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National Research Council Committee
Review of Acute Exposure Guideline
Levels of Selected Airborne Chemicals
This report is the twelfth volume in the series Acute Exposure Guideline
Levels for Selected Airborne Chemicals.
In the Bhopal disaster of 1984, approximately 2,000 residents living near a
chemical plant were killed and 20,000 more suffered irreversible damage to their
eyes and lungs following accidental release of methyl isocyanate. The toll was
particularly high because the community had little idea what chemicals were
being used at the plant, how dangerous they might be, or what steps to take in an
emergency. This tragedy served to focus international attention on the need for
governments to identify hazardous substances and to assist local communities in
planning how to deal with emergency exposures.
In the United States, the Superfund Amendments and Reauthorization Act
(SARA) of 1986 required that the U.S. Environmental Protection Agency (EPA)
identify extremely hazardous substances (EHSs) and, in cooperation with the
Federal Emergency Management Agency and the U.S. Department of Transpor-
tation, assist local emergency planning committees (LEPCs) by providing guid-
ance for conducting health hazard assessments for the development of emer-
gency response plans for sites where EHSs are produced, stored, transported, or
used. SARA also required that the Agency for Toxic Substances and Disease
Registry (ATSDR) determine whether chemical substances identified at hazard-
ous waste sites or in the environment present a public health concern.
As a first step in assisting the LEPCs, EPA identified approximately 400
EHSs largely on the basis of their immediately dangerous to life and health val-
ues, developed by the National Institute for Occupational Safety or Health. Al-
though several public and private groups, such as the Occupational Safety and
Health Administration and the American Conference of Governmental Industrial
Hygienists, have established exposure limits for some substances and some ex-
posures (e.g., workplace or ambient air quality), these limits are not easily or
directly translated into emergency exposure limits for exposures at high levels
3
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4 Acute Exposure Guideline Levels
but of short duration, usually less than 1 hour (h), and only once in a lifetime for
the general population, which includes infants (from birth to 3 years of age),
children, the elderly, and persons with diseases, such as asthma or heart disease.
The National Research Council (NRC) Committee on Toxicology (COT)
has published many reports on emergency exposure guidance levels and space-
craft maximum allowable concentrations for chemicals used by the U.S. De-
partment of Defense (DOD) and the National Aeronautics and Space Admini-
stration (NASA) (NRC 1968, 1972, 1984a,b,c,d, 1985a,b, 1986a, 1987, 1988,
1994, 1996a,b, 2000a, 2002a, 2007a, 2008a). COT has also published guidelines
for developing emergency exposure guidance levels for military personnel and
for astronauts (NRC 1986b, 1992, 2000b). Because of COT’s experience in rec-
ommending emergency exposure levels for short-term exposures, in 1991 EPA
and ATSDR requested that COT develop criteria and methods for developing
emergency exposure levels for EHSs for the general population. In response to
that request, the NRC assigned this project to the COT Subcommittee on Guide-
lines for Developing Community Emergency Exposure Levels for Hazardous
Substances. The report of that subcommittee, Guidelines for Developing Com-
munity Emergency Exposure Levels for Hazardous Substances (NRC 1993),
provides step-by-step guidance for setting emergency exposure levels for EHSs.
Guidance is given on what data are needed, what data are available, how to
evaluate the data, and how to present the results.
In November 1995, the National Advisory Committee (NAC)1 for Acute
Exposure Guideline Levels for Hazardous Substances was established to iden-
tify, review, and interpret relevant toxicologic and other scientific data and to
develop acute exposure guideline levels (AEGLs) for high-priority, acutely toxic
chemicals. The NRC’s previous name for acute exposure levels—community
emergency exposure levels (CEELs)—was replaced by the term AEGLs to re-
flect the broad application of these values to planning, response, and prevention
in the community, the workplace, transportation, the military, and the remedia-
tion of Superfund sites.
AEGLs represent threshold exposure limits (exposure levels below which
adverse health effects are not likely to occur) for the general public and are ap-
plicable to emergency exposures ranging from 10 minutes (min) to 8 h. Three
levels—AEGL-1, AEGL-2, and AEGL-3—are developed for each of five expo-
sure periods (10 min, 30 min, 1 h, 4 h, and 8 h) and are distinguished by varying
degrees of severity of toxic effects. The three AEGLs are defined as follows:
1
NAC completed its chemical reviews in October 2011. The committee was composed
of members from EPA, DOD, many other federal and state agencies, industry, academia,
and other organizations. From 1996 to 2011, the NAC discussed over 300 chemicals and
developed AEGLs values for at least 272 of the 329 chemicals on the AEGLs priority
chemicals lists. Although the work of the NAC has ended, the NAC-reviewed technical
support documents are being submitted to the NRC for independent review and finaliza-
tion.
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NRC Committee Review of Acute Exposure Guideline Levels 5
AEGL-1 is the airborne concentration (expressed as ppm [parts per mil-
lion] or mg/m3 [milligrams per cubic meter]) of a substance above which it is
predicted that the general population, including susceptible individuals, could
experience notable discomfort, irritation, or certain asymptomatic nonsensory
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 sus-
ceptible 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 sus-
ceptible individuals, could experience life-threatening adverse health effects or
death.
Airborne concentrations below AEGL-1 represent exposure levels that can
produce mild and progressively increasing but transient and nondisabling odor,
taste, and sensory irritation or certain asymptomatic nonsensory adverse effects.
With increasing airborne concentrations above each AEGL, there is a progres-
sive increase in the likelihood of occurrence and the severity of effects described
for each corresponding AEGL. Although the AEGL values represent threshold
levels for the general public, including susceptible subpopulations, such as in-
fants, children, the elderly, persons with asthma, and those with other illnesses,
it is recognized that individuals, subject to idiosyncratic responses, could experi-
ence the effects described at concentrations below the corresponding AEGL.
SUMMARY OF REPORT ON
GUIDELINES FOR DEVELOPING AEGLS
As described in Guidelines for Developing Community Emergency Expo-
sure Levels for Hazardous Substances (NRC 1993) and the NRC guidelines re-
port Standing Operating Procedures for Developing Acute Exposure Guideline
Levels for Hazardous Chemicals (NRC 2001a), the first step in establishing
AEGLs for a chemical is to collect and review all relevant published and unpub-
lished information. Various types of evidence are assessed in establishing AEGL
values for a chemical. These include information from (1) chemical-physical
characterizations, (2) structure-activity relationships, (3) in vitro toxicity studies,
(4) animal toxicity studies, (5) controlled human studies, (6) observations of
humans involved in chemical accidents, and (7) epidemiologic studies. Toxicity
data from human studies are most applicable and are used when available in
preference to data from animal studies and in vitro studies. Toxicity data from
inhalation exposures are most useful for setting AEGLs for airborne chemicals
because inhalation is the most likely route of exposure and because extrapola-
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6 Acute Exposure Guideline Levels
tion of data from other routes would lead to additional uncertainty in the AEGL
estimate.
For most chemicals, actual human toxicity data are not available or critical
information on exposure is lacking, so toxicity data from studies conducted in
laboratory animals are extrapolated to estimate the potential toxicity in humans.
Such extrapolation requires experienced scientific judgment. The toxicity data
for animal species most representative of humans in terms of pharmacodynamic
and pharmacokinetic properties are used for determining AEGLs. If data are not
available on the species that best represents humans, data from the most sensi-
tive animal species are used. Uncertainty factors are commonly used when ani-
mal data are used to estimate risk levels for humans. The magnitude of uncer-
tainty factors depends on the quality of the animal data used to determine the no-
observed-adverse-effect level (NOAEL) and the mode of action of the substance
in question. When available, pharmacokinetic data on tissue doses are consid-
ered for interspecies extrapolation.
For substances that affect several organ systems or have multiple effects,
all end points (including reproductive [in both genders], developmental, neuro-
toxic, respiratory, and other organ-related effects) are evaluated, the most impor-
tant or most sensitive effect receiving the greatest attention. For carcinogenic
chemicals, excess carcinogenic risk is estimated, and the AEGLs corresponding
to carcinogenic risks of 1 in 10,000 (1 10-4), 1 in 100,000 (1 10-5), and 1 in
1,000,000 (1 10-6) exposed persons are estimated.
REVIEW OF AEGL REPORTS
As NAC began developing chemical-specific AEGL reports, EPA and
DOD asked the NRC to review independently the NAC reports for their scien-
tific validity, completeness, and consistency with the NRC guideline reports
(NRC 1993, 2001a). The NRC assigned this project to the COT Committee on
Acute Exposure Guideline Levels. The committee has expertise in toxicology,
epidemiology, occupational health, pharmacology, medicine, pharmacokinetics,
industrial hygiene, and risk assessment.
The AEGL draft reports were initially prepared by ad hoc AEGL devel-
opment teams consisting of a chemical manager, chemical reviewers, and a staff
scientist of the NAC contractors—Oak Ridge National Laboratory and subse-
quently Syracuse Research Corporation. The draft documents were then re-
viewed by NAC and elevated from “draft” to “proposed” status. After the AEGL
documents were approved by NAC, they were published in the Federal Register
for public comment. The reports were then revised by NAC in response to the
public comments, elevated from “proposed” to “interim” status, and sent to the
NRC Committee on Acute Exposure Guideline Levels for final evaluation.
The NRC committee’s review of the AEGL reports prepared by NAC and
its contractors involves oral and written presentations to the committee by the
authors of the reports. The NRC committee provides advice and recommenda-
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NRC Committee Review of Acute Exposure Guideline Levels 7
tions for revisions to ensure scientific validity and consistency with the NRC
guideline reports (NRC 1993, 2001a). The revised reports are presented at sub-
sequent meetings until the committee is satisfied with the reviews.
Because of the enormous amount of data presented in AEGL reports, the
NRC committee cannot verify all of the data used by NAC. The NRC committee
relies on NAC for the accuracy and completeness of the toxicity data cited in the
AEGL reports. Thus far, the committee has prepared eleven reports in the series
Acute Exposure Guideline Levels for Selected Airborne Chemicals (NRC 2001b,
2002b, 2003, 2004, 2007b, 2008b, 2009, 2010a,b, 2011, 2012). This report is the
twelfth volume in that series. AEGL documents for butane, chloroacetaldehyde,
chlorobenzene, chloroform, methyl bromide, methyl chloride, and propane are
each published as an appendix in this report. The committee concludes that the
AEGLs developed in these appendixes are scientifically valid conclusions based
on the data reviewed by NAC and are consistent with the NRC guideline reports.
AEGL reports for additional chemicals will be presented in subsequent volumes.
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NRC Committee Review of Acute Exposure Guideline Levels 9
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