentration x time (Ct) values. An uncertainty factor of 3 
was applied to account for sensitive humans; a greater uncertainty 
factor is not needed because the endpoint of mild eye irritation is not 
expected to vary greatly among humans.
    AEGL-2 values were based on a study in which rats exposed to 8,000 
ppm-min crotonaldehyde had about a 20-40% reduction in pulmonary 
function (manifested as a decrease in carbon monoxide and ether uptake 
rates compared to pre-exposure values). The animals had proliferative 
lesions of the respiratory bronchioles but there was little or no 
evidence of alveolar edema (Rinehart, 1967). The individual 
experimental concentrations and exposure times were not given, but 
exposure was stated to be for 5-240 mins. AEGL-2 values were calculated 
by dividing 8,000 ppm-min by 10, 30, 60, 240, or 480 mins. 
(concentration and time appeared to be equally important for toxicity). 
An uncertainty factor of 30 was used: 3 to account for sensitive humans 
(crotonaldehyde acts primarily as a surface-contact irritant and the 
irritation response is not expected to vary greatly among humans) and 
10 for extrapolation from animals to humans (based on the lack of 
actual concentration and time data, and the stated variability in the 
animal responses, and the absence of supporting animal or human 
studies).
    The AEGL-3 was based on a LC50 study in which Wistar 
rats were exposed to crotonaldehyde vapor for 5 mins. to 4 hrs. 
(Rinehart, 1967). The 10-min., 30-min., 1-hr., and 4-hr. AEGLs were 
obtained using the respective LC01 values (268, 138, and 26 
ppm, respectively; calculated by probit analysis from mortality data). 
The 8-hr. AEGLs were derived from the 4-hr. LC01; scaling 
across time was performed using the exponential relationship 
Cn x t = k , where n = 1.2 was derived by Ten Berge et al. 
(1986) from this study LC50 data. During exposure, all 
animals gasped and had a lowered breathing rate; those exposed to 
>1,000 ppm had an excitatory stage. Rats lost up to 25% of their body 
weight by 1-3 days post-exposure, after which time they began to 
recover their weight. Most rats died by 4 days after exposure and had 
clear or slightly blood-tinged nasal exudate; all animals that died 
within 1 day also had terminal convulsions. An uncertainty factor of 10 
was applied: 3 to account for extrapolation of rats to humans, and 3 to 
account for sensitive humans. Similar or higher AEGL-3 values were 
obtained from LC50 studies in rats, mice, and guinea pigs.

                                             Summary of Proposed AEGL Values For Crotonaldehyde [ppm(mg/m3)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10 mins.            30 mins.              1 hr.              4 hrs.              8 hrs.            (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)            0.19 (0.53)         0.19 (0.53)         0.19 (0.53)         0.19 (0.53)         0.19 (0.53)         Human mild eye
                                                                                                                                      irritation
                                                                                                                                      (Fannick, 1982)
AEGL-2 (Disabling)               27 (76)             8.9 (25)            4.4 (13)            1.1 (3.2)           0.56 (1.6)          Rat impaired
                                                                                                                                      pulmonary
                                                                                                                                      function,
                                                                                                                                      bronchiole lesions
                                                                                                                                      (Rinehart, 1967)
AEGL-3 (Lethal)                  44 (130)            27 (76)             14 (40)             2.6 (7.4)           1.5 (4.2)           Rat lethality
                                                                                                                                      threshold using
                                                                                                                                      LC1 values
                                                                                                                                      (Rinehart, 1967).
--------------------------------------------------------------------------------------------------------------------------------------------------------

    2. References--i. Fannick, N. 1982. Sandoz Colors and Chemicals, 
East Hanover, New Jersey (Health Hazard Evaluation Report, No. HETA-81-
102-1244), Cincinnati, OH. United States National Institute for 
Occupational Safety and Health, Hazard Evaluations and Technical 
Assistance Branch.
    ii. Rinehart, W. 1967. The effect on rats of single exposures to 
crotonaldehyde vapor. American Industrial Hygiene Association Journal. 
28:561-566.
    iii. Ten Berge, W.F., Zwart, A., and Appelman, L.M. 1986. 
Concentration-time mortality response relationship of irritant and 
systemically acting vapors and gases. Journal of Hazardous Materials. 
13:302-309.

J. Methyl Isocyanate (MIC)

    1. Description. Methyl isocyanate (MIC) is one of the most reactive 
of all isocyanates and is rapidly degraded in aqueous medium (Varma and 
Guest, 1993). Because of its reactivity, MIC is used as an intermediate 
in the synthesis of N-methylcarbamate and N -methylurea insecticides 
and herbicides (Hartung, 1994). During the night of December 2/3, 1984, 
an estimated 30 tons of MIC was released from a chemical plant in 
Bhopal, India, resulting in one of the worst industrial accidents in 
history (Karlsson et al., 1985).
    Signs of severe irritation to the respiratory tract were reported 
for victims of the Bhopal disaster and autopsies revealed the cause of 
death to be pulmonary edema (Weill, 1988). Long-term pulmonary and 
ocular effects have been documented in survivors. The spontaneous 
abortion rate (Arbuckle and Sever, 1998) and the infant death rate 
(Varma, 1987) among women who were pregnant at the time of the release 
were significantly increased in the months following the disaster. 
Numerous animal studies corroborate the epidemiological findings in 
humans. A compilation of case reports in industrial workers 
consistently noted skin and respiratory irritation in MIC exposed 
workers but no definitive case of sensitization (Ketcham, 1973). The 
mechanism of action for the pulmonary, skin, and eye effects is 
irritation, but the mechanism of action for the systemic effects is 
unknown.
    AEGL-1 values were not derived. Although human and animal data were 
available for irritation levels, the irritation threshold for MIC may 
be above the level of concern for systemic effects such as embryo and 
fetal lethality.
    Systemic and developmental toxicity data from rats and mice were 
used for derivation of AEGL-2. An increase in cardiac arrhythmias 
occurred in rats 4 months after a 2-hr. exposure to 3 ppm (Tepper et 
al., 1987). Pregnant Swiss-Webster mice were exposed to analytically 
monitored concentrations of 0, 2, 6, 9, and 15 ppm MIC for 3 hrs. on 
gestation day 8 (Varma, 1987). Placental weights and fetal body weights 
were significantly reduced at all concentrations. Exposures to 
concentrations of 9 and 15 ppm resulted in deaths of two dams in each 
group, a significant increase in complete litter resorption among 
surviving dams, and fetuses with significant reductions in the lengths 
of the mandible and long bones. The concentration of 2 ppm for 3 hrs. 
was an experimentally derived

[[Page 39273]]

lowest-observed effect level for decreased fetal body weights. Values 
scaled for the derivation of the 10- and 30-min., and 1-, 4-, and 8-hr. 
time points were calculated from the equation Cn x t = k, 
where n = 1. The value of n was empirically derived from regression 
analysis of lethality data for rats. Identical AEGL-2 values are 
derived based on the exposures of 3 ppm for 2 hrs. and 2 ppm for 3 hrs. 
The experimental concentrations were reduced by a factor of 3 to 
estimate a threshold for effects on cardiac arrhythmias or fetal body 
weights. A total uncertainty factor of 30 was applied including 3 for 
interspecies variation because similar developmental toxicity results 
have been obtained in both rats and mice and 10 for intraspecies 
variation since the mechanism of action for systemic effects is 
unknown.
    The neonatal survival study with mice by Schwetz et al. (1987) was 
used for derivation of AEGL-3 values. Pregnant mice were exposed to 0, 
1, or 3 ppm for 6 hours/day on gestation days 14-17. Dams were allowed 
to litter for evaluation of neonatal survival. A concentration-related 
increase in the number of dead fetuses at birth was observed in both 
exposure groups and an increase in pup mortality during lactation was 
observed in the 3 ppm group. No differences in pup body weights 
occurred during lactation between the treated and control groups. The 
6-hr. exposure to 1 ppm was used to derive AEGL-3 values and is 
considered a NOEL for pup survival during lactation. Values scaled for 
the derivation of the 10- and 30-min., and 1-, 4-, and 8-hr. time 
points were calculated from the equation Cn x t = k, where n 
= 1. The value of n was empirically derived from regression analysis of 
lethality data for rats. A total uncertainty factor of 30 was applied 
including 3 for interspecies variation because similar developmental 
toxicity results have been obtained in both rats and mice and 10 for 
intraspecies variation since the mechanism of action for systemic 
effects is unknown. However, because n was derived from exposures 
ranging from 7.5 to 240 mins., it is felt that extrapolation from 6 
hrs. to the 10-min. AEGL-3 value is valid.
    The proposed values for the three AEGL classifications for the five 
time periods are listed in the table below.

                                           Summary of Proposed AEGL Values for Methyl Isocyanate [ppm (mg/m3)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10 mins.            30 mins.              1 hr.              4 hrs.              8 hrs.            (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)            NA                  NA                  NA                  NA                  NA                  NA
AEGL-2 (Disabling)               0.40 (0.94)         0.13 (0.32)         0.067 (0.16)        0.017 (0.034)       0.0083 (0.019)      Decreased fetal
                                                                                                                                      body weights
                                                                                                                                      (Varma, 1987);
                                                                                                                                      cardiac
                                                                                                                                      arrhythmias
                                                                                                                                      (Tepper et al.,
                                                                                                                                      1987)
AEGL-3 (Lethal)                  1.2 (2.8)           0.40 (0.95)         0.20 (0.47)         0.050 (0.12)        0.025 (0.059)       Decreased pup
                                                                                                                                      survival during
                                                                                                                                      lactation (Schwetz
                                                                                                                                      et al., 1987)
--------------------------------------------------------------------------------------------------------------------------------------------------------
NA: Not assigned, since AEGL-1 effects would occur at concentration levels higher than AEGL-2 levels.

    2. References--i. Arbuckle, T.E. and Sever, L.E. . 1998. Pesticide 
exposures and fetal death: a review of the epidemiologic literature. 
Critical Reviews in Toxicology . 28:229-270.
    ii. Hartung, R. 1994. Cyanides and Nitriles. Patty's Industrial 
Hygiene and Toxicology . 4th Ed. G.D. Clayton and F.E. Clayton, Eds. 
New York: John Wiley & Sons, Inc. pp. 3161-3172.
    iii. Karlsson, E., Karlsson, N., Lindberg, G., Lindgren, B., and 
Winter S. 1985. The Bhopal catastrophe--consequences of a liquefied gas 
discharge. National Defense Research Institute, Sweden. NTIS ISSN 0347-
2124.
    iv. Ketcham, N.H. 1973. Methyl isocyanate (MIC) survey of 
experience concerning human sensitization. Union Carbide Corporation. 
EPA/OTS; Doc #86- 910000666D.
    v. Schwetz, B.A., Adkins, Jr., B., Harris, M., Moorman, M., and 
Sloane, R. 1987. Methyl isocyanate: reproductive and developmental 
toxicology studies in Swiss mice. Environmental Health Perspectives. 
72:149-152.
    vi. Tepper, J.S., Wiester, M.J., Costa, D.L., Watkinson, W.P., and 
Weber, M.F. 1987. Cardiopulmonary effects in awake rats four and six 
months after exposure to methyl isocyanate. Environmental Health 
Perspectives 72:95-103.
    vii. Varma, D.R. 1987. Epidemiological and experimental studies on 
the effects of methyl isocyanate on the course of pregnancy. 
Environmental Health Perspectives. 72:153-157.
    viii. Varma, D.R. and Guest, I.. 1993. The Bhopal accident and 
methyl isocyanate toxicity. Journal of Toxicology and Environmental 
Health. 40:513-529.
    ix. Weill, H. 1988. Disaster at Bhopal: the accident, early 
findings and respiratory health outlook in those injured. Physiology. 
23:587-590.

K. Hydrogen Chloride (HCl)

    1. Description. Hydrogen chloride (HCl) is a colorless gas with a 
pungent suffocating odor. It is used in the manufacture of organic and 
inorganic chemicals, oil well acidizing, steel pickling, food 
processing, and processing of minerals and metals. A large amount of 
HCl is released from solid rocket fuel exhaust. It is an upper 
respiratory irritant at relatively low concentrations and may cause 
damage to the lower respiratory tract at higher concentrations. 
Hydrogen chloride is very soluble in water, and the aqueous solution is 
highly corrosive.
    The AEGL-1 values are based on a 45 min. NOAEL in exercising adult 
asthmatics (Stevens et al., 1992). No uncertainty factors were applied 
for inter- or intraspecies variability since the study population 
consisted of sensitive humans. Additionally, the same value was applied 
across the 10- and 30-min., and 1-, 4-, and 8-hr. exposure time points 
since mild irritancy is a threshold effect and generally does not vary 
greatly over time. Thus, prolonged exposure will not result in an 
enhanced effect.
    The AEGL-2 for the 30-min., 1-, 4-, and 8-hr. time points was based 
on severe nasal or pulmonary histopathology in rats exposed to 1,300 
ppm HCl for 30 mins. (Stavert et al.,1991). An uncertainty factor of 3 
was applied for interspecies variability because the test species 
(rodents) is 2-3 times more sensitive to the effects of HCl than 
primates. An uncertainty factor of 3 was applied for intraspecies 
extrapolation since the mechanism of action is direct irritation and 
the subsequent effect or response is not expected to vary greatly among 
individuals. An additional modifying factor of 3 was applied to account 
for the sparse database of effects defined by AEGL-2 and since the 
effects observed at the concentration used to derive AEGL-2 values were 
somewhat severe. Thus, the total uncertainty and

[[Page 39274]]

modifying factor adjustment is 30-fold. It was then time-scaled to the, 
and 1-, 4-, and 8-hr. AEGL exposure periods using the Cn x t 
= k relationship, where n = 1 based on regression analysis of combined 
rat and mouse LC50 data (1 min. to 100 min1.) as reported by 
Ten Berge et al., 1986. The 10-min. AEGL-2 value was derived by 
dividing the mouse RD50 of 309 ppm by a factor of 3 to 
obtain a concentration causing irritation (Barrow et al., 1977). One-
third of the mouse RD50 for HCl corresponds to an 
approximate decrease in respiratory rate of 30%, and decreases in the 
range of 20 to 50% correspond to moderate irritation (ASTM, 1991).
    The AEGL-3 was based on an estimated NOEL for death of one-third of 
a 1-hr. LC50 reported for rats (Vernot et al., 1977; 
Wohlslagel et al., 1976). An uncertainty factor of 3 was applied for 
interspecies variability because the test species (rodents) is 2-3 
times more sensitive to the effects of HCl than primates. An 
uncertainty factor of 3 was applied for intraspecies extrapolation 
since the mechanism of action is direct irritation and the subsequent 
effect or response is not expected to vary greatly among individuals. 
Thus, the total uncertainty factor is 10. It was then time-scaled to 
the specified 10- and 30-min., and 1-, 4-, and 8-hr. AEGL exposure 
periods using the Cn x t = k relationship, where n = 1 based 
on regression analysis of combined rat and mouse LC50 data 
(1 min. to 100 mins.) as reported by Ten Berge et al., 1986.
    The calculated values are listed in the table below.

                                           Summary of Proposed AEGL Values For Hydrogen Chloride [ppm (mg/m3)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10 mins.            30 mins.              1 hr.              4 hrs.              8 hrs.            (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)            1.8 (2.7)           1.8 (2.7)           1.8 (2.7)           1.8 (2.7)           1.8 (2.7)           NOAEL in exercising
                                                                                                                                      human asthmatics
                                                                                                                                      (Stevens et al.,
                                                                                                                                      1992)
AEGL-2 (Disabling)               100 (160)           43 (65)             22 (33)             5.4 (8.1)           2.7 (4.1)           Mouse RD50
                                                                                                                                      (Barrowet al,
                                                                                                                                      1977);
                                                                                                                                      Histopathology in
                                                                                                                                      rats (Stavert et
                                                                                                                                      al., 1991)
AEGL-3 (Lethality)               620 (940)           210 (310)           100 (160)           26 (39)             13 (19)             Estimated NOEL for
                                                                                                                                      death from 1-hr.
                                                                                                                                      rat LC50
                                                                                                                                      (Wohlslagel et
                                                                                                                                      al., 1976; Vernot
                                                                                                                                      et al., 1977)
--------------------------------------------------------------------------------------------------------------------------------------------------------

    2. References--i. ASTM. (American Society for Testing and 
Materials). 1991. Standard Test Method for estimating sensory irritancy 
of airborne chemicals. Method E981, Volume 11.04, p. 610-619. ASTM 
Philadelphia, PA.
    ii. Barrow, C.S., Alarie, Y., Warrick, M., and Stock, M.F. 1977. 
Comparison of the sensory irritation response in mice to chlorine and 
hydrogen chloride. Archives of Environmental Health. 32:68-76.
    iii. Stavert , D.M., Archuleta, D.C., Behr, M.J., and Lehnert, B.E. 
1991. Relative acute toxicities of hydrogen fluoride, hydrogen 
chloride, and hydrogen bromide in nose- and pseudo-mouth-breathing 
rats. Fundamental and Applied Toxicology. 16:636-655.
    iv. Stevens, B., Koenig, J.Q., Rebolledo, V., Hanley, Q.S., and 
Covert, D.S. 1992. Respiratory effects from the inhalation of hydrogen 
chloride in young adult asthmatics. Journal of Occupational Medicine. 
34: 923-929.
    v. Ten Berge, W.F., Zwart, A., and Appleman, L.M. 1986. 
Concentration-time mortality response relationship of irritant and 
systemically acting vapours and gases. Journal of Hazardous Materials. 
13:301-309.
    vi. Vernot, E.H., MacEwen, J.D., Haun, C.C., and Kinkead, E.R. 
1977. Acute toxicity and skin corrosion data for some organic and 
inorganic compounds and aqueous solutions. Toxicology and Applied 
Pharmacology. 42:417-423.
    vii. Wohlslagel, J., DiPasquale, L..C., and Vernot, E.H. 1976. 
Toxicity of solid rocket motor exhaust: effects of HCl, HF, and alumina 
on rodents. Journal of Combustion Toxicology. 3:61-70.

L. Phosphine

    1. Description. Phosphine is a colorless gas used as a fumigant 
against insects and rodents in stored grain. The pesticide is usually 
applied as a metal phosphide and reacts with moisture to liberate 
phosphine gas. Phosphine is also used in the semiconductor industry. 
Information concerning human exposure to phosphine is of limited use in 
derivation of AEGL values since exposure durations and concentrations 
are not precisely reported. Appropriate animal data are more abundant; 
however, data consistent with the definition of AEGL-1 values are not 
available. Therefore, due to insufficient data, AEGL-1 values were not 
derived.
    The AEGL-2 was based on a NOEL for renal, cardiac, and liver 
histopathology in mice exposed to 5 ppm phosphine 6 hours/day for 4 
days (Morgan et al, 1995). Values were derived assuming a single 6 hr. 
exposure. An uncertainty factor of 3 was applied to account for 
interspecies variability since lethality data from rats, mice, rabbits, 
and guinea pigs suggest little species variability. An uncertainty 
factor of 10 was applied to account for intraspecies variability since 
the human data suggest that children may be more sensitive than adults 
when exposed to presumably similar phosphine concentrations (total UF = 
30). The concentration-exposure time relationship for many irritant and 
systemically-acting vapors and gases may be described by Cn 
x t = k, where the exponent, n, ranges from 0.8 to 3.5 (Ten Berge , 
1986). To obtain conservative and protective AEGL values for the 30-
min., 1-, 4-, and 8-hr. time points in the absence of an empirically 
derived chemical-specific scaling exponent, temporal scaling was 
performed using n = 3 when extrapolating to shorter time points and n = 
1 when extrapolating to longer time points using the Cn x t 
= k equation. The 30-min AEGL-2 value was also adopted as the 10-min. 
value due to the fact that reliable data are limited to durations 4 
hrs., and it is considered inappropriate to extrapolate back to 10-
mins.
    The AEGL-3 was based on a NOEL for lethality (18 ppm phosphine) in 
Sprague Dawley rats exposed to phosphine for 6 hrs. (Newton, 1991). An 
uncertainty factor of 3 was applied to account for interspecies 
variability since lethality data from rats, mice, rabbits, and guinea 
pigs suggest little species variability. An uncertainty factor of 10 
was applied to account for intraspecies variability since the human 
data suggest that children may be more sensitive than adults when 
exposed to presumably similar phosphine concentrations (total UF = 30). 
The concentration-exposure time relationship for many irritant and 
systemically-acting vapors and gases may be described by Cn 
x t = k, where the exponent, n, ranges from 0.8 to 3.5 (Ten Berge , 
1986). To obtain conservative and protective AEGL values for the 30-
min., 1-, 4-, and 8-hr.

[[Page 39275]]

time points in the absence of an empirically derived chemical-specific 
scaling exponent, temporal scaling was performed using n = 3 when 
extrapolating to shorter time points and n = 1 when extrapolating to 
longer time points using the Cn x t = k equation. The 30-min 
AEGL-3 value was also adopted as the 10-min. value due to the fact that 
reliable data are limited to durations 4 hrs., and it is considered 
inappropriate to extrapolate back to 10-mins.
    The calculated values are listed in the table below.

                                               Summary of Proposed AEGL Values For Phosphine [ppm(mg/m3)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10 mins.            30 mins.              1 hr.              4 hrs.              8 hrs.            (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)                                                                                                                Appropriate data
                                                                                                                                      not available
AEGL-2 (Disabling)               0.38 (0.54)         0.38 (0.54)         0.30 (0.42)         0.19 (0.27)         0.13 (0.18)         NOEL for
                                                                                                                                      histopathology in
                                                                                                                                      mice exposed to 5
                                                                                                                                      ppm phosphine 6
                                                                                                                                      hours/day for 4
                                                                                                                                      days. Values were
                                                                                                                                      calculated
                                                                                                                                      assuming a single
                                                                                                                                      6 hr exposure
                                                                                                                                      (Morgan et al.,
                                                                                                                                      1995)
AEGL-3 (Lethality)               1.4 (1.9)           1.4 (1.9)           1.1 (1.6)           0.69 (0.97)         0.45 (0.63)         NOEL for lethality
                                                                                                                                      in rats exposed to
                                                                                                                                      18 ppm phosphine
                                                                                                                                      for 6 hrs.
                                                                                                                                      (Newton, 1991)
--------------------------------------------------------------------------------------------------------------------------------------------------------

    2. References--i. Newton, P.E. 1991. Acute Inhalation exposures of 
rats to phosphine. Bio/Dynamics, Inc. East Millstone, NJ. Project No. 
90-8271.
    ii. Morgan, D.L., Moorman, M.P., Elwell, M.R., Wilson, R.E., Ward, 
S.M., Thompson, M.B., O'Connor, R.W., and Price, H.C. 1995. Inhalation 
toxicity of phosphine for Fischer 344 rats and B6C3F1 mice. Inhalation 
Toxicology. 7: 225-238.
    iii. Ten Berge, W.F. 1986. Concentration-time mortality response 
relationship of irritant and systemically acting vapours and gases. 
Journal of Hazardous Materials. 13:301-309.

M. Nickel Carbonyl

    1. Description. Nickel carbonyl, formed by the reaction of carbon 
monoxide with metallic nickel, is used in nickel refining, in the 
synthesis of acrylic and methacrylic esters, and for other organic 
synthesis. In air, nickel carbonyl rapidly decomposes to nickel and 
carbon monoxide with a 50% decomposition at room temperature and total 
decomposition at 150-200 deg.C.
    Human data are limited to case reports, primarily of nickel 
workers, that affirm the extreme toxicity of the compound. However, 
definitive exposure terms are lacking in these reports. Significant 
signs and symptoms of toxicity are known to occur in the absence of 
recognizable odor. Human case studies have shown that a latency period 
of 10 occurs between initial signs of toxicity and subsequent serious 
effects that may progress to death. The primary target of nickel 
carbonyl-induced acute toxicity appears to be the lungs, although 
extrapulmonary involvement has also been reported. The specific 
mechanism of toxicity is unclear but appears to involve damage to 
pulmonary tissue.
    Animal data are limited to lethality and developmental toxicity. 
Lethality values (LC50) are available for rats, mice, cats, 
and rabbits. Thirty-minute LC50 values for these species 
range from 33.6 to 266 ppm. These lethality data indicate notable 
species variability in the lethal response to inhaled nickel carbonyl; 
smaller species are generally more sensitive. Developmental toxicity 
has been demonstrated in rats and hamsters following single 30-min. 
(11.2-42 ppm, rats) or 15-min. (8.4 ppm, hamsters) exposures of dams 
during gestation.
    Limited data in rats have provided equivocal evidence of pulmonary 
carcinogenicity following acute or long-term exposure to nickel 
carbonyl. Studies of respiratory tract cancer in nickel workers suggest 
that nickel dusts and nickel sulfides may be more relevant than nickel 
carbonyl. Data are unavailable for a quantitative assessment of the 
carcinogenic potential of nickel carbonyl in humans or animals.
    Exposure-response data over multiple time periods are unavailable 
for nickel carbonyl and, empirical derivation of a scaling factor (n) 
was not possible. The concentration exposure time relationship for many 
irritant and systemically acting vapors and gases may be described by 
Cn x t = k, where the exponent, n, ranges from 0.8 to 3.5. 
In the absence of an empirically derived exponent (n), and to obtain 
conservative and protective AEGL values, temporal scaling was performed 
using n = 3 when extrapolating to shorter time points and n = 1 when 
extrapolating to longer time points using the Cn x t = k 
equation.
    Neither human nor animal data are available for deriving AEGL-1 
values. Both human and animal data affirm the extreme toxicity of 
nickel carbonyl, and human exposures indicate that signs and symptoms 
of toxicity may occur in the absence of detection. Therefore, AEGL-1 
values are not recommended.
    With the exception of teratogenicity and fetotoxicity data in rats 
and hamsters, neither human nor animal data are available that identify 
effects consistent with AEGL-2. The developmental effects are notable 
(ocular malformations, fetotoxicity, and neonate lethality) and the 
exposures producing these effects approach those known to cause 
lethality in animal species. The AEGL-2 values were based upon 
significantly increased incidences of malformations in the offspring of 
Syrian hamsters which had been exposed to 8.4 ppm nickel carbonyl for 
15 mins. per day on gestation days 4 or 5 (Sunderman et al., 1980). As 
previously noted, time scaling was accomplished by the use of linear 
C1 x t = k) extrapolation for 30-min., 1-hr. and 4-hr. AEGL-
2 time points and exponential extrapolation C 3 x t = k) for 
the 10-min. AEGL-2 values. A total uncertainty factor adjustment of 100 
(10 for interspecies variability and 10 for intraspecies variability) 
was applied. The interspecies uncertainty factor adjustment is 
justified by the absence of human data and only limited data in animal 
species with which to assess species variability in the toxic responses 
to nickel carbonyl. The uncertainty factor for individual variability 
accounted for lack of data with which to identify sensitive 
subpopulations or to determine individual variability in the toxic 
responses to nickel carbonyl.
    AEGL-3 values were derived based upon an estimated lethality 
threshold in mice (3.17 ppm) exposed to nickel carbonyl for 30 mins. 
(Kincaid et al., 1953). Lethality data were available for several 
species (rats, mice, rabbits, and cats). A total uncertainty adjustment 
of 10 was applied (each uncertainty factor of 3 is the approximate 
logarithmic mean of 10 which is 3.16; hence, 3.16 x 3.16 = 10). 
Analysis of the available data indicated that the mouse was the most 
sensitive species and larger species tended to be somewhat less 
sensitive. Therefore the uncertainty factor adjustment for interspecies 
variability

[[Page 39276]]

was limited to 3. An additional factor of 3 was applied to account for 
uncertainties regarding individual variability in the lethal response 
due to direct contact pulmonary damage by nickel carbonyl.
    There are limited, equivocal data showing the development of 
pulmonary tumors in rats exposed chronically to nickel carbonyl and 
equivocal data suggestive of a tumorigenic response following a single 
massive exposure of rats to nickel carbonyl. However, a quantitative 
cancer assessment was not feasible.

                                            Summary of Proposed Aegl Values For Nickel Carbonyl [ppm mg/m3)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10 mins.            30 mins.              1 hr.              4 hrs.              8 hrs.            (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)            NR                  NR                  NR                  NR                  NR                  Not recommended
AEGL-2 (Disabling)               0.096 (0.66)        .042 (0.29)         0.021 (0.14)        0.0053 (0.037)      NA                  Developmental
                                                                                                                                      toxicity in
                                                                                                                                      hamsters;
                                                                                                                                      gestational
                                                                                                                                      exposure (15
                                                                                                                                      mins., 8.4 ppm)
AEGL-3 (Lethal)                  0.46 (3.2)          0.32 (2.2)          0.16 (1.1)          0.040 (0.27)        NA                  Estimated lethality
                                                                                                                                      threshold (LC01 of
                                                                                                                                      3.17 ppm); mouse
                                                                                                                                      lethality data
                                                                                                                                      (Kincaid et al.,
                                                                                                                                      1953)
--------------------------------------------------------------------------------------------------------------------------------------------------------
NR: Not recommended. Numeric values for AEGL-1 are not recommended because:
1. The lack of available data,
2. An inadequate margin of safety exists between the derived AEGL-1 and the AEGL-2, or
3. The derived AEGL-1 is greater than the AEGL-2. Absence of an AEGL-1 does not imply that exposure below the AEGL-2 is without adverse effects.
NA: Not appropriate. AEGL values for 8 hrs. were not developed due to the rapid decomposition of nickel carbonyl under ambient atmospheric conditions.

    2. References--i. Kincaid, J.F., Strong, J.S., and Sunderman, F.W. 
1953. Nickel poisoning. Experimental study of the effects of acute and 
subacute exposure to nickel carbonyl. Archives of Industrial Hygiene 
and Occupational Medicine. 8:48-60.
    ii. Sunderman, F.W., Jr., Shen, S.K., Reid, M.C., and Alpist, P.R. 
1980. Teratogenicity and embryotoxicity of nickel carbonyl in Syrian 
hamsters. Teratogenicity Carcinogenicity Mutagenicity. 1:223-233.

N. Iron Pentacarbonyl

    1. Description. Iron pentacarbonyl is one of several iron 
carbonyls. It is formed by the interaction of carbon monoxide with 
finely divided iron. Iron pentacarbonyl is used in the manufacture of 
powdered iron cores for electronic components, as a catalyst and 
reagent in organic reactions, and as an anti-knock agent in gasoline. 
Iron pentacarbonyl is pyrophoric in air (-15 deg.C flashpoint), burning 
to ferric oxide.
    Quantitative toxicity data and odor detection data for humans are 
unavailable. Qualitative descriptions of the signs and symptoms of iron 
pentacarbonyl exposure include giddiness and headache, and occasionally 
dyspnea and vomiting. With the exception of dyspnea, these signs and 
symptoms are alleviated upon removal from exposure but fever, cyanosis, 
and coughing may occur at 12 to 36 hrs. after exposure. This 
information could not be validated and additional details were 
unavailable.
    Animal data are limited to lethality findings in rats, mice, and 
rabbits. Based upon the limited data available, the rat appears to be 
the most sensitive species as determined by the 30-min. LC50 
of 118 ppm and a 4-hr LC50 of 10 ppm relative to the 30- 
min. LC50 of 285 ppm for the mouse. A steep exposure-
response relationship is suggested by data showing 50% lethality in 
rats following only two 6-hr exposures to 3 ppm. For mice, a 1.35-fold 
increase in the LC50 results in near 100% mortality for the 
same exposure duration, suggesting a steep exposure-response 
relationship for this species as well. Similarly, a 2.8-fold increase 
in exposure concentration (86-244 ppm) results in a mortality rate in 
rats of 4/12 to 11/12. No reproductive/developmental toxicity, 
genotoxicity, or carcinogenicity data are available for iron 
pentacarbonyl.
    Although exposure-response data for the same toxicity endpoint over 
multiple time periods were limited to several LC50 values, 
these data suggested a near-linear relationship. Therefore, the value 
of n was set at unity for the exponential temporal scaling equation, 
Cn x t=k AEGL values were developed for 10 mins., 30 mins., 
1 hr., and 4 hrs. only. AEGL values were not developed for the 8-hr. 
time point due to the rapid decomposition of iron pentacarbonyl under 
ambient atmospheric conditions.
    Data consistent with AEGL-1 effects were limited to labored 
breathing and signs of irritation in rats exposed to 5.2 ppm for 4 hrs. 
and no observable effects in rats exposed for 6 hours/day to 1 ppm for 
28 days. However, analysis of the overall data set for iron 
pentacarbonyl indicated a very steep exposure-response curve with 
little margin between exposures producing no observable effects and 
those resulting in lethality. Therefore, it was the consensus of the 
NAC/AEGL Committee on AEGLs to recommend no AEGL-1 values.
    Limited data in rats revealed that there is only a small margin 
between exposures causing little or no toxicity and those causing more 
severe effects and death. No effect was observed following exposure of 
rats to 1 ppm, 6 hours/day for up to 28 days while a single exposure to 
2.91 ppm for 6 hours/day caused notable signs of toxicity with a 10% 
mortality. The occurrence of deaths in laboratory species several days 
following cessation of exposure is also a factor to consider in the 
derivation of AEGL-2 values showed. In the absence of exposure-response 
data for serious and/or possibly irreversible effects, AEGL-2 value 
were developed by a three-fold reduction in the AEGL-3 values. This 3-
fold reduction was justified by the apparently steep exposure-response 
relationship in rats where there appears to be about a three-fold 
difference between exposures that produce no lethality and those 
resulting in 50-100% lethality. The AEGL-2 values also reflect the 
application of uncertainty factors of 10 for interspecies variability 
and 3 for intraspecies variability as described for the development of 
AEGL-3 values.
    Animal data consistent with AEGL-3 were limited to 30-min. 
LC50 values for rats (118 ppm) and mice (285 ppm), a 45.5-
min. LClo value for rabbits (250 ppm), and 4-hr. 
LC50 in rats (10 ppm). In addition to a 4-hr. 
LC50 value for rats, Biodynamics (1988) also provided 4-hr. 
LC16 estimate of 6.99 ppm and an estimated lethality 
threshold (4 hrs) of 5.2 ppm for male and female rats. Data from a 
study by BASF (1995), however,

[[Page 39277]]

showed that a single 6-hr exposure to 2.91 ppm resulted in 10% (1 of 10 
rats) mortality and that a second exposure resulted in 50% mortality. 
Remaining rats, however, survived an additional 26 6-hr. exposures. A 
total uncertainty factor of 30 was applied. An uncertainty factor of 10 
was applied to account for interspecies variability and justified due 
to the absence of definitive quantitative lethality data in humans and 
the uncertainties regarding the mechanism of iron pentacarbonyl-induced 
lethality. An additional factor of 3 was applied to account for 
uncertainties regarding individual variability in the toxic response to 
iron pentacarbonyl. The adjustment for this area of uncertainty was 
limited to 3 because the available data did not indicate a high level 
of variability among test species and because the mechanism of action 
for the observed toxic responses appears to be a port-of-entry effect 
mediated by contact irritation and destruction of pulmonary epithelium. 
The AEGL values for iron pentacarbonyl are presented in the table 
below.
    Neither quantitative nor qualitative data are available regarding 
the potential carcinogenicity of iron pentacarbonyl by any route of 
exposure. Therefore, a quantitative assessment of potential risk is not 
possible. Genotoxicity tests in several strains of Salmonella 
typhimurium were negative.

                                          Summary of Proposed AEGL Values For Iron Pentacarbonyl [ppm (mg/m3)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10 mins.            30 mins.              1 hr.              4 hrs.              8 hrs.            (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)            NR                  NR                  NR                  NR                  NR                  Not recommended;
                                                                                                                                      insufficient data
AEGL-2 (Disabling)               1.2 (9.6)           0.40 (3.2)          0.19 (1.5)          0.050 (0.40)        NA                  Based upon a three-
                                                                                                                                      fold reduction in
                                                                                                                                      the AEGL-3 values
AEGL-3 (Lethal)                  3.5 (28)            1.2 (9.6)           0.58 (4.6)          0.15 (1.2)          NA                  Estimated lethality
                                                                                                                                      threshold in rats
                                                                                                                                      (6-hr. exposure to
                                                                                                                                      2.91 ppm) (BASF,
                                                                                                                                      1995). n = 1; UF =
                                                                                                                                      30 (10 for
                                                                                                                                      interspecies
                                                                                                                                      variability, 3 for
                                                                                                                                      individual
                                                                                                                                      variability)
--------------------------------------------------------------------------------------------------------------------------------------------------------
NR: Not recommended. Numeric values for AEGL-1 are not recommended because:
1. The lack of available data,
2. An inadequate margin of safety exists between the derived AEGL-1 and the AEGL-2, or
3. The derived AEGL-1 is greater than the AEGL-2. Absence of an AEGL-1 does not imply that exposure below the AEGL-2 is without adverse effects.
NA: Not appropriate; AEGL values for 8 hr. were not developed due to the rapid decomposition of iron pentacarbonyl under ambient atmospheric conditions.

    2. References --i. BASF (Badische Anilin & Soda Fabrik). 1995. 
Study on the inhalation toxicity of eisenpentacarbonyl as a vapor in 
rats--28 day test. BASF Department of Toxicology. Environmental 
Protection Agency/Office of Toxic Substances, Document #89-950000244.
    ii. Biodynamics. 1988. An acute inhalation toxicity study of iron 
pentacarbonyl in the rat. Final Report. Environmental Protection 
Agency/Office of Toxic Substances, Document #88-920001300.

V. Next Steps

    The NAC/AEGL Committee plans to publish ``Proposed'' AEGL values 
for five-exposure periods for other chemicals on the priority list of 
85 in groups of approximately 10 to 20 chemicals in future Federal 
Register notices during the calendar year 2000.
    The NAC/AEGL Committee will review and consider all public comments 
received on this notice, with revisions to the ``Proposed'' AEGL values 
as appropriate. The resulting AEGL values will be established as 
``Interim'' AEGLs and will be forwarded to the NRC/NAS, for review and 
comment. The ``Final'' AEGLs will be published under the auspices of 
the NRC/NAS following concurrence on the values and the scientific 
rationale used in their development.

List of Subjects

    Environmental protection, Hazardous substances.

    Dated: June 16, 2000.
Susan H. Wayland,
Acting Assistant Administrator for Prevention, Pesticides and Toxic 
Substances.
[FR Doc. 00-15916 Filed 6-22-00; 8:45 am]
BILLING CODE 6560-50-F