`[Federal Register Volume 62, Number 210 (Thursday, October 30, 1997)]
[Notices]
[Pages 58840-58851]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-28642]



[[Page 58839]]

_______________________________________________________________________

Part IV





Environmental Protection Agency





_______________________________________________________________________



National Advisory Committee for Acute Exposure Guideline Levels for 
Hazardous Substances; Notices

  Federal Register / Vol. 62, No. 210 / Thursday, October 30, 1997 / 
Notices  

[[Page 58840]]


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ENVIRONMENTAL PROTECTION AGENCY

[OPPTS-00218; FRL-5737-3]


National Advisory Committee for Acute Exposure Guideline Levels 
for Hazardous Substances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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

SUMMARY: The National Advisory Committee for Acute Exposure Guideline 
Levels for Hazardous Substances (NAC/AEGL Committee ) is developing 
Acute Exposure Guideline Levels (AEGLs) on an on going basis to assist 
Federal and State agencies and private sector organizations with their 
needs for short-term hazardous chemical exposure information (one time 
only exposures during chemical emergency situations). The NAC/AEGL 
Committee has completed work on ``Proposed AEGLs'' for 12 chemicals. 
The purpose of today's notice is to solicit comments on proposed values 
and the accompanying scientific rationale for their development. More 
specifically, this notice solicits comments on the proposed AEGL 
values, the methodologies used to determine no-observed-adverse-effect-
levels (NOAELs) or lowest-observed-adverse-effect-levels (LOAELs) for 
specific effects, the uncertainty factors selected for intraspecies and 
interspecies extrapolation, the uncertainity factors used to 
accommodate for sensitive or susceptible individuals in the human 
population, the use of modifying factors and the values applied, and 
other aspects related to the development of the AEGL values.

DATES: Submit written comments on or before December 1, 1997.

ADDRESSES: Submit three copies of written comments on the Proposed 
AEGLs, identified by docket control number (OPPTS-00218; FRL- 5737-3) 
to: Environmental Protection Agency, Office of Pollution Prevention and 
Toxics (OPPT), Document Control Office (7407), Rm. G-009, 401 M St., 
SW., Washington, DC 20460.
    Comments and data may also be submitted electronically to: 
[email protected]. Follow the instructions under Unit V. of 
this document. No Confidential Business Information (CBI) should be 
submitted through e-mail.
    All comments which contain information claimed as CBI must be 
clearly marked as such. Three sanitized copies of any comments 
containing information claimed as CBI must also be submitted and will 
be placed in the public record for this notice. Persons submitting 
information on any portion of which they believe is entitled to 
treatment as CBI by EPA must assert a business confidentiality claim in 
accordance with 40 CFR 2.203(b) for each such portion. This claim must 
be made at the time that the information is submitted to EPA. If a 
submitter does not assert a confidentiality claim at the time of 
submission, EPA will consider this as a waiver of any confidentiality 
claim and the information may be made available to the public by EPA 
without further notice to the submitter.
FOR FURTHER INFORMATION CONTACT: Susan B. Hazen, Director, 
Environmental Assistance Division (7408), Rm. ET-543B, Office of 
Pollution Prevention and Toxics, Environmental Protection Agency, 401 M 
St., SW., Washington, DC 20460; telephone: (202) 554-1404; TDD: (202) 
554-0551; e-mail: TSCA-H[email protected].

SUPPLEMENTARY INFORMATION:

Electronic Availability
Internet
    Electronic copies of this notice and various support documents are 
available from the EPA Home Page at the Federal Register--Environmental 
Documents entry for this document under ``Laws and Regulations'' 
(http://www.epa.gov/fedrgstr/).
Fax-On-Demand
    Using a faxphone call (202) 401-0527 and select item 3800 for an 
index of items in this category. For a more specific item number, see 
the table in Unit IV. of this document.

I. 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 objective stated in 
the charter 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 
using 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 May 21, 1997 (62 FR 27734 (FRL-5718-9)). This 
list is intended to be expanded and also may be modified as priorities 
of the stakeholder member organizations are further developed.
    While the development of AEGLs for chemicals is not statutorily 
based; at least one EPA rulemaking references their planned adoption. 
In the final Clean Air Act and Amendment section 112 Risk Management 
rulemaking (June 20, 1996, 61 FR 31685, (FRL-5516-5)), ``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 toxicity 
reference for substances under this rule.'' Federal and State agencies 
and private organizations may also adopt AEGLs for chemical emergency 
programs in the future.
    The NAC/AEGL Committee meets four times per year and plans to 
develop AEGL values for 30-40 chemicals per year during the next 8 to 
10 years. Since its first meeting on June 19-21, 1996, the NAC/AEGL 
Committee has completed work on ``Proposed AEGLs'' for 12 chemicals. 
The basic approach and guidance used to derive AEGLs has been the 
National Academy of Sciences (NAS) publication, ``Guidelines for 
Developing Community Emergency Exposure Levels for Hazardous 
Substances'' (National Academy Press, Washington, DC, 1993; copies are 
available in the Docket). The NAC/AEGL Committee meetings have been 
public and numerous public comments and presentations have been made. 
At this time, the NAC/AEGL Committee is providing further opportunity 
for public input through this notice. Comments are welcome on both the 
AEGL values and their related Technical Support Documents (filed in the 
public Docket).
    The NAC/AEGL Committee will review comments received and revise the 
Proposed AEGLs as deemed appropriate. The resulting values will be 
established as ``Interim AEGLs'' and will be available for use in 
various public and private sector programs on human health effects 
related to short-term exposures to hazardous chemicals. It is planned 
that Interim AEGLs will be forwarded to the National Research Council, 
National Academy of Sciences (NRC/NAS) for further review, 
collaboration with the NAC/AEGL Committee, and possible revision of the

[[Page 58841]]

AEGL values and the methodologies used to derive them. It is 
anticipated that ``Final AEGLs'' will be published under the auspices 
of the NAS following concurrence on the values and the scientific 
rationale used for their development. Until Final AEGLs are published 
by the NAS, the Interim AEGLs are intended for use as needed by 
individuals or organizations in both the public and private sectors.

II. Characterization of the AEGLs

    The AEGLs represent short-term threshold or ceiling exposure values 
intended for the protection of the general public, including 
susceptible or sensitive individuals, but not hypersusceptible or 
hypersensitive individuals. The AEGLs represent biological reference 
values for this defined human population and consist of three 
biological endpoints for each of four different exposure periods of 30 
minutes (mins), l hour (hr), 4 hours (hrs), and 8 hrs. In certain 
instances, AEGL values have been and will be developed for additional 
exposure periods of 5 or 10 mins. The biological endpoints include 
AEGL-1, AEGL-2, and AEGL-3 and are defined as follows:
    AEGL-1 is the airborne concentration (expressed as parts per 
millions (ppm) or milligrams (mg)/meters (m)3) of a 
substance at or above which it is predicted that the general 
population, including ``susceptible'' but excluding 
``hypersusceptible'' individuals, could experience notable discomfort. 
Airborne concentrations below AEGL-1 represent exposure levels that 
could produce mild odor, taste, or other sensory irritations.
    AEGL-2 is the airborne concentration (expressed as ppm or mg/
m3) of a substance at or above which it is predicted that 
the general population, including ``susceptible'' but excluding 
``hypersusceptible'' individuals, could experience irreversible or 
other serious, long-lasting effects or impaired ability to escape. 
Airborne concentrations below the AEGL-2 but at or above AEGL-1 
represent exposure levels that may cause notable discomfort.
    AEGL-3 is the airborne concentration (expressed as ppm or mg/
m3) of a substance at or above which it is predicted that 
the general population, including ``susceptible'' but excluding 
``hypersusceptible'' individuals, could experience life-threatening 
effects or death. Airborne concentrations below AEGL-3 but at or above 
AEGL-2 represent exposure levels that may cause irreversible or other 
serious, long-lasting effects or impaired ability to escape.

III. 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 data bases, 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 and ``Draft AEGL'' values are 
prepared in conjunction with designated 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 
Draft AEGL values and the relevant data and information for each 
chemical presented at the meeting, the NAC/AEGL Committee attempts to 
reach a consensus on acceptable values. 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 notice the NAC/AEGL Committee publishes Proposed AEGL 
values and the accompanying scientific rationale for their development 
for 12 hazardous substances. These values represent the first exposure 
levels proposed and published by the NAC/AEGL Committee. 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 (NAS) in 1993 
(copies of this guidance document are available for review in the 
Docket). The term Community Emergency Exposure Levels (CEELs) used by 
the NAS is synonymous with AEGLs in every way. The NAC/AEGL Committee 
has adopted the term Acute Exposure Guideline Levels or AEGLs to better 
connote the broad application of the values to the population defined 
by the NAS in its guidance document and addressed by the NAC/AEGL 
Committee in its development of the AEGLs. 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 proposed values 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. It has been planned to have the NAS 
subcommittee participate in the peer review of the Interim AEGLs and in 
the resolution of issues regarding the AEGL values and the data and 
basic methodology used for setting AEGLs. It is anticipated that 
``Final AEGL'' values will be published under the auspices of the NAS.

IV. List of Twelve Chemicals With Proposed AEGL Values

                                                                        
------------------------------------------------------------------------
                                                      Fax-On-Demand item
             CAS No.                 Chemical name            no.       
------------------------------------------------------------------------
57-14-7.........................  1,1-Dimethylhydraz  3852              
                                   ine                                  
60-34-4.........................  Methylhydrazine     3853              
62-53-3.........................  Aniline             3854              
75-21-8.........................  Ethylene oxide      3861              
302-01-2........................  Hydrazine           3891              
540-59-0........................  1,2-Dichloroethene  3895              
540-73-8........................  1,2-Dimethylhydraz  3852              
                                   ine                                  
7697-37-2.......................  Nitric acid         3912              
7782-41-4.......................  Fluorine            3915              
7782-50-5.......................  Chlorine            3916              
7784-42-1.......................  Arsine              3921              
7803-51-2.......................  Phosphine           3923              
------------------------------------------------------------------------

Chemicals With Proposed AEGLs (Alphabetical Order)

Aniline

    Aniline is an aromatic amine used chiefly in the chemical industry 
in the manufacture of dyes, dye intermediates, rubber accelerators, 
antioxidants, drugs, photographic chemicals, isocyanates, herbicides, 
and fungicides. The primary effect of an acute exposure to aniline is 
on the hemoglobin of the red blood cell, resulting in the formation of 
methemoglobin. The effect may occur following inhalation, ingestion, or 
cutaneous absorption. In addition to methemoglobinemia, chronic 
exposures or exposures to high concentrations may produce signs and 
symptoms of headache, paresthesia, tremor, pain,

[[Page 58842]]

narcosis/coma, cardiac arrhythmia, and possibly death.
    All AEGL values are based on a study in which rats were exposed to 
concentrations of 0, 10, 30, 50, 100, or 150 ppm for 8 hrs (Kim and 
Carlson, 1986). The only reported effect was formation of 
methemoglobin. At a constant concentration (100 ppm), the formation of 
methemoglobin over time was basically linear, reaching an asymptote at 
8 hrs.
    The AEGL-1 was based on a concentration of 100 ppm for 8 hrs which 
resulted in elevation of methemoglobin from a control value of 1.1% 
(range, 0.4-2.1%) to 22%. This level of methemoglobin results in 
clinical cyanosis but no hypoxic symptoms. Additional studies on oral 
ingestion showed that humans are much more sensitive than rats to 
aniline exposure as indicated by formation of methemoglobin. Thus, an 
uncertainty factor of 10 was used for interspecies extrapolation. 
Several sources also indicate that newborns are more sensitive to 
methemoglobin-forming chemicals than adults; thus, an intraspecies 
uncertainty factor of 10 was applied. The data were scaled across time 
using C1 x t = k (the relationship between concentration of 
aniline and methemoglobin formation at a fixed time [8 hrs] is linear 
as is the relationship between time and severity of effect when 
concentration is held constant; in addition, data from several 
lethality [LC50] studies show that the relationship between 
C and t is linear).
    The AEGL-2 was based on the same study with rats in which a 
concentration of 150 ppm for 8 hrs resulted in elevation of 
methemoglobin from a control value of 1.1% to 41%. This level of 
methemoglobin is associated with fatigue, lethargy, exertional dyspnea, 
and headache in humans and was considered the threshold for disabling 
effects. The 150 ppm concentration was divided by a combined 
uncertainty factor of 100 and scaled across time using the same reasons 
and relationships as for the AEGL-1 above. Because of the small data 
base and the lack of recent, reliable human inhalation studies, 
uncertainty factors of 10 were applied for each of the interspecies and 
intraspecies variabilities.
    Data on concentrations of aniline inducing methemoglobin levels at 
the threshold for lethality were not available. Based on the fact that 
the relationship between concentration of aniline and methemoglobin 
formation is linear, the dose-response curve from the study on which 
the AEGL-1 and AEGL-2 were based was extrapolated to a concentration 
resulting in >70% formation of methemoglobin, the threshold for 
lethality. The concentration of 250 ppm for 8 hrs was chosen as the 
threshold for lethality. The AEGL-3 was based on dividing the 250 ppm 
value by a combined uncertainty factor of 100 and scaled across time 
using the same reasons and relationships as for the AEGL-1 above. The 
uncertainty factors of 10 for each of the interspecies and intraspecies 
variabilities are supported by the small data base of information and 
the lack of recent, reliable human inhalation studies.
    Studies with repeated exposures at approximately the same 
concentrations in the rat resulted in additional effects on the blood 
and spleen, but concentrations up to 87 ppm, 6 hrs/day, 5 days/week, 
for 2 weeks were not disabling or life-threatening. The calculated 
values are listed in the table below. Because aniline is absorbed 
through the skin, a skin notation was added to the summary table.

                                                   Summary Table of Proposed AEGL Values for Aniline a                                                  
--------------------------------------------------------------------------------------------------------------------------------------------------------
           Classification                   30-minute                1-hour                  4-hour                 8-hour          Endpoint (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1                               16 ppm (61 mg/m3)       8.0 ppm (30 mg/m3)      2.0 ppm (7.6 mg/m3)     1.0 ppm (3.8 mg/m3)   22% methemoglobin--  
                                                                                                                                    cyanosis (Kim and   
                                                                                                                                    Carlson, 1986)      
                                                                                                                                                        
AEGL-2                               24 ppm (91 mg/m3)        12 ppm (46 mg/m3)       3.0 ppm (11 mg/m3)    1.5 ppm (5.7 mg/m3)    41% methemoglobin--  
                                                                                                                                    lethargy (Kim and   
                                                                                                                                    Carlson, 1986)      
                                                                                                                                                        
AEGL-3                               40 ppm (152 mg/m3)      20 ppm (76 mg/m3)       5.0 ppm (19 mg/m3)     2.5 ppm (9.5 mg/m3)    >70% methemoglobin-- 
                                                                                                                                    lethality           
                                                                                                                                    (extrapolated from  
                                                                                                                                    data of Kim and     
                                                                                                                                    Carlson, 1986)      
--------------------------------------------------------------------------------------------------------------------------------------------------------
aCutaneous absorption may occur; direct skin contact with the vapor or liquid should be avoided.                                                        

References

    1. Kim, Y.C. and G.P. Carlson. 1986. The effect of an unusual 
workshift on chemical toxicity. Part II. Studies on the exposure of 
rats to aniline. Fundamental and Applied Toxicology 7:144-152.

Arsine

    Arsine is an extremely toxic, colorless gas used in the 
semiconductor industry. Exposure to arsine may also result from mining 
and manufacturing processes involving arsenicals, and from paints and 
herbicides containing arsenicals.
    Arsine is a potent hemolytic agent, ultimately causing death via 
renal failure. Numerous human case reports are available documenting 
the extreme toxicity of arsine exposure but these reports lack 
definitive quantitative exposure data.
    Exposure-response data from animal studies were used to derive AEGL 
values for arsine. AEGL values derived with animal data were more 
conservative than AEGLs estimated from limited anecdotal human data. 
The greater conservatism afforded by the animal data may be justified 
by the incomplete and often equivocal data for human exposures, the 
documented extreme toxicity of arsine, and the known latency involved 
in arsine-induced lethality. The AEGL values for the various exposure 
periods of concern (0.5, 1, 4, and 8 hrs) were scaled from the 
experimental exposure duration using exponential scaling (C2 
x t = k), where n = 2 represented an estimate of the concentration-time 
relationship. 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 1 to 3.5 (ten 
Berge et al 1986). The mid-point value of 2 was used as the exponent n 
for scaling the AEGL values for arsine across time, because no exposure 
versus time data were available.
    Based upon the available data, derivation of AEGL-1 values was 
considered to be inappropriate. The available human and animal data 
affirm that there is little margin between exposures that result in 
little or no signs of toxicity and those that result in lethality. The 
mechanism of arsine toxicity (induction of hemolysis that may rapidly 
result in renal failure and death), and the fact that toxicity in 
animals and humans has been demonstrated at concentrations at or below 
the odor threshold also support

[[Page 58843]]

such a conclusion by the NAC/AEGL Committee.
    The AEGL-2 values were based upon exposure levels that did not 
result in significant alterations in hematologic parameters in mice 
exposed to arsine for 1 hr (Peterson and Bhattacharyya, 1985). AEGL-2 
derivations based upon several data sets were similar, thereby 
providing validation to the proposed AEGLs. Derivation of AEGLs based 
upon limited data for humans resulted in values indicative of 
potentially hazardous exposures. Uncertainty factor application 
included a factor of 10 for interspecies variability because of 
uncertainties regarding species-specific sensitivity to arsine-induced 
hemolysis. Uncertainty regarding intraspecies variability was limited 
to 3 because the hemolytic response to arsine is not expected to vary 
greatly among individuals.
    The AEGL-3 values were based upon data assessing the lethality in 
mice exposed to arsine for 1 hr (Peterson and Bhattacharyya, 1985). A 
total uncertainty factor application of 30 was applied as for AEGL-2 
values and for the same reasons. Derivation of AEGL-3 values using 
limited data in monkeys affirmed the values derived based upon the 
mouse data. AEGL-3 values derived from limited human exposure data 
resulted in levels considered potentially hazardous.
    The three AEGL exposure levels reflect the narrow range between 
exposures resulting in minor effects and those producing lethality. A 
conservative approach in the development of AEGLs for arsine was 
justified by the known steep dose-response curve, the induction of 
hemolysis by arsine at extremely low concentrations, and the potential 
of hemolysis to progress to life-threatening renal failure.

                                                       Summary of Proposed AEGL Values for Arsine                                                       
--------------------------------------------------------------------------------------------------------------------------------------------------------
           Classification                   30-minute                1-hour                  4-hour                 8-hour          Endpoint (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1.............................  NAa...................  NAa...................  NAa..................  NAa..................  Inappropriate based  
                                                                                                                                    upon steep dose-    
                                                                                                                                    response            
                                                                                                                                    relationship,       
                                                                                                                                    mechanism of        
                                                                                                                                    toxicity, and       
                                                                                                                                    because toxicity    
                                                                                                                                    occurs at or below  
                                                                                                                                    the odor threshold  
                                                                                                                                                        
AEGL-2.............................  0.24 ppm (0.8 mg/m3)..  0.17 ppm (0.5 mg/m3)..  0.08 ppm (0.3 mg/m3).  0.06 ppm (0.3 mg/m3).  Absence of           
                                                                                                                                    significant         
                                                                                                                                    hematological       
                                                                                                                                    alterations in mice 
                                                                                                                                    consistent with the 
                                                                                                                                    known continum of   
                                                                                                                                    arsine toxicity     
                                                                                                                                    (Peterson and       
                                                                                                                                    Bhattacharyya, 1985)
                                                                                                                                                        
AEGL-3.............................  0.7 ppm (2.2 mg/m3)...  0.5 ppm (1.6 mg/m3)...  0.25 ppm (0.8 mg/m3).  0.18 ppm (0.6 mg/m3).  Estimated threshold  
                                                                                                                                    for nonlethality in 
                                                                                                                                    mice (Peterson and  
                                                                                                                                    Bhattacharyya, 1985)
--------------------------------------------------------------------------------------------------------------------------------------------------------
a NA Not appropriate                                                                                                                                    

References

    1. Peterson, D.P. and Bhattacharyya, M.H. 1985. Hematological 
responses to arsine exposure: quantitation of exposure response in 
mice. Fundamental and Applied Toxicology 5:499-505.

Chlorine

    Chlorine is a greenish-yellow, highly reactive halogen gas with a 
pungent, suffocating odor. Like other halogens, chlorine does not occur 
in the elemental state in nature; it rapidly combines with both 
inorganic and organic substances. Chlorine is used in the manufacture 
of a wide variety of chemicals, as a bleaching agent in industry and 
household products, and as a biocide in water and waste treatment 
plants.
    Chlorine is an irritant to the eyes and respiratory tract; reaction 
with moist surfaces produces hydrochloric and hypochlorous acids. Its 
irritant properties have been studied in human volunteers and its acute 
inhalation toxicity has been studied in several laboratory animal 
species. The data from the human and laboratory animal studies were 
sufficient for development of three AEGLs for four time periods (i.e., 
30 mins and 1, 4, and 8 hrs). Probit and regression analyses of the 
animal exposure time-concentration-mortality data determined that the 
relationship between concentration and time is approximately 
C2 x t = k.
    The AEGL-1 was based on the observation that exposure to human 
volunteers, including a sensitive individual, of 0.5 ppm for 4 hrs 
produced no sensory irritation but did result in transient changes in 
some pulmonary function parameters for the sensitive individual (Rotman 
et al., 1983). Because both sexes were tested and all subjects were 
undergoing light exercise, making them more vulnerable to sensory 
irritation, and because a sensitive individual was included in the 
test, no uncertainty factor to account for differences in human 
sensitivity was applied. The 0.5 ppm exposure for 4 hrs was scaled to 
the other time periods using the relationship C2 x t = k. 
The scaling factor n = 2 was based on probit and regression analyses of 
animal lethality data.
    The AEGL-2 values were derived based on the same study (Rotman et 
al., 1983) in which healthy human subjects experienced transient 
changes in pulmonary function measurements and a sensitive individual 
experienced an asthmatic attack (shortness of breath and wheezing) at a 
concentration of 1 ppm for 4 hrs. The sensitive individual remained in 
the exposure chamber for the full 4 hrs. Because both sexes were tested 
and all subjects were undergoing light exercise, making them more 
vulnerable to sensory irritation, and because a sensitive individual 
was included in the test, no uncertainty factor to account for 
differences in human sensitivity was applied. The 4-hr 1 ppm 
concentration was scaled to the other time periods using the 
C2 x t = k relationship. The scaling factor or exponent of n 
= 2 is based on probit and regression analyses of animal lethality 
data.
    In the absence of human data, the AEGL-3 values were based on 
animal lethality data. Because the mouse was shown to be more sensitive 
than other mammals to irritant gases including chlorine and does not 
provide an appropriate basis for quantitatively predicting mortality in 
humans, a value below that resulting in no deaths in the rat, 213 and 
322 ppm in two studies (MacEwen and Vernot, 1972; Zwart and Woutersen, 
1988) and above that resulting in no deaths in the mouse (150 ppm) for 
exposure periods of 1 hr was chosen. Mice exposed to chlorine 
experienced delayed deaths attributable to bronchopneumonia. The AEGL-3 
values were derived from a 1-hr concentration of 200 ppm. This value 
was divided by a combined uncertainty factor of 10. An uncertainty 
factor of 3

[[Page 58844]]

was used to extrapolate from rats to humans, since interspecies values 
for the same endpoint differed by a factor of approximately 2 within 
each of several studies. An uncertainty factor of 3 was used to account 
for differences in human sensitivity, since the toxic effect is due to 
a chemical reaction with biological tissue of the respiratory tract 
which is unlikely to be different among individuals. The AEGL-3 values 
were scaled to the other exposure periods based on the C2 x 
t = k relationship. The scaling factor or exponent of n = 2 is based on 
probit and regression analyses of animal lethality data.
    Based on the large data base and the extensive, well-conducted 
studies, confidence in the AEGL values is high. The calculated values 
are listed in the table below.

                                                      Summary of Proposed AEGL Values for Chlorine                                                      
--------------------------------------------------------------------------------------------------------------------------------------------------------
           Classification                   30-minute                1-hour                  4-hour                 8-hour          Endpoint (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1                               1.4 ppm (4.1 mg/m3)...  1.0 ppm (2.9 mg/m3)...  0.5 ppm (1.5 mg/m3)..  0.5 ppm (1.5 mg/m3)..  Pulmonary function-- 
                                                                                                                                    human (Rotman et    
                                                                                                                                    al., 1983)          
                                                                                                                                                        
AEGL-2                               2.8 ppm (8.1 mg/m3)...  2.0 ppm (5.8 mg/m3)...  1.0 ppm (2.9 mg/m3)..  0.7 ppm (2.0 mg/m3)..  Asthmatic attack--   
                                                                                                                                    human (Rotman et    
                                                                                                                                    al., 1983)          
                                                                                                                                                        
AEGL-3                               28 ppm (81 mg/m3).....  20 ppm (58 mg/m3).....  10 ppm (29 mg/m3)....  7.1 ppm (21 mg/m3)...  Lethality--rat       
                                                                                                                                    (MacEwen and Vernot,
                                                                                                                                    1972; Zwart and     
                                                                                                                                    Woutersen, 1988)    
--------------------------------------------------------------------------------------------------------------------------------------------------------

References

    1. MacEwen, J.D. and E.H. Vernot. 1972. Toxic Hazards Research 
Unit Annual Technical Report: 1972. AMRL-TR-72-62, Aerospace Medical 
Research Laboratory, Wright-Patterson Air Force Base, OH; National 
Technical Information Service, Springfield, VA.
    2. Rotman, H.H., M.J. Fliegelman, T. Moore, R.G. Smith, D.M. 
Anglen, C.J. Kowalski, and J.G. Weg. 1983. Effects of low 
concentration of chlorine on pulmonary function in humans. Journal 
of Applied Physiology 54:1120-1124.
    3. Zwart, A. and R.A. Woutersen. 1988. Acute inhalation toxicity 
of chlorine in rats and mice: time-concentration-mortality 
relationships and effects on respiration. Journal of Hazardous 
Material 19:195-208.

1,2-Dichloroethene

    1,2-dichloroethene is a flammable, colorless liquid existing in 
both cis- and trans- forms and as a mixture of these two isomers. It 
has been used as an intermediate in the production of chlorinated 
solvents and as a low-temperature extraction solvent for decaffeinated 
coffee, dyes, perfumes, lacquers, and thermoplastics. The compound is a 
narcotic. Data on narcosis in humans, cats, rats, and mice, and 
systemic effects in cats, rats, and mice were available for development 
of AEGLs. The data were considered adequate for derivation of the three 
AEGL classifications for four time periods.
    The AEGL-1 was based on a human exposure concentration of 1,100 ppm 
trans-1,2-dichloroethene for 5 mins (Lehmann and Schmidt-Kehl 1936). 
Although this is a no-effect-level for narcotic effects it represents a 
concentration that is above the odor threshold. Because of the mode of 
action and similarity in response to this chemical as an irritant, this 
value was divided by an uncertainty factor of 3 to protect sensitive 
individuals and by a modifying factor of 2 to account for the probable 
difference in toxicity between the cis- and trans- isomers. It was then 
scaled to the 30-min, 1-, 4-, and 8-hr exposures using the 
cn x t = k relationship, where n = 2. 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 1 to 3.5 (ten Berge et al 1986). Because no 
exposure versus time data were available, the mid-point value of 2 was 
used as the exponent n for scaling the AEGL values for dichloroethene 
across time.
    The AEGL-2 was based on slight dizziness in humans exposed to 3300 
ppm trans-1,2-dichloroethene for 5 mins (Lehmann and Schmidt-Kehl 
1936). Because of the mode of action and similarity in response to this 
chemical, this value was divided by an uncertainty factor of 3 to 
protect sensitive individuals and by a modifying factor of 2 to account 
for the probable difference in toxicity between the cis- and trans- 
isomers. It was then scaled up to the 30-minute (min), 1-, 4-, and 8-hr 
exposure periods using the cn x t = k relationship, where 
the mid-point of the exponential range n = 2 was used.
    The AEGL-3 was based on fibrous swelling and hyperemia of cardiac 
muscle with little striation in rats exposed to 3000 ppm trans-1,2-
dichloroethene for 8 hrs. Because the lethality data are limited and 
quite variable across species for the data that do exist this value was 
divided by an uncertainty factor of 10 to account for interspecies 
variation. An additional uncertainty factor of 3 was applied to protect 
sensitive individuals and a modifying factor of 2 was also applied to 
account for the probable difference in toxicity between the cis- and 
trans- isomers. The 8-hr AEGL value was then scaled to the 30-min, 1-, 
and 4-hr exposures using the cn x t = k relationship, where 
the midpoint of the experimental range n = 2 was used. The calculated 
values are listed in the table below.

                                                 Summary of Proposed AEGL Values for 1,2-Dichloroethene                                                 
--------------------------------------------------------------------------------------------------------------------------------------------------------
           Classification                   30-minute                1-hour                  4-hour                 8-hour          Endpoint (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)                19 ppm (75 mg/m3)       13 ppm (53 mg/m3)       6.6 ppm (26 mg/m3)     4.7 ppm (19 mg/m3)     No effect in humans  
                                                                                                                                    (Lehmann and Schmidt-
                                                                                                                                    Kehl, 1936)         
                                                                                                                                                        
AEGL-2 (Disabling)                   56 ppm (224 mg/m3)      40 ppm (160 mg/m3)      20 ppm (80 mg/m3)      14 ppm (56 mg/m3)      Slight dizziness in  
                                                                                                                                    humans (Lehmann and 
                                                                                                                                    Schmidt-Kehl, 1936) 
                                                                                                                                                        

[[Page 58845]]

                                                                                                                                                        
AEGL-3 (Lethality)                   200 ppm (800 mg/m3)     141 ppm (564 mg/m3)     71 ppm (284 mg/m3)     50 ppm (200 mg/m3)     Fibrous swelling and 
                                                                                                                                    hyperemia of cardiac
                                                                                                                                    muscle with poorly  
                                                                                                                                    maintained striation
                                                                                                                                    in rats (Freundt et 
                                                                                                                                    al., 1977)          
                                                                                                                                                        
--------------------------------------------------------------------------------------------------------------------------------------------------------

References

    1. Freundt, K.J., Liebalt, G.P., and Lieberwirth, E. 1977. 
Toxicity studies on trans-1,2-dichloroethylene. Toxicology 7:141-
153.
    2. Lehmann, K.B. and Schmidt-Kehl, L. 1936. The thirteen most 
important chlorinated aliphatic hydrocarbons from the standpoint of 
industrial hygiene. Archive Fur Hygiene 116:9-268.
    3. 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.

1,1- and 1,2-Dimethylhydrazine

    Dimethylhydrazine occurs as a symmetrical (1,2-dimethylhydrazine) 
and asymmetrical (1,1-dimethylhydrazine) isomer. Both compounds are 
clear, colorless liquids. Asymmetrical dimethylhydrazine (1,1-
dimethylhydrazine) is a component of jet and rocket fuels and is also 
used as an absorbent for acid gas, as a plant growth control agent, and 
in chemical synthesis. Although it has been evaluated as a high-energy 
rocket fuel, commercial use of the symmetrical isomer (1,2-
dimethylhydrazine) is limited to small quantities and it is usually 
considered to be a research chemical. Because data are limited for 1,2-
dimethylhydrazine (symmetrical dimethylhydrazine), the AEGL values are 
based upon 1,1-dimethylhydrazine (asymmetrical). Limited data suggest 
that1,1-dimethylhydrazine may be somewhat more toxic than 1,2-
dimethylhydrazine.
    Data on acute exposures of humans to both isomers of 
dimethylhydrazine are limited to case reports of accidental exposures. 
Signs and symptoms of exposure include respiratory irritation, 
pulmonary edema, nausea, vomiting, and neurological effects. However, 
definitive exposure data (concentration and duration) were unavailable 
for these exposures.
    Toxicity data of varying degrees of completeness are available for 
several laboratory species, including, rhesus monkeys, dogs, rats, 
mice, and hamsters (Weeks et al., 1963). Most of the animal studies 
were conducted using 1,1-dimethylhydrazine, although limited data 
suggest that 1,2-dimethylhydrazine exerts similar toxic effects. Minor 
nonlethal effects such as respiratory tract irritation appear to occur 
at cumulative exposures of <100 (ppm)(hrs). At cumulative exposures at 
or only slightly greater than 100 (ppm)(hrs), more notable effects have 
been reported, including, muscle fasciculation, behavioral changes, 
tremors, and convulsions. At only slightly higher exposure levels, 
lethality has been demonstrated. The available data suggest that there 
is very little margin between exposure levels resulting in no 
significant toxicity and those causing substantial lethality 
(LC50900-2,000 ppm hrs).
    Developmental toxicity of dimethylhydrazines has been demonstrated 
in rats following parenteral administration of maternally toxic doses. 
Both isomers of dimethylhydrazine have been shown to be carcinogenic in 
rodents following oral exposure and 6-month inhalation to 1,1-
dimethylhydrazine resulted in an increased tumor response in mice, 
although these findings are compromised by the contaminant 
dimethylnitrosamine. Inhalation slope factors are currently 
unavailable. It was the consensus of the NAC/AEGL Committee that AEGL-1 
values for dimethylhydrazine are inappropriate. This conclusion was 
based upon the onset of toxic effects at or below the odor threshold, 
and a concentration-response relationship for dimethylhydrazine that 
indicated little margin between exposures producing no toxic response 
and those resulting in significant toxicity.
    Behavioral changes and muscle fasciculations in dogs exposed for 15 
mins to 360 ppm 1,1-dimethylhydrazine (Weeks et al., 1963) served as 
the basis for deriving AEGL-2 values. Following temporal scaling 
(C1 x t = k) to AEGL-specific exposure durations, the values 
were adjusted by an uncertainty factor of 30. An uncertainty factor of 
3 for interspecies variability was applied because the toxic response 
to dimethylhydrazine was similar across the species tested. An 
uncertainty factor of 10 for intraspecies variability was applied 
because of the uncertainties regarding the mechanism of action of 
dimethylhydrazine toxicity and its impact on susceptible individuals.
    The AEGL-3 was derived from the 1-hr LC50 (981 ppm) for 
1,1-dimethylhydrazine in dogs (Weeks et al., 1963). Because of the 
steep slope of the dose-response curve of 1,1-dimethyl hydrazine, a 
modifying factor of 3 was applied to the 1-hr LC50 of 981 
ppm. Hence, the modified lethality threshold used to determine the 
AEGL-3 was 327 ppm. The downward adjustment of the LC50 
using a modification factor of 3 was considered a conservative approach 
and, in part, justified the total uncertainty factor of 30 (3 for 
interspecies variability and 10 for intraspecies variability). An 
uncertainty factor of 3 for interspecies variability was applied 
because the toxic response to dimethylhydrazine was similar across the 
species tested. An uncertainty factor of 10 for intraspecies 
variability was applied because of the uncertainties regarding the 
mechanism of action of dimethylhydrazine toxicity and its potential 
impact on susceptible individuals. Temporal scaling as previously 
described was applied to obtain exposure values for AEGL-specific 
exposure periods.
    An estimation of AEGLs based upon carcinogenic potential resulting 
from a one time, short term exposure was conducted and the assessment 
revealed that AEGLs derived from carcinogenic toxicity for a 
10-4 carcinogenic risk exceeded AEGL-3 values based on non 
cancer endpoints. The relationship of the various AEGL values reflects 
the exposure-response relationship shown by available animal data.

[[Page 58846]]



                                           Summary of Proposed AEGL Values for 1,1- and 1,2-Dimethylhydrazines                                          
--------------------------------------------------------------------------------------------------------------------------------------------------------
           Classification                   30-minute                1-hour                  4-hour                 8-hour          Endpoint (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1.............................  NAb...................  NAb...................  NAb..................  NAb..................  Inappropriate because
                                                                                                                                    notable toxicity may
                                                                                                                                    occur at            
                                                                                                                                    concentrations below
                                                                                                                                    the odor threshold; 
                                                                                                                                    concentration-      
                                                                                                                                    response            
                                                                                                                                    relationships       
                                                                                                                                    suggest little      
                                                                                                                                    margin between      
                                                                                                                                    exposures causing   
                                                                                                                                    minor effects and   
                                                                                                                                    those resulting in  
                                                                                                                                    serious toxicity.a  
                                                                                                                                                        
AEGL-2.............................  6 ppm (14.7 mg/m3)      3 ppm (7.4 mg/m3)       0.8 ppm (2 mg/m3)      0.4 ppm (1 mg/m3)      Behavioral changes   
                                                                                                                                    and muscle          
                                                                                                                                    fasciculations in   
                                                                                                                                    dogs exposed to 360 
                                                                                                                                    ppm for 15 mins     
                                                                                                                                    (Weeks et al., 1963)
                                                                                                                                                        
AEGL-3.............................  22 ppm (54 mg/m3)       11 ppm (27 mg/m3)       3 ppm (7.4 mg/m3)      1.5 ppm (3.7 mg/m3)..  Lethality threshold  
                                                                                                                                    of 327 ppm for 1-hr 
                                                                                                                                    estimated from 1-hr 
                                                                                                                                    LC50 in dogs (Weeks 
                                                                                                                                    et al., 1963)       
--------------------------------------------------------------------------------------------------------------------------------------------------------
aRefer to AEGL-1 for hydrazine if hydrazine is also present.                                                                                            
bNA Not appropriate                                                                                                                                     

References

    1. Weeks, M.H., Maxey, G.C., Sicks, and Greene, E.A. 1963. Vapor 
toxicity of UDMH in rats and dogs from short exposures. American 
Industrial Hygiene Association Journal 24:137-143.

Ethylene Oxide

    Ethylene oxide is a highly flammable gas produced in very large 
quantities in the United States (5.3-6.3 billion pounds). It is very 
reactive with nucleophiles, such as water, alcohols, halides, amines, 
and sulfhydryl compounds. Ethylene oxide is used as an intermediate in 
the production of ethylene glycol and nonionic surfactants; a small 
amount is used as a fumigant for sterilizing foods and heat-sensitive 
medical equipment. The odor detection level for ethylene oxide is 260 
ppm (468 mg/m3) to 700 ppm (1,260 mg/m3).
    The database of toxicity to ethylene oxide vapor in humans and 
experimental animals is very extensive including data on all aspects of 
toxicity except lethality in humans. Pharmacokinetics data show that 
ethylene oxide is readily absorbed from the respiratory tract of both 
humans and animals. It alkylates proteins and DNA, and it is 
metabolized by hydrolysis and glutathione conjugation.
    In humans, inhaled ethylene oxide vapor affects the eyes, 
respiratory tract, central and peripheral nervous systems, 
gastrointestinal tract (probably secondary effects to nervous system 
toxicity), hematopoietic system, and possibly the reproductive system, 
and fetus. Acute exposure to ethylene oxide at the odor detection level 
(260 ppm) causes eye and upper respiratory tract irritation 
and signs and symptoms of effects on the central and peripheral nervous 
system. Acute exposure to a calculated concentration of 500 ppm for 2 
to 3 minutes caused hematologic effects and more severe effects on the 
central nervous system than those noted at the odor detection level. 
Effects observed after acute exposure are reversible, including severe 
nervous system effects. Peripheral nervous damage is exacerbated by 
repeated exposures. Human studies have provided suggestive evidence of 
reproductive toxicity, some evidence of an association between exposure 
to ethylene oxide and genetic damage to somatic cells and limited 
evidence of carcinogenicity.
    Acute lethality studies in experimental animals showed that mice 
are the most sensitive species (4-hrs LC50 = 660-835 ppm) 
(Jacobson et al., 1956), followed by the dog (4-hrs LC50 = 
960 ppm) (Jacobson et al., 1956) and rat (4-hrs LC50 = 1537-
1972 ppm; 1-hr LC50 = 4439-5748 ppm) (Jacobson et al., 
1956). Immediate deaths were due to respiratory failure and delayed 
deaths were due to secondary respiratory infections. Experimental 
animals exposed to lethal and nonlethal concentrations of ethylene 
oxide showed evidence of eye and respiratory irritation and effects on 
the central and peripheral nervous system (Embree et al., 1977). 
Additional studies in animals exposed to ethylene oxide for various 
durations up to 6 hrs/day provided evidence of reproductive toxicity at 
50 ppm, developmental toxicity at 50 ppm, genetic 
toxicity in germ cells at 75 ppm, and carcinogenicity at 100 
ppm.
    Data were available for deriving AEGL-2 and -3 values. Values for 
AEGL-1 were not derived because the odor threshold and concentrations 
causing mild sensory irritation would be above the AEGL-2 levels.
    The AEGL-2 values were based on a rat study showing central nervous 
system depression, diarrhea, and eye and respiratory tract irritation 
after exposure to 1,000 ppm of ethylene oxide for 4 hrs (Embree et al., 
1977); genetic toxicity (dominant lethality) was also seen at this 
concentration in this same study. An uncertainty factor of 10 was 
applied for intraspecies variability, because of the steep slope of the 
dose response relationship from severe irritation and central nervous 
system depression to the lethality threshold. An uncertainty factor of 
3 was applied for interspecies sensitivity, because modes of action are 
likely to be similar between rodents and humans and systemic uptake of 
ethylene oxide is similar across species. The time-scaling approach 
used ten Berge's equation in which Cn t = k, and n = 1.2 
based on analysis of rat lethality data.
    AEGL-3 values were derived from lethality data in the rat. An 
LC01 value (628 ppm), which is considered an approximation 
of the lethality threshold, was estimated from data in a 4-hr acute 
inhalation study with rats reported by Jacobson et al. (1956). An 
uncertainty factor of 10 for intraspecies sensitivity was applied to 
the LC01 estimated value and this was followed by scaling to 
the different AEGL exposure periods based on ten Berge's equation 
(Cn t = k, where n = 1.2 was used based on reported 
lethality data for 1- and 4-hr exposures). An interspecies uncertainty 
factor of 3 was applied because systemic uptake, distribution, and 
modes of action are likely to be similar between rodents and humans. 
There are differences in metabolism kinetics, but they are unlikely to 
affect responses to high acute exposures. Assessment of carcinogenicity 
data (lung adenomas/carcinomas in female mouse) (NTP, 1987) showed that 
extrapolating the total cumulative exposure over a 2-year period to 
single exposures and estimating a 10-4 risk resulted in 
AEGL-3 values of 2,764, 1,382, 346, and 173 ppm for 0.5-, 1-, 4-, and 
8-hr exposures. These values exceed those derived from lethality data.

[[Page 58847]]

    AEGL values derived for ethylene oxide are summarized below:

                                                   Summary of Proposed AEGL Values for Ethylene Oxide                                                   
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                           Exposure Periods                                                             
           Classification           ----------------------------------------------------------------------------------------------  Endpoint (Reference)
                                            30-minute                1-hour                  4-hour                 8-hour                              
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1.............................  No values derived       No values derived       No values derived      No values derived                           
                                                                                                                                                        
AEGL-2.............................  190 ppm (342 mg/m3)     110 ppm (198 mg/m3)     33 ppm (59 mg/m3)      19 ppm (34 mg/m3)      Central nervous      
                                                                                                                                    system effects      
                                                                                                                                    Embree et al., 1977 
                                                                                                                                                        
AEGL-3.............................  360 ppm (648 mg/m3)     200 ppm (360 mg/m3)     63 ppm (113 mg/m3)     35 ppm (63 mg/m3)      Lethality threshold  
                                                                                                                                    Jacobson et al.,    
                                                                                                                                    1956                
--------------------------------------------------------------------------------------------------------------------------------------------------------

References

    1. Embree, J.W., Lyon, J.P., and Hine, C.H. 1977. The mutagenic 
potential of ethylene oxide using the dominant-lethal assay in rats. 
Toxicology and Applied Pharmacology 40:261-267.
    2. Jacobson, K.H., Hackley, E.B., and Feinsliver, L. 1956. The 
toxicity of inhaled ethylene oxide and propylene oxide vapors. 
Archive for Industrial Health 13:237-244.

Fluorine

    Fluorine is a reactive, highly irritant gas used in the nuclear 
energy industry, as an oxidizer of liquid rocket fuels, and in the 
manufacture of various fluorides and fluorocarbons. Fluorine is a 
severe irritant to the eyes, mucous membranes, lungs, and skin; the 
eyes and the respiratory tract are the target organ/tissues of an acute 
exposure. Data on irritant effects in humans and lethal and sublethal 
effects in five species of mammals (dog, rat, mouse, guinea pig, and 
rabbit) were available for development of AEGLs (Keplinger and Suissa, 
1968). Regression analyses of the concentration-exposure durations (for 
the fixed endpoint of mortality) for all of the animal species reported 
determined that the relationship between concentration and time is 
Cn x t = k, where n = approximately 2 (actual value for n 
for the most sensitive species, the mouse = 1.77). The data were 
considered adequate for derivation of the three AEGL classifications 
for four time periods.
    The AEGL-1 was based on the observation that human volunteers could 
tolerate exposure to 10 ppm for 15 mins without irritant effects 
(Keplinger and Suissa, 1968). An uncertainty factor of 3 was applied to 
this NOAEL value to protect sensitive individuals, since fluorine 
reacts corrosively with the tissues of the respiratory tract and 
effects are not likely to differ greatly among individuals, including 
sensitive individuals. The value was then scaled to the 30-min and 1-, 
4-, and 8-hr exposure durations using the C1.77 x t = k 
concentration-exposure duration relationship. It was the consensus of 
the NAC/AEGL Committee that at mildly irritating concentrations there 
is a tolerance to irritating gases. Therefore, the calculated 30-min 
and 1-hr values of 2.3 and 1.5 ppm, respectively, were rounded to 2 ppm 
and the calculated 4- and 8-hr values of 0.7 and 0.5 ppm, respectively, 
were rounded to 1 ppm.
    The AEGL-2 was based on an animal study in which mild lung 
congestion was observed in mice at 67 ppm for 30 mins and 30 ppm for 60 
mins (Keplinger and Suissa, 1968). Although concentrations causing 
irritant effects for each species for the same time periods suggested 
similar species sensitivity, the mouse data, because of slightly lower 
values, were chosen as the basis for developing the AEGL-2 and AEGL-3. 
Because the action of irritant and corrosive gases is directly on the 
tissues, with no pharmacokinetic component involved in the toxicity, 
there is likely to be little difference among species in response to 
fluorine exposure. Because similar sensitivity was observed among all 
species in the key study, no uncertainty factor for interspecies 
variability was applied. The values were divided by an intraspecies 
uncertainty factor of 3 to protect sensitive individuals, since effects 
are not likely to differ greatly among individuals. The values also 
were adjusted by a modifying factor of 2, based on a limited data base. 
AEGL-2 values for the other exposure periods were scaled based on the 
C1.77 x t = k relationship.
    The AEGL-3 values were derived from exposure concentrations equal 
to one half of the LC50 values reported (Keplinger and 
Suissa, 1968). The experimental \1/2\ LC50 concentrations 
tested resulted in no deaths in any species for up to 45 days post 
exposure, but did produce severe lung congestion in the mouse 
(Keplinger and Suissa, 1968). For the mouse, the 60-min value was 75 
ppm. Because of the similar species sensitivity in the key study, no 
uncertainty factor for interspecies variability was applied. The values 
were divided by an uncertainty factor of 3 to protect sensitive 
individuals and by a modifying factor of 2, based on a limited data 
base. AEGL-3 values for the other exposure times were calculated based 
on the C1.77 x t = k relationship.
    The calculated values are listed in the table below.

                                                      Summary of Proposed AEGL Values for Fluorinea                                                     
--------------------------------------------------------------------------------------------------------------------------------------------------------
           Classification                   30-minute                1-hour                  4-hour                 8-hour          Endpoint (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1.............................  2ppm (3.1 mg/m3)        2 ppm (3.1 mg/m3)       1 ppm (1.6 mg/m3)      1 ppm (1.6 mg/m3)      No irritant effect-  
                                                                                                                                    humans (Keplinger   
                                                                                                                                    and Suissa, 1968)   
                                                                                                                                                        
AEGL-2b............................  11 ppm (17 mg/m3).....  5.0 ppm (7.8 mg/m3)...  2.3 ppm (3.6 mg/m3)..  1.5 ppm (2.3 mg/m3)..  Mild lung congestion--
                                                                                                                                    mice (Keplinger and 
                                                                                                                                    Suissa, 1968)       
                                                                                                                                                        
AEGL-3.............................  19 ppm (29 mg/m3).....  13 ppm (20 mg/m3).....  5.7 ppm (8.8 mg/m3)..  3.9 ppm (6.0 mg/m3)..  Severe lung          
                                                                                                                                    congestion--mice    
                                                                                                                                    (Keplinger and      
                                                                                                                                    Suissa, 1968)       
--------------------------------------------------------------------------------------------------------------------------------------------------------
a AEGL-1 values were rounded off because of tolerance to low concentrations of irritant gases. AEGL-2 and AEGL-3 values were rounded to two significant 
  figures.                                                                                                                                              
b30-min and 1-hr AEGL-2 values are based on separate data points.                                                                                       


[[Page 58848]]

References

    1. Keplinger, M.L. and L.W. Suissa. 1968. Toxicity of fluorine 
short-term inhalation. American Industrial Hygiene Association 
Journal 29:10-18.


Hydrazine

    Hydrazine is a highly reactive reducing agent used in various 
chemical manufacturing processes. Hydrazine is used by the military as 
a missile and rocket propellant, and in power sources.
    Human data on the toxicity of hydrazine following acute inhalation 
exposure are limited to anecdotal accounts that lack definitive 
exposure data. The utility of this information is compromised by 
concurrent exposure to other chemicals and involvement of simultaneous 
multiple exposure routes.
    Studies have shown that the toxicity of methylated derivatives of 
hydrazine is qualitatively similar to that of hydrazine except in dogs 
wherein methylhydrazine has been observed to cause intravascular 
hemolysis. Based upon limited acute toxicity data, methylhydrazine and 
symmetrical dimethylhydrazine appear to be somewhat more toxic in rats 
and mice than is hydrazine while asymmetrical hydrazine appears to be 
slightly less toxic.
    Data from animal studies indicate that hydrazine may be metabolized 
to acetylhydrazine, diacetylhydrazine, ammonia, and urea, and may form 
hydrazones with pyruvate and 2-oxoglutarate. The biotransformation of 
hydrazine is mediated, at least in part, by hepatic monooxygenases. The 
role of metabolism and absorption/excretion kinetics is uncertain 
regarding immediate port-of-entry toxic effects from acute inhalation 
exposures. The highly reactive nature of hydrazine per se is a 
plausible determinant of acute port-of-entry toxic effects.
    AEGLs were based upon data sets defining toxicity endpoints that 
were specific for the AEGL level. Values for the specific exposure 
durations were derived based upon exponential scaling (Cn x 
t = k, where n = 2) from the experimental exposure period. This method 
was more appropriate for concentration-dependent effects than linear 
(Haber's Law) scaling. 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 1 to 3.5 
(ten Berge et al 1986). Because no exposure versus time data were 
available, the mid-point value of 2 was used as the exponent n for 
scaling the AEGL values for hydrazine across time.
    AEGL-1 values were based upon a study by House (1964) in which male 
monkeys exhibited skin flushing and eye irritation after a 24-hr 
continuous exposure to 0.4 ppm hydrazine. A total uncertainty factor of 
10 was applied to derive the AEGL-1 values.1 An uncertainty 
factor of 3 was applied for interspecies variability because the 
contact irritation response to the highly reactive hydrazine is not 
likely to vary greatly among species, and because a nonhuman primate 
was the test species. An uncertainty factor of 3 was applied for 
intraspecies variability because the contact irritation from the highly 
reactive hydrazine is not expected to vary greatly among individuals. 
The 24-hr experimental value was scaled to 8 hrs using Cn x 
t = k, where n = 2 as described above. Because hydrazine is extremely 
reactive and the effects are considered to be concentration dependent 
rather than time dependent, the 0.1 ppm AEGL-1 value derived for the 8-
hr duration was also applied to the 30-min, 1-hr, and 4-hr durations.
---------------------------------------------------------------------------

    1 Each uncertainty factor of 3 is actually the geometric mean of 
10 which is 3.16, hence 3.16 x 3.16 = 10.
---------------------------------------------------------------------------

    The AEGL-2 was derived based upon data from a study by Latendresse 
et al. (1995) in which rats exposed to hydrazine (750 ppm) for 1 hr 
exhibited nasal lesions. Following a dosimetric adjustment based upon 
regional gas dose (U.S. EPA 1994), the values were scaled to AEGL-
specific durations as for AEGL-1 and a total uncertainty factor of 30 
applied. An uncertainty factor of 10 for interspecies variability was 
applied to account for a deficiency in data pertaining to species 
variability and also variability in the data that are available. An 
uncertainty factor of 3 was applied for intraspecies variability 
because the toxic response to hydrazine is not likely to vary 
considerably among individuals of the same species, including 
susceptible individuals.
    The AEGL-3 values were derived based upon a rat inhalation study 
(HRC, 1993) that provided data to estimate a lethality threshold 
(LC01 = 337 ppm). Temporal scaling was again applied using 
the exponential expression C2 x t = k. Dosimetric conversion 
using a regional gas dose methodology (U.S. EPA 1994) was applied and 
resulting exposure values adjusted by a total uncertainty factor of 30. 
An uncertainty factor of 10 for interspecies variability was applied to 
account for a deficiency in data pertaining to species variability and 
also variability in the data that are available. An uncertainty factor 
of 3 was applied for intraspecies variability because the toxic 
response to hydrazine is not likely to vary considerably among 
individuals of the same species.
    An estimation of AEGLs based upon carcinogenic potential resulting 
from a one-time, short term exposure was conducted using the inhalation 
cancer slope factor for hydrazine. The assessment revealed that AEGLs 
derived from noncarcinogenic toxicity endpoints were lower values and 
so the AEGL-3 values were based on the noncarcinogenic endpoint.
    The proposed AEGLs, their respective toxicity endpoints and 
references are summarized below.

                                                      Summary of Proposed AEGL Values for Hydrazine                                                     
--------------------------------------------------------------------------------------------------------------------------------------------------------
           Classification                   30-minute                1-hour                  4-hour                 8-hour          Endpoint (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1.............................  0.1 ppm (0.1 mg/m3)...  0.1 ppm (0.1 mg/m3)...  0.1 ppm (0.1 mg/m3)..  0.1 ppm (0.1 mg/m3)..  Eye and facial       
                                                                                                                                    irritation inmonkeys
                                                                                                                                    (House, 1964)a      
                                                                                                                                                        
AEGL-2.............................  8 ppm (10 mg/m3)......  6 ppm (8 mg/m3).......  3 ppm (4 mg/m3)......  2 ppm (3 mg/m3)......  Nasal lesions        
                                                                                                                                    (Latendresse et al.,
                                                                                                                                    1995)               
                                                                                                                                                        
AEGL-3.............................  47 ppm (61 mg/m3).....  33 ppm (43 mg/m3).....  17 ppm (22 mg/m3)....  12 ppm (16 mg/m3)....  Lethality in rats    
                                                                                                                                    (HRC, 1993)         
--------------------------------------------------------------------------------------------------------------------------------------------------------
a Because the contact irritation response to the extremely reactive hydrazine is concentration dependent rather than time-dependent, the AEGL-1 is the  
  same of all time periods.                                                                                                                             


[[Page 58849]]

References

    1. House, W.B. 1964. Tolerance criteria for continuous exposure 
inhalation exposure to toxic materials. Part III. Effects on animals 
of 90-day exposure to hydrazine, unsymmetrical dimethylhydrazine 
(UMDH), decaborane, and nitrogen dioxide. ASD-TR-61-519 (iii). 
Wright-Patterson AFB, OH. 84 pp.
    2. HRC (Huntington Research Centre, Ltd.). 1993. Hydrazine 64% 
aqueous solution: acute inhalation toxicity in rats 1-hr exposure. 
Huntington Research Centre, Cambridge, England. CMA 8/930523.
    3. Latendresse, J.R., Marit, G.B., Vernot, E.H., Haun, C.C., and 
Flemming, C.D. 1995. Oncogenic potential of hydrazine in the nose of 
rats and hamsters after 1 or 10 1-hr exposures. Fundamental and 
Applied Toxicology 27:33-48.
    4. 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. U.S. EPA 1994. EPA/600/8-90/066F, Methods for Derivation of 
Inhalation Reference Concentrations and Application of Inhalation 
Dosimetry.

Methylhydrazine

    Methylhydrazine is a clear, colorless liquid used extensively in 
military applications as a missile and rocket propellant, in chemical 
power sources, and as a solvent and chemical intermediate. Upon contact 
with strong oxidizers (e.g., hydrogen peroxide, nitrogen tetroxide, 
chlorine, and fluorine) spontaneous ignition may occur.
    Human volunteers exposed to 90 ppm methylhydrazine for 10 mins 
reported minor irritation as the only effect of exposure (MacEwen et 
al., 1970).
    Toxicity data are available for multiple laboratory species 
including, rhesus monkeys, squirrel monkeys, beagle dogs, rats, mice, 
and hamsters. Nonlethal toxic effects include irritation of the 
respiratory tract, hemolytic responses, and some evidence of renal and 
hepatic toxicity. Lethal exposures are usually preceded by convulsions. 
Lethal toxicity varies somewhat among species. One-hour LC50 
values of 162, 82, 96, 244, 122, and 991 ppm have been determined for 
rhesus monkeys, squirrel monkeys, beagle dogs, rats, mice, and 
hamsters, respectively. Concentration-time relationships appear to 
follow Haber's Law although there appears to be a critical threshold 
for lethality with little margin between exposures causing only minor, 
reversible effects, and those resulting in lethality.
    In a 1-year inhalation bioassay using dogs, rats, mice, and 
hamsters, methylhydrazine concentrations of 2 ppm and 5 ppm, there was 
no evidence of treatment-related carcinogenicity in dogs or rats even 
after a 1-year post exposure observation period. However, mice exposed 
to 2 ppm for the same duration exhibited an increased incidence of lung 
tumors, nasal adenomas, nasal polyps, nasal osteomas, hemangioma, and 
liver adenomas and carcinomas. In hamsters exposed to 2 or 5 ppm, there 
was an increase in nasal polyps and nasal adenomas (5 ppm only), 
interstitial fibrosis of the kidney, and benign adrenal adenomas.
    It was the consensus of the NAC/AEGL Committee that the setting of 
AEGL-1 values for methylhydrazine would be inappropriate. This 
conclusion was based on the occurrence of toxic effects at or below the 
odor threshold, and a concentration-response relationship for 
methylhydrazine that indicated little margin between exposures 
producing no toxic response and those resulting in significant 
toxicity.
    The AEGL-2 values were derived by applying a modifying factor of 3 
to each of the AEGL-3 values. This estimate of a threshold for 
irreversible effects was justified because of the absence of exposure-
response data related to irreversible or other serious, long-lasting 
effects and the steep dose-response relationship indicated by the data 
that was available on methylhydrazine. For AEGL-3, lethality data (1-hr 
LC50 of 82 ppm) for squirrel monkeys (Haun et al., 1970) was 
adjusted using a modifying factor of 3 to estimate a lethality 
threshold (27 ppm). The lethality data for the species tested indicated 
a linear relationship between concentration and time. Therefore, 
temporal scaling to obtain time-specific AEGL values was described as 
C1 x t = k where the exponent n = 1. The derived exposure 
values were adjusted by a total uncertainty factor of 10. An 
uncertainty factor of 3 was applied for interspecies variability 
because a sensitive nonhuman primate was used to estimate the lethality 
threshold, and an uncertainty factor of 3 was used for intraspecies 
variability due to the steep exposure-response 
relationship.2
---------------------------------------------------------------------------

    2Each uncertainty factor of 3 is the geometric mean of 10 which 
is 3.16; hence, 3.16. x 3.16 = 10.
---------------------------------------------------------------------------

    The AEGL values reflect the steep exposure-response relationship 
exhibited by the toxicity data. Additional information regarding the 
mechanism(s) of action and metabolism of methylhydrazine may provide 
insight into understanding and defining the threshold between nonlethal 
and lethal exposures.
    An estimation of AEGLs based upon carcinogenic potential resulting 
from a one-time, short-term exposure was conducted and the assessment 
revealed that AEGLs derived from carcinogenic toxicity for a 
10-4 carcinogenic risk exceeded AEGL-3 values based on non 
cancer endpoints.

                                                   Summary of Proposed AEGL Values for Methylhydrazine                                                  
--------------------------------------------------------------------------------------------------------------------------------------------------------
           Classification                   30-minute                1-hour                  4-hour                 8-hour          Endpoint (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1.............................  NA....................  NA....................  NA...................  NA...................  Inappropriate because
                                                                                                                                    notable toxicity may
                                                                                                                                    occur at            
                                                                                                                                    concentrations below
                                                                                                                                    the odor threshold; 
                                                                                                                                    concentration-      
                                                                                                                                    response            
                                                                                                                                    relationships       
                                                                                                                                    suggest little      
                                                                                                                                    margin between      
                                                                                                                                    exposures causing   
                                                                                                                                    minor effects and   
                                                                                                                                    those resulting in  
                                                                                                                                    serious toxicity.a  
                                                                                                                                                        
AEGL-2.............................  2 ppm (3.8 mg/m3)       1 ppm (1.9 mg/m3)       0.2 ppm (0.4 mg/m3)    0.1 ppm (0.2 mg/m3)    Three-fold reduction 
                                                                                                                                    in AEGL-3.          
                                                                                                                                                        
AEGL-3.............................  6 ppm (11.3 mg/m3)      3 ppm (5.6 mg/m3)       0.7 ppm (1.1 mg/m3)    0.3 ppm (0.6 mg/m3)    1-hr LC50 of 82 ppm  
                                                                                                                                    reduced 3-fold to   
                                                                                                                                    estimate a lethality
                                                                                                                                    threshold; UF-10    
--------------------------------------------------------------------------------------------------------------------------------------------------------
a Refer to AEGL-1 for hydrazine if hydrazine is also present.                                                                                           


[[Page 58850]]

References

    1. Haun, C.C., MacEwen, J.D., Vernot, E.H., and Egan, G.F. 1970. 
Acute inhalation toxicity of monomethylhydrazine vapor. American 
Industrial Hygiene Association Journal 31:667-677.
    2. MacEwen, J.D., Theodore, J., and Vernot, E.H. 1970. Human 
exposure to EEL concentrations of monomethylhydrazine. Proceedings. 
First Annual Conference on Environmental Toxicology. AMRL-TR-70-102, 
Aerospace Medical Research Laboratory, Wright-Patterson Air Force 
Base, OH.

Nitric Acid

    Nitric acid is a highly corrosive, strongly oxidizing acid. The 
course of toxicity following inhalation exposure to nitric acid is 
consistent between humans and animals. Nitric acid fumes may cause 
immediate irritation of the respiratory tract, pain, and dyspnea which 
are followed by a period of recovery that may last several weeks. After 
this time, a relapse may occur with death caused by bronchopneumonia 
and/or pulmonary fibrosis. For exposure to nonlethal concentrations, 
allergic or asthmatic individuals appear to be a sensitive 
subpopulation.
    For derivation of the AEGL values, both human and animal data were 
utilized. For AEGL-1, humans exposed to 1.6 ppm (4.13 mg/m3) 
for 10 mins showed no changes in pulmonary function (Sackner and Ford, 
1981). An uncertainty factor of 3 was applied to account for sensitive 
populations, since the mechanism of action of an irritant gas is not 
expected to vary greatly among individuals. Scaling to the 30-min, 1-, 
4-, and 8-hr exposure periods was not performed because this was a no 
effect level and irritation is generally concentration dependent but 
not time dependent. The derived AEGL-1 value is above the odor 
threshold which provides a warning of exposure before an individual 
would experience notable discomfort.
    AEGL-2 values were derived from data on human studies (Diem, 1907). 
Individuals exposed to 12 ppm (31 mg/m3) nitric acid for 1 
hour experienced respiratory irritation, pressure in the chest, slight 
stabbing pains in the trachea and larynx, coughing, marked secretion 
from the nose and salivary glands, burning of the eyes and lacrimation, 
and burning and itching of facial skin. An uncertainty factor of 3 was 
applied to the 1-hr exposure level reported in this study and scaling 
of the value to 30 mins, 4 hrs, and 8 hrs was accomplished as described 
below.
    Very little data were available for determining AEGL-3 levels. 
Human case reports of severe injury or death did not contain exposure 
concentrations and in most animal studies, nitric acid was administered 
by intratracheal instillation. Extrapolation from a mortality versus 
concentration curve in the published literature indicated that the 
LC0 was approximately one-third the LC50 value of 
138 ppm (356 mg/m3) for the rat. This concentration was 
reported as nitrogen dioxide (NO2) instead of total nitric 
acid. From the estimated LC0 an uncertainty factor of 3 was 
applied to account for sensitive individuals. Due to the steepness of 
the dose-response curve for nitric acid, application of additional 
uncertainty factors would lower the AEGL-3 values below the values 
derived for AEGL-2 which were based on human data and, since the 
mechanism of action appears to be the same in both humans and animals 
with the production of both pulmonary edema and bronchiolitis 
obliterans, additional uncertainty factors were not used.
    The concentration-exposure time relationship is described by the 
equation cn t = k. Although insufficient data on nitric acid 
were available to calculate the exponent n, structure-activity 
relationships indicated that nitric acid and NO2 have 
parallel dose-response curves for a 30-min exposure. Therefore, for 
extrapolation to the various time points for the AEGL-2 and -3 levels, 
a previously published n of 3.5 derived from NO2 data was 
used.
    The calculated values for the three AEGL classifications for the 
four time periods are listed in the table below.

                                                  Summary Table of Proposed AEGL Values for Nitric Acid                                                 
--------------------------------------------------------------------------------------------------------------------------------------------------------
           Classification                   30-minute                1-hour                  4-hour                 8-hour          Endpoint (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1.............................  0.5 ppm (1.3mg/m3)....  0.5 ppm (1.3mg/m3)....  0.5 ppm (1.3mg/m3)...  0.5 ppm (1.3mg/m3)...  No observed effect   
                                                                                                                                    level (NOEL) for    
                                                                                                                                    changes in pulmonary
                                                                                                                                    function in humans  
                                                                                                                                    (Sackner and Ford,  
                                                                                                                                    1981); UF=3         
                                                                                                                                                        
AEGL-2.............................  5 ppm (13mg/m3)         4 ppm (10mg/m3)         3 ppm (8mg/m3)         2 ppm (5mg/m3)         Irritation with      
                                                                                                                                    cough; burning of   
                                                                                                                                    eyes and skin;      
                                                                                                                                    lacrimationand      
                                                                                                                                    salivation (Diem,   
                                                                                                                                    1907); UF=3         
                                                                                                                                                        
AEGL-3.............................  15 ppm (39mg/m3)        13 ppm (34mg/m3)        8 ppm (21mg/m3)        7 ppm (18mg/m3)        LC0 estimated from a 
                                                                                                                                    30-min LC50 in the  
                                                                                                                                    rat (Gray et al.,   
                                                                                                                                    1954); UF=3         
--------------------------------------------------------------------------------------------------------------------------------------------------------

References

    1. Diem, L.1907. [Experimentelle Untersuchungen uber die 
Einatmung von Saltpetersaure-Dampfen].Thesis, D-8700, Wurzburg. (as 
cited in Henschler, 1991).
    2. Gray, E.Le B., Patton, F.M., Goldberg, S.B., and Kaplan, 
E.1954. Toxicity of the oxides of nitrogen. Part II. Acute 
inhalation toxicity of nitrogen dioxide, red fuming nitric acid, and 
white fuming nitric acid. Archive for Industrial Hygiene and 
Occupational Medicine 10:418-422.
    3. Henschler, D.1991. Occupational Toxicants Critical Data 
Evaluation for MAK Values and Classification of Carcinogens, Vol. 3. 
VCH Publishers, New York (USA) and Weinheim (FRG).
    4. Sackner, M.A. and Ford, D. 1981. Effects of breathing nitrate 
aerosols in high concentrations for 10 mins on pulmonary function of 
normal and asthmatic adults, and preliminary results in normals 
exposed to nitric acid fumes. American Review of Respiratory 
Diseases 123:151.

Phosphine

    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 duration and concentration 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 and pulmonary pathology in 
Fischer 344 rats exposed to 3.1 ppm phosphine 6 hrs/day, 5 days/week 
for 13 weeks (Newton et al, 1993). Scaling to the 30-min, 1-, 4-, and 
8-hr exposures was accomplished using the cn x t = k 
relationship, where n = 2. The

[[Page 58851]]

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 1 to 3.5 (ten Berge et al 
1986). For scaling the AEGL values for phosphine across time, the mid-
point value of 2 was used as the exponent n because no exposure versus 
time data were available. An uncertainty factor of 3 was used for 
interspecies extrapolation since the rat is the most sensitive species. 
An uncertainity factor of 10 was used for intraspecies extrapolation 
since the data indicate that children are more sensitive than adults 
when exposed to phosphine.
    The AEGL-3 was based on a NOEL for lethality (18 ppm phosphine) in 
Sprague Dawley rats exposed to phosphine for 6 hrs. Scaling to the 30-
min, 1-, 4-, and 8-hr exposures was accomplished using the 
cn x t = k relationship, where n = 2. An uncertainty factor 
of 3 was used for interspecies extrapolation since the rat is the most 
sensitive species and an uncertainity factor of 10 was used for 
intraspecies extrapolation since data indicate that children are more 
sensitive than adults when exposed to phosphine.
    The calculated values are listed in the table below.

                                                     Summary Table of Proposed AEGL Values Phosphine                                                    
--------------------------------------------------------------------------------------------------------------------------------------------------------
           Classification                   30-minute                1-hour                  4-hour                 8-hour          Endpoint (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)                  ....................    ....................    ...................    ...................  Appropriate data not 
                                                                                                                                    available           
                                                                                                                                                        
AEGL-2 (Disabling).................  0.36 ppm (0.52 mg/m3).  0.25 ppm (0.35 mg/m3).  0.13 ppm (0.18mg/m3).  0.09 ppm (0.13 mg/m3)  NOEL for renal and   
                                                                                                                                    pulmonary pathology 
                                                                                                                                    in rats exposed to  
                                                                                                                                    3.1 ppm phosphine, 6
                                                                                                                                    hr/day, 5 days/week 
                                                                                                                                    for 13 weeks (Newton
                                                                                                                                    et al., 1993)       
                                                                                                                                                        
AEGL-3 (Lethality).................  2.1 ppm (2.9 mg/m3)...  1.5 ppm (2.1 mg/m3)...  0.74 ppm (1.0 mg/m3).  0.52 ppm (0.73 mg/m3)  NOEL for lethality in
                                                                                                                                    rats exposed to 18  
                                                                                                                                    ppm phosphine for 6 
                                                                                                                                    hr.(Newton, 1991)   
--------------------------------------------------------------------------------------------------------------------------------------------------------

References

    1. Newton, P.E. 1991. Acute Inhalation exposures of rats to 
phosphine. Biology Dynamics, Inc. East Millstone, NJ. Project No. 
90-8271.
    2. Newton, P.E., Schroeder, R.E., Sullivan, J.B., Busey, W.M., 
and Banas, D.A. 1993. Inhalation toxicity of phosphine in the rat: 
acute, subchronic, and developmental. Inhalation Toxicology 5:223-
239.

V. Public Record and Electronic Submission

    The official record for this notice, as well as the public version, 
has been established for this notice under docket control number 
(OPPTS-00218; FRL-5737-3) (including comments and data submitted 
electronically as described below). A public version of this record, 
including printed, paper versions of electronic comments, which does 
not include any information claimed as CBI, is available for inspection 
from 12 noon to 4 p.m., Monday through Friday, excluding legal 
holidays. The official record is located in the TSCA Nonconfidential 
Information Center, Rm. NE-B607, 401 M St., SW., Washington, DC.
    Electronic comments can be sent directly to EPA at:
    [email protected]


    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 disks in WordPerfect in 5.1/6.1 file format or 
ASCII file format. All comments and data in electronic form must be 
identified by the docket control number (OPPTS-00218; FRL-5737-3). 
Electronic comments on this notice may be filed online at many Federal 
Depository Libraries.
    All comments which contain information claimed as CBI must be 
clearly marked as such. Three sanitized copies of any comments 
containing information claimed as CBI must also be submitted and will 
be placed in the public record for this notice. Persons submitting 
information on any portion of which they believe is entitled to 
treatment as CBI by EPA must assert a business confidentiality claim in 
accordance with 40 CFR 2.203(b) for each such portion. This claim must 
be made at the time that the information is submitted to EPA. If a 
submitter does not assert a confidentiality claim at the time of 
submission, EPA will consider this as a waiver of any confidentiality 
claim and the information may be made available to the public by EPA 
without further notice to the submitter.

List of Subjects

    Environmental protection, Hazardous substances.

    Dated: October 20, 1997.

Lynn R. Goldman,

Assistant Administrator for Prevention, Pesticides and Toxic 
Substances.

[FR Doc. 97-28642 Filed 10-29-97; 8:45 am]
BILLING CODE 6560-50-F`