[Federal Register Volume 65, Number 240 (Wednesday, December 13, 2000)]
[Notices]
[Pages 77866-77874]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-31730]


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ENVIRONMENTAL PROTECTION AGENCY

[OPPTS-00302; FRL-6752-5]


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 7 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 record for these 7 chemicals.

DATES:  Comments, identified by the docket control number OPPTS-00302, 
must be received by EPA on or before January 12, 2001.

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-00302 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  For general information contact: 
Barbara Cunningham, Acting Director, Environmental Assistance Division, 
Office of Pollution Prevention and Toxics (7408), Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; 
telephone number: (202) 554-1404 and TDD: (202) 554-055; 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 
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,'' ``Regulations and Proposed Rules,'' 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-00302. 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-00302 in the subject line on 
the first page of your response.
    1. By mail. Submit your comments to: Document Control Office 
(7407), Office of Pollution Prevention and Toxics (OPPT), Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460. 
(Note: for express delivery, please see ``In person or by courier'' in 
this unit).
    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

[[Page 77867]]

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 6.1/8.1 or ASCII file format. All comments in electronic 
form must be identified by docket control numbers OPPTS-00302. 
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 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 this 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 on 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 Clean Air Act 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 
minutes to 8 hours. AEGL-2 and AEGL-3 levels, and AEGL-1 levels as 
appropriate, will be developed for each of five exposure periods (10 
and 30 minutes, 1 hour, 4 hours, and 8 hours) 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 milligram/meter cube (mg/m\3\) 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/m\3\) 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 
an impaired ability to escape.
     AEGL-3 is the airborne concentration (expressed as ppm or 
mg/m\3\) of a substance above which it is predicted that the general 
population, including susceptible individuals, could experience life-
threatening health 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

[[Page 77868]]

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 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 
consensus. Once the NAC/AEGL Committee reaches a consensus, 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 7 hazardous substances. These values represent the 
fourth set of exposure levels proposed and published by the NAC/AEGL 
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); for 10 chemicals in the Federal 
Register of March 15, 2000 (65 FR 14186-14196) (FRL-6492-4); and for 14 
chemicals in the Federal Register of June 23, 2000 (65 FR 39263-39277) 
(FRL-6591-2) 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 
(NRC/NAS) in 1993. The term Community Emergency Exposure Levels (CELLS) 
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 
consensus 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 arbiter 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. List of Chemicals

    On behalf of the NAC/AEGL Committee, EPA is providing an 
opportunity for public comment on the AEGLs for the 7 chemicals 
identified in Table 1. Table 1 also provides the fax-on-demand item 
number for the chemical specific documents, which may be obtained as 
described in Unit 1.B.

A. Fax-On-Demand Table

                         Table 1.--Fax-On-Demand
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                                                      Fax-On-Demand item
             CAS No.                 Chemical name            no.
------------------------------------------------------------------------
75-44-5.........................  Phosgene..........  4862
78-82-0.........................  Isobutyronitrile..  4869
107-12-0........................  Propionitrile.....  4877
126-98-7........................  Methacrylonitrile.  4888
7790- 91-2......................  Chlorine            4922
                                   trifluoride.
151-56-4........................  Ethylenimine......  4890
75-55-8.........................  Propylenimine.....  4863
------------------------------------------------------------------------

B. Executive Summaries

    The following are executive summaries from the chemical specific 
Technical Support Documents (which may be obtained as described in Unit 
1.B. 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 in 
reviewing the complete Technical Support Document for a chemical when 
deciding issues related to use of the AEGL values within various 
programs.
    1. Phosgene--i. Description. Phosgene is a colorless gas at ambient 
temperature and pressure. Its odor has been described as similar to 
new-mown hay. Phosgene is manufactured from a reaction of carbon 
monoxide and chlorine gas in the presence of activated charcoal. The 
production of dyestuffs, isocyanates, carbonic acid esters 
(polycarbonates), acid chlorides, insecticides, and pharmaceutical 
chemicals requires phosgene.
    Appropriate data were not available for deriving AEGL-1 values for 
phosgene.
    AEGL-2 values were based on chemical pneumonia in rats (2 ppm for 
90 minutes) (Gross et al., 1965). An uncertainty factor (UF) of 3 was 
applied for interspecies extrapolation since little species variability 
is observed both with lethal and non lethal endpoints after exposure to 
phosgene. An UF of 3 was applied to account for sensitive human 
subpopulations since the mechanism of phosgene toxicity (binding to 
macromolecules and irritation) is not expected to vary greatly between 
individuals (total UF = 10). The 1.5 hour value was then scaled to the 
30-minute, 1-hour, 4-hour, and 8-hour AEGL exposure periods, using C\n\ 
x t = k, where n = 1 (Haber's Law) since Haber's Law has been shown to 
be valid for phosgene within certain limits. Haber's Law was originally 
derived from phosgene data (USEPA, August 1986). The 30-minute value 
was also adopted as the 10-minute value since extrapolation would yield 
a 10-minute AEGL-2 value close to concentrations producing alveolar 
edema in rats exposed for 10-minutes (Diller et al., 1985) and may not 
be protective.
    The 30-minute, 1-hour, 4-hour, and 8-hour AEGL-3 values were based 
on a 30-minute no-effect-level for death in rats (15 ppm) (Zwart et 
al., 1990). An UF of 3 was applied for interspecies extrapolation since 
little species variability is observed both with lethal and non-lethal 
endpoints after exposure to phosgene. An UF of 3 was applied to account 
for sensitive-human subpopulations since the mechanism of phosgene 
toxicity (binding to macromolecules and irritation) is not expected to 
vary greatly between individuals (total UF = 10). The value was then 
scaled to the 1-, 4-, and 8-hour AEGL periods, using C\n\ x t = k, 
where n = 1 (Haber's Law) since Haber's Law has been shown to be valid 
for phosgene within certain limits. Haber's Law was originally derived 
from phosgene data (USEPA, August 1986). The 10-minute AEGL-3 value was 
based on a 10-minute no-effect-level for death in rats and mice (Zwart 
et al., 1990). An UF of 3 was applied for interspecies extrapolation 
since little species variability is

[[Page 77869]]

observed both with lethal and non lethal endpoints after exposure to 
phosgene. An UF of 3 was applied to account for sensitive human 
subpopulations since the mechanism of phosgene toxicity (binding to 
macromolecules and irritation) is not expected to vary greatly between 
individuals (total UF = 10).
    The calculated values are listed in Table 2 below:

                                                                   Table 2.--Phosgene
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                                              Summary of Proposed Aegl Values for Phosgene [ppm (mg/m\3\)]
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         Classification               10-minutes          30-minutes            1-hour              4-hours             8-hours       Endpoint/Reference
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)             NA                  NA                  NA                  NA                  NA                  NA
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AEGL-2 (Disabling)                0.60 (2.5)          0.60 (2.5)          0.30 (1.2)          0.080 (0.33)        0.040 (0.16)        Chemical pneumonia
                                                                                                                                       rats (Gross et
                                                                                                                                       al., 1965)
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AEGL-3 (Lethal)                   3.6 (15)            1.5 (6.2)           0.75 (3.1)          0.20 (0.82 )        0.090 (0.34 )       30-minute r 10-
                                                                                                                                       minute no-effect-
                                                                                                                                       level for death
                                                                                                                                       in rats (Zwart et
                                                                                                                                       al., 1990)
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NA means not applicable

    ii. References. a. Diller, W. F., Bruch, J., and Dehnen, W. 1985. 
Pulmonary changes in rats following low phosgene exposure. Archives of 
Toxicology. 57:184-190.
    b. Gross, P., Rinehart, W.E., and Hatch, T. 1965. Chronic 
pneumonitis caused by phosgene. Archieves of Environmental Health. 
10:768-775.
    c. USEPA, August 1986. Health Assessment Document for Phosgene. 
EPA/600/8-86/022A. p. 1-4 to 1-5.
    d. Zwart, A., Arts, J.H.E., Klokman-Houweling, J.M., and Schoen, 
E.D. 1990. Determination of concentration-time-mortality relationships 
to replace LC50 values. Inhalation Toxicology. 2:105-117. 
November 1977.
    2. Isobutyronitrile--i. Description. Isobutyronitrile is a 
colorless liquid at ambient temperature and pressure. It has an almond-
like odor and may cause irritation or burning of the eyes and skin. It 
is metabolized to cyanide in the body and signs of exposure may include 
weakness, headache, confusion, nausea, vomiting, convulsion, dilated 
pupils, weak pulse, shallow and gasping breathing, and cyanosis (EPA, 
1985).
    Data were insufficient for derivation of AEGL-1 values for 
isobutyronitrile.
    The AEGL-2 was based on a no-effect-level from a developmental 
toxicity study in rats (100 ppm, 6 hour/day, days 6-20 of gestation) 
(Saillenfait et al., 1993). Although no interspecies information 
concerning isobutyronitrile toxicity was available, data from another 
nitrile (methacrylonitrile) suggest that the rat is not the most 
sensitive species. Therefore, an interspecies UF of 10 will be applied. 
In the absence of chemical-specific data and since much of the acute 
toxicity of nitriles is due to cyanide, the intraspecies UF will be the 
same as that used in the derivation of hydrogen cyanide AEGL-2 values 
(NAC/AEGL Committee, 1997). Thus, an UF of 3 will be applied to account 
for sensitive individuals since human accidental and occupational 
exposures suggest little intraindividual variability of hydrogen 
cyanide toxicity (NAC/AEGL Committee, 1997). Therefore, the total UF is 
30. The concentration-time relationship for many irritant and 
systemically acting vapors and gases may be described by C\n\ x t = k 
(ten Berge et al., 1986). Since much of the acute toxicity of 
isobutyronitrile is thought to be due to cyanide, the empirically 
derived chemical-specific value of n = 2.6 derived from cyanide rat 
lethality data) (NAC/AEGL Committee, 1997) will be used for scaling the 
AEGL values for isobutyronitrile across time.
    The AEGL-3 was based on a estimated no-effect-level for death in 
rats (1/3 of the 1-hour LC50: 1,800 ppm  3 = 600 
ppm) (Eastman Kodak Co., 1986a). Although no interspecies information 
concerning isobutyronitrile toxicity was available, data from another 
nitrile (methacrylonitrile) suggest that the rat is not the most 
sensitive species. Therefore, an interspecies UF of 10 will be applied. 
In the absence of chemical-specific data and since much of the acute 
toxicity of nitriles is due to cyanide, the intraspecies UF will be the 
same as that used in the derivation of hydrogen cyanide AEGL-3 values 
(NAC/AEGL Committee, 1997). Thus, an UF of 3 will be applied to account 
for sensitive individuals since human accidental and occupational 
exposures suggest little intraindividual variability of hydrogen 
cyanide toxicity (NAC/AEGL Committee, 1997). Therefore, the total UF is 
30. The concentration-time relationship for many irritant and 
systemically acting vapors and gases may be described by C\n\ x t = k 
(ten Berge et al., 1986). Since much of the acute toxicity of 
isobutyronitrile is thought to be due to cyanide, the empirically 
derived chemical-specific value of n = 2.6 (derived from cyanide rat 
lethality data, (NAC/AEGL Committee, 1997) will be used for scaling the 
AEGL values for isobutyronitrile across time.
    The calculated values are listed in Table 3 below:

                                                               Table 3.--Isobutyronitrile
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                          Summary of Proposed AEGL Values for Isobutyronitrile [ppm (mg/m\3\)]
---------------------------------------------------------------------------------------------------------------------------------------------------------
         Classification               10-minutes          30-minutes            1-hour              4-hours             8-hours       Endpoint/Reference
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)             ID                  ID                  ID                  ID                  ID                  Insufficient data
                                                                                                                                       to derive AEGL-1
                                                                                                                                       values
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-2 (Disabling)                13 (36)             8.7 (24)            6.6 (18)            3.9 (11)            3.0 (8.4)           No-effect-level in
                                                                                                                                       rats (Saillenfait
                                                                                                                                       et al., 1993)
--------------------------------------------------------------------------------------------------------------------------------------------------------

[[Page 77870]]

 
AEGL-3 (Lethal)                   40 (112)            26 (73)             20 (56)             12 (34)             9.0 (23)            Estimated no-
                                                                                                                                       observed-effect
                                                                                                                                       level (NOEL) for
                                                                                                                                       death in rats
                                                                                                                                       (Eastman Kodak,
                                                                                                                                       1986a)
--------------------------------------------------------------------------------------------------------------------------------------------------------
ID Insufficient data.

    ii. References. a. Eastman Kodak Company. 1986a. Acute inhalation 
toxicity and one-hour LC10 value of isobutyronitrile in the 
rat. (Study No. TX-86-193) Eastman Kodak Company, Rochester, NY 14650.
    b. NAC/AEGL Committee. 1997. Acute Exposure Guideline Levels for 
Hydrogen Cyanide. NAC Pro Draft 3:11/97.
    c. Saillenfait, A. M., Bonnet, P., Gurnier, J. P., and de Ceaurriz, 
J. 1993. Relative developmental toxicities of inhaled aliphatic 
mononitriles in rats. Fundamental Applied Toxicology. 20:365-375.
    d. 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 Hazardous Materials. 
13:301-309.
    e. USEPA. 1985. Chemical Profile. Isobutyronitrile. Washington, DC. 
December, 1985.
    3. Propionitrile--i. Description. Propionitrile is a colorless 
liquid at ambient temperature and pressure. It has a pleasant, 
ethereal, sweetish odor and may cause irritation or burning of the eyes 
and skin. It is metabolized to cyanide in the body and signs of 
exposure may include weakness, headache, confusion, nausea, vomiting, 
convulsion, dilated pupils, weak pulse, shallow and gasping breathing, 
and cyanosis (Hazardous Substances Data Bank (HSDB), 1998).
    Data were insufficient for derivation of AEGL-1 values for 
propionitrile.
    The AEGL-2 was based on headache, nausea, dizziness, vomiting, 
confusion, and disorientation in a 34-year-old male worker exposed to 
approximately 33.8 ppm propionitrile for 2 hours (Scolnick et al., 
1993). In the absence of chemical-specific data and since much of the 
acute toxicity of propionitrile appears to be due to cyanide, an UF of 
3 was applied to account for sensitive individuals since human 
accidental and occupational exposures suggest little intraindividual 
variability of hydrogen cyanide toxicity (NAC/AEGL Committee, 1997). A 
modifying factor of 2 was also applied to account for the poor 
database. Thus, the total uncertainty/modifying factor is 6. The 
concentration-time relationship for many irritant and systemically 
acting vapors and gases may be described by C\n\ x t = k (ten Berge et 
al., 1986). Since much of the acute toxicity of proprionitrile is 
thought to be due to cyanide, the empirically derived chemical-specific 
value of n = 2.6 (derived from cyanide rat lethality data, (NAC/AEGL 
Committee, 1997) was used for scaling the AEGL-2 values for 30-minutes, 
1-, 4-, and 8-hours. The 30-minute AEGL-2 value was also adopted as the 
10-minute value due to the fact that reliable data are limited to 
durations 2 hours, and it is considered inappropriate to 
extrapolate back to 10-minutes.
    The AEGL-3 was based on a 4-hour no-effect-level for death in rats 
of 690 ppm (Younger Labs, 1978). An interspecies UF of 10 was applied 
since toxicity information suggests that the rat is not the most 
sensitive species. In the absence of chemical-specific data and since 
much of the acute toxicity of proprionitrile appears to be due to 
cyanide, an UF of 3 was applied to account for sensitive individuals 
since human accidental and occupational exposures suggest little 
intraindividual variability of hydrogen cyanide toxicity (NAC/AEGL 
Committee, 1997). Thus, the total UF is 30. The concentration-time 
relationship for many irritant and systemically acting vapors and gases 
may be described by C\n\ x t = k (ten Berge et al., 1986). Since much 
of the acute toxicity of propionitrile is thought to be due to cyanide, 
the empirically derived chemical-specific value of n = 2.6 (derived 
from cyanide rat lethality data, (NAC/AEGL Committee, 1997) was used 
for scaling the AEGL values for values for 30-minutes, 1-hour, and 8-
hours. The 30-minute AEGL-3 value was also adopted as the 10-minute 
value due to the fact that the values are derived from a 4 hour 
exposure, and it is considered inappropriate to extrapolate back to 10-
minutes.
    The calculated values are listed in the Table 4 below:

                                                                 Table 4.--Propionitrile
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                  Summary of Proposed AEGL Values for Propionitrile [ppm (mg/m\3\)]
------------------------------------------------------------------------------------------------------------------------------------- Endpoint/Reference
         Classification               10-minutes          30-minutes            1-hour              4-hours             8-hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)             ID                  ID                  ID                  ID                  ID                  Insufficient data
                                                                                                                                       to derive AEGL-1
                                                                                                                                       values
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-2 (Disabling)                9.6 (22)            9.6 (22)            7.4 (17)            4.3 (9.8)           3.3 (7.6)           Headache, nausea,
                                                                                                                                       vomiting,
                                                                                                                                       dizziness,
                                                                                                                                       confusion in a
                                                                                                                                       human subject
                                                                                                                                       (Scolnick et al.,
                                                                                                                                       1993)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-3 (Lethal)                   51 (120)            51 (120)            39 (89)             23 (53)             18 (41)             No-effect-level
                                                                                                                                       for death in rats
                                                                                                                                       (Younger Labs,
                                                                                                                                       1978)
--------------------------------------------------------------------------------------------------------------------------------------------------------
ID Insufficient data.


[[Page 77871]]

    ii. References. a. HSDB. 1998. Propionitrile. Reviewed 9/24/92. 
Updated 6/2/98. Retrieved 6/16/98.
    b. NAC/AEGL Committee. 1997. Acute Exposure Guideline Levels for 
Hydrogen Cyanide. NAC Pro Draft 3:11/97.
    c. Scolnick, B., Hamel, D., and Woolf, A.D. 1993. Successful 
treatment of life threatening propionitrile exposure with sodium 
thiosulfate followed by hyperbaric oxygen. Journal of Occupational 
Medicine. 35:577-580.
    d. 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.
    e. Younger Labs. 1978. Initial Submission: Toxicological 
Investigation of Propionitrile with Cover Letter Dated 081992. 
OTS0546148.
    4. Methacrylonitrile--i. Description. Methacrylonitrile is a 
colorless liquid at ambient temperature and pressure. It has an odor 
similar to bitter almonds and may cause irritation or burning of the 
eyes and skin. It is metabolized to cyanide in the body and signs of 
exposure may include weakness, headache, confusion, nausea, vomiting, 
convulsion, dilated pupils, weak pulse, shallow and gasping breathing, 
and cyanosis (HSDB, 1998).
    Data were insufficient for derivation of AEGL-1 values for 
methacrylonitrile.
    The AEGL-2 values were set as 1/3 of the AEGL-3 values. The values 
obtained from this approach are supported by a repeated-exposure study 
in which dogs were exposed to 13.5 ppm methacrylonitrile, 7 hours/day, 
5 days/week for 90 days (Pozzani et al., 1968). Convulsions and loss of 
motor control of the hindlimbs were observed starting at day 39 of 
exposure.
    The AEGL-3 was based on a no-effect-level for death in mice (19 ppm 
for 4 hours) (Pozzani et al., 1968). An interspecies UF of 3 will be 
applied since the mouse is the most sensitive species. In the absence 
of chemical-specific information on intraspecies variability and since 
much of the acute toxicity of nitriles is due to cyanide, the 
intraspecies UF will be the same as that used in the derivation of 
hydrogen cyanide AEGL-3 values (NAC/AEGL Committee, 1997). Thus, an UF 
of 3 will be applied to account for sensitive individuals since human 
accidental and occupational exposures suggest little intraindividual 
variability of hydrogen cyanide toxicity (NAC/AEGL Committee, 1997). 
Thus, the total UF is 10. The concentration-time relationship for many 
irritant and systemically acting vapors and gases may be described by 
C\n\ x t = k (ten Berge et al., 1986). In the absence of chemical-
specific information and since much of the acute toxicity of 
methacryonitrile is thought to be due to cyanide, the empirically 
derived chemical-specific value of n = 2.6 (derived from cyanide rat 
lethality data, (NAC/AEGL Committee, 1997) will be used for scaling the 
30-minute, 1-, and 8-hour AEGL values for propionitrile across time. 
The 30-minute AEGL-3 value was also adopted as the 10-minute value due 
to the fact that reliable data are limited to durations 4 
hours, and it is considered inappropriate to extrapolate back to 10-
minutes.
    The calculated values are listed in Table 5 below:

                                                               Table 5.--Methacrylonitrile
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                          Summary of Proposed AEGL Values for Methacrylonitrile [ppm (mg/m\3\)]
---------------------------------------------------------------------------------------------------------------------------------------------------------
         Classification               10-minutes          30-minutes            1-hour              4-hours             8-hours       Endpoint/Reference
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)             ID                  ID                  ID                  ID                  ID                  Insufficient data
                                                                                                                                       to derive AEGL-1
                                                                                                                                       values
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-2 (Disabling)                1.5 (4.1)           1.5 (4.1)           1.1 (3.0)           0.70 (1.9)          0.50 (1.4)          1/3 of the AEGL-3
                                                                                                                                       values
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-3 (Lethal)                   4.5 (12)            4.5 (12)            3.4 (9.3)           2.0 (5.5)           1.5 (4.1)           4-hr. no-effect-
                                                                                                                                       level for death
                                                                                                                                       in mice (Pozzani
                                                                                                                                       et al., 1968)
--------------------------------------------------------------------------------------------------------------------------------------------------------
ID Insufficient data.

    ii. References. a. HSDB. 1998. Methacrylonitrile. Reviewed 9/24/92. 
Updated 6/3/98. Retrieved 6/16/98.
    b. NAC/AEGL Committee. 1997. Acute Exposure Guideline Levels for 
Hydrogen Cyanide. NAC Pro Draft 3: 11/97.
    c. Pozzani, U.C., Kinkead, E.R., and King, J.M. 1968. The mammalian 
toxicity of methacrylonitrile. American Industrial Hygiene Association 
Journal. 29:202-210.
    d. 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.
    5. Chlorine trifluoride--i. Description. Chlorine trifluoride is an 
extremely reactive and corrosive oxidizing agent used in nuclear 
reactor fuel processing, as a fluorinating agent, as an incendiary, 
igniter and propellant for rockets, and as a pyrolysis inhibitor for 
fluorocarbon polymers. It is unstable in air and rapidly hydrolyses to 
hydrogen fluoride (HF) and a number of chlorine-containing compounds 
including chlorine dioxide (ClO2). The toxic effects of 
ClF3 are likely due to HF and ClO2.
    Chlorine trifluoride is a mucous membrane irritant. Contact with 
the skin and eyes produces burns and inhalation causes pulmonary 
irritation and edema. Inhalation studies with the monkey, dog, rat, and 
mouse for several endpoints and exposure durations were located. Data 
on irritant effects were available for the dog and rat; data on 
sublethal and lethal concentrations were available for the monkey, rat, 
and mouse. Although human exposures have occurred, no data on exposure 
concentrations were located.
    The AEGL-1 was based on the threshold for notable discomfort 
(lacrimation) that was observed in dogs after 3 hours during a 6-hour 
exposure to an average concentration of 1.17 ppm (Horn and Weir, 1956). 
The only other sign of exposure was mild sensory irritation (nasal 
discharge) that usually occurred within 45 minutes. Nasal discharge in 
the sensitive nose of the dog was considered below the definition of 
the AEGL-1. No effects were observed in rats exposed to this 
concentration for 6 hours. The 1.17 ppm concentration for an exposure 
duration of 3 hours was divided by a combined interspecies and 
intraspecies UF of 10 (3 for interspecies differences [the dog was more 
sensitive than the rat] and 3 for intraspecies differences in 
sensitivity [the mechanism of toxicity is irritation; response to such 
a basic chemical effect on tissue is not expected to vary

[[Page 77872]]

significantly among individuals]). Scaling across time was based on 
C\n\ x t = k where n = 1 (Haber's Law); this concentration-exposure 
duration relationship was determined from several lethality studies. 
Because of the long exposure duration of the key study, the 10-minute 
AEGL-1 was set equal to the 30-minute AEGL-1.
    The AEGL-2 was based on signs of strong irritation (salivation, 
lacrimation, rhinorrhea, and blinking of the eyes) in dogs exposed to a 
concentration of 5.15 ppm for 6 hours (Horn and Weir, 1955). Although 
these effects appeared reversible by the end of the day, they may 
impair the ability to escape. Rats exposed to this concentration for 6 
hours appeared unaffected. The 6-hour concentration of 5.15 ppm was 
divided by a combined interspecies and intraspecies UF of 10 and scaled 
across time using the same reasons and relationships as for the AEGL-1 
in this unit. Because of the long exposure duration of the key study, 
the 10-minute AEGL-2 was set equal to the 30-minute AEGL-2.
    Lethality data (1-hour LC50 values) were available for 
the monkey, rat, and mouse. The AEGL-3 was based on the calculated 1-
hour LC01 for the mouse, the most sensitive species based on 
LC50 values (MacEwen and Vernot, 1970). This concentration, 
135 ppm, was divided by a combined interspecies and intraspecies UF of 
10 and scaled across time using the same reasons and relationships as 
for the AEGL-1 in this unit. Death was due to extreme irritation 
resulting in massive lung hemorrhaging. Data from another study in 
which dogs exposed to a concentration of 21 ppm for 6 hours showed 
extreme signs of irritation but no deaths resulted in essentially the 
same AEGL-3 values when adjusted by an UF of 10 and scaled across time 
using Haber's Law.
    The calculated values are listed in Table 6 below:

                                                             Table 6.--Chlorine Trifluoride
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                        Summary of Proposed AEGL Values for Chlorine Trifluoride [ppm (mg/m\3\)]
---------------------------------------------------------------------------------------------------------------------------------------------------------
         Classification               10-minutes          30-minutes            1-hour              4-hours             8-hours       Endpoint/Reference
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)             0.70 (2.7)          0.70 (2.7)          0.35 (1.3)           0.090 (0.34)        0.040 (0.15)       Threshold, notable
                                                                                                                                       discomfort--dog
                                                                                                                                       (Horn and Weir,
                                                                                                                                       1956)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-2 (Disabling)                6.2 (24)            6.2 (24)            3.1 (12)            0.77 (2.9)          0.39 (1.5)          Strong irritation--
                                                                                                                                       dog (Horn and
                                                                                                                                       Weir, 1955)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-3 (Lethal)                   81 (308)            27 (103)            14 (53)             3.4 (13)            1.7 (6.5)           Lethality (LC01)--
                                                                                                                                       mouse (MacEwen
                                                                                                                                       and Vernot, 1970)
--------------------------------------------------------------------------------------------------------------------------------------------------------

    ii. References. a. Horn, H.J. and R.J. Weir. 1955. Inhalation 
toxicology of chlorine trifluoride. I. Acute and subacute toxicity. 
A.M.A. Archives of Industrial Health. 12:515-521.
    b. Horn, H.J. and R.J. Weir. 1956. Inhalation toxicology of 
chlorine trifluoride. II. Chronic toxicity. A.M.A. Archives of 
Industrial Health. 13:340-345.
    c. MacEwen, J.D. and E.H. Vernot. 1970. Toxic Hazards Research Unit 
Annual Technical Report: 1970. AMRL-TR-70-77, Aerospace Medical 
Research Laboratory, Wright-Patterson Air Force Base, OH; National 
Technical Information Service, Springfield,VA
    6. Ethyleneimine--i. Description. Ethylenimine is a volatile, 
clear, colorless, flammable explosive liquid that has an odor similar 
to that of ammonia and an odor detection level of 2 ppm. It is a very 
reactive direct-acting alkylating agent, the activity of which is 
similar to that of nitrogen mustards. It is also very caustic, 
attacking numerous substances including plastics, metals, and glass 
that does not contain carbonate or borax. Estimates of domestic 
production of ethylenimine range between 3.3 and 4.85 million pounds. 
Ethylenimine is used in the manufacture of products, such as 
triethylenemelamine, paper, textile chemicals, adhesive binders, and 
petroleum refining chemicals. Ethylenimine is stored in 320-pound 
cylinders, but shipping quantities are unknown.
    Relevant data on ethylenimine consisted of only a few case studies 
in humans and acute inhalation lethality studies in laboratory animals. 
One individual died after a brief exposure to an unknown concentration 
of ethylenimine. Death was preceded by eye irritation, salivation, 
vomiting, respiratory tract irritation, breathlessness, and pulmonary 
edema; death may have been due to medical treatment. Individuals 
exposed to ethylenimine at estimated concentrations of 235-353 ppm and 
N-ethylethylenimine at 722 to 1,084 ppm for 11/2 to 2 hours suffered 
severe eye and respiratory tract irritation and vomiting that were 
delayed for 1 to 5 hours after exposure, followed by hemoglobinemia, 
eosinophilia, and albuminuria. Effects reported for occupational 
exposure to ethylenimine included skin sensitization, slow-healing 
dermatitis, rapidly reversible irritation to the eyes and respiratory 
tract, and blistering, reddening, and edema of the scrotum. Direct 
contact of liquid ethylenimine to the tongue caused delayed 
inflammation and edematous swelling of the oral cavity and inflammation 
of eyes, and direct contact of liquid with the skin causes necrotizing 
painless burns. Ethylenimine was genotoxic in all test systems 
investigated including bacteria, fungi, plants, insects, and mammalian 
cells in vitro. It is clastogenic in cultured human cells. Subcutaneous 
injection of rats with ethylenimine produced sarcomas at the injection 
site.
    Acute inhalation LC50 values were 2,558, 1,407, 545, 
268, 259, 58, and 35 ppm for rats exposed to ethylenimine for 5, 10, 
15, 60, 120, 240, or 480 minutes, respectively; 2,906, 2,824, 1,283, 
364, 235, 158, 45, and 27 ppm for guinea pigs exposed for 5, 10, 15, 
30, 60, 120, 240, or 480 minutes, respectively; and 2,236 ppm for mice 
exposed for 10 minutes. In all studies, death and other signs of 
toxicity were delayed depending on exposure concentration. Signs of 
toxicity included eye irritation, respiratory tract irritation, 
respiratory difficulty, prostration, complete loss of muscular 
coordination (mouse only), and convulsions (mouse only). Systemic 
effects included lung damage, congestion in lungs and all internal 
organs, damage to the kidney tubules, and albuminuria in rats and 
guinea pigs.
    AEGL-1 values were not derived, because ethylenimine is an 
insidious agent (effects are delayed) that has an odor similar to that 
of ammonia, and an odor detection limit at 2 ppm; consequently, 
ethylenimine has no specific warning properties (sensory irritation or 
odor). The odor detection level is similar to or higher than the

[[Page 77873]]

AEGL-2 values for 4-hour and 8-hour exposures; therefore, it is not 
valid nor would it be a benefit to the public to propose AEGL-1 values.
    No animal studies designed specifically to examine nonlethal 
effects of ethylenimine were located in the literature, and the human 
study involved exposure to another substance that could have 
contributed to the observed toxic effects. Therefore, the AEGL-2 values 
were based on a NOEL for extreme respiratory difficulty in guinea pigs 
(10 ppm for 240 minutes) in the study by Carpenter et al. (1948). An UF 
of 3 was applied for intraspecies variability because of the insidious 
nature of ethylenimine, and effects of exposure may not become apparent 
before exposure is terminated. Under these conditions; individuals with 
respiratory or heart diseases are not expected to respond differently 
from the general population. The very reactive alkylating activity of 
ethylenimine also suggests that it would be similarly effective in all 
individuals. A UF of 3 was also applied for interspecies sensitivity 
because of the reactive alkylating activity of ethylenimine and the 
similarity of the mode of action in different species. Further, the 
available evidence suggests that humans may be less sensitive than 
rodents. The total UF is 10. Scaling across the pertinent time frames 
was based on the equation C\0.91\ x t = k, where n was derived from the 
LC50 data for guinea pigs. The AEGL-2 values do not take 
into account the potential carcinogenicity of ethylenimine.
    AEGL-3 values were based on the acute inhalation study in rats 
(Carpenter et al. , 1948). The LC01 (lethality threshold) of 
15 ppm for the 8-hour exposure duration was estimated by probit 
analysis. The 8-hour LC01 was selected because it had the 
smallest standard error. A total UF of 10 (3 for intraspecies 
variability and 3 for interspecies sensitivity) was applied to the 
LC01 value. Scaling across the pertinent time frames was 
based on the equation C\1.1\ x t = k, where n was derived from 
LC50 data for rats.
    The calculated values are listed in Table 7 below:

                                                                 Table 7.--Ethylenimine
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                          Summary of Proposed AEGL Values for Ethylenimine\a,b\ [ppm (mg/m\3\)]
---------------------------------------------------------------------------------------------------------------------------------------------------------
         Classification               10-minutes          30-minutes            1-hour              4-hours             8-hours       Endpoint/Reference
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)                                                          No values derived for AEGL-1
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-2 (Disabling)                33 (59)             9.8 (185)           4.6 (8.2)           1.0 (1.8)           0.47 (0.84 )        NOEL for extreme
                                                                                                                                       respiratory
                                                                                                                                       difficulty
                                                                                                                                       (Carpenter et
                                                                                                                                       al., 1948)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-3 (Lethal)                   51 (91)             19 (34)             9.9 (18)            2.8 (5.0)           1.5 (2.7)           Threshold for
                                                                                                                                       lethality
                                                                                                                                       (Carpenter et
                                                                                                                                       al., 1948)
--------------------------------------------------------------------------------------------------------------------------------------------------------
a AEGL-2 and -3 values do not take into consideration the potential cancer risk due to exposure to ethylenimine.
b Effects at these concentrations may be delayed until sometime after exposure; toxic levels may be absorbed through the skin.

    ii. Reference. Carpenter, C. P.; Smyth, H. F., Jr.; Shaffer, C. B. 
1948. The acute toxicity ethyleneimine to small animals. Journal of 
Industrial Hygiene and Toxicology. 30:2-6.
    7. Propyleneimine--i. Description. Propylenimine is an aziridine 
compound used to modify latex surface coating resins to improve 
adhesion and to modify bonding properties of textiles, paper, and dyes; 
it is also used in photography, in the pharmaceutical industry, in 
gelatins, and in organic syntheses. Propylenimine is a colorless oily 
liquid that has an odor similar to that of ammonia. It is flammable and 
is an explosion hazard. Propylenimine is similar in structure and 
toxicity to ethylenimine.
    No data were found in the literature concerning toxicity or the 
odor detection threshold for exposure to propylenimine in humans. A 
time-response study conducted in rats and guinea pigs showed that 1/6 
guinea pigs died after exposure to 500 ppm for 60 minutes and 0/6 died 
after exposure to the same concentration for 30 minutes (Carpenter et 
al., 1948). In rats, 5/6 died after exposure to 500 ppm for 240 minutes 
and 0/6 died after exposure to the same concentration for 120 minutes. 
No concentration-response data were available for deriving AEGL values 
from animal studies. Therefore, a relative potency approach was used to 
derive AEGL-2 values, because the toxicity of propylenimine is 
considered to be qualitatively similar to that of ethylenimine. The 
study of Carpenter et al. (1948) showed that propylenimine is 4 to 8 
times less toxic than ethylenimine depending on the species: 4 or 5 
times less toxic to the guinea pig and 8 times less toxic to the rat. 
Tumors developed at multiple sites in rats treated orally with 
propylenimine for 28 or 60 weeks; therefore, International Agency for 
Research on Cancer (IARC) has classified propylenimine as Group 2B 
(possibly carcinogenic to human). Propylenimine is mutagenic in 
salmonella and drosophila.
    No AEGL-1 values were proposed for ethylenimine, and no values are 
proposed for propylenimine. Propylenimine has an odor similar to that 
of ammonia, the odor detection and irritation thresholds are not known, 
and propylenimine is probably an insidious agent similar to 
ethylenimine. It would not be valid nor beneficial to propose AEGL-1 
values for propylenimine.
    The derivation of AEGL-2 values is based on the relative toxicity 
approach. The AEGL values proposed for ethylenimine based on a no-
effect-level for extreme respiratory difficulty were as follows: 33, 
9.8, 4.6, 1.0, and 0.47 ppm for 10 minutes, 30 minutes, 1 hour, 4 
hours, and 8 hours, respectively. The NAC/AEGL Committee selected 5 as 
the appropriate relative toxicity value for deriving AEGL-2 values for 
propylenimine. The NAC/AEGL Committee also proposed that a modifying 
factor of 2 should be applied to account for a deficient database. 
Therefore, the resulting values for propylenimine based on a relative 
toxicity value of 5 and a modifying factor of 2 are 83, 25, 12, 2.5, 
and 1.2 ppm for exposure durations of 10 minutes, 30 minutes, 1 hour, 4 
hours, and 8 hours, respectively.
    It was the consensus of the NAC/AEGL Committee to consider a 500 
ppm exposure for 30 minutes as the no-effect-level for lethality and to 
use this concentration to derive AEGL-3 values. An UF of 10 (3 for 
intraspecies sensitivity and 3 for interspecies sensitivity) was 
applied to the no-effect-levels for lethality. Propylenimine is an 
insidious agent and signs of toxicity may not become apparent until 
after exposure. Propylenimine a very reactive direct-acting alkylating 
agent, and its mode of action is not expected to vary

[[Page 77874]]

considerably across species or within the population. Time 
extrapolation was based on the equation, C\n\ x t = k, where n = 0.91 
derived by probit analysis of LC50 data for guinea pigs 
exposed to ethylenimine.
    The calculated values are listed in Table 8 below:

                                                                 Table 8.--Propylenimine
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                         Summary of Proposed AEGL Values for Propylenimine\a,b\ [ppm (mg/m\3\)]
---------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                             ppm (mg/m\3\)
         Classification          ---------------------------------------------------------------------------------------------------- Endpoint/Reference
                                      10-minutes          30-minutes            1-hour              4-hours             8-hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1                                                                         No values derived for AEGL-1
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-2\c\                         83 (200)            25 (58)             12 (28)             2.5 (5.8)           1.2 (2.8)           NOEL for extreme
                                                                                                                                       respiratory
                                                                                                                                       difficulty
                                                                                                                                       (Carpenter et
                                                                                                                                       al., 1948)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-3                            167 (390)           50 (120 )           23 (54 )            5.1 (12)            2.4 (5.6 )          Lethality
                                                                                                                                       threshold
                                                                                                                                       (Carpenter et
                                                                                                                                       al., 1948)
--------------------------------------------------------------------------------------------------------------------------------------------------------
a AEGL-2 and -3 values do not take into consideration the potential cancer risk due to inhalation exposure to propylenimine.
b Effects including lethality, irritation to eyes, and irritation to the respiratory tract may be delayed until after exposure; toxic levels of
  propylenimine may be absorbed through the skin.
c AEGL values for propylenimine = AEGL for ethylenimine x 5 (relative potency factor)  2 (modifying factor).

    ii. Reference. Carpenter, C.P., Smyth, H.F., Jr., Shaffer, C.B. 
1948. The acute toxicity of ethylenimine to small animals. Journal of 
Industrial Hygiene and Toxicology. 30:2-6.

IV. Next Steps

    The NAC/AEGL Committee plans to publish ``Proposed'' AEGL values 
for five-exposure periods for other chemicals on the priority list in 
groups of approximately 10 to 20 chemicals in future Federal Register 
notices during the calendar year 2001.
    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: December 6, 2000.
Stephen L. Johnson,
Acting Assistant Administrator for Prevention, Pesticides and Toxic 
Substances.

[FR Doc. 00-31730 Filed 12-12-00; 8:45 am]
BILLING CODE 6560-50-S