[Federal Register Volume 68, Number 138 (Friday, July 18, 2003)]
[Notices]
[Pages 42710-42726]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-18306]


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

ENVIRONMENTAL PROTECTION AGENCY

[OPPT-2002-0027; FRL-7189-8]


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

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 
AEGLs on an ongoing basis to provide Federal, State, and local agencies 
with information on short-term exposures to hazardous chemicals. This 
notice provides AEGL values and executive summaries for 10 chemicals 
for public review and comment. Comments are welcome on both the AEGL 
values in this notice and the technical support documents placed in the 
public version of the official docket for these 10 chemicals.

DATES: Comments, identified by docket ID number OPPT-2002-0027, must be 
received on or before August 18, 2003.

ADDRESSES: Comments may be submitted electronically, by mail, or 
through hand delivery/courier. Follow the detailed instructions as 
provided in Unit I. of the SUPPLEMENTARY INFORMATION.

FOR FURTHER INFORMATION CONTACT: For general information contact: 
Barbara Cunningham, Acting Director, Environmental Assistance Division 
(7408M), Office of Pollution Prevention and Toxics, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; 
telephone number: (202) 554-1404; e-mail address: [email protected].
    For technical information contact: Paul S. Tobin, Designated 
Federal Officer (DFO), Office of Pollution Prevention and Toxics 
(7406M), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (202) 564-8557; e-mail address: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

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

B. How Can I Get Copies of this Document and Other Related Information?

    1. Docket. EPA has established an official public docket for this 
action under docket identification (ID) number OPPT-2002-0027. The 
official public docket consists of the documents specifically 
referenced in this action, any public comments received, and other 
information related to this action. Although a part of the official 
docket, the public docket does not include Confidential Business 
Information (CBI) or other information whose disclosure is restricted 
by statute. The official public docket is the collection of materials 
that is available for public viewing at the EPA Docket Center, Rm. 
B102-Reading Room, EPA West, 1301 Constitution

[[Page 42711]]

Ave., NW., Washington, DC. The EPA Docket Center is open from 8:30 a.m. 
to 4:30 p.m., Monday through Friday, excluding legal holidays. The EPA 
Docket Center Reading Room telephone number is (202) 566-1744 and the 
telephone number for the OPPT Docket, which is located in EPA Docket 
Center, is (202) 566-0280.
    2. Electronic access. You may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr/.
    An electronic version of the public docket is available through 
EPA's electronic public docket and comment system, EPA Dockets. You may 
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public 
comments, access the index listing of the contents of the official 
public docket, and to access those documents in the public docket that 
are available electronically. Although not all docket materials may be 
available electronically, you may still access any of the publicly 
available docket materials through the docket facility identified in 
Unit I.B.1. Once in the system, select ``search,'' then key in the 
appropriate docket ID number.
    Certain types of information will not be placed in the EPA Dockets. 
Information claimed as CBI and other information whose disclosure is 
restricted by statute, which is not included in the official public 
docket, will not be available for public viewing in EPA's electronic 
public docket. EPA's policy is that copyrighted material will not be 
placed in EPA's electronic public docket but will be available only in 
printed, paper form in the official public docket. To the extent 
feasible, publicly available docket materials will be made available in 
EPA's electronic public docket. When a document is selected from the 
index list in EPA Dockets, the system will identify whether the 
document is available for viewing in EPA's electronic public docket. 
Although not all docket materials may be available electronically, you 
may still access any of the publicly available docket materials through 
the docket facility identified in Unit I.B.1. EPA intends to work 
towards providing electronic access to all of the publicly available 
docket materials through EPA's electronic public docket.
    For public commenters, it is important to note that EPA's policy is 
that public comments, whether submitted electronically or in paper, 
will be made available for public viewing in EPA's electronic public 
docket as EPA receives them and without change, unless the comment 
contains copyrighted material, CBI, or other information whose 
disclosure is restricted by statute. When EPA identifies a comment 
containing copyrighted material, EPA will provide a reference to that 
material in the version of the comment that is placed in EPA's 
electronic public docket. The entire printed comment, including the 
copyrighted material, will be available in the public docket.
    Public comments submitted on computer disks that are mailed or 
delivered to the docket will be transferred to EPA's electronic public 
docket. Public comments that are mailed or delivered to the docket will 
be scanned and placed in EPA's electronic public docket. Where 
practical, physical objects will be photographed, and the photograph 
will be placed in EPA's electronic public docket along with a brief 
description written by the docket staff.

C. How and To Whom Do I Submit Comments?

    You may submit comments electronically, by mail, or through hand 
delivery/courier. To ensure proper receipt by EPA, identify the 
appropriate docket ID number in the subject line on the first page of 
your comment. Please ensure that your comments are submitted within the 
specified comment period. Comments received after the close of the 
comment period will be marked ``late.'' EPA is not required to consider 
these late comments. If you wish to submit CBI or information that is 
otherwise protected by statute, please follow the instructions in Unit 
I.D. Do not use EPA Dockets or e-mail to submit CBI or information 
protected by statute.
    1. Electronically. If you submit an electronic comment as 
prescribed in this unit, EPA recommends that you include your name, 
mailing address, and an e-mail address or other contact information in 
the body of your comment. Also include this contact information on the 
outside of any disk or CD ROM you submit, and in any cover letter 
accompanying the disk or CD ROM. This ensures that you can be 
identified as the submitter of the comment and allows EPA to contact 
you in case EPA cannot read your comment due to technical difficulties 
or needs further information on the substance of your comment. EPA's 
policy is that EPA will not edit your comment, and any identifying or 
contact information provided in the body of a comment will be included 
as part of the comment that is placed in the official public docket, 
and made available in EPA's electronic public docket. If EPA cannot 
read your comment due to technical difficulties and cannot contact you 
for clarification, EPA may not be able to consider your comment.
    i. EPA Dockets. Your use of EPA's electronic public docket to 
submit comments to EPA electronically is EPA's preferred method for 
receiving comments. Go directly to EPA Dockets at http://www.epa.gov/edocket/, and follow the online instructions for submitting comments. 
Once in the system, select ``search,'' and then key in docket ID number 
OPPT-2002-0027. The system is an ``anonymous access'' system, which 
means EPA will not know your identity, e-mail address, or other contact 
information unless you provide it in the body of your comment.
    ii. E-mail. Comments may be sent by e-mail to [email protected], 
Attention: Docket ID Number OPPT-2002-0027. In contrast to EPA's 
electronic public docket, EPA's e-mail system is not an ``anonymous 
access'' system. If you send an e-mail comment directly to the docket 
without going through EPA's electronic public docket, EPA's e-mail 
system automatically captures your e-mail address. E-mail addresses 
that are automatically captured by EPA's e-mail system are included as 
part of the comment that is placed in the official public docket, and 
made available in EPA's electronic public docket.
    iii. Disk or CD ROM. You may submit comments on a disk or CD ROM 
that you mail to the mailing address identified in Unit I.C.2. These 
electronic submissions will be accepted in WordPerfect or ASCII file 
format. Avoid the use of special characters and any form of encryption.
    2. By mail. Send your comments to: Document Control Office (7407M), 
Office of Pollution Prevention and Toxics (OPPT), Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001.
    3. By hand delivery or courier. Deliver your comments to: OPPT 
Document Control Office (DCO) in EPA East Building Rm. 6428, 1201 
Constitution Ave., NW., Washington, DC. Attention: Docket ID Number 
OPPT-2002-0027. The DCO is open from 8 a.m. to 4 p.m., Monday through 
Friday, excluding legal holidays. The telephone number for the DCO is 
(202) 564-8930.

D. How Should I Submit CBI to the Agency?

    Do not submit information that you consider to be CBI 
electronically through EPA's electronic public docket or by e-mail. You 
may claim information that you submit to EPA as CBI by marking any part 
or all of that information as CBI (if you submit CBI on disk or CD ROM, 
mark the outside

[[Page 42712]]

of the disk or CD ROM as CBI and then identify electronically within 
the disk or CD ROM the specific information that is CBI). Information 
so marked will not be disclosed except in accordance with procedures 
set forth in 40 CFR part 2.
    In addition to one complete version of the comment that includes 
any information claimed as CBI, a copy of the comment that does not 
contain the information claimed as CBI must be submitted for inclusion 
in the public docket and EPA's electronic public docket. If you submit 
the copy that does not contain CBI on disk or CD ROM, mark the outside 
of the disk or CD ROM clearly that it does not contain CBI. Information 
not marked as CBI will be included in the public docket and EPA's 
electronic public docket without prior notice. If you have any 
questions about CBI or the procedures for claiming CBI, please consult 
the technical person listed under FOR FURTHER INFORMATION CONTACT.

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

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

II. Background

A. What Action is the Agency Taking?

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

B. Characterization of the AEGLs

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

C. Development of the AEGLs

    The NAC/AEGL Committee develops the AEGL values on a chemical-by-
chemical basis. Relevant data and information are gathered from all 
known sources including published scientific literature, State and 
Federal agency publications, private industry, public 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 together with ``draft'' AEGL values 
prepared in conjunction with NAC/AEGL Committee members. Both the 
``draft'' AEGLs and ``draft'' technical support documents are reviewed 
and revised as necessary by the NAC/AEGL Committee members prior to 
formal NAC/AEGL Committee meetings. Following deliberations on the AEGL 
values and the relevant data and information for each chemical, the 
NAC/AEGL Committee attempts to reach a consensus. Once the NAC/AEGL 
Committee reaches a consensus, the values are considered ``Proposed'' 
AEGLs. The Proposed AEGL values and the accompanying scientific 
rationale

[[Page 42713]]

for their development are the subject of this notice.
    The NAC/AEGL Committee publishes proposed AEGL values and the 
accompanying scientific rationale for their development for 10 
hazardous substances. These values represent the sixth set of exposure 
levels proposed and published by the NAC/AEGL Committee EPA published 
the first ``Proposed'' AEGLs for 12 chemicals from the initial priority 
list in the Federal Register of October 30, 1997 (62 FR 58840-58851) 
(FRL-5737-3); for 10 chemicals in the Federal Register of March 15, 
2000 (65 FR 14186-14196) (FRL-6492-4); for 14 chemicals in the Federal 
Register of June 23, 2000 (65 FR 39263-39277) (FRL-659-2); for 7 
chemicals in the Federal Register of December 13, 2000 (65 FR 77866-
77874) (FRL-6752-5) for 18 chemicals in the Federal Register of May 2, 
2001 (66 FR 21940-21964) (FRL-6776-3); and for 8 chemicals in the 
Federal Register of February 15, 2002 (67 FR 7164-7176) (FRL-6815-8) in 
order to provide an opportunity for public review and comment. In 
developing the proposed AEGL values, the 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. The 
term Community Emergency Exposure Levels (CEELS) is synonymous with 
AEGLs in every way. The NAC/AEGL Committee has adopted the term Acute 
Exposure Guideline Levels to better connote the broad application of 
the values to the population defined by the NAS and addressed by the 
NAC/AEGL Committee. The NAC/AEGL Committee invites public comment on 
the proposed AEGL values and the scientific rationale used as the basis 
for their development.
    Following public review and comment, the NAC/AEGL Committee will 
reconvene to consider relevant comments, data, and information that may 
have an impact on the NAC/AEGL Committee's position and will again seek 
consensus for the establishment of Interim AEGL values. Although the 
Interim AEGL values will be available to Federal, State, and local 
agencies and to organizations in the private sector as biological 
reference values, it is intended to have them reviewed by a 
subcommittee of the NAS. The NAS subcommittee will serve as a peer 
review of the Interim AEGLs and as the final arbiter in the resolution 
of issues regarding the AEGL values, and the data and basic methodology 
used for setting AEGLs. Following concurrence, ``Final'' AEGL values 
will be published under the auspices of the NAS.

D. Use of Human Data

    The NAC/AEGL Program is working to ensure that emergency responders 
and risk managers in this country and abroad are armed with vital 
information they need to protect the public and themselves from harm in 
the event of chemical accidents or homeland security emergencies. 
Because of the serious nature of chemical emergency situations, it is 
essential that involved personnel have access to the most comprehensive 
and realistic assessments of human health hazards posed by released 
chemicals. Under estimation of human health hazard would not be 
protective, while over estimation might suggest a larger than necessary 
response zone. The Department of Army and Federal Emergency Management 
Agency Chemical Stockpile Emergency Preparedness Program (CSEPP), for 
example, has adopted, as outlined in CSEPP Policy Paper Number 20, 
AEGLs for sulfur mustard and nerve agents for use in CSEPP community 
emergency planning and response activities ``to prevent or minimize 
exposures above AEGL-2, above which some temporary but potentially 
escape-impairing effects could occur.'' Thus, with the application of 
the procedures discussed in this unit, the AEGL Program recognizes the 
importance of considering all available domestic and international test 
data, both animal and human, to determine threshold levels of harm for 
a range of exposure scenarios critical to those at the front line in 
defending public health.
    The process for development of AEGL values incorporates essential 
scientific and ethical considerations posed by the possible use of 
research with human subjects. All human studies that were used as key 
or supporting evidence to derive AEGL values were judged acceptable for 
use according to ethical considerations detailed in the Standing 
Operating Procedures for Developing Acute Exposure Guideline Levels for 
Hazardous Substances, Subcommittee on Acute Exposure Guideline Levels, 
National Research Council, National Academy Press, 2001, p. 53. The SOP 
states ``The NAC/AEGL Committee is dependent upon existing clinical, 
epidemiologic, and case report studies published in the literature for 
data on humans. Many of these studies do not necessarily follow current 
guidelines on ethical standards that require effective, documented, 
informed consent from participating human subjects. Further, recent 
studies that followed such guidelines may not include that fact in the 
publication. Although human data may be important in deriving AEGL 
values that protect the general public, utmost care must be exercised 
to ensure first of all that such data have been developed in accordance 
with ethical standards. No data on humans known to be obtained through 
force, coercion, misrepresentation, or any other such means will be 
used in the development of AEGLs. The NAC/AEGL Committee will use its 
best judgment to determine whether the human studies were ethically 
conducted and whether the human subjects were likely to have provided 
their informed consent. Additionally, human data from epidemiologic 
studies and chemical accidents may be used. However, in all instances 
described here, only human data, documents, and records will be used 
from sources that are publicly available or if the information is 
recorded by the investigator in such a manner that subjects cannot be 
identified directly or indirectly. These restrictions on the use of 
human data are consistent with the `Common Rule' published in the Code 
of Federal Regulations (Protection of Human Subjects, 40 CFR 26, 
2000).'' Additionally, EPA has recently asked the NAC/AEGL Committee to 
add an explicit documentation step early in the AEGL development 
process that the studies proposed for consideration have been 
consistent with the Program's Standing Operating Procedures (SOPs).

III. List of Chemicals

    On behalf of the NAC/AEGL Committee, EPA is providing an 
opportunity for public comment on the AEGLs for the 10 chemicals 
identified in Table 1 of this unit.

A. Proposed AEGL Chemical Table

                Table 1.--10 Chemicals for Proposed AEGLs
------------------------------------------------------------------------
                  CAS No.                           Chemical name
------------------------------------------------------------------------
75-86-5                                     Acetone cyanohydrin
-------------------------------------------
7664-41-7                                   Ammonia
-------------------------------------------
7726-95-6                                   Bromine
-------------------------------------------
79-11-8                                     Chloroacetic acid
-------------------------------------------
7782-41-4                                   Fluorine
-------------------------------------------
70892-10-3                                  Jet Fuel 8
-------------------------------------------
78-93-3                                     Methyl ethyl ketone
-------------------------------------------
10025-87-3                                  Phosphorus oxychloride
-------------------------------------------
7719-12-2                                   Phosphorus trichloride
-------------------------------------------

[[Page 42714]]

 
1330-20-7                                   Xylenes
------------------------------------------------------------------------

B. Executive Summaries

    The following are executive summaries from the chemical specific 
technical support documents (which may be obtained as described in Unit 
I.B. and III.) that support the NAC/AEGL Committee's development of 
AEGL values for each chemical substance. This information provides the 
following information: A general description of each chemical, 
including its properties and principle uses; a summary of the rationale 
supporting the AEGL-1, 2, and 3 concentration levels; a summary table 
of the AEGL values; and a listing of key references that were used to 
develop the AEGL values. More extensive toxicological information and 
additional references for each chemical may be found in the complete 
technical support documents. Risk managers may be interested to review 
the complete technical support document for a chemical when deciding 
issues related to use of the AEGL values within various programs.
    1. Acetone cyanohydrin--i. Description. Acetone cyanohydrin is a 
colorless to yellowish liquid with a characteristic bitter almond odor 
due to the presence of free HCN. The major use of acetone cyanohydrin 
is in the production of [alpha]-methacrylic acid and its esters; the 
latter are used for the production of plexiglass. Further uses of 
acetone cyanohydrin are in the production of acrylic esters, 
polyacrylic plastics, and synthetic resins as well as in the 
manufacture of insecticides, pharmaceuticals, fragances, and perfumes. 
Acetone cyanohydrin decomposes spontaneously to acetone and hydrogen 
cyanide; this process is catalyzed by heat and contact with water 
(especially under alkaline conditions).
    Fatal cases and life-threatening poisonings in workers have been 
described after accidental inhalation, skin contact, and oral uptake. 
Initial symptoms following mild exposure to acetone cyanohydrin are 
predominantly cardiac palpitation, headache, weakness, dizziness, 
nausea, vomiting, and nose, eye, throat, and skin irritation. The 
systemic toxicity of acetone cyanohydrin is caused by free cyanide ions 
and is primarily due to complex formation with the iron moiety in the 
tissue enzyme ferri cytochrome c oxidase or cytochrome a3. 
The blockage of the electron transport system of mitochondria results 
in inhibition of oxygen utilization and causes tissue hypoxia and 
cellular and tissue destruction.
    Four studies exposed rats repeatedly to acetone cyanohydrin 
concentrations of about 10, 30, and 60 ppm for 6 hours/day, 5 days/week 
for a total of 4 weeks (Monsanto Co., 1986a; using groups of 10 male 
and 10 female rats), 10 weeks (Monsanto Co., 1982b; using groups of 15 
male rats) and 14 weeks (Monsanto Co., 1986b; using groups of 15 male 
and 15 female rats) or for 6 hours/day for 21 days (Monsanto Co., 
1982c; using groups of 15 female rats). Death was observed at 60 ppm 
after the first exposure in 3 animals of the Monsanto Co. (1986a) 
study, but not in subsequent exposures or in the other studies at a 
similar exposure concentration. Preceding death, respiratory distress, 
prostration, convulsions, and tremors were observed. In all studies, 
exposure to 60 and 30 ppm caused signs of irritation (red nasal 
discharge, clear nasal discharge, perioral wetness, encrustations) 
during the first and subsequent weeks of exposure. At 10 ppm, red nasal 
discharge was not observed in one study (Monsanto Co., 1986a); its 
incidence was not increased compared to control group in two studies 
(Monsanto Co., 1982b; 1982c) and increased compared to the control 
group in the fourth study (Monsanto Co., 1986b). No other effects were 
reported in these four studies.
    The AEGL-1 was based on a repeated exposure study in rats in which 
a concentration of 9.2 ppm for 6 hours/day, 5 days/week for 4 weeks did 
not result in red nasal discharge (Monsanto Co., 1986a). An uncertainty 
factor of 3 was applied for interspecies variability because the 
lowest-observed-effect-level (LOEL) for irritation in humans exposed to 
cyanide at the workplace is about 6-10 ppm cyanide (El Ghawabi et al., 
1975), which is a factor of about 3 below the irritation threshold of 
acetone cyanohydrin in rats (about 30 ppm) and because a multiple 
exposure study was used for the derivation of AEGL values. An 
uncertainty factor of 3 was applied for intraspecies variability 
because decomposition of acetone cyanohydrin does not involve enzyme-
catalyzed steps and the binding to evolutionary conservative iron-
containing proteins/enzymes, i.e., the target protein cytochrome c 
oxidase, is unlikely to differ substantially between individuals. A 
modifying factor of 2 was applied due to the lack of more adequate and 
supporting data for the derivation of AEGL-1 values. The exposure 
duration-specific values were derived by time scaling according to the 
dose-response regression equation C\n\ x t = k, using the default of n 
= 3 for shorter exposure periods and n = 1 for longer exposure periods, 
due to the lack of suitable experimental data for deriving the 
concentration exponent. For the 10-minute AEGL-1 the 30-minute value 
was applied because the derivation of AEGL values was based on a long 
experimental exposure period and no supporting studies using short-
exposure periods were available for characterizing the concentration-
time-response relationship.
    The AEGL-2 was based on a repeated exposure study in rats in which 
a concentration of 29.9 ppm for 6 hours/day, 5 days/week for 4 weeks 
did not result in respiratory distress (red nasal discharge as a sign 
of irritation was observed during the first and subsequent weeks of 
exposure) (Monsanto Co., 1986a). An uncertainty factor of 3 was applied 
for interspecies variability because repeated exposure of humans at the 
workplace to cyanide concentrations only about 3-fold lower than the 
lethality threshold of about 60 ppm acetone cyanohydrin in rats did not 
lead to life-threatening or irreversible health effects and because a 
multiple exposure study was used for the derivation of AEGL values. An 
uncertainty factor of 3 was applied for intraspecies variability 
because decomposition of acetone cyanohydrin does not involve enzyme-
catalyzed steps and the binding to evolutionary conservative iron-
containing proteins/enzymes, i.e., the target protein cytochrome c 
oxidase, is unlikely to differ substantially between individuals. The 
exposure duration-specific values were derived by time scaling 
according to the dose-response regression equation C\n\ x t = k, using 
the default of n = 3 for shorter exposure periods and n = 1 for longer 
exposure periods, due to the lack of suitable experimental data for 
deriving the concentration exponent. For the 10-minute AEGL-2 the 30-
minute value was applied because the derivation of AEGL values was 
based on a long experimental exposure period and no supporting studies 
using short-exposure periods were available for characterizing the 
concentration-time-response relationship.
    For the derivation of AEGL-3 values, it was taken into account 
that:
    a. Acetone cyanohydrin decomposes spontaneously into hydrogen 
cyanide and acetone,
    b. The decomposition of acetone cyanohydrin is accelerated by heat 
and water,

[[Page 42715]]

    c. The systemic toxic effects of acetone cyanohydrin are caused by 
free cyanide ions, and
    d. Hydrogen cyanide has a far higher vapor pressure than acetone 
cyanohydrin.
    From these facts it was concluded that with every exposure to 
acetone cyanohydrin a concomitant exposure to hydrogen cyanide will 
occur. It therefore seemed reasonable to apply the AEGL-3 values (on a 
ppm basis) derived for hydrogen cyanide to acetone cyanohydrin. This 
procedure is supported by a close similarity of acetone cyanohydrin and 
hydrogen cyanide regarding lethal effects in rats exposed for 6 hours.
    The proposed AEGL values are listed in Table 2 of this unit.

                                       Table 2.--Summary Table of Proposed AEGL Values for Acetone Cyanohydrin\a\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10-minutes          30-minutes            1-hour              4-hours             8-hours           (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)             1.1 ppm             1.1 ppm             0.84 ppm            0.53 ppm            0.35 ppm            No red nasal
                                  (3.9 mg/m\3\).....  (3.9 mg/m\3\).....  (2.9 mg/m\3\).....  (1.9 mg/m\3\).....  (1.2 mg/m\3\).....   discharge in rats
                                                                                                                                       (Monsanto Co.,
                                                                                                                                       1986a)
--------------------------------------------------------------------------------------------------------------------------------------------------------
 
--------------------------------------------------------------------------------------------------------------------------------------------------------
 
--------------------------------------------------------------------------------------------------------------------------------------------------------
\a\ Cutaneous absorption may occur; direct skin contact with the liquid should be avoided; fatal intoxications have been reported upon skin contact.


    ii. References. a. El Ghawabi A.; M. Gaafar; A. El Saharta; S.H. 
Ahmed; K.K. Malash; and R. Fares. 1975. Chronic cyanide exposure: a 
clinical radioisotope and laboratory study. British Journal of 
Industrial Medicine. 32:215-219.
    b. Monsanto Co. 1982b. Male fertility study of Sprague-Dawley rats 
exposed by inhalation route to acetone cyanohydrin. Monsanto Co. Report 
No. ML-82-144. Monsanto Co., St. Louis, MO, USA.
    c. Monsanto Co. 1982c. Female fertility study of Sprague-Dawley 
rats exposed by inhalation route to acetone cyanohydrin. Monsanto Co. 
Report No. ML-82-125. Monsanto Co., St. Louis, MO, USA.
    d. Monsanto Co. 1986a. One-month inhalation toxicity of acetone 
cyanohydrin in male and female Sprague-Dawley rats with cover letter 
dated 04-25-86. Report No. BN-81-178. Monsanto Co., St. Louis, MO, USA.
    e. Monsanto Co. 1986b. Three-month inhalation toxicity of acetone 
cyanohydrin in male and female Sprague-Dawley rats with cover letter 
dated 04-25-86. Report No. ML-82-143. Monsanto Co., St. Louis, MO, USA.
    2. Ammonia--i. Description. Ammonia is a colorless, corrosive, 
alkaline gas that has a very pungent odor. The odor detection level 
ranges from 5-53 ppm. Ammonia is used as a compressed gas and in 
aqueous solutions. It also is used as a household cleaning product, in 
fertilizers, and as a refrigerant. Exposures to ammonia occur as a 
result of accidents during highway and railway transportation, by 
releases at manufacturing facilities, and from farming accidents.
    Ammonia is very soluble in water. Because of its exothermic 
properties, ammonia forms ammonium hydroxide and produces heat when it 
contacts moist surfaces, such as mucous membranes. The corrosive and 
exothermic properties of ammonia can result in immediate damage (severe 
irritation and burns) to eyes, skin, and mucous membranes of the oral 
cavity and respiratory tract. In addition, ammonia is effectively 
scrubbed in the nasopharyngeal region of the respiratory tract because 
of its high solubility in water.
    The data for deriving AEGL values were obtained primarily from case 
studies of accident victims, experimental studies in humans, and 
experimental studies on lethality and irritation in animals. The case 
studies were of limited use for quantitative evaluation, but the 
experimental studies in humans and animals contained quantitative data 
that would be used for deriving AEGL values.
    No reliable quantitative lethality data were available for humans 
dying as a result of exposure to ammonia. One case study reported the 
death of an individual exposed to a high but unknown concentrations of 
ammonia. Other case studies also contained no exposure estimates, but 
showed that high concentrations of ammonia cause severe damage to the 
respiratory tract, particularly in the tracheobronchial and pulmonary 
regions. Death, however, is most likely to occur when damage causes 
pulmonary edema. Non-lethal, irreversible, or long-term effects occur 
when damage progresses to the tracheobronchial region, manifested by 
reduced performance on pulmonary function tests, bronchitis, 
bronchiolitis, emphysema, and bronchiectasis. Nondisabling, reversible 
effects are manifested by irritation to the eyes, throat, and 
nasopharyngeal region of the respiratory tract. The odor of ammonia is 
detected by humans at concentrations >5 ppm; the odor is highly 
penetrating at 50 ppm (10 minutes). Experimental studies on human 
volunteers, showed that slight irritation may occur at 30 ppm (10 
minutes), moderate irritation to the eyes, nose, throat, and chest 
occurs at 50 ppm (10 minutes to 2 hours), moderate to highly intense 
irritation occurs at 80 ppm (30 minutes to 2 hours), highly intense 
irritation occurs at 110 ppm (30 minutes to 2 hours), unbearable 
irritation occurs at 140 ppm (30 minutes to 2 hours), and excessive 
lacrimation and irritation at 500 ppm. In addition, some subjects were 
able to breathe 140 ppm for up to 2 hours or 500 ppm for 30 minutes 
without suffering long-lasting effects. Reflex glottis closure, a 
response to irritant vapors, occurred at 570 ppm for 21- to 30-year-old 
subjects, 1,000 ppm for 60-year-old subjects, and 1,790 ppm for 86- to 
90-year-old subjects.
    Acute lethality studies in animals showed that the LC50 
values for rats ranged from 40,300 ppm for a 10-minute exposure to 
7,338 and 16,600 ppm for 60-minute exposures. For the mouse, 
LC50 values were 21,430 ppm for a 30-minute exposure (almost 
all animals died in less than 13 minutes), 10,096 ppm for a 10-minute 
exposure, and 4,230 and 4,837 ppm for 60-minute

[[Page 42716]]

exposures. Comparative data for the same exposure duration show that 
mice are more sensitive than rats to the acute toxic effects of ammonia 
(10 minute LC50 values for mice and rats, are 10,096 ppm and 
40,300 ppm, respectively). The lowest lethal concentrations reported 
was 1,000 ppm for the cat. However, cats were exposed via an 
endotracheal tube, which probably exacerbated the effects in the 
tracheobronchial region by bypassing the scrubbing action of the 
nasopharyngeal region. Rats exposed by inhalation to lethal 
concentrations of ammonia, showed signs of dyspnea, irritation to the 
eyes and nose, and hemorrhage in the lungs. Mice exposed to lethal 
concentrations of ammonia showed signs of irritation to the eyes and 
nose, along with tremors, ataxia, convulsions, seizures, and pathologic 
lesions in the alveoli. Cats exposed to the lowest lethal concentration 
showed evidence of severe airway damage, bronchopneumonia, bronchitis, 
bronchiolitis, and emphysema. Toxic effects at non-lethal 
concentrations in mice and rats consisted of mild effects on 
respiratory epithelium of the nasal cavity (mice and rats), reduction 
in the respiratory rate (mice), and evidence of eye irritation (rat). 
The RD50 (concentration causing a 50% reduction in 
respiratory rate) for the mouse was 300 ppm for a 30-minute exposure.
    The AEGL values for the three toxicity levels (nondisabling, 
disabling, and lethal) were derived from both human and animal data. 
The odor of ammonia is detected by humans at concentrations ranging 
from 5 to 53 ppm and data showed that it is irritating to the upper 
respiratory tract of humans at 30 ppm. The AEGL-1 value of 25 ppm is 
based the concentration slightly below the lowest concentration showing 
irritation in humans. An intraspecies uncertainty factor of 1 was 
applied, because 25 ppm is below the concentration causing irritation; 
however, if irritation did occur, it would be mild or only slightly 
noticeable, confined to the nasal cavity and eyes (ammonia is 
efficiently scrubbed), and would not be expected to affect asthmatic or 
other sensitive individuals to a greater degree than nonasthmatic 
individuals. Atopic and nonatopic subjects did not respond differently 
to a nasal exposure to ammonia. The AEGL-1 values are based on human 
data; therefore, an interspecies uncertainty factor is not applicable. 
Because upper respiratory tract irritation at low ammonia 
concentrations is not expected to change or become more severe with 
duration of exposure, except for adaptation, the same value of 25 ppm 
is applied to all AEGL-1 exposure durations.
    The AEGL-2 values were based on a study of nonexpert human subjects 
who had no previous exposure to ammonia and were not familiar with 
effects of ammonia. At least one of eight subjects reported nuisance or 
offensive irritation to the eyes and throat during exposure to 110 ppm 
of ammonia for 1 hour (Verberk, 1977). The effects reported were less 
serious than those described in the AEGL-2 definition, no residual 
effects were reported after termination of exposure, and pulmonary 
function was not affected by exposure. At the next highest 
concentration, some of the subjects reported the effects to be 
unbearable and left the chamber between 30 minutes and 1 hour. Their 
responses suggest that this concentration would impair escape. An 
intraspecies uncertainty factor of 1 was used for deriving the AEGL 2 
values because the responses of the non-expert group ranged from just 
perceptible to offensive, but the AEGL-2 value was based on the 
response of the most sensitive individuals. The reported effects from 
this group involved primarily the upper respiratory tract and eyes and 
is unlikely to affect asthmatics differently from the most sensitive 
non-expert individuals. In addition, atopic subjects responded 
similarly to non-atopic subjects to a brief nasal exposure to ammonia, 
and exercising subjects showed only a small equivocal decrease in 
pulmonary function. The equation C\n\ H t = k, where n = 2, was used to 
extrapolate to 5-, 10-, and 30-minute exposure durations. This equation 
was based on mouse and rat lethality data. The same AEGL-2 values were 
established for 1-, 4-, and 8-hour exposures, because the responses of 
the subjects exposed to 110 ppm of ammonia were similar after 1- and 2-
hour exposures.
    The AEGL-3 values were based on LC01 values of 3,317 and 
3,374 ppm derived by probit analysis of mouse lethality data reported 
by Kapeghian et al. (1982) and MacEwen and Vernot (1972), respectively. 
An uncertainty factor of 3 was applied to account for intraspecies 
variability because at high concentrations of ammonia, severe 
irritation is elicited immediately upon contact with the eyes and 
mucous membranes of the respiratory tract and the severity of effects 
such as pulmonary edema and damage to the tracheobronchial region would 
be similar in asthmatics and non-asthmatics. There is no reason to 
apply a larger uncertainty factor to protect individuals with asthma 
because the severe damage to the respiratory tract would have a greater 
and longer-lasting consequence than that of asthma. Another reason for 
not applying a larger intraspecies uncertainty factor to protect 
children is the evidence from one study showing that a child recovered 
from an accidental exposure to ammonia, whereas the mother carrying the 
child suffered severe permanent damage to the lungs. An interspecies 
uncertainty factor or 1 was applied to the mouse data, because the 
mouse was the most sensitive species among mammals. In addition, 
applying a larger uncertainty factor would result in a 30-minute AEGL-3 
value less than the 500 ppm that human can tolerate for 30 minutes 
without lethal or long-term consequences. The equation, C\n\ H t = k 
(where n = 2) based on mouse lethality data, was used to extrapolate to 
different exposure durations
    The proposed AEGL values are listed in Table 3 of this unit.

                                          Table 3.--Summary of Proposed AEGL Values for Ammonia [ppm (mg/m\3\)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                           Exposure duration
        Classification        ----------------------------------------------------------------------------------------------------------     Endpoint
                                   5-minutes        10-minutes        30-minutes          1-hour           4-hours          8-hours        (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)          25                25                25                25                25               25               No-observed-
                               (17)............  (17)............  (17)............  (17)............  (17)...........  (17)...........   adverse-effect-
                                                                                                                                          level (NOAEL)
                                                                                                                                          for irritation
                                                                                                                                          (MacEwen et
                                                                                                                                          al., 1970);
                                                                                                                                          Verberk, 1977
-------------------------------------------------
 
------------------------------===================

[[Page 42717]]

                              ===================
 
--------------------------------------------------------------------------------------------------------------------------------------------------------


    ii. References. a. Kapeghian, J.C.; Mincer, H.H.; and Hones, A.B., 
et al. 1982. Acute inhalation toxicity of ammonia in mice. Bulletin of 
Environmental Contamination and Toxicology. 29:371-378.
    b. MacEwen, J.D.; Theodore, J; and Vernot, E.H. 1970. Human 
exposure to EEL concentrations of monomethylhydrazine, AMRL-TR-70-102, 
Paper No 23. Proceedings of the 1st Annual Conference on Environmental 
Toxicology. September 9-11, 1970. Wright-Patterson AFB, OH. pp. 355-
363.
    c. MacEwen, J.D. and Vernot, E.H. 1972. Toxic Hazards Research Unit 
Annual Technical Report: 1972. SysteMed Report No. W-72003, AMRL-TR-72-
62. Sponsor: Aerospace Medical Research Laboratory, Wright-Patterson 
AFB, OH. AD-755-358.
    d. Verberk, M.M. 1977. Effects of ammonia on volunteers. 
International Archives of Occupational and Environmental Health. 39:73-
81.
    3. Bromine--i. Description. The halogen bromine (Br2) is 
a dark reddish-brown volatile liquid at room temperature. Its oxidizing 
potential lies between that of chlorine and iodine. Bromine is used as 
a water disinfectant, for bleaching fibers and silk, and in the 
manufacture of medicinal bromine compounds, dyestuffs, flame 
retardants, agricultural chemicals, inorganic bromide drilling fluids, 
and gasoline additives.
    Bromine is a skin, eye, and respiratory tract irritant. Inhalation 
causes respiratory tract irritation and pulmonary edema. Although 
accidental human exposures have occurred, concentrations were either 
not reported or were judged unreliable. Aside from old and anecdotal 
information, the data base is limited to one study with human subjects 
and two lethality studies with the mouse as the test species. One of 
the lethality studies (Bitron and Aharonson 1978) provided data 
sufficient for derivation of the relationship between concentrations 
that result in lethality (LC50 values) and exposure 
duration: C\2.2\ x t = k.
    The AEGL-1 was based on exposures of 20 healthy human volunteers to 
concentrations of 0.1 to 1.0 ppm for at least 30 minutes (Rupp and 
Henschler 1967). Eye irritation, but not nose or throat irritation, 
occurred during a 30-minute exposure to 0.1 ppm. At concentrations $0.5 
ppm, there was a stinging and burning sensation of the conjunctiva. The 
30-minute 0.1 ppm was chosen as the basis for the AEGL-1. The 0.1 ppm 
concentration was divided by an intraspecies uncertainty factor of 3 to 
protect susceptible individuals. An intraspecies uncertainty factor of 
3 was considered sufficient because workers have been occupationally 
exposed to 1 ppm with no symptoms other than ``excess irritation'' 
(Elkins 1959). Furthermore, effects at this low concentration appear to 
be limited to the eyes and upper respiratory tract; there was no 
penetration to the lower respiratory tract. The resulting 30-minute 
AEGL-1 value of 0.03 ppm was time-scaled to the other AEGL exposure 
durations using the \\C\2.2\ x t = k relationship derived from the 
mouse lethality study.
    The AEGL-2 was based on the concentration of 1 ppm for 30 minutes 
which the volunteers in the above study (Rupp and Henschler 1967) found 
irritating (stinging and burning sensation of the conjunctiva; nose and 
throat irritation). The 30-minute 1 ppm value was divided by an 
intraspecies uncertainty factor of 3 to protect susceptible individuals 
and time scaled to the other AEGL-2 exposure durations using the 
concentration-exposure duration relationship from the mouse lethality 
study of C\2.2\ x t = k. An intraspecies uncertainty factor of 3 was 
considered sufficient as the symptoms may be below those defining an 
AEGL-2. However, no reliable studies with exposures to higher 
concentrations were located.
    Both lethality studies with the mouse described the inhalation 
toxicity of chlorine and bromine. However, both studies reported lower 
LC50 values for chlorine than those reported in more recent 
well-conducted studies. Nevertheless, the study that reported the lower 
lethal concentrations for chlorine was used for derivation of the AEGL-
3 values for bromine (Schlagbauer and Henschler 1967). The data in this 
study showed a clear concentration-response relationship; the exposure 
duration was 30 minutes. Using probit analysis, a 30-minute 
LC50 value of 204 ppm and a 30-minute 
LC01 of 116 ppm were calculated. The 30-minute 
LC01 of 116 ppm was used as the basis for calculation of 
AEGL-3 values. The 116 ppm LC01 was divided by a combined 
uncertainty factor of 10 (3 for interspecies differences [the mouse was 
the most sensitive species for lethal effects in tests with other 
halogens] and 3 for intraspecies differences [at high concentrations 
bromine is corrosive to the mucous membranes of the respiratory system; 
effects are not expected to differ greatly among individuals]) and 
scaled across time using the relationship C\2.2\ x t = k, derived from 
the same study.
    The proposed AEGL values are listed in Table 4 of this unit.

                                          Table 4.--Summary of Proposed AEGL Values for Bromine [ppm (mg/m\3\)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10-minutes          30-minutes            1-hour              4-hours             8-hours           (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)             0.055               0.033               0.024               0.013               0.0095              Rupp and Henschler
                                  (0.36)............  (0.22)............  (0.16)............  (0.09)............  (0.06)............   1967
------------------------------------------------------
                                                                                                                                      (3.6)
---------------------------------=====================

[[Page 42718]]

                                 =====================
 
--------------------------------------------------------------------------------------------------------------------------------------------------------


    ii. References. a. Bitron, M.D. and E.F. Aharonson. 1978. Delayed 
mortality of mice following inhalation of acute doses of 
CH2, SO2, Cl2, and Br2. 
American Industrial Hygiene Association Journal. 39:129-138.
    b. Elkins, H.B. 1959. Inorganic compounds: Bromine. Chemistry of 
Industrial Toxicology. John Wiley & Sons, New York. p. 89.
    c. Rupp, H. and D. Henschler. 1967. Effects of low chlorine and 
bromine concentrations in man. Internationales Archiv fuer 
Gewerbepathologie und Gewerbehygiene. 23:79-90.
    d. Schlagbauer, M. and D. Henschler. 1967. Inhalation toxicity of 
chlorine and bromine with single and repeated exposures. 
Internationales Archiv fuer Gewerbepathologie und Gewerbehygiene. 
23:91-98.
    4. Chloroacetic acid--i. Description. Monochloroacetic acid (MCAA) 
is a colorless crystalline material, which is highly soluble in water 
and soluble in organic solvents. Its vapor pressure at room temperature 
is moderate with reported values between 0.2 hPa (crystalline 
substance) and 10 hPa (solution in water). MCAA has a pungent odor.
    MCAA is produced by chlorination of acetic acid or hydrolysis of 
trichloroethene using sulfuric acid. The world production capacity was 
estimated at 362,500 tons/year in 1987. MCAA or its sodium salt, sodium 
monochloroacetate, are used primarily in the industrial production of 
carboxymethylcellulose, herbicides, thioglycolic acid as well as in the 
production plastics, pharmaceuticals, flavors, cosmetics, and other 
organic chemicals.
    MCAA is an acid (pKa 2.85) and therefore can cause eye 
and skin irritation upon contact with a diluted MCAA solution and skin 
corrosion and conjunctival burns upon contact with more concentrated 
solutions. The systemic toxicity of MCAA is caused by inhibition of 
enzymes of the glycolytic pathway and the tricarboxylic acid cycle. 
This metabolic blockage damages organs with a high energy-demand, such 
as heart, central nervous system (CNS), and muscles, and leads to 
metabolic acidosis due to the accumulation of lactic acid and citric 
acid in the body.
    No studies are available reporting severe toxic effects in humans 
after inhalation exposure to MCAA. Mortality was reported in a child 
after oral uptake of 5-6 ml of an 80% MCAA solution (Rogers, 1995). 
Several lethal accidents have been reported, in which workers were 
dermally exposed to hot, liquid MCAA. An inadequately described study 
reported an irritation threshold of 1.48 ppm (Maksimov and Dubinina, 
1974); no respiratory tract irritation, effects on lung function 
parameters or irritation of skin and mucous membranes were reported for 
33 workers potentially exposed to MCAA concentrations 
between <0.13 ppm for 3 hours and 0.31 ppm for 7 hours (Clariant GmbH, 
2000).
    The only animal study reporting lethal effects after inhalation 
exposure was an inadequately described study in which a LC50 
of 46.8 ppm for 4 hours was reported for rats (Maksimov and Dubinina, 
1974). Several studies report lethal effects after oral exposure with 
LD50 values mostly between 50-200 mg/kilogram (kg) for rats, 
mice and guinea pigs. In a single inhalation experiment on rats, eye 
squint and slight lethargy were observed during exposure to an 
analytical concentration of 66 ppm for 1 hour (Dow Chemical Co., 1987). 
In an inadequately reported study, an irritation threshold in rats of 
6.16 ppm and a no-observed-effect-level (NOEL) for histological changes 
in the respiratory tract in rats and guinea pigs of 1.5 ppm after 4 
months have been reported (Maksimov and Dubinina, 1974).
    No relevant studies of adequate quality were available for the 
derivation of the AEGL-1. Therefore, due to insufficient data, AEGL-1 
values were not derived.
    The AEGL-2 was based on a single inhalation study in rats (Dow 
Chemical Co., 1987) in which eye squint and lethargy were observed in 
rats exposure to 66 ppm for 1 hour. A total uncertainty factor of 10 
was used. A factor of 3 was applied for interspecies variability 
because the effect level was considered below that of an AEGL-2 and 
because the available data do not point at a large interspecies 
variability for more severe (lethal) effects. A factor of 3 was applied 
for intraspecies variability because a higher factor was not considered 
adequate on the basis of a comparison with human data for oral 
exposure. The other exposure duration-specific values were derived by 
time scaling according to the dose-response regression equation C\n\ x 
t = k, using the default of n = 3 for shorter exposure periods and n=1 
for longer exposure periods, due to the lack of suitable experimental 
data for deriving the concentration exponent.
    No relevant studies of adequate quality were available for the 
derivation of the AEGL-3 value. Therefore, due to insufficient data and 
the uncertainties of a route-to-route extrapolation, AEGL-3 values were 
not derived.
    The proposed AEGL values are listed in Table 5 of this unit.

                                         Table 5.--Summary of Proposed AEGL Values For Monochloroacetic Acid\ a\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10-minutes          30-minutes            1-hour              4-hours             8-hours           (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)             Insufficient data   I.D.                I.D.                I.D.                I.D.                I.D.
                                   (I.D.)
------------------------------------------------------
 
---------------------------------=====================
--------------------------------------------------------------------------------------------------------------------------------------------------------
\a\ Skin contact with molten MCAA or MCAA solutions should be avoided; dermal penetration is rapid and fatal intoxications have been observed when 10%
  or more of the body surface was involved.



[[Page 42719]]

    ii. References. a. Clariant GmbH, 2000. Unpublished. Letter of Dr. 
Kreiling dated 23.08.2000. Dow Chemical Co., 1987. Monochloroacetic 
acid: an acute vapor inhalation limit study with Fischer 344 rats. 
Unpublished Report, Dow Chemical Company, Midland, USA.
    b. Maksimov, G.G. and O.N. Dubinina, 1974. Materials of 
experimental substantiation of maximally permissible concentration of 
monochloroacetic acid in the air of production area. Gigiena Truda i 
Professional nye Zabolevarija. 9:32-35.
    c. Rogers D.R. 1995. Accidental fatal monochloroacetic acid 
poisoning. American Journal of Forensic Medicine and Pathology. 16:115-
116.
    5. Fluorine--i. Description. Fluorine is a reactive, highly 
irritating and corrosive 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 inhalation exposure. Death is 
due to pulmonary edema. 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 AEGL values.
    Regression analyses of the concentration-exposure durations (for 
the fixed endpoint of mortality) for all of the animal species reported 
in the key study (Keplinger and Suissa 1968) determined that the 
relationship between concentration and time is C\n\ x t = k, where n = 
approximately 2 (actual value of n for the most sensitive species in 
irritation and lethality studies, the mouse, is 1.77). This 
concentration exposure duration relationship was applied both the AEGL-
2 and AEGL-3 levels because the irritant and corrosive action of 
fluorine on the respiratory tissues differs by only a matter of degree 
for these AEGL levels:
    a. Respiratory irritation with edema resulting in mild, reversible 
lung congestion, and
    b. Severe respiratory irritation resulting in severe lung 
congestion.
Although the data base for fluorine is small, the data from the key 
study, augmented with data from several other studies, 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 minutes without irritant effects 
(Keplinger and Suissa 1968). Although this value is below the 
definition of an AEGL-1 (notable discomfort), it provides the longest 
exposure duration for which no irritation in humans was reported. An 
intraspecies uncertainty factor of 3 was applied because fluorine is 
highly corrosive to the tissues of the respiratory tract and effects 
are not expected to vary greatly among individuals, including 
susceptible individuals. Although no data on asthmatics were found, the 
uncertainty factor of 3 was considered adequate to protect this 
sensitive subpopulation because the value was a NOAEL and because 
shorter-term, repeated exposures produced no substantially greater 
effects in healthy individuals. The value is supported by a second 
study in which volunteers ``tolerated'' exposure to 10 ppm for an 
undefined period of time. Furthermore, occupational exposure 
concentrations for healthy adults have ranged up to 17 ppm, albeit for 
short, undefined periods of time (Lyon 1962). A modifying factor of 2 
was applied based on a limited data base. The resulting value of 1.7 
ppm was used across all AEGL-1 exposure durations because at mildly 
irritating concentrations there is accommodation to irritating gases. 
As noted, this value is supported by limited workplace monitoring data: 
Workers exposed to fluorine at average yearly concentrations up to 1.2 
ppm (range, 0.0-17 ppm) over a 4-year period reported fewer incidences 
of respiratory complaints or diseases than a similar group of 
nonexposed workers (Lyon 1962). The workers are assumed to encompass a 
small range of sensitivity; the additional intraspecies uncertainty 
factor of 3 was considered sufficient to protect sensitive individuals.
    Mild lung congestion was selected as the threshold for 
irreversible, long-lasting effects as defined by the AEGL-2. The AEGL-2 
was based on an animal study in which mild lung congestion was observed 
in mice at 67 ppm for 30 minutes and 30 ppm for 60 minutes (Keplinger 
and Suissa 1968). Effects were slightly less serious in three other 
species. Although concentrations causing irritant effects or lethality 
for three other 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 
similar sensitivity was observed among five species in the key study, 
no uncertainty factor for interspecies variability was applied. 
Fluorine is a highly corrosive gas that reacts directly with the 
tissues of the respiratory tract, with no pharmacokinetic component 
involved in the toxicity; therefore, there is likely to be little 
difference among individuals in response to fluorine at concentrations 
that define the AEGL-2. The 30- and 60-minute values for the mouse were 
divided by an intraspecies uncertainty factor of 3 to protect sensitive 
individuals, since effects are not likely to differ greatly among 
individuals, and by a modifying factor of 2, based on a limited data 
base. The 30-minute value was used for the 10- and 30-minute AEGL-2 and 
the 60-minute value was used for the 60-minute AEGL-2. The 4-hour AEGL-
2 value was scaled from the 60-minute value based on the C\1.77\ x t = 
k relationship. The value of n was derived from regression analysis of 
the mouse lethality data in the key study. The 8-hour-AEGL-2 value was 
set equal to the 4-hour value because at low concentrations the 
hygroscopic fluorine would react with and/or be scrubbed by the nasal 
passages and because at low concentrations there is accommodation to 
irritant gases. The 10- and 3-minute AEGL-2 values are supported by 
studies in which human volunteers found short-term exposures to 15-25 
ppm irritating to the eyes, nose, and throat (Rickey 1959; Keplinger 
and Suissa 1968).
    The AEGL-3 values were derived from the highest exposures that 
resulted in no deaths in five species over four exposure durations (13 
tests) for up to 45 days post exposure, but did produce severe lung 
congestion in the mouse (Keplinger and Suissa 1968). Severe lung 
congestion in the sensitive mouse was considered the threshold for 
lethality as defined by the AEGL-3. For the mouse, the 60-minute value 
was 75 ppm. Because of the similar species sensitivity in the key 
study, based on both irritant effects and lethality, no uncertainty 
factor for interspecies variability was applied. The values were 
divided by an uncertainty factor of 3 to protect sensitive individuals 
(fluorine is a highly reactive, corrosive gas whose effect on 
respiratory tract tissues is not expected to differ greatly among 
individuals) and by a modifying factor of 2, based on a limited data 
base. Using the 60-minute value of 75 ppm, AEGL-3 values for the other 
exposure times were calculated based on the C\1.77\ x t = k 
relationship. The value of n was derived from regression analysis of 
the mouse lethality data in the key study. The 8-hour value was set 
equal to the 4-hour value because fluorine would react with or be 
scrubbed by the nasal passages at fairly low concentrations. The safety 
of setting the 8-hour value equal to the 4-hour value is supported by 
another study in which a 7-hour experimental exposure concentrations

[[Page 42720]]

resulting in an overall 60% mortality for four species (Eriksen 1945; 
Stokinger 1949) is higher than the extrapolated 7-hour values for the 
mouse and rat based on the Keplinger and Suissa study.
    The proposed AEGL values are listed in Table 6 of this unit.

                                         Table 6.--Summary of Proposed AEGL Values for Fluorine [ppm (mg/m\3\)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10-minutes          30-minutes            1-hour              4-hours             8-hours           (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1\a, b\ (Nondisabling)       1.7                 1.7                 1.7                 1.7                 1.7                 No irritant
                                  (2.6).............  (2.6).............  (2.6).............  (2.6).............  (2.6).............   effects--humans
                                                                                                                                       (Keplinger and
                                                                                                                                       Suissa 1968)
------------------------------------------------------
                                                                                                                                      (31)
---------------------------------=====================
 
--------------------------------------------------------------------------------------------------------------------------------------------------------
\a\The characteristic, pungent odor of fluorine will be noticeable at this concentration.
\b\The same value was used across all time periods because at low concentrations there is accommodation to irritant gases.
\c\30-Minute and 1-hour values are based on separate data points.


    ii. References. a. Eriksen, N. 1945. A Study of the Lethal Effect 
of the Inhalation of Gaseous Fluorine (F2) at Concentrations 
from 100 ppm to 10,000 ppm. DOE/EV/03490-T3, United States Atomic 
Energy Commission. Pharmacology Report 435. University of Rochester, 
Rochester, NY.
    b. Keplinger, M.L. and L.W. Suissa. 1968. Toxicity of fluorine 
short-term inhalation.American Industrial Hygiene Association Journal. 
29:10-18.
    c. Lyon, J.S. 1962. Observations on personnel working with fluorine 
at a gaseous diffusion plant. Journal of Occupational Medicine. 4:199-
201.
    d. Rickey, R.P. 1959. Decontamination of Large Liquid Fluorine 
Spills. AFFTC-TR-59-31, U.S. Air Force, Air Research and Development 
Command, Air Force Flight Test Center, Edwards Air Force Base, CA; AD-
228-033, Defense Technical Information Center, Ft. Belvoir, VA.
    e. Stokinger, H.E. 1949. Toxicity following inhalation of fluorine 
and hydrogen fluoride, Chapter 17. Pharmacology and Toxicology of 
Uranium Compounds. C. Voegtlin and H.C. Hodge, eds. McGraw-Hill Book 
Company, New York.
    6. Jet Fuel 8--i. Description. Jet propellant (JP) fuels, used in 
military and civilian aircraft, are complex mixtures of aliphatic and 
aromatic hydrocarbons made by blending various distillate stocks of 
petroleum. The primary military fuel for land-based military aircraft 
is JP-8; JP-5 was developed by the U.S. Navy for shipboard service. The 
composition of these two fuels is basically that of kerosene (with 
additives) and they have similar chemical and physical characteristics. 
Worldwide, approximately 60 billion gallons of military JP-8 and the 
equivalent commercial Jet A and Jet A-1 are consumed on an annual 
basis. The military jet fuels contain additives that are not contained 
in commercial jet fuels. Civilian and military personnel may be exposed 
to jet fuels during fuel production, aircraft fueling operations, 
aircraft maintenance operations, and accidental spills or pipeline 
leaks.
    Although several jet fuels are discussed in this document (JP-4, 
JP-5, JP-7, and JP-8), the discussion focuses on the toxicity of JP-8 
with some attention to the chemically similar JP-5. These two fuels 
have a similar composition and appear to have similar toxicities. 
Monitoring data indicate that exposures to JP-4 which has a higher 
vapor pressure than JP-8 and JP-5 were higher than to the presently 
used JP-8 and JP-5. Data were located on acute sensory and systemic 
effects of JP-8 and JP-5 to mice and rats; subchronic studies addressed 
systemic effects, particularly effects on the lungs. For all fuels, 
tests of eye irritation were generally negative, whereas mild skin 
irritation occurred for some fuels. Several short-term and repeated 
exposure studies addressed the particular issue of the toxicity of 
aerosols. Exposure to aerosols of jet fuels induces more toxic effects 
than exposure to vapors, with the lungs and immune system identified as 
the target organs. Animal studies also addressed neurotoxicity, 
developmental/reproductive effects, and carcinogenicity. These fuels 
are generally not considered genotoxic or carcinogenic and, in a 
preliminary study, JP-8 failed to cause spermatotoxic effects in 
humans. A nephropathy and resulting carcinogenic effect, unique to male 
rats exposed to hydrocarbons, is not relevant to humans. No information 
relevant to time scaling was available.
    The AEGL-1 is based on the sensory irritation study of Whitman et 
al. (2001), specifically the RD50 (the concentration that 
reduces the respiratory rate by 50%) for JP-8 of 2,876 mg/m\3\ vapor 
plus aerosol. The RD50 test is a standard test for 
estimating sensory irritancy of airborne chemicals (ASTM E981-84). In 
the key study, male Swiss-Webster mice were exposed for 30 minutes to 
681; 1,090; 1,837; or 3,565 mg/m\3\. JP-8 is not a primary irritant and 
reductions in the respiratory rate did not occur within 10 minutes at 
the lower concentrations. However, reductions in the respiratory rate 
within the 30-minute exposure durations were concentration-dependent 
and allowed calculation of an RD50. Based on the correlation 
between RD50 data and sensory irritancy levels for numerous 
chemicals, a 0.1-fold reduction of the RD50 results in a 
concentration that elicits some sensory irritation in humans but that 
can be tolerated for hours to days (Alarie 1981). Using this reasoning, 
the resulting concentration of 290 mg/m\3\ can be tolerated over all 
AEGL-1 exposure durations. The 290 mg/m\3\ value is supported by the 
lack of adverse health effects in animal studies with repeated 
exposures to 1,000 mg/m\3\ of JP-8 vapor (continuous exposures up to 90 
days) (Mattie et al. 1991; Briggs 2001; Rossi et al. 2001). Dividing 
the 1,000 mg/m\3\ value by an interspecies uncertainty factor of 1 (no 
species differences were observed in multiple studies with rats and 
mice and the exposures were repeated) and an intraspecies uncertainty 
factor of 3 (to account for potential differences in human 
susceptibilities to sensory irritation) results in 330 mg/m\3\, a value 
similar to that derived from the RD50 study. The repeated 
nature of the support studies also supports the use of a single value 
for all exposure durations.
    The AEGL-2 is based on several studies with rodents (rats and mice) 
that indicate that exposure to 1,100 mg/m\3\ of JP-8 would not elicit 
adverse health effects but may be the threshold for such effects. The 
shorter-term studies (30

[[Page 42721]]

minutes to 4 hours) with exposures to 3,430-5,000 mg/m\3\ of JP-8 or 
JP-5 in the vapor/aerosol form (MacEwen and Vernot 1985; Wolfe et al. 
1996; Whitman et al. 2001) with support from the studies using repeated 
exposures to 1,000 mg/m\3\ (Mattie et al. 1991; Briggs 2001; Rossi et 
al. 2001) were used as the basis for the AEGL-2. No uncertainty factors 
were applied to the 1,000 mg/m\3\ concentration because there were no 
adverse effects and the exposures were repeated for up to 90 days. The 
higher concentrations of JP-8, 3430 and 4,440 mg/m\3\, and of JP-5, 
5,000 mg/m\3\, were divided by an interspecies factor of 1 (there were 
no species differences) and by an intraspecies uncertainty factor of 3 
to protect potentially sensitive individuals. An intraspecies 
uncertainty factor of 3 is considered adequate because the thresholds 
for both sensory irritation and central nervous system depression to 
solvents do not generally differ by more than 3-fold. The resulting 
value is 1,100 mg/m\3\ (1,100-1,700 mg/m\3\), approximately the same 
concentration as in the no-adverse-effect repeated exposure studies. No 
information was available for time scaling. Central nervous system 
depression is a concentration-related effect. Therefore, the 1,100 mg/
m\3\ value was used for the 4-hour and shorter time period. But, 
because the exposures to 1,000 mg/m\3\ were repeated for up to 90 days, 
the 1,100 \\mg/m\3\ value can also be used for the longest AEGL 
exposure duration of 8 hours. The fact that the exposures in most of 
these studies, especially at the higher concentrations, were to both 
the vapor and the more toxic aerosol supports the appropriateness of 
the derived value.
    It should be noted that, because of its relatively low vapor 
pressure, JP-8 might not attain a sustained vapor concentration high 
enough to cause death. In a laboratory study reported by Wolfe et al. 
(1996), the highest vapor concentration of JP-8 that could be attained 
was 3,430 mg/m\3\. The highest vapor/aerosol concentration that could 
be attained was 4,440 mg/m\3\. The highest vapor/aerosol attainable 
under ambient concentrations has been estimated at 700 mg/m\3\. 
However, higher concentrations might be attained in closed spaces at 
high temperatures. A concentration of 500 mg/m\3\ is assumed to be the 
upper bound for a stable cloud of inhalable dust (and aerosols). Based 
on the likelihood that lethal concentrations of JP-8 cannot be 
sustained under ambient conditions, an AEGL-3 was not determined.
    The proposed AEGL values are listed in Table 7 of this unit.

                                           Table 7.--Summary of Proposed AEGL Values for JP-8 (mg/m\3\)\a, b\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10-minutes          30-minutes            1-hour              4-hours             8-hours           (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)             290                 290                 290                 290                 290                 Slight sensory
                                                                                                                                       irritation in
                                                                                                                                       humans (mouse
                                                                                                                                       RD50 test)
                                                                                                                                       (Whitman et al.
                                                                                                                                       2001)
---------------------------------                                                                                                      >3,430 mg/m\3\--
---------------------------------=====================
--------------------------------------------------------------------------------------------------------------------------------------------------------
\a\ The values apply to JP-8 vapor or vapor/aerosol and not to the pure aerosol.
\b\ The values apply to JP-8 vapor and not to JP-8+100.
\c\ A lethal concentration was not attained in the available toxicity studies; the low vapor pressure of JP-8 may preclude attainment of a lethal
  concentration.


    ii. References. a. Alarie, Y. 1981. Dose-response analysis in 
animal studies: prediction of human responses. Environmental Health 
Perspectives. 42:9-13.
    b. Briggs, G.B. 2001. Evaluation of military fuel potential to 
produce male reproductive toxicity. Presented at the International 
Conference on the Environmental Health and Safety of Jet Fuel held in 
San Antonio, TX, August 8-11, 2001.
    c. MacEwen, J.D. and E.H. Vernot. 1985. Investigation of the 1-hour 
emergency exposure limit of JP-5. In Toxic Hazards Research Unit Annual 
Report, Report No. AAMRL-TR-85-058; Aerospace Medical Research 
Laboratory, Wright-Patterson Air Force Base, OH. pp. 137-144. Available 
from Defense Technical information Center, Doc. No. AD-A161558.
    d. Mattie, D.R.; C.L. Alden; T.K. Newell; C.L. Gaworski; and C.D. 
Flemming. 1991. A 90-day continuous vapor inhalation toxicity study of 
JP-8 jet fuel followed by 20 or 21 months of recovery in Fischer 344 
rats and C57BL/6 mice. Toxicologic Pathology. 19:77-87.
    e. Rossi, J., III; A.F. Nordholm; R.L Carpenter; G.D. Ritchie; and 
W. Malcomb. 2001. Effects of repeated exposure of rats to JP-5 or JP-8 
jet fuel vapor on neurobehavioral capacity and neurotransmitter levels. 
Journal of Toxicology and Environmental Health. Part A 63:397-428.
    f. Whitman, F.T.; J.J. Freeman; G.W. Trimmer; J.L. Martin; E.J. 
Febbo; W.J. Bover; and R.L. Harris. 2001. Sensory Irritation Study in 
Mice. Final Report, Project No. 162951, ExxonMobil Biomedical Sciences, 
Inc., Annandale, NJ.
    g. Wolfe, R.E.; E.R. Kinkead; M.L. Feldmann; H.F. Leahy; W.W. 
Jederberg; K.R. Still; and D.R. Mattie. 1996. Acute toxicity evaluation 
of JP-8 jet fuel containing additives. AL/OE-TR-1996-0136, NMRI-94-114, 
Armstrong Laboratory, Occupational and Environmental Health 
Directorate, Toxicology Division, Wright-Patterson AFB, OH.
    7. Methyl ethyl ketone--i. Description. Methyl ethyl ketone (MEK) 
is a volatile solvent with a sweet/sharp acetone-like odor. MEK is 
widely used as a solvent in common household products such as inks, 
paints, cleaning fluids, varnishes, and glues. In most industrial 
applications it is used as a component of a mixture of organic 
solvents. It has also been detected in a wide variety of

[[Page 42722]]

natural products and may be a minor product of normal mammalian 
metabolism. In 1999, U.S. production capacity was 675 million pounds.
    The inhalation toxicity of MEK is low. Low concentrations are only 
mildly irritating. At high concentrations MEK causes a narcotic effect 
on the central nervous system as evidenced by neurobehavioral effects 
in animals. MEK is not teratogenic, but at high concentrations is 
mildly fetotoxic to rats and mice. Data on human exposures were 
available from clinical studies and workplace monitoring. Animal 
studies with a variety of species (baboon, rat, mouse, and guinea pig) 
addressed irritation, neurotoxicity, developmental toxicity, chronic 
toxicity/carcinogenicity, and lethality. Exposure durations ranged from 
acute to chronic. Genotoxicity was also addressed.
    Two studies with human volunteers exposed to 100, 200, or 350 ppm 
were evaluated for the AEGL-1; the exposure times were 5 minutes 
(Nelson et al. 1943) and 4 hours (Dick et al. 1992). Although a 
concentration of 200 ppm was judged unobjectionable in both studies, 
slight nose and throat irritation were noted at 100 ppm in the Nelson 
et al. (1943) study. Therefore, 100 ppm was selected as the threshold 
for sensory irritation. The safety of this value is supported by 
numerous clinical studies in which volunteers were routinely exposed to 
200-400 ppm for up to 4 hours without reports of irritation or changes 
in neurobehavioral parameters. Because this is a threshold value and 
slight irritation should not increase in intensity with time, an 
intraspecies uncertainty factor of 1 was applied. Because accommodation 
to slight irritation occurs, the 100 ppm concentration was used across 
all AEGL-1 exposure durations. Furthermore, MEK is rapidly metabolized 
and will not accumulate in the blood or in the body which further 
supports using the same value for all the time intervals.
    The AEGL-2 was based on the chronic study of Cavender et al. (1983) 
in which rats were exposed to 5,000 ppm for 5 days/week for 90 days. No 
lesions were reported in this study, but the concentration is close to 
the threshold for neurotoxicity as evidenced by somnolence in another 
repeated exposure study in which rats were exposed to 6,000 ppm for 
several weeks (Altenkirch et al. 1978). Because this was a no-effect 
repeated-exposure study, no interspecies uncertainty factor was 
applied. Because the threshold for narcosis differs by no more than 2- 
to 3-fold among the general population, an intraspecies uncertainty 
factor of 3 was applied to protect sensitive individuals. Because the 
threshold for narcosis is concentration dependent, the resulting 1,700 
ppm concentration was applied across all AEGL-2 exposure durations.
    The AEGL-3 values were based on two different studies. The 10- and 
30-minute values were based on a study with mice in which a 30-minute 
exposure to 31,426 ppm was projected to reduce the respiratory rate by 
50%; there were no deaths at the highest tested concentration of 26,416 
ppm (Hansen et al. 1992). Because a 30-minute exposure of rats to 3 
times this concentration (92,239 ppm) also resulted in no deaths 
(Klimisch 1988), the 31,426 ppm value was adjusted by an interspecies 
uncertainty factor of 1. Because the threshold for narcosis differs by 
no more than 2- to 3-fold among the general population, an intraspecies 
uncertainty factor of 3 was applied to protect sensitive individuals. 
The resulting value of 10,000 ppm was used for the 10-minute and 30-
minute AEGL-3 exposure durations. The longer-term values were based on 
an MLE01 of 7,500 ppm calculated by Fowles et al. (1999) 
from a 4-hour study with rats exposed to several concentrations for 4 
hours (La Belle and Brieger 1955). In this study the 4-hour 
LC50 was 11,700 ppm and the highest concentration resulting 
in no deaths was 7,850 ppm for 4 hours. The 7,500 ppm concentration was 
divided by an intraspecies uncertainty factor of 3. The resulting value 
of 2,500 ppm was used for both the 4-hour and 8-hour AEGL-3 values 
because MEK would reach equilibrium in the body prior to this time 
period. The 4-hour 2,500 ppm value was time scaled to the 1 hour time 
using the default n value of 3 for scaling to shorter time intervals.
    The proposed AEGL values are listed in Table 8 of this unit.

                                    Table 8.--Summary of Proposed AEGL Values for Methyl Ethyl Ketone [ppm (mg/m\3\)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10-minutes          30-minutes            1-hour              4-hours             8-hours           (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)             100                 100                 100                 100                 100                 Threshold for
                                  (293).............  (293).............  (293).............  (293).............  (293).............   sensory
                                                                                                                                       irritation in
                                                                                                                                       humans (Nelson et
                                                                                                                                       al. 1943)
------------------------------------------------------
 
---------------------------------=====================
 
--------------------------------------------------------------------------------------------------------------------------------------------------------
\a\Based on Hansen et al. (1992).
\b\This value is more than one-half of the lower explosive limit of 18,000 ppm.
\c\Based on La Belle and Brieger (1955).


    ii.References. a. Altenkirch, H.; G. Stoltenburg; and H.M. Wagner. 
1978. Experimental studies on hydrocarbon neuropathies induced by 
methyl-ethyl-ketone (MEK). Journal of Neurology. 219:159-170.
    b. Cavender, F.L; H.W. Casey; H. Salem; J.A. Swenberg; and E.J. 
Gralla. 1983. A 90-day vapor inhalation toxicity study of methyl ethyl 
ketone. Fundamental and Applied Toxicology. 3:264-270.
    c. Dick, R.B.; E.F. Krieg, Jr.; J. Setzer; and B. Taylor. 1992. 
Neurobehavioral effects from acute exposures to methyl isobutyl ketone 
and methyl ethyl ketone. Fundamental and Applied Toxicology. 19:453-
473.
    d. Fowles, J.R.; G.V. Alexeeff; and D. Dodge. 1999. The use of the 
benchmark dose methodology with acute inhalation lethality data. 
Regulatory Toxicology and Pharmacology. 29:262-278.
    e. Hansen, L.F.; A. Knudsen; and G.D. Nielsen. 1992. Sensory 
irritation effects of methyl ethyl ketone and its receptor activation 
mechanism. Pharmacology & Toxicology. 71:201-208.
    f. Klimisch, H. 1988. The inhalation hazard test; principle and 
method. Archives of Toxicology. 61:411-416.
    g. La Belle, C. and H. Brieger. 1955. The vapor toxicity of a 
composite solvent and its principal components.

[[Page 42723]]

Archives of Industrial Health. 12:623-627.
    h. Nelson, K.W.; J.F. Ege, Jr.; M. Ross; L.E. Woodman; and L. 
Silverman. 1943. Sensory response to certain industrial solvent vapors. 
Journal of Industrial Hygiene and Toxicology. 25:282-285.
    8. Phosphorus oxychloride--i. Description. Phosphorus oxychloride 
(CAS No. 10025-87-3), a colorless fuming liquid with a pungent odor, is 
stable to above 300[deg] C but is highly reactive with water yielding 
phosphoric acid and hydrogen chloride. It is used in the manufacture of 
plasticizers, hydraulic fluids, gasoline additives, fire retarding 
agents, and in the manufacture of alkyl and aryl orthophosphate 
triesters.
    Information regarding exposure of humans to phosphorus oxychloride 
are limited to qualitative reports that indicate notable dermal, 
ocular, pharyngeal and pulmonary irritation following acute and 
subchronic (intermittent) exposures. Most reports lacked exposure terms 
although one report of occupational exposures indicated that air 
concentrations of phosphorus oxychloride ranged from 1.6 to 11.2 ppm. 
The effects often persisted after cessation of exposure, especially in 
those individuals experiencing more severe effects. Neither odor 
detection data nor lethality data are available for humans.
    Quantitative data in animals are limited to reports of lethality. 
These data include a 4-hour LC50 for rata (44.4 ppm) and 
guinea pigs (52.5 ppm), and an unverified 4-hour LC50 of 32 
ppm for rats. A 5-15 minute exposure of rats and guinea pigs to 0.96 
ppm phosphorus oxychloride was noted as a ``threshold response'' in a 
Russian report. A brief report from industry indicated immediate 
adverse responses (at 2 minutes) and death (18 minutes) following 
exposure to a very high concentration (25,462 ppm). The available 
studies affirm the extreme irritation properties of phosphorus 
oxychloride, although the exposures described also resulted in 
lethality. No information was available regarding reproductive/
developmental toxicity, genotoxicity, or carcinogenicity.
    There are no definitive data regarding the metabolism or precise 
mechanism of action of phosphorus oxychloride toxicity. Based upon the 
limited human and animal toxicity data, and the chemical properties of 
phosphorus oxychloride, it may be assumed that the primary effect 
involves damage to epithelial tissue and, for respiratory effects, 
subsequent pulmonary edema. The lethal potency of phosphorus 
oxychloride, however, does not appear to be explained simply by the 
activity of its degradation products (phosphoric acid and hydrogen 
chloride).
    In the absence of odor detection data and quantitative data 
pertaining to effects consistent with AEGL-1 definition, AEGL-1 values 
were not developed.
    Exposure-response data pertaining to AEGL-2 level effects were 
unavailable and, therefore no AEGL-2 values were developed. Because of 
the lack of exposure-response data for any effects, estimating AEGL-2 
values by a reduction in AEGL-3 values was considered tenuous and 
difficult to justify.
    AEGL-3 values were developed using an estimate of the lethality 
threshold based upon the 4-hour LC50 of 48.4 ppm in rats 
that was reported by Weeks et al. (1964). Although exposure-response 
data were unavailable, the lethality threshold was estimated a one 
third of the 4-hour LC50 (i.e., 48.4 ppm/3 = 16.1 ppm). Due 
to uncertainties regarding species variability in the lethal response 
to phosphorus oxychloride and the lack of lethality data in humans, an 
order-of-magnitude uncertainty adjustment was applied for interspecies 
variability. Contact irritation resulting in damage to epithelial 
tissue appears to be involved in the toxic response to phosphorus 
oxychloride. It is likely that this response is a function of the 
extreme reactivity of phosphorus oxychloride with tissues (e.g., 
pulmonary epithelium) and not likely to vary greatly among individuals. 
The uncertainty adjustment for intraspecies variability, therefore, was 
limited to 3. The concentration exposure time relationship for many 
irritant and systemically acting vapors and gases may be described by 
C\n\ x t = k, where the exponent, n, ranges from 0.8 to 3.5. In the 
absence of an empirically derived exponent (n), and to obtain 
conservative and protective AEGL values, temporal scaling was performed 
using n = 3 when extrapolating to shorter time points and n = 1 when 
extrapolating to longer time points using the C\n\ x t = k equation.
    The range of interspecies variability remains uncertain due to 
limited animal data and the absence of quantitative exposure-response 
data for humans. The absence of exposure-response data for non-lethal 
effects in animals or humans is a significant data deficiency.
    The proposed AEGL values are listed in Table 9 of this unit.

                                          Table 9.--Summary of Proposed AEGL Values for Phosphorus Oxychloride
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10-minutes          30-minutes            1-hour              4-hours             8-hours           (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)             NR                  NR                  NR                  NR                  NR                  Data unavailable
                                                                                                                                       for development
------------------------------------------------------
---------------------------------=====================
 
--------------------------------------------------------------------------------------------------------------------------------------------------------
NR: Not recommended. Numeric values for AEGL-1and AEGL-2 are not recommended due to the lack of available data Absence of AEGL-1 and AEGL-2 values does
  not imply that exposure below the AEGL-3 is without effect.


    ii. References. Weeks, M.H.; Mussleman, N.P.; Yevich, P.P.; 
Jacobson, K.H.; and Oberst, F.W. 1964. Acute vapor toxicity of 
phosphorus oxychloride, phosphorus trichloride and methyl phosphonic 
dichloride. Industrial Hygiene Journal. 25:470-475.
    9. Phosphorus trichloride--i. Description. Phosphorus trichloride 
(CAS No. 007719-12-2) is a colorless, clear fuming liquid with a 
pungent, irritating odor. In the presence of water, the chemical 
decomposes rapidly in a highly exothermic reaction to phosphonic acid, 
hydrogen chloride, and pyrophosphonic acids.

[[Page 42724]]

    No acute lethality data are available in humans. Qualitative data 
regarding human exposures indicate signs and symptoms of exposure 
consistent with a highly irritating chemical; ocular and dermal 
irritation, respiratory tract irritation, shortness of breath, and 
nausea.
    Lethality data in animals are available for rats, cats, and guinea 
pigs. Cursory studies conducted nearly 100 years ago in Germany 
provided preliminary data on lethal and nonlethal effects in cats and 
guinea pigs following various treatment regimens with inhaled 
phosphorus trichloride. Although results of the studies indicated the 
respiratory tract to a be a critical target, the methods and results of 
these studies were not verifiable. Weeks et al. (1964) reported 4-hour 
LC50 values of 104.5 ppm and 50.1 ppm for rats and guinea 
pigs, respectively. An unpublished study by Hazleton Laboratories 
(1983) identified a NOAEL of 3.4 ppm and a LOAEL (histopathologic 
changes in the respiratory tract) of 11 ppm following repeated exposure 
(6 hours/day, 5 days/week for 4 weeks) of rats. There are no data 
regarding reproductive/developmental toxicity, genotoxicity, or 
carcinogenicity of phosphorus trichloride. Definitive data regarding 
the mechanism of action of phosphorus trichloride are unavailable. 
Decomposition products (hydrogen chloride, phosphonic acid, and 
pyrophosphonic acids) are responsible, at least in part, for the 
contact irritation reported by humans, and the irritation and tissue 
damage observed in animal species.
    The concentration-time relationship for may irritant and 
systemically acting vapors and gases may be described by C\n\ x t = k, 
where the exponent n ranges from 0.8 to 3.5. Due to the limited 
toxicity data for this chemical, an empirical derivation of n was not 
possible. In the absence of an empirically derived exponent (n), and to 
obtain conservative and protective AEGL values, temporal scaling was 
performed using n = 3 when extrapolating to shorter time points and n = 
1 when extrapolating to longer time points using the C\n\ x t = k 
equation. For 10-minute AEGL-3 values were set at equivalence to the 
30-minute values due to uncertainties in extrapolating from the 
experimental exposure durations of 4 hours and greater.
    Quantitative data consistent with AEGL-1 effects were unavailable. 
Occupational exposures of humans to 1.8-3.6 ppm for 2-6 hours and 
exposure of rats to 3.4 ppm for 6 hours/day, 5 days/week for 4 weeks 
were without notable effect. These data can be considered a NOAEL for 
AEGL-1 effects. Because they were derived from controlled experiments, 
the AEGL-1 values were based upon the Hazleton Laboratories (1983) 
report. These data as well as the AEGL-1 values are supported by the 
human experience data reported by Sassi (1952). The interspecies 
uncertainty factor was limited to 3 because of the concordance of the 
animal data with the human experience and because the most sensitive 
species tested (guinea pig) was only about 2-fold more sensitive. The 
intraspecies uncertainty factor was limited to 3 because primary 
effects of phosphorus trichloride (irritation and subsequent tissue 
damage) appear to be due, in part, to hydrogen chloride and phosphonic 
acid resulting from chemical dissociation. Additional reduction of the 
AEGL-1 values would be inconsistent with available human and animal 
data .
    Information consistent with AEGL-2 effects were limited to an 
occupational exposure report and a multiple exposure study with rats. 
For occupational exposures, there was notable irritation following 2-6 
hours of exposure to approximately 14-27 ppm phosphorus trichloride and 
more severe but reversible irritation following exposures of 1-8 weeks. 
Reports providing qualitative information but no exposure terms 
affirmed the potential for respiratory tract irritation following acute 
exposures to phosphorus trichloride. Data for rats showed upper 
respiratory tract involvement following multiple exposures over 4 weeks 
to 11 ppm but not to 3.4 ppm (Hazleton Laboratories, 1983). For 
development of AEGL-2 values, the 11 ppm exposure in rats was 
considered a NOAEL for AEGL-2 effects. Uncertainty factor application 
was the same as for the AEGL-1 tier.
    AEGL-3 values were developed based upon a 3-fold reduction of the 
4-hour LC50 (Weeks et al., 1964) as an estimate of the 
lethality threshold (50.1 ppm/3 = 16.7 ppm). A total uncertainty factor 
adjustment of 10 was used to develop the AEGL-3 values. Animal data 
indicated some variability in the toxic response to phosphorus 
trichloride with guinea pigs being the more sensitive among the species 
tested. Therefore, uncertainty adjustment regarding interspecies 
variability was limited to 3. To account for intraspecies variability, 
a factor of 3 was applied. The uncertainty of intraspecies variability 
was limited to 3 because primary effects of phosphorus trichloride 
(irritation and subsequent tissue damage) appear to be due, in part, to 
hydrogen chloride and phosphonic acid resulting from chemical 
dissociation. The total uncertainty factor of 10 may be justified by 
human exposure data showing that repeated 2 to 6-hour exposures of up 
to 27 ppm were without life-threatening consequences. Furthermore, the 
results of the Hazleton Laboratories (1983) study showed no fatalities 
in rats following multiple 6-hour exposures to 11 ppm.
    The proposed AEGL values are listed in Table 10 of this unit.

                                          Table 10.--Summary of Proposed AEGL Values for Phosphorus Trichloride
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10-minutes          30-minutes            1-hour              4-hours             8-hours           (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)             0.78 ppm            0.78 ppm            0.62 ppm            0.39 ppm            0.26 ppm            NOAEL of 3.4 ppm
                                                                                                                                       in rats exposed 6
                                                                                                                                       hours/day, 5 days/
                                                                                                                                       week for 4 weeks
                                                                                                                                       (Hazleton
                                                                                                                                       Laboratories,
                                                                                                                                       1983)
-------------------------------------------------------------------------=====================

[[Page 42725]]

                                                                         =====================
--------------------------------------------------------------------------------------------------------------------------------------------------------
\a\Based upon animal data, lethality may be delayed.


    ii. References. a. Hazleton Laboratories. 1983. Subacute inhalation 
toxicity study in rats-- phosphorus trichloride. Final Report. Project 
No. 241-141. Hazleton Laboratories America, Inc. Unpublished.
    b. Weeks, M.H.; Mussleman, N.P.; Yevich, P.P.; Jacobson, K.H.; and 
Oberst, F.W. 1964. Acute vapor toxicity of phosphorus oxychloride, 
phosphorus trichloride and methyl phosphonic dichloride. American 
Industrial Hygiene Journal. 25:470-475.
    10. Xylenes--i. Description. Xylene is found in a number of 
consumer products, including solvents, paints, or coatings, and as a 
blend in gasoline. Mixed xylenes are comprised of 3 isomers: M-xylene, 
o-xylene, and p-xylene, with the m-isomer predominating. Ethyl benzene 
is also present in the technical product formulation. Absorbed xylene 
is rapidly metabolized and is excreted almost exclusively in the urine 
as methylhippuric acid isomers in humans and as methylhippuric acid 
isomers and toluic acid glucuronides in animals. In both humans and 
animals, xylene causes irritation and effects the central nervous 
system following acute inhalation exposure. No consistent developmental 
or reproductive effects were observed in the studies found in the 
available literature. Commercial xylene and all 3 isomers have 
generally tested negative for genotoxicity. Xylenes are currently not 
classifiable as to its carcinogenicity by the International Agency on 
Research for Cancer (IARC) or the EPA because of inadequate evidence.
    The AEGL-1 is based upon slight eye irritation noted during a 30-
minute exposure to 400 ppm mixed xylenes (Hastings et al., 1986). An 
interspecies uncertainty factor was not applied because the key study 
used human data. An intraspecies uncertainty factor of 3 was applied 
because the toxic effect (slight irritation) was less severe than that 
defined for the AEGL-1 tier (notable discomfort). The resulting value 
of 130 ppm is supported by several other studies, including: A 150 ppm 
p-xylene exposure resulting in eye irritation in a contact lens wearer 
(Hake et al., 1981); a 15-minute exposure to 230 ppm mixed xylenes 
resulting in mild eye irritation and dizziness in one individual; and a 
3-hour exposure to 200 ppm m- or p-xylene (Ogata et al., 1970), a 4-
hour exposure to 200 ppm m-xylene (Savolainen et al., 1981), and a 5.5 
hour exposure to 200 ppm m-xylene (Laine et al., 1993) all representing 
no-effect levels.
    The AEGL-2 is based upon poor coordination resulting when rats were 
exposed to 1,300 ppm mixed xylenes for 4 hours (Carpenter et al., 
1975). This concentration represents the threshold for reversible 
equilibrium disturbances. This concentration and endpoint are 
consistent with the preponderance of available data for 4-hour 
exposures in rats: The EC50 for decreased rotarod 
performance was 1982 ppm (Korsak et al., 1993); the minimum narcotic 
concentrations for m-, o-, and p-xylene ranged from 1,940-2,180 ppm 
(Moln[aacute]r et al., 1986); and exposure to 1,600 ppm p-xylene 
resulted in hyperactivity, fine tremor, and unsteadiness (Bushnell, 
1989), induced flavor aversion (Bushnell and Peele, 1988), and caused 
changes in the flash evoked potential suggestive of increased arousal 
(Dyer et al., 1988). In dogs, exposure to 1,200 ppm for 4 hours 
represented a threshold for eye irritation (Carpenter et al., 1975). An 
interspecies uncertainty factor of 1 was applied because rats receive a 
greater systemic dose of inhaled xylene as compared to humans. An 
intraspecies uncertainty factor of 3 was applied because the minimum 
alveolar concentration (MAC) for volatile anesthetics should not vary 
by more than a factor of 2-3-fold among humans. A 3-fold factor is also 
adequate to account for moderate physical activity during exposure, 
which would result in greater uptake of the chemical.
    The AEGL-3 derivation is based upon prostration occurring in all 10 
rats exposed for 4 hours to 2,800 ppm mixed xylenes, with recovery 
occurring within 1 hour of exposure (Carpenter et al., 1975). Although 
coordination initially remained poor, it returned to normal the 
following day. This concentration also represents a no-effect level for 
lethality. An interspecies uncertainty factor of 1 was applied because 
rats receive a greater systemic dose of inhaled xylene as compared to 
humans. An intraspecies uncertainty factor of 3 was applied because the 
MAC for volatile anesthetics should not vary by more than a factor of 
2-3-fold among humans. A 3-fold factor is also adequate to account for 
moderate physical activity during exposure, which would result in 
greater uptake of the chemical.
    The two primary effects of concern for xylene are those of 
irritation and central nervous system effects. Irritation is considered 
a threshold effect and therefore should not vary over time. The AEGL-1 
value based on irritation is therefore not scaled across time, but 
rather the threshold value is applied to all times.
    Data indicate that once steady state is reached, concentration, not 
duration, is the prime determinant in xylene-induced central nervous 
system toxicity. Pharmacokinetic modeling in both humans and rats 
indicate that venous blood concentrations rapidly increase during the 
first 15 minutes of exposure, followed by minimal increases in blood 
concentrations with continuing exposure (i.e., increases follow a 
hyperbolic curve). Likewise, available human data indicate that once 
the initial increase in blood xylene concentration is reached, blood 
concentrations level off with increasing exposure duration. Conversely, 
available human and animal data demonstrate that increasing exposure 
concentrations correlate with increases in venous blood xylene 
concentrations. Therefore, the AEGL 2- and -3 values are set equal 
across time once steady state is approached (starting at approximately 
1 hour), while pharmacokinetic modeling was used to extrapolate to 
exposure durations of 10- and 30-minutes.
    The AEGL values should be protective of human health. The AEGL-1 
values are consistent with other human studies, and represent a value 
consistent with exposure concentrations that might result in mild eye 
irritation. The AEGL-2 levels are protective, especially when 
considering numerous human studies investigating the effects of 
exposure to

[[Page 42726]]

200 ppm xylene with 20-minute peak exposures to 400 ppm, in some cases 
additionally combining peak exposures with physical exercise resulting 
in greater uptake of the chemical, and finding only minimal central 
nervous system effects. The difficultly in defining an AEGL-2 level for 
xylene comes from its ``all-or-nothing'' continuum of toxicity: 
Toxicity ranges from mild irritation to narcosis, with little happening 
in between. The AEGL-3 levels represent the threshold for narcosis, and 
are protective as supported by human data demonstrating that exposure 
to 690 ppm for 15 minutes resulted in lightheadedness/dizziness and a 
30 minute exposure to 700 ppm resulted in nausea, vomiting, dizziness, 
or vertigo.
    The proposed AEGL values are listed in Table 11 of this unit.

                                         Table 11.--Summary of Proposed AEGL Values for Xylenes [ppm (mg/m\3\)]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                           Endpoint
         Classification               10-minutes          30-minutes            1-hour              4-hours             8-hours           (Reference)
--------------------------------------------------------------------------------------------------------------------------------------------------------
AEGL-1 (Nondisabling)             130                 130                 130                 130                 130                 Eye irritation in
                                  (560).............  (560).............  (560).............  (560).............  (560).............   human volunteers
                                                                                                                                       exposed to 400
                                                                                                                                       ppm mixed xylenes
                                                                                                                                       for 30 minutes
                                                                                                                                       (Hastings et al.,
                                                                                                                                       1986)
---------------------------------
AEGL-2 (Disabling)                990                 480                 430                 430                 430                 Rats exposed to
                                  (4,300)...........  (2,100)...........  (1,900)...........  (1,900)...........  (1,900)...........   1,300 ppm mixed
                                                                                                                                       xylenes for 4
                                                                                                                                       hours exhibited
                                                                                                                                       poor coordination
                                                                                                                                       (Carpenter et
                                                                                                                                       al., 1975)
---------------------------------
AEGL-3 (Lethal)                   2,100               1,000               930                 930                 930                 Rats exposed to
                                  (9,100)...........  (4,300)...........  (4,000)...........  (4,000)...........  (4,000)...........   2,800 ppm for 4
                                                                                                                                       hours exhibited
                                                                                                                                       prostration
                                                                                                                                       followed by a
                                                                                                                                       full recovery
                                                                                                                                       (Carpenter et
                                                                                                                                       al., 1975)
--------------------------------------------------------------------------------------------------------------------------------------------------------


    ii. References. a. Bushnell, P.J. 1989. Behavioral effects of acute 
p-xylene inhalation in rats: Autoshaping, motor activity, and reversal 
learning. Neurotoxicology and Teratology. 10:569-577.
    b. Bushnell, P.J. and Peele, D.B. 1988. Conditioned flavor aversion 
induced by inhaled p-xylene in rats. Neurotoxicology and Teratology. 
10:273-277.
    c. Carpenter, C.P.; Kinkead, E.R.; Geary, D.L. Jr.; Sullivan, L.J.; 
and King, J.M. 1975b. Petroleum hydrocarbon toxicity studies. V. Animal 
and human response to vapors of mixed xylene. Toxicology and Applied 
Pharmacology. 33:543-58.
    d. Dyer, R.S.; Bercegeay, M.S.; and Mayo, L.M. 1988. Acute 
exposures to p-xylene and toluene alter visual information processing. 
Neurotoxicology and Teratology. 10:147-153.
    e. Hake, C.R.L.; Stewart, R.D.; and Wu, A., et al. 1981. p-Xylene: 
Development of a biological standard for the industrial worker. Report 
to the National Institute for Occupational Safety and Health, 
Cincinnati, OH, by the Medical College of Wisconsin, Inc., Milwaukee, 
WI. PB82-152844.
    f. Hastings, L.; Cooper, G.P.; and Burg, W. 1986. Human sensory 
response to selected petroleum hydrocarbons. In: MacFarland, H.N. ed. 
Advances in Modern Environmental Toxicology. Vol. VI. Applied 
Toxicology of Petroleum Hydrocarbons. Princeton, NJ: Princeton 
Scientific Publishers. pp. 255-270.
    g. Korsak, Z.; Swiercz, R.; and Jedrychowski, R. 1993. Effects of 
acute combined exposure to--n-butyl alcohol and m-xylene. Polish 
Journal of Occupational Medicine and Environmental Health. 6:35-41.
    h. Laine, A.; Savolainen, K.; and Riihim[auml]ki, V., et al. 1993. 
Acute effects of m-xylene inhalation onbody sway, reaction times, and 
sleep in man. International Archives of Occupational and Environmental 
Health. 65:179-188.
    i. Moln[aacute]r, J.; Paksy, K.[Aacute].;and N[aacute]ray, M. 1986. 
Changes in the rat's motor behavior during 4-hour inhalation exposure 
to prenarcotic concentrations of benzene and its derivatives. Acta 
Physiologica Hungarica. 67:349-354.
    j. Ogata, M.; Tomokuni, K.; and Takatsuka, Y. 1970. Urinary 
excretion of hippuric acid and m- or p-methylhippuric acid in the urine 
of persons exposed to vapours of toluene and m- or p-xylene as a test 
of exposure. British Journal of Industrial Medicine. 27:43-50.
    k. Savolainen, K.; Riihim[auml]ki, V.; Laine, A.; and Kekoni, J. 
1981. Short-term exposure of human subjects to m-xylene and 1,1,1-
trichloroethane. International Archives of Occupational Environmental 
Health. 49:89-98.

IV. Next Steps

    The NAC/AEGL Committee plans to publish ``Proposed'' AEGL values 
for five-exposure periods for other chemicals on the priority list of 
85 in groups of approximately 10 to 20 chemicals in future Federal 
Register notices during the calendar year 2003.
    The NAC/AEGL Committee will review and consider all public comments 
received on this notice, with revisions to the ``Proposed'' AEGL values 
as appropriate. The resulting AEGL values will be established as 
``Interim'' AEGLs and will be forwarded to the National Research 
Council, National Academy of Sciences (NRC/NAS), for review and 
comment. The ``Final'' AEGLs will be published under the auspices of 
the NRC/NAS following concurrence on the values and the scientific 
rationale used in their development.

List of Subjects

    Environmental protection, Hazardous chemicals, Worker protection.


    Dated: July 7, 2003.
Susan B. Hazen,
Acting Assistant Administrator for Prevention, Pesticides and Toxic 
Substances.

[FR Doc. 03-18306 Filed 7-17-03; 8:45 am]
BILLING CODE 6560-50-S