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APPENDIX D
Description of Derivation
of Short-Term Action Levels
SOURCE: This information is included in this report to illustrate various
rationales for deriving short-term action levels. The authors do
not necessarily endorse the specific values given for application
to Superfund sites.
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SB
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
'Office of Air Quality Planning and Standards
/ Research Triangle Park, North Carolina 27711
FEB 9 1993
Mr. Bart Eklund
Radian Corporation
P.O. Box 201088
Austin, Texas 78720-1088
Dear Bart:
Please find the enclosed draft document, "De minimis Levels for Section
112(b) Hazardous Air Pollutants." This document contains descriptions of
exposure limits including their intended use and how they were developed.
As I re-examine this document in the context of our conversation, I
am not convinced that it contains any information you do not already possess.
However, in an attempt to avoid any duplication of effort, I am sending
you a copy. Please understand that the document does not represent the
Environmental Protection Agency policy, and that it is a draft which
has not been reviewed for accuracy by the Agency. Feel free to call me at
(919) 541-2962, if you have any questions. I appreciate the opportunity
to be of service and trust this information will be helpful to you.
incere
Kelly Rimer
Pollutant Assessment Branch
Enclosure
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DE MINIMIS LEVELS
FOR
SECTION 112 (b) HAZARDOUS AIR POLLUTANTS
Submitted to:
Office of Air Quality Planning and Standards
U.S. Environmental Protection Agency
Research Triangle Park, NC
Submitted by:
Clement International Corporation
9300 Lee Highway
Fairfax, VA 22031
September 30, 1991
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TABLE OP CONTEXTS
Page
INTRODUCTION 1
PERMISSIBLE EXPOSURE LIMITS -. 3
RECOMMENDED EXPOSURE LIMITS 6
EMERGENCY RESPONSE PLANNING GUIDELINES 8
EMERGENCY EXPOSURE GUIDANCE LEVEL 11
LEVELS OF CONCERN 14
CAPCOA NONCANCER ACCEPTABLE ACUTE EXPOSURE LEVELS 17
OTHER APPROACHES
Calabrese and Kenyon Ambient Air Level Goals 19
Minnesota Pollution Control Agency Regulatory Limits for Short-
Term Exposures 22
ACGIH Threshold Limit Values 25
The State of Maryland Screening Levels 27
Potency-based Method for Acute Toxicity 30
SUMMARY 33
TABLES
Table 1. Summary of Characteristics of Short-Term Exposure Levels 44
Table 2. Hazardous Air Pollutants -- Exposure Limits Established
by Other Organizations ^8
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INTRODUCTION
The Clean Air Act Amendments of 1990 requires the promulgation of
emission standards for major sources and area sources of hazardous air
pollutants listed in Section 112(b). Under Section 112(g), any physical
change or change in the operation of a major source that results an actual
emission increase for that source exceeding a de minimis level requires the
revision of the permit for that facility. Consequently, EPA must determine
what constitutes a de minimis level for each of the 190 hazardous air
pollutants (HAPs) listed in Section 112(b).
One approach to setting de minimis values is to determine a health
benchmark for each pollutant, and to identify the de minimis emission rate
that would ensure that the benchmark is not exceeded. EPA has determined that
both long-term and short-term benchmarks may be needed. Long-term levels are
protective for chronic health effects including cancer, while short-term
levels ensure that there is negligible concern for acute effects. For long-
term effects, benchmarks can be readily derived using the Agency's cancer
potency estimates and reference concentrations (RfCs). At this time, the
Agency has not established methodologies for evaluating short-term exposures.
A project has been initiated by the Agency to develop a method for short-term
RfCs, but this effort will not be complete for a number of years.
Consequently, there is a need to determine whether there are interim
approaches to setting short-term benchmarks that could serve the immediate
needs of Section 112(g).
This report focuses on issues to be examined when determining how short-
term de minimis levels can be developed. These issues include: what is a
short-term level in terms of duration and magnitude, what are the acute
effects they should protect against, what populations should be protected,
should technical and economic feasibility be considered when determining de
rainimis levels, and what have other Federal, state and private sector
organizations already accomplished.
This report considered short-term exposure to be 1 hour or less:
however, a review of the various approaches discussed will show that this
exposure limit is not commonly used among regulatory and advisory agencies.
Worker health has been the focus of several organizations, such as the
National Institute for Occupational Safety and Health, the Occupational Safety
and Health Administration, and the American Conference of Governmental
Industrial Hygienists. These organizations average worker exposure over an 8-
hour day to derive a time-weighted average (TWA) exposure level and assume a
40-hour workweek and a 40 year working lifetime. It is understood that the
TWA may be exceeded during the workday but that the average concentration (the
threshold limit value [TLV], permissible exposure limit [PEL], or recommended
exposure limit [REL]) should not be. To protect workers in the event of a
sudden release, other exposure limits are also used. These include a 15-
minute short-term exposure limit (STEL), which should not be exceeded for more
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than 15 minutes in an 8-hour day, a ceiling value (TLV-C), which snrr_d never
be exceed for any length of time, and an immediately dangerous to life or
health (IDLH) value, which, if exceeded for more than 30 minuces, may cause
irreparable damage to health or death by preventing the escape of the exposed
worker.
Although TLVs, PELs, and RELs are the most commonly used values for
worker exposure limits, other organizations have developed their own
methodologies and time limits to protect the general public from toxic
emissions from local facilities. California has developed a one-hour
noncancer acceptable exposure limit derived from several other methods.
Maryland uses both a one-hour and an eight-hour exposure limit to protttct the
general public, and the American Industrial Hygiene Association uses three
one-hour exposure levels to protect against different types of effects in the
community.
The body of this report consists of a description of various exposure
limits, their uses, and how they were developed. At the end of each
description there is also a brief list of the advantages and disadvantages of
using the method to develop de minimis levels. Table 1 presents a summary of
the characteristics of each method for developing short-term exposure levels.
These include such considerations as whether the method and/or exposure level
is subjected to peer review, whether the method uses primary data or secondary
sources, whether there is an opportunity for public comment, and the target
population the value is supposed to protect. Table 2 lists the actual
exposure value for each of the methods discussed in the text. In addition,
Table 2 also contains other chemicals that are members of the chemical groups
listed in the Section 112(b), such as tetramethyllead, which is considered to
be a lead compound, but for which there are specific exposure levels developed
by other organizations.
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OCCUPATIONAL SAFETY AMD HEALTH ADMINISTRATION
PERMISSIBLE EXPOSURE LIMITS
The Occupational Safety and Health Act of 1970, requires the
Occupational Safety and Health Administration to promulgate Permissible
Exposure Limits (FELs) for air contaminants commonly used in the workplace. A
PEL is the maximum airborne concentration of a substance to which a worker may
be exposed over a specified time period. At present, OSHA has established
PELs for 600 substances, with time weighted averages (TWAs) for 150 of the
Section 112(b) hazardous air pollutants, including 44 short-term exposure
limits (STELs) and 24 ceiling values (some of the PELs are for chemicals
classified within the substance groups listed in Section 112(b), e.g.,
hydrogen cyanide).
PELs are based primarily on Threshold Limit Values (TLVs) that have been
developed by the American Conference of Governmental Industrial Hygienists
(ACGIH). TLVs may be expressed as a time-weighted average (TWA; usually 8
hours), a 15-minute short-term exposure limit (STEL), or a threshold limit
value ceiling (TLV-C) which should not be exceeded at any time.
The most recent list of PELs was published by OSHA in January 1989.
Although many of the PELs are based directly on TLVs, some are not. To
develop the 1989 PELs, OSHA compared the 1987-1988 TLVs with the then current
PEL list. In cases where the TLVs and PELs were identical, OSHA did not
modify the PELs. Where the TLV and PEL differed, the PEL was considered for
modification. If a TLV existed for a substance, but there was no PEL, the
substance was also considered for adoption of a PEL.
For those chemicals considered for modification or adoption of a PEL,
OSHA compared the ACGIH TLV and, if available, the NIOSH Recommended Exposure
Limit (REL). The background documentation used to determine the TLV and REL
was reviewed by OSHA and the more appropriate value, in OSHA's view, was then
adopted as the proposed PEL. OSHA based its decision on both the scientific
validity of the supporting studies and whether the published documentation for
the TLV or REL would meet OSHA's legal requirements for establishing a PEL.
The legal requirements included a determination that: (1) there was
substantial evidence of significant risk at the current PEL; (2) significant
risk might exist in the workplace if there was no PEL; (3) the adoption of a
new or revised PEL would substantially reduce the risk; and (4) the new or
revised PEL was technically feasible. The proposed PELs, with their
supporting documentation and the rationale for each level, were made available
for public comment. In the Federal Register notice, OSHA summarized all of
the studies reviewed to develop the PELs, listed all references, and presented
justification for the proposed PELs. After review of the public comments and
any additional data submitted to OSHA, the PELs were modified as necessary and
adopted as final effective March 1989 (29 CFR 1910).
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In establishing a new or revised PEL, OSHA had to conduct a feasibility
analysis to determine if the level established by each PEL could actually be
achieved in the workplace and at what cost. OSHA used several data sources to
make these analyses. OSHA's Integrated Management Information System contains
over 77,000 exposure measurements organized by type of industry and process
and indicates the number of workers included in each measurement. OSHA also
used two National Occupational Hazard Surveys to estimate the number of
workers potentially exposed to each substance in any industry segment. OSHA
had all of these data reviewed by approximately 20 industrial hygiene and
industrial engineering experts. In addition, OSHA conducted a nationwide
survey of 5,700 firms asking for information on substances present in the
workplace, processes used, and controls in place. All of this information was
used by OSHA to ensure that PELs reflected accurate assessments of technical
and economic feasibility and costs.
OSHA divided all of the chemicals with proposed PELs into 18 categories
based on the health effect for which there was the greatest concern, e.g.,
cancer, sensory irritation, respiratory effects, narcosis, analogy with
another chemical, etc. In presenting the final rule, OSHA discussed the
rationale for each PEL on a chemical-by-chemical basis for each category of
health effect. The rationale included a brief review of the toxicity data
used to establish the PEL, a discussion of various comments received, and
OSHA's responses to the comments. For example, a PEL of 50 ppm TWA was
proposed for n-hexane, based on its neurotoxic effects. This limit is equal
to the ACGIH TLV of 50 ppm but lower than the NIOSH REL of 100 ppm. NIOSH
submitted comments to OSHA agreeing that the lower value was appropriate for
the PEL. OSHA presented a summary of the data used by ACGIH to establish the
TLV, and discussed comments received from several groups, some of whom agreed
that the PEL was appropriate (worker unions and NIOSH) and some of whom wanted
che PEL modified (industry trade organizations). OSHA presented its
interpretation of the relevant toxicity data to justify the value it selected
for each PEL.
The 600 PELs are based only on recommended exposure limits (e.g., TLVs) ;
information on medical surveillance, exposure monitoring, industrial hygiene
requirements and other ancillary provisions were not considered when
developing the PELs.
Advantaees of Using PELs for Short-term Benchmarks
• There are STELs or Ceiling Values for 50 chemicals that are on the
Section 112(b) list (44 STELs, 24 Ceiling Values, and 5 with both
STELs and Ceiling Values). This is the largest data base other
than TLVs to work from; only 60 compounds on the Section 112(b)
list do not have any type of PEL.
• The data used to establish the STEL or Ceiling Value have already
been reviewed by OSHA for scientific validity. In addition, the
STEL or Ceiling Value is based on either an ACGIH TLV or a NIOSH
REL, both of which are widely accepted by industry, particularly
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the TLVs. Both of these exposure values have been determined by a
review of the scientific literature.
• These values have been subjected to comment by the public,
including affected industries and occupational health
organizations such as NIOSH.
Disadvantages of Using PELs for Short-term Benchmarks
• PELs are designed to protect only workers during a limited
exposure period of an 8-hour workday and a 40-hour workweek.
Workers are assumed to represent healthy populations; no attempt
is made to identify or consider sensitive populations, even among
workers.
• Data would have to be reviewed to determine appropriate exposure
limits for general population.
• Secondary data sources (e.g., ACGIH and NIOSH background
documentation) were reviewed for the majority of chemicals;
unpublished data and original studies were not reviewed in most
cases unless submitted by outside sources e.g., industry, during
the comment period.
REFERENCE:
29 CFR Part 1910 Air Contaminants; Final Rule (Federal Register 54 (12):2232-
2983, 1/19/89)
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MATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH
RECOMMENDED EXPOSURE LIMITS
As mandated by the Occupational Safety and Health Act of 1970, the
National Institute for Occupational Safety and Health (NIOSH) develops
Recommended Exposure Limits (RELs) for hazardous substances in the workplace.
Unlike OSHA PELs, RELs are only recommendations for occupational safety and
health standards; they are not enforceable by law. However, OSHA and the Mine
Safety and Health Administration review the RELs when developing their
standards for worker protection. A REL is based on an 8 or 10-hour workday,
40 hours per week, for a 40 year exposure period (working lifetime). RELs
consist of time-weighted average, short-term (15-minute; STELs), and ceiling
values.
The background information used by NIOSH in developing a REL is
contained in a Criteria Document. Data included in the Criteria Document must
be publicly available (i.e., unpublished industry studies that may not be
released are not included) . All available scientific data are included.
Although most data in the Criteria Document come from peer-reviewed journals,
NIOSH does not have a policy of quality checking all studies. Criteria
Documents are reviewed by internal NIOSH specialists, as well as an outside
panel of peer reviewers, including representatives from industry and other
Federal agencies. The development of a Criteria Document is lengthy and may
take 2 to 3 years prior to publication.
NIOSH considers a broad variety of information when developing RELs,
including medical monitoring data and all aspects of toxicology, such as human
case studies as well as experimental human and animal studies, reproductive
effects, carcinogenicity, and acute and chronic effects. Uptake, metabolism,
and elimination of the chemical are also included. To date, most RELs have
been established for chemicals for which the endpoint is a chronic effect
other than cancer. For example, the recommended standard for styrene is based
on human nervous system effects and on eye and respiratory system irritation.
In addition to presenting exposure effects data, a Criteria Document includes
information on the physical and chemical properties of the compound, uses,
production methods, and potential for worker exposure. The document also
describes recommended labelling of the substance in the workplace, discusses
environmental sampling, analytical methods, biological monitoring of workers,
medical surveillance, other applicable occupational health standards (TLVs,
STELs, ceiling values), and methods for worker protection.
NIOSH prefers to use toxicity studies that most closely represent actual
worker exposure conditions, e.g., if the primary concern for worker exposure
is by inhalation of a vapor, an animal study (or rarely human study) in which
the subjects were exposed by inhalation to a vapor is more significant than a
study in which the subjects were dosed orally by a liquid form. RELs may be
developed based on exposures other than airborne concentrations, e.g., medical
monitoring has shown that airborne concentrations of lead are not the best
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indicator of levels of lead to which workers have been exposed. Rather, blood
levels are a better indicator, and the REL reflects this by recommending that
air concentrations should be such that worker blood lead levels do not exceed
0.060 mg/100 g whole blood.
NIOSH has adopted a quantitative approach to establishing exposure
limits for potential carcinogens. This approach is similar to EPA's, in chat
it includes an assessment of cancer potency and a subsequent risk assessment.
For reproductive effects for glycol ethers, NIOSH used EPA criteria to
determine the most sensitive species and appropriate endpoints. Although
NIOSH recommends exposure limits for the workplace, it feels that by
protecting workers the health of the general public is protected as well.
However, the Criteria Document specifically states that the standards are not
intended "for the population-at-large, " and that any such extrapolation is not
warranted.
Advantages of Using RELs as Short-term Benchmarks
• Data are peer reviewed by outside and internal experts and all
data must be publicly available.
• Quantitative RELs exist for 120 chemicals on the Section 112(b)
Hazardous Air Pollutants List, with an addition 29 substances
having only a carcinogen designation (no quantitative value).
• Most RELs are established for chronic effects although acute
effects are also included.
Disadvantages of Using RELS as Short-term Benchmarks
• RELs are based on worker exposure (i.e., 40-hr/week, 40 year
lifetime) and workers are assumed to represent healthy
populations; no effort is made to identify or consider sensitive
populations, even among workers.
• Although all available scientific literature on the substance is
reviewed, emphasis is given to reports of worker exposure and
subsequent health effects.
• Airborne concentrations are not always the focus of RELs if other
types of exposure, e.g., dermal, are more likely.
REFERENCES:
NIOSH. 1990. NIOSH Pocket Guide to Chemical Hazards. Washington, DC: U.S.
Department of Health and Human Services, Centers for Disease Control, National
Institute for Occupational Safety and Health. June.
Personal communication with Ralph Zumwalde of NIOSH. September 17, 1991.
7
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AMERICAN INDUSTRIAL HYGIENE ASSOCIATION
EMERGENCY RESPONSE PLANNING GUIDELINES
Emergency Response Planning Guidelines (ERPGs) are published by the
American Industrial Hygiene Association (AIHA). The purpose of the guidelines
is to protect against adverse health effects from short-term exposures to
airborne chemicals in an emergency situation. The guidelines are intended for
voluntary use by industry in emergency planning for accidental releases to a
community. Specifically, ERPGs, when "used, together with other information
such as volatility and storage volumes, [can] provide computerized estimates
of the potential spread and airborne concentration in case of a release. From
chese estimates, action plans can be developed." Thus, ERPGs are ncc intended
for use as exposure guidelines.
There are three levels for each ERPG that protect "nearly all
individuals" following one-hour exposures to an airborne chemical:
• ERPG-3 is the maximum concentration in air below which no "life-
threatening health effects" would occur;
• ERPG-2 is the maximum concentration in air below which no
"irreversible or other serious health effects or symptoms which
could impair an individual's ability to take protective action"
would occur; and
• ERPG-1 is the maximum concentration in air below which no "mild,
transient adverse health effects" would occur and no
"objectionable odor" would be detected.
Thus, industry can use ERPG levels as guides to determine what action should
be taken in the event of an accidental release of a chemical at one of the
ERPG levels.
ERPGs were developed by chemical companies that agreed to participate
with AIHA in the process. Each company followed specific guidelines and
methodologies, previously established by the Organization of Resources
Counselors (ORC) ERPG Task Force, to insure consistency in the development of
each ERPG. In addition, the ORC Task Force identified those chemicals for
which ERPGs were to be developed. Once the ERPGs were developed and the data
documented, the AIHA EPRG Committee of scientific experts reviewed, revised
and approved the ERPG documents and exposure levels for publication.
Each chemical with an ERPG value is reviewed on a case-by-case basis.
All of the data reviewed for establishing an ERPG value and their references
are included in the documentation, along with the rationale used to derive
each ERPG level.
The procedure for developing ERPGs emphasizes the use of industrial
hygienists, toxicologists, medical experts, and other health professionals to
8
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collect and review the data as well as Co develop the values and their
supporting documents. It is also suggested that data be taken from
computerized literature searches of databases (i.e., MEDLINE and TOXLINE) and
from industry (i.e., unpublished data). The procedures emphasize the use of
the original sources of data, rather than secondary sources, whenever
possible.
In general, ERPGs are based upon various types of data. In order of
preference, these data are: (1) human data; (2) animal data from acute
inhalation toxicity studies that contain clinical and histopathologic testing;
(3) inhalation data from repeated exposure studies that contain clinical and
histopathologic testing; (4) inhalation mortality data; or (5) data from
studies that use other routes of exposure. In addition, dose-response data
may be used. Other data that are to be considered when developing ERPGs
include: (1) acute and short-term exposure data; (2) data for serious adverse
effects from short-term exposures, such as carcinogenesis or reproductive and
developmental effects; and (3) data for immediate and delayed effects.
Data from subacute, subchronic, and chronic toxicity studies, metabolism
and pharmacokinetics data, physical/chemical properties, and the currently
existing exposure limits for each chemical are also summarized in the ERPG
documents.
Advantages of Using the ERPGs for Short-term Benchmarks
• ERPGs are intended to be protective of reversible and irreversible
acute and serious health effects from short-term exposures to
airborne chemicals.
• ERPGs are based upon original data, especially human data when
available, thus they are highly likely to insure the protection
intended by the limits.
• ERPGs are based upon data from exposures to sensitive individuals
of the population, when available, therefore, they are highly
likely to protect these individuals as well as other members of
the general population.
• ERPGs are applicable to l>hour exposures.
• The methodology for deriving ERPGs has been reviewed by members of
the general scientific community.
• The rationale and the supporting data for each ERPG have been peer
reviewed.
• ERPGs are established by industry and are therefore be more likely
to be accepted by industry.
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Disadvantages of Using the ERPGs as Shore-term Benchmarks
• Very few ERPGs have been derived and only 7 chemicals with ERPGs
are on the CAA Section 112(b) list;
• Since the maximum duration of exposure is one hour, it is not
likely that ERPGs can be used to set ambient exposure levels that
exceed one-hour without some modification;
• ERPGs are guidelines for "emergency planning and response" and
"are not absolute levels demarcating safe from hazardous;"
therefore, ERPGs are not intended for use as exposure guidelines.
REFERENCE:
American Industrial Hygiene Association (AIHA) . Concepts and Procedures for
the Development of Emergency Response Planning Guidelines (ERPGs). 1989.
10
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NATIOHAL RESEARCH COUNCIL
EMERGENCY EXPOSURE GUIDANCE LEVEL
Emergency Exposure Guidance Levels (EEGLs) are developed by the National
Research Council's Committee on Toxicology (COT) for the Department of
Defense. The EEGL is intended for use in emergency inhalation exposures of 1
to 24 hours by military personnel; these situations are expected to occur
rarely during the lifetime of an individual. EEGLs are expected to protect
against those effects that may impair escape, judgement, or performance or
that are irreversible. Therefore, irritation, discomfort or other transient
effects may occur from exposures to an EEGL. In addition, the EEGL does not
protect the general population in an emergency, nor against effects from
continuous short-term exposures.
EEGLs are based upon epidemiological, clinical, physiological, and acute
toxicity data in animals and humans. In addition, serious and chronic effects
that may occur from short-term exposures and immediate and delayed effects are
considered as well. When data for several endpoints exist for a chemical, all
of the data are considered and the most "seriously debilitating, work-
limiting, or sensitive" effect is used for deriving an EEGL.
The EEGL document contains: (1) the data used to derive the EEGL values;
(2) a summary of the physical and chemical properties of the chemical; (3)
data on the pharmacokinetics and metabolism of the chemical; (4) exposure
limits from other sources; (5) the Committee's current and prior
recommendations for an EEGL value; (6) the rationale for the EEGL value; (7)
the rationale for modifying an existing EEGL, if applicable; (8)
recommendations for future research; and (9) references used for the data.
EEGLs may also be derived using safety factors to compensate for
inadequate data. For instance, a safety factor of 10 is used when only animal
data are available or if there are no data for the expected route of exposure.
Extrapolation, e.g., when oral animal data are available and human inhalation
exposure is expected, is done by (1) assuming that the oral dose in rats is
equivalent to that in humans and then using the appropriate human breathing
rates, weight, and exposure durations to calculate the inhaled concentration
by humans or (2) converting the oral dose in rats to an inhalation dose in
rats and then assuming that dose to be equivalent to the inhalation dose in
humans.
EEGLs have not been derived for complex mixtures, however, it is
recommended by the Committee that a "proportional reduction in EEGLs for each
of the constituents of a mixture" be used, based upon the assumption that the
toxic effects of each component in a mixture are additive.
When possible, Barber's law (CT - concentration (C) x time (t)), which
assumes that CT is constant over short periods of time, is used to develop
EEGLs for different exposure durations. However, prior to applying the law,
all data are considered to determine if Harber's law holds true.
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The shore-term public emergency exposure guidance Level (SPECIE is
intended for emergency single short-cerm exposures co the general population.
Therefore, sensitive individuals are protected from single exposures to the
SPEGL. SPEGLs are derived from EEGLs and may be equivalent to 0.1 - 0.5 times
the EEGL. However, for the protection of children, the elderly or other
sensitive groups, a safety factor of 2 may be used and to protect fetuses or
newborns, a safety factor of 10 may be used.
Advantages of Using EEGLs and SPEGLs for Short-term Benchmarks
• EEGLs and SPEGLs apply to airborne contaminants.
• EEGLs and SPEGLs are based upon original data, especially human
data when available, thus, they are highly likely to insure the
protection intended by the limits.
• The rationale for each EEGL and SPEGL and the supporting data for
each has been peer reviewed.
• The maximum duration of exposure is 24 hours, thus, EEGLs and
SPEGLs may be useful for setting daily ambient exposure levels.
• One chemical may have several EEGLs and SPEGLs for different
exposure durations (i.e., within 1 to 24 hours) which makes these
values more applicable to various exposure conditions.
Advantages of Using SPEGLs for Short-term Benchmarks
• Four of the five chemicals with SPEGLS are on the CAA Section
112(b) list.
• SPEGLs are intended to protect sensitive individuals as well as
the general population.
Disadvantages of Using EEGLs and SPEGLs for Short-term Benchmarks
• EEGLs and SPEGLs are intended to protect against some acute,
reversible health effects (i.e., those that would impair emergency
escape), but not all acute effects.
• EEGLs and SPEGLs are intended for rare or occasional exposures and
not repeated exposures such as those likely to be encountered with
ambient air pollutants.
• EEGLs and SPEGLs are guidelines for emergency planning in military
situations and are not intended for use as regulatory standards.
Disadvantages of Using EEGLs for Short-term Benchmarks
• Only 18 chemicals with EEGLs are on the CAA Section 112(b) list.
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• EEGLs are intended to protect healthy military personnel and not
the general population or sensitive individuals of the population.
The disadvantage of using SPEGLs as the basis for short-term ambient
benchmarks is that the values have been developed for only five chemicals on
the Section 112(b) list: hydrazine, monomechyl hydrazine, 1, 1'-
dimethylhydrazine, hydrogen chloride, and nitrogen dioxide.
REFERENCE:
Committee on Toxicology, National Research Council. Criteria and Methods for
Preparing Emergency Exposure Guidance Level (EEGL), Short-Term Public
Emergency Guidance Level (SPEGL), and Continuous Exposure Guidance Level
(CEGL) Documents. National Academy Press, Washington, D.C., 1986.
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SARA TITLE III - EXTREMELY HAZARDOUS SUBSTANCES LIST
LEVELS OP CONCERN
Short-term exposure limits for chemicals on the Superfund Amendments and
Reauthorization Act (SARA) Title III Section 302 list of Extremely Hazardous
Substance (EHS) are called "Levels of Concern" (LOCs). These levels are the
airborne concentrations of chemicals on the EHS list at which no serious,
irreversible health effects or death may occur following a single, short-term
exposure.
LOCs were derived from the "Immediately Dangerous to Life and Health"
(IDLH) values developed by the National Institute for Occupational Safety and
Health (NIOSH). IDLH values are approximately one or two orders of magnitude -
below the median lethal concentration (LC50) or dose (LD50) taken from acute
toxicity studies in mammalian species. IDLH values may also be based upon the
lowest inhalation exposure concentration that causes death or irreversible
health effects in any species (LCLO) . Finally, the IDLH may be equivalent to 5
500 times the Permissible Exposure Limit (PEL) if no acute toxicity data are
available for a chemical.
The LOG is defined as one-tenth of the IDLH. Since the IDLH is designed
to protect workers, is based upon a 30-minute exposure duration, and protects
against serious and irreversible health effects, a safety factor of 10 was
used to derive the LOCs: (1) to insure protection of the general population,
including sensitive individuals; (2) to protect against health effects from
exposures which occur for more than 30 minutes; and (3) to protect against
serious and reversible health effects.
For chemicals on the EHS list that have no IDLH value, animal acute
toxicity data, i.e., LD50 and LC50 data, have been used to derive LOG values.
LD50 is the oral or dermal dose at which 502 of the test animals died
following exposure to a chemical and LC50 is the inhalation concentration at
which 50% of the animals died. The LC50 data are preferred when available.
These data were taken from the NIOSH Registry of Toxic Effects of Chemical
Substances (RTECS) data base. Estimated IDLH values derived from these data
are equivalent to one-tenth (1/10) of the LC50 or one-one hundredth (1/100) of
the LD50. The LOG is then equal to one-tenth (1/10) of the estimated IDLH.
For chemicals on the EHS list that have no LD50 or LC50 data available,
LDLO or LCLO data have been used to derive LOG values. The LDLO and LCLO
values represent the lowest lethal dose or concentration, respectively, of a
chemical. LCLO values are preferred when available because they are based on
inhalation exposures. Estimated IDLH values derived from these data are
equivalent to the unmodified LCLO or one-tenth of the LDLO. The LOG is then
equal to one-tenth (1/10) of the estimated IDLH.
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Advantages of Using LOG Values for Shore-term Benchmarks
• LOG values apply co airborne contaminants.
• LOG values are intended co protect against reversible and
irreversible acute and serious health effects from short-term
exposures.
• LOG values are intended to protect the general population,
including sensitive individuals.
• LOG values exist for many (55) of the chemicals on the CAA Section
112(b) list.
Disadvantages of Using LOG Values for Short-term Benchmarks
• Most of the LOG values are based upon animal LC50, LD50, LCLO and
LDLO data, which may not protect against all health effects in
humans.
• The remaining LOG values are derived from secondary sources (i.e.,
the RTECS data base); thus, data used to derived LOG values may
not be peer reviewed or may be inaccurately recorded in RTECS.
• A safety factor of 10 was applied to the IDLHs to protect
sensitive individuals of the population and for protection against
serious reversible health effects; however, it is not known if
this safety factor is sufficient to provide adequate protection in
these cases.
• The methodology for deriving LOCs has not been reviewed by members
of the general scientific community.
• The rationale for each LOG and some of the supporting data of each
have not been peer reviewed.
• It is not known what the maximum duration of exposure at the LOG
would be for protection against adverse effects.
When setting exposure limits, it is important to consider serious,
chronic effects, as well as acute effects that may be induced by short-term
exposures to chemicals. LOG values and most of the other exposure levels (see
Table 1) reviewed in this report protect against chronic (serious,
irreversible) health effects from short-term exposures. Effects such as
chronic respiratory disease, increased susceptibility to infection, visual
impairment, or death may occur following short-term inhalation exposures
(i.e., as with the accidental release of methyl isocyanate in Bhopal, India).
In a report previously prepared by Clement for the EPA Office of Toxic
Substances, several LOG values were reviewed to determine if the levels were
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protective againsc chronic effects that occur from shore-term exposures to
potential neurotoxic agents. In one case study of lindane, it was found that
che current LOG did not protect a worker against convulsions induced by a
single exposure to the pesticide (the route of exposure was not reported).
REFERENCE:
US EPA Technical Guidance for Hazards Analysis, Emergency Planning for
Extremely Hazardous Substances, 1987.
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CAPCOA
NONCANCER ACCEPTABLE ACUTE EXPOSURE LEVELS
The California Air Pollution Control Officers Association has developed
risk assessment guidelines for its members to use in the preparation of health
risk assessments required under the California Air Toxics "Hot Spots"
Information and Assessment Act of 1987. This law mandates a statewide
inventory of air toxics emissions from individual facilities. A risk
assessment should include an evaluation of both the potential cancer and
noncancer effects of long-term and short-term exposures to emissions from a
particular facility. CAPCOA has developed one-hour maximum concentrations
considered to be acceptable exposure levels for 13 substances. Air pollution
control districts and individual facilities should compare their emissions
levels and the potential for acute effects of emissions of these substances to
the CAPCOA levels. Exposures below the CAPCOA acceptable level are not
expected to result in adverse effects to the exposed population. If exposure
is to more than one substance on the list, a hazard index approach, which
assumes that multiple subthreshold exposure will result in an adverse health
effect, should be used. The hazard index approach, established by EPA,
assumes that the effects of each substance are additive for a given adverse
response.
Of the 13 chemicals for which noncancer acceptable acute exposure levels
have be^tn established by CAPCOA, 12 are on the Section 112(b) list of
hazardous air pollutants. Several sources were used to develop these exposure
levels. Scientific data (including original studies) were used whenever
possible. Particular emphasis was given to inhalation studies that used
exposure times as close to one hour as possible. An uncertainty factor of 10
was applied to animal data when extrapolating to humans. A second uncertainty
factor of 10 was also applied to account for interspecies variation.
Preference was given to studies that produced a scientifically valid no
observed adverse exposure level or a lowest observed adverse exposure level.
The resulting levels were considered to be protective of the general
population, including sensitive populations. It should be noted that these
exposure levels were reviewed by members of the California Department of
Health Services ojnjty and were not subject to outside peer review or general
public comment.
Advantaees of CAPCOA Approach for Short-term Benchmarks
• Exposure levels are for one-hour and may be used directly by OAQPS
without further manipulation.
Disadvantages of CAPCOA Approach for Short-term Benchmarks
• Noncancer acute exposure levels have been developed for only 11 of
the substances on the Section 112(b) list.
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Methodology used Co develop the exposure levels have nee been
reviewed by experts outside of the California Department of Health
Services and CAPCOA.
REFERENCES:
CAPCOA. 1991. Air Toxics "Hoc Spots" Program: Risk Assessmenc Guidelines.
Sacramenco, CA: AB 2588 Risk Assessment CommiCCee of the California Air
Pollucion Concrol Officers Association. January.
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CALABRESE AND KENYON
AMBIENT AIR LEVEL GOALS
Calabrese and Kenyon (L991) have developed a methodology for developing
Ambienc Air Level Goals. An ambient: air level goal (AALG) is the level of a
toxicant below which the risk of an adverse health effect for an exposed
population is less than a predetermined de minimis value such as one in a
million (10*6) or one in one hundred thousand (10*5). These values are called
goals rather than standards because no technical or economic feasibility
studies are conducted to determine if the levels are realistic. The authors
present two methods of deriving AALGs: the first is a model-based approach for
non-threshold health effects, such as cancer, that estimates the risk at a
given dose. The second is for a threshold effect, which is based on a
modification of the no observed adverse effect level (NOAEL) or lowest
observed adverse effect level (LOAEL) by some uncertainty factors.
Use of either of these methods is predicated on a selection scheme that
includes such factors as production volume, known toxic effects and monitoring
studies. In addition, a preliminary screening of data using the Registry of
Toxic Effects of Chemical Substances will give a better indication of the
endpoint of concern and references to the available toxicology literature.
After the pertinent toxicologic studies have been evaluated, an AALG may be
derived for either a carcinogen (or mutagen) or a noncarcinogen. For
chemicals that are preliminarily classified as carcinogens, Calabrese and
Kenyon present a method for developing an AALG based on EPA's weight-of-
evidence classification and quantitative risk assessment procedures.
For chemicals that are noncarcinogens, AALGs may be developed by
dividing the NOAEL or LOAEL by applicable uncertainty factors that account for
inter- and intraspecies differences, extrapolating from a LOAEL to a NOAEL,
and differences between healthy populations and sensitive populations. It is
recommended that for chemicals with a Reference Concentration (RfC), that this
level be used as the AALG with or without adjustment for relative source
contribution. The authors present selection criteria for selecting NOAELs and
LOAELs, including the use of occupational limits as their surrogates.
Although the authors recommend that occupational exposure limits (TLVs and
RELs) not be used as the starting point in the development of AALGs, they
recognize that these levels are frequently the most expedient and economically
justified starting point. Consequently, their methodology includes a scheme
to develop NOAELs and LOAELs by applying safety factors to TLVs or RELs. The
AALGs derived from the NOAEL should be based on the endpoint of greatest
concern, or if the chemical has several endpoints of concern, an AALG may be
developed for each endpoint and then the most conservative value can be
chosen.
Calabrese and Kenyon acknowledge that limitations do exist when
developing AALGs from NOAELs. These limitations include ignoring the shape of
the dose-response curve, selecting an appropriate NOAEL, and incorporating the
quality of the relevant studies. Uncertainty factors may be applied to
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account for a variety of factors including: (1) differences between animals
and humans; (2) differences between healthy individuals and more sensitive
populations; (3) extrapolating downward from a. LOAEL to a NOAEL; and (4)
extrapolating from a less-than-lifetime or subchronic study to a lifetime or
chronic value (this may not be a major consideration for developing de minimis
levels for acute effects).
Although an occupational exposure level may be used to develop a NOAEL,
Calabrese and Kenyon point out several reasons as to why this approach is
questionable, with emphasis on the use of TLVs. First, the TLVs are not
intended to be used for regulatory purposes since they are guidelines and are
not thresholds for "safe" exposures. TLVs are not necessarily based upon
effective or no-effect doses from animal or human studies, and there is no way
to determine the extent to which each TLV was based upon actual experimental
data. Secondly, the TLVs may not be protective of sensitive individuals in
the population because they are designed to protect generally healthy workers.
Calabrese and Kenyon emphasize that any TLV or REL used to derive an AALG
should be applicable to the general population, including sensitive
populations, as well as to workers. In addition, there should be evidence
that the occupational exposure limit may be used as a human NOAEL or LOAEL.
Although the issue of acute effects in general is not discussed in this
book, Calabrese and Kenyon do discuss sensory irritation at some length. A^
djaclsion table_i£ presented that facilitates extrapolating from occupational
data^or other sensory irritation A»r* fg_j»ri__AftL5 NOAELs and LOAELs are
preferred, but^in some cases a mouse RD50 may be used (an RD50 is the
concentration that decreases the respiratory rate in a test organism by 502) .
To demonstrate the applicability of their method, Calabrese and Kenyon
derive AALGs for 110 chemicals, 73 of which are on the Section 112(b) list.
The discussion includes a summary of existing occupational limits and the
basis for derivation, a toxicity profile that includes all aspects of relevant
toxicity, and the rationale for the selection of the AALG. For example,
acetonitrile (listed in Section 112(b)) has a AALG for systemic toxicity of
0.068 mg/m3 for a 24-hour time weighted average. This value is based on a
mouse NOAEL of 100 ppm from an NTP study. This value was adjusted for
continuous exposure and converted to a human equivalent inhalation exposure
dose.
Advantages of Using the AALG Approach for Short-term Benchmarks
• Method is well defined with specified uncertainty factors and may
be applied to a variety of chemicals.
• Uses best toxicity data available, whether occupational exposure
limits or other types of human or animal data (NOAEL, LOAEL, LC50)
and encourages review of all background documentation used in
support of occupational exposure limits.
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• Because ic is based on widely-accepted chemical guidelines (RELs,
TLVs), limits derived using this method are more likely to be
acceptable to affected industries.
• Sensitive populations can be incorporated into the AALG value.
• Either of several methods may be used to derive AALG values based
on amount and type of data available.
Disadvantages of Using the AALG Approach for Short-term Benchmarks
• Does not really present new starting point for developing AALG,
but uses preestablished limits, such as RELs and NOAELs.
• Intended for long-term (chronic or lifetime) exposures; however,
eliminating uncertainty factor in derivation may be sufficient to
determine short-term exposure limits.
• Acute effects other than sensory irritation and LD50 data are not
incorporated into this method as endpoints. Methods to protect
against other acute effects, such as nausea, are not provided.
REFERENCE:
Calabrese, E.J., and Kenyon. E.M. 1991. Air Toxics and Risk Assessment.
Chelsea, MI: Lewis Publishers.
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MINNESOTA POLLUTION CONTROL AGKffCY
REGULATORY LIMITS FOR SHORT-TERN EXPOSURES
The proposed methodology of the Minnesota Pollution Control Agency for
setting One-Hour Regulatory Limits for airborne emissions is outlined below.
Data will be taken from scientific reviews, original scientific studies,
and other exposure limit documents. Searches of the TOXLINE data base will
also be conducted for irritation and/or inhalation exposure data from the last
10 years. The Registry of Toxic Effects of Chemical Substances (RTECS) and
the Hazardous Substances Databank (HSDB) will be used to supplement TOXLINE.
The Agency for Toxic Substances and Disease Registry (ATSDR) Toxicity
Profiles, the World Health Organization (WHO) Health Criteria, the National
Institute for Occupational Safety and Health (NIOSH), and EPA health documents
will also be used as sources of original data. All original data taken from
regulatory documents will be reviewed for "adequacy" prior to use in the
development of any exposure limits.
Data will be reviewed for effects that occur following 3 minute to 8
hour exposures and that meet the EPA definitions of (1) adverse effect or (2)
functional impairment. In addition, any short-term exposure data for eye,
nose or throat irritation, dizziness, headache, nausea, fatigue, or other
"subjective sensations or reactions (excluding odor)", changes in
physiological or respiratory function, increased physiological or
psychological stress, and decreased resistance to disease will be considered.
Observed adverse effect levels (OAELs), lowest observed adverse effect
levels (LOAELs), and/or no observed adverse effect levels (NOAELs) will be
identified, using specific criteria, from all significant data. Exposure
Limits will be based upon these levels using the safety factors of 10, 5, and
1, respectively. In addition, another safety factor of 10 may be used to
protect sensitive individuals, however, this safety factor can be reduced to 3
if the OAELs, LOAELs, or NOAELs are based upon data taken from exposures to
sensitive individuals. When several OAELs, LOAELs, and/or NOAELs can be
identified from various studies, the "best" study will be chosen based upon
its ability to "meet the criteria of sound study design, demonstration of a
graded dose-response relationship, and sensitive measurement of effect".
Extrapolation of data using a probabilistic approach will be used as an
alternative to the above strategy when the data are suitable for applying the
model (Lewis and Alexeef, 1989).
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In addition, RD50 data1 may be used for setting exposure limits.
However, prior to the use of such data, several criteria must be met: (1)
there are no other "adequate" human data that can be used; (2) sensory
irritation (the endpoint of the RD50 studies) must be identified as the
critical effect, since all exposure limits are based upon the critical effect;
and (3) all additional toxicity data have been considered. If RD50 values
were used to establish exposure limits, large safety factors would be applied
(i.e., 1,000) and the RD50 data "would be supplemented with supporting
documentation."
Calabrese and Kenyon (1991) have proposed potential short-term ambient
air levels, called Ambient Air Limit Goals (AALGs) for several chemicals.
Most of the AALGs are based upon TLV values. AALGs will be considered as
potential exposure limits by the Minnesota Air Quality Staff; however, all
original data will be reviewed prior to making any final decisions.
Once potential short-term exposure limits have been identified by the
Air Quality staff, according to the methods described above, the proposed
exposure limits will undergo a review process that consists of several steps:
(1) the proposed exposure limits will be reviewed by the staff toxicologist;
(2) the Minnesota Department of Health's Health Risk Assessment Section will
then review the proposed exposure limits; (3) the Human Health Subcommittee
members will review the proposed exposure limits and all of the supporting
data for comment; and (4) experts in respiratory health that are not
affiliated with the Minnesota Pollution Control Agency or the Minnesota
Department of Health will review the proposed limits.
Advantages of Using the Minnesota Approach for Short-term Benchmarks
• These values are protective against reversible and irreversible
serious and acute effects from short-term exposures to airborne
chemicals.
• These values are based upon original animal and human data, thus
they are highly likely to insure the protection intended by the
limits.
• The limits will be applicable to 1-hour exposures.
• The methodologies, supporting data, and rationale for these levels
are all peer reviewed.
• These values are intended to protect all members of the general
population, including sensitive individuals and when available.
1RD50 is the concentration at which a SOX decrease in respiration rate is
noted in animals (usually mice) following a short-term exposure (usually 4
hours) to a chemical; this concentration has been correlated with irritation
levels in humans.
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use data from exposures Co sensitive populations to derive the
exposure limits.
• These values are intended to be used as ambient exposure levels
and, therefore, no manipulation of the values will be needed prior
to their application.
Disadvantages of Using the Minnesota Approach for Short-term Benchmarks
• No Regulatory Limits for airborne chemicals have been developed as
yet and it may be years before an extensive list of chemicals with
these limits is available.
• These values will be based upon one-hour exposures and, therefore,
may not be applicable to daily exposures or other exposures that
exceed one-hour.
REFERENCES:
Minnesota Pollution Control Agency, Air Quality Division, Air Toxics Program.
Proposed Procedures for Setting Regulatory Limits for Short-Term Exposures.
3/6/91 (First Draft); 6/19/91 (Second Draft).
Lewis and Alexeef. Quantitative risk assessment of non-cancer health effects
for acute exposure to air pollutants. Presented at the 82nd annual meeting of
the Air and Waste Management Association, Anaheim, CA. 1989.
Edward J. Calabrese and Elaina M. Kenyon (Eds). Air Toxics and Risk
Assessment. Lewis Publishers, Inc., Michigan. 1991.
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AMERICAN CONFERENCE OF GOVERNMENTAL INDUSTRIAL HYGIENISTS
THRESHOLD LIMIT VALUES
The following discussion on the derivation of Threshold Limit Values
(TLVs) is included because several of the other short-term exposure levels
discussed in this report are based upon TLVs. In addition, TLVs may be useful
for setting ambient short-term exposure limits for airborne chemicals. The
potential uses of these values as protective ambient-air levels and a detailed
discussion of the advantages and disadvantages for applying TLVs outside of
the workplace can be found elsewhere (Calabrese and Kenyon, 1991; Chemical
Manufacturers Association, 1988); therefore, only a brief discussion of the
applications of TLVs to setting short-term ambient exposure levels will be
presented here.
TLVs are issued by the American Conference of Governmental Industrial
Hygienists (ACGIH) as guidelines to protect workers from effects of repeated
daily chemical exposures during the workweek and are referred to as TLV Time-
Weighted Averages (TWA). Weekly exposure to TLV-TWAs should not exceed more
than four 15-minute exposures/day with at least a 60 minute interval between
exposures. In addition, there are two TLV categories that protect workers
from short-term exposures; TLV-Ceilings (C), which are intended to protect
workers from single short-term exposures that are not to be exceeded at any
time during the 8-hour workday, and TLV-Short-Term Exposure Limits (STELs),
whl-ch are not to be exceeded for more than 15-minutes during an 8-hour
workday.
Each TLV has documented supporting data, much of which is respiratory
and ocular irritation data from industrial exposures. In addition, there are
some acute toxicity data (LCSOs and LDSOs) and other animal data which
describe systemic effects, cancer, and mutagenic effects. The documentation
also contains information on the physical properties of each chemical, the
rationale for choosing each TLV, and the references for the supporting data.
TLVs are derived by the Chemical Substances TLV Committee on a chemical-
by-chemical basis from available animal and human data and industrial
experiences. The kind of data used, and the effects that each TLV protects
against, vary for each chemical. Thus, there is no consistent format for
choosing data for derivation of TLVs other than to use the "best available
data". In addition, the final decision for setting TLVs is a "judgment" based
upon the data, but the judgment process used is not always well described in
the TLV documentation.
Advantages of Using TLVs for Short-term Benchmarks
• TLVs apply to airborne contaminants.
• TLVs are intended to protect against reversible and irreversible
acute and serious health effects from short-term exposures.
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• TLVs exist for many of the chemicals on the CAA Section L12(b)
list.
• TLV-Cs and TLV-STELs protect against effects following short-term
exposures of either (1) one-time exposures during an 8-hour period
or (2) 15 minute exposures in an 8-hour period. Both of these
values may be applicable to short-term ambient exposure levels.
In addition, these exposures are allowed on a daily basis, thus,
these levels are suitable for ambient air exposures that may be
randomly repeated.
Disadvantages of Using TLVs for Short-term Benchmarks
• TLVs are not necessarily directly derived from a complete
toxicology data base and, therefore, may not adequately protect
against all health effects in humans.
• TLVs only protect a specific, healthy segment of the population
between the ages of 18-65; they are not intended to protect the
general population or sensitive individuals of the population.
• TLVs-TWA protect against effects following daily 8-hour exposures
over a 40-hour workweek. These exposure durations may not be
applicable to short-term exposure levels in ambient air since they
are lifetime daily exposures.
• The methodology for deriving TLVs has not been reviewed by members
of the general scientific community.
• The rationale for each TLV and some of the supporting data of each
have not been peer reviewed.
REFERENCES:
ACGIH. Threshold Limit Values for Chemical Substances and Physical Agents,
1990-1991.
Edward J. Calabrese and Elaina M. Kenyon (Eds). Air Toxics and Risk
Assessment. Lewis Publishers, Inc., Michigan. 1991.
Chemical Manufacturers Association. Chemicals in the Community: Methods to
Evaluate Airborne Chemical Levels. Washington, D.C., 1988.
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THE STATE OF MARYLAND SCREENING LEVELS
The State of Maryland uses I-hour and 8-hour Screening levels as guides
for ambient air emission levels that are protective of public health from
noncancer effects. Thus, they are not standards.
A screening level can be equivalent to either the TLV-TWA, TLV-STEL, or
TLV-C divided by a factor of 100. Screening levels based upon the TLV-TWA are
used for protection from 8-hour exposures, whereas, the other TLV-Based
Screening Levels protect against 1-hour exposures. A safety factor of 100 is
used with the TLVs to allow protection of the general public.
The State of Maryland has a second approach to generating screening
levels which uses safety factors with NOEL or LC50 data. These screening
levels are referred to as Threshold-Based Screening Levels and are used only
when a substance has no TLV. The preferred data for these values are human
and long-term studies rather than animal and short-term studies. The data are
multiplied by factors that convert long-term exposures to short-term
exposures. The following formulae, given in order of preference, are used to
develop Threshold-Based Screening Levels:
(i) Divide a 90-day inhalation NOEL in mg/m3 for rats, mice, or
rabbits by 100;
(ii) Multiply a 90-day oral NOEL in mg/kg for rats by 2.7 x 10'3,
for mice by 9.0 x 10"4, or for rabbits by 1.3 x 10"3;
(iii) Divide a 7-day inhalation NOEL in mg/m3 for rats, mice, or
rabbits by 700;
(iv) Multiply a 7-day oral NOEL in mg/kg for rats by 3.8 x 10"4,
for mice by 1.3 x 10'4, or for rabbits by 1.9 x 10'4;
(v) Divide an LC50 in mg/m3 for rats, mice, or rabbits by 10,000;
or
(vi) Multiply an oral LD50 in mg/kg for rats by 4.1 x 10"5, for
mice by 1.4 x 10'5, or for rabbits by 2.0 x 10'5.
When data from two or more animal tests can be used to develop Threshold-Based
Screening Levels, the data producing the lowest screening level are preferred.
A third approach to generating screening levels is used when the other
two approaches do not adequately protect against health effects or are too
stringent. The levels generated by this approach are called Special Screening
Levels. No information was provided on the development of Special Screening
Levels. However, Special Screening Levels must provide "a. scientifically
appropriate basis for screening analysis" and must protect human health prior
to approval by the Department of the Environment.
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Each of these screening levels may be subject to scientific review and
public comment, but the reviews are not required and are implemented only upon
request of the Maryland State Department of the Environment.
Screening levels may be replaced by Acceptable Ambient Levels (AALs) ,
which are derived by the releasing facility, if it can be shown that AALs will
protect public health from noncancer effects. In general, AALs are used only
if a source cannot meet a-screening level. AALs are based upon "a'detailed
review of the scientific information" but there is no specific methodology for
development of AALs.
Advantages of Using the State of Maryland Screening Levels for Short-term
Benchmarks
• These values are intended to protect against reversible and
irreversible serious and acute effects from short-term exposures
to airborne chemicals.
• These values are applicable co 1-hour or 8-hour exposures.
• These values are intended to protect the general population.
• These values are intended to be used as ambient exposure levels
and, therefore, no manipulation of the values will be needed prior
to their application.
• Approximately 23 chemicals on the CAA Section 112(b) list have 8-
hour Screening Levels and 3 chemicals have 1-hour Screening
Levels.
• Additional Screening Levels can easily be developed using
available TLV exposure limits and with more effort using available
NOEL or LC50 data from animal studies.
Disadvantages of Using the State of Maryland Screening Levels for Short-term
Benchmarks
• These values are based upon 1-hour or 8-hour exposures and,
therefore, may not be applicable to daily exposures or other
exposures that exceed eight-hours.
• It is not explicit if these limits are intended to protect
sensitive individuals of the population.
• Application of a safety factor of 100 to the TLVs may not be
adequate to protect the general population.
• The methodologies, supporting data, and rationale for these levels
are not always peer reviewed, and the extent to which some of the
values are reviewed is not clearly defined.
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Some of these values are based upon NOEL and LC50 animal data, Co
which safecy factors have been applied. Thus, che values based
upon chese daca may noc adequacely protect against all health
effects in humans.
Some of these values are based upon TLV-TWA, TLV-STEL, and TLV-C
limits and, therefore, have all of the disadvantages of the TLVs.
REFERENCES:
Maryland Department of the Environment Overview of Maryland's Proposed Air
Toxics Regulations, June 1988.
Maryland Department of the Environment Toxic Air Pollutants. July 1990.
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A POTENCY-BASED METHOD FOR ACUTE TOXIC ITT
For most of the chemicals on Che Section 112(b) list, some toxicity data
for acute exposures are available. For most chemicals, there may be toxicity
data to identify an exposure concentration for a particular acute exposure
duration (i.e. 1-hour or 8-hours) at which adverse effects may not be
expected. However, the range of exposure concentrations over a range of
exposure durations that is likely to be without adverse effects in exposed
populations is not well characterized. For most chemicals, as either the time
or the dose increases, the number of animals exhibiting a specified effect or
the severity of that effect also increases. Also, in many cases, chemicals do
not follow Harber's Law under acute situations in which high exposures may
occur for short durations. Therefore, in evaluating acute exposure
situations, the risk assessor/risk manager may have to make decisions
regarding the impact of ambient levels on exposed populations for a exposure
concentration/duration combination for which specific empirical data do not
exist.
To address this issue, Clement International, for the OAQPS/PAB (Clement
1991a) investigated the development of a dose-duration-response model for
acute/short-term exposures. Two dose-duration-response models, which
represent continuations of the work proposed by Hertzberg (1989) and Knauf and
Hertzberg (1989), have been investigated. Both of these models take into
account the duration of exposure, the dose, and the severity of the effect
seen at that dose/duration. Both models estimate the probability (P) of an
effect of severity greater than index i at a dose (d) for a duration (T);
expressed mathematically, the P(s>i|d,T).
To develop these probability estimates, all adequate data on adverse
health effects resulting from less than 24 hour exposures (or other exposure
duration can be specified) are used. This approach to using acute data has a
significant advantage over other methods in that all acute effects, including
minor, sublethal, and lethal are used in this assessment. The following steps
are conducted: (1) all the primary literature or competent review sources for
a chemical are critically reviewed for dose-response information; (2)
administered doses are converted to human equivalent units according to the
RfC methodology; (3) for each adequate study, responses for each animal in
each dose group are assigned a severity index; and (4) data generated are
input to the dose-response model. A severity scale similar to those developed
by Dourson et al. (1985) and Hertzberg and Miller (1985) is devised. It is a
rank-order scale, in that the difference between severity categories is not an
arithmetic assignment, i.e., an index of 2 is not twice as severe an index of
1.
Rather than a single dose for a single endpoint, these models allow for
the estimation of a family of curves, each of which represents the probability
of the occurrence of an adverse effect of a specified level of severity, or
the no adverse effect curve if the lowest level of severity is so defined, for
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any dose-duration combination. Both the maximum likelihood estimate and the
corresponding lower confidence limit (e.g., 95X or 99Z) for each curve can be
derived.
For application in source category ranking schemes, Clement developed an
extension to these models by allowing estimation of the potency of the
chemical (Clement 1991b). The potency is estimated by allowing the model to
solve for d*. which is set equal to the 95X lower bound on dose for a
specified probability that severity will exceed an index of 2 for variable
time and dose. Expressed mathematically this is the 95X lower bound on dose
for T-24 [P(s>2|d,T)-cr] . The choice of T-24 hours is based on the assumption
that, for a given acute dose, the longer the exposure the worse the acute
effect, although any time could be used. Severity exceeding an index of 2 is
recommended because these effects are in the observable range, and for the
purpose of de minimis levels, it is desirable to choose an effect associated
with a dose that is higher than threshold for any effect yet still in the low
dose region. Then potency, P, is defined as a/d* - P, where a is synonymous
with risk. We propose that a - 0.01 is reasonable for comparison across
chemicals for this purpose, although o could be set to any level of interest.
A value for a of 0.01 has been proposed in alternative methodologies to
evaluate noncancer health effects (Crump, 1984). Finally, based on this
potency, any release that would result in an a > 0.01 (or any other level
deemed reasonable) could be regarded as having exceeded the de minimis level.
Advantages of Using a Potency-Based Approach for Short-term Benchmarks
• Data are derived by critical review of the primary
literature.
• All of the data for a chemical can be used rather than just
one study or one data set within a study and dose-response
information can be included.
• The probability of the occurrence of an adverse effect for
any dose/duration/severity combination can be estimated.
• The potency can be estimated for any risk level (a) deemed
appropriate for the chemical or application.
• Once the primary literature has been reviewed and the data
have been compiled on data entry forms and entered into the
appropriate model, the process could be automated.
Disadvantages of Using a Potency-Based Approach for Short-term Benchmarks
• Although much of the data needed by this scheme exist, a
review of the primary literature and the running of the
suggested models would be labor intensive.
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This method has been applied to only 2 chemicals on the
Section 112(b) list of chemicals.
REFERENCES:
Clement International Corporation (Clement). 1991a. Health Effects and Dose-
Response Assessment for Hydrogen Chloride Following Short-term Exposure.
Prepared for Air Risk Information Support Center, Office of Air Quality
Planning and Standards and Office of Health Evaluation Assessment, U.S.
Environmental Protection Agency, Research Triangle Park, NC.
Clement International Corporation (Clement). 1991b. Consideration of
Multiple Health Endpoints in Source Category Ranking. Prepared for Office of
Air Quality Planning and Standards, Pollution Assessment Branch, U.S.
Environmental Protection Agency, Research Triangle Park, NC.
Crump, K. 1984. A new method for determining allowable daily intakes.
Fundamental and Applied Toxicology 4:854-871.
Dourson, M. L. , Hertzberg, R. C., Hartung, R., and Blackburn, K. 1985. Novel
methods for the estimation of acceptable daily intake. Toxicology and
Industrial Health 1(4):23-41.
Hertzberg, R. 1989. Fitting a model to categorical response data with
application to species extrapolation of toxicity. Proceedings of 26th Hanford
Life Sciences Symposium. Modeling for Scaling to Man: Biology, Dosimetry, and
Response. Health Phys (Suppl 1):405-409.
Hertzberg, R. and Miller, M. 1985. A statistical model for species
extrapolation using categorical response data. Toxicology and Industrial
Health 1(4):43-57.
Knauf, L. and Hertzberg, R. 1989. Statistical methods for estimating risk
for exposure above the reference dose. Internal Report, U. S. Environmental
Protection Agency, Environmental Criteria and Assessment Office, Research
Triangle Park, NC.
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SUMMARY
As can be seen from the approaches described above, there is no single,
already established, method that provides an all encompassing scientifically
valid basis for determining short-term ambient benchmarks for acute effects.
If the method gives a value for short-term exposures, it is probably designed
to protect only workers at a facility. In cases where the general population
is protected by the exposure limit, it is probably for a lifetime exposure.
Any method used by OAQPS to establish de minimis levels will require some
modification; however, the amount of modification will vary for each method.
Each of the methods described in this document is, to a greater or
lesser extent, flexible with few if any formal mechanisms for defining the
types of data that are to be reviewed, criteria for deeming a study
scientifically valid, enumerating the uncertainty factors that must be used,
and applying the method or exposure value to other similar chemicals. In
part, this is a function of the variability of data available for a specific
substance. While chemicals have been well characterized in terms of toxicity,
this is not the case for many of the chemicals on the Section 112(b) list. In
addition, all of the methods described in this document are resource
intensive, i.e., they require a review of original data or, for most methods,
secondary data collected by health specialists e.g., supporting documentation
for TLVs. Some methods, such as the development of PELs, also require that
technical and economic feasibility studies be performed.
Other Approaches
The issue of ambient emissions and community exposure is also being
reviewed by other organizations. The Chemical Manufacturers Association (CMA)
has produced a document that presents eight approaches that may be used by
industry "for placing emission levels in context." Four of the approaches use
data sets as the starting point, i.e. , TLVs or NOELs, and then modify these
values by dividing them by fixed or variable factors. A model-driven
approach, or health risk assessment, uses dose-response relationships to
estimate cancer potency and is only applicable to potential carcinogens.
Finally, three integrated methods are discussed in the CMA report including
the NOAEL adjustment method described above for Calabrese and Kenyon, a method
for dividing the TLV by fixed or variable factors, and a method described by
Lewis et al. that adjusts the NOEL by various factors depending on the type .
and quality of data. As is the case with most of the methods described above,
the CMA methods focus on the long-term effects of airborne contaminants and
not short-term, acute exposures.
A unique aspect of the CMA document is that is presents the advantages
and disadvantages for each method in terms of resource (personnel and data)
requirements, the scientific basis for the method, the flexibility of the
method, the complexity of communicating the method and the results to the
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general public as well as scientific experts, and whether or not the method
has been used by public and regulatory agencies. Because several of the
methods discussed in the CMA document are variations of those discussed in
this document, such as the Calabrese method, the advantages and disadvantages
described for each CMA approach are applicable to the approaches discussed in
this report.
The National Research Council (NRC) of the National Academy of Sciences
is conducting a study to develop methodologies for setting short-term exposure
levels for the EPA Office of Toxic Substances and the Agency for Toxic
Substances and Disease Registry (ATSDR) . It is expected that the exposure
limits will be used by the EPA as guidelines for chemicals on the Extremely
Hazardous Substance list and by ATSDR as guidelines for personnel exposed
during evaluations of hazardous waste sites. The NRC is currently reviewing
various methods used to develop exposure levels, including methods for the
development of EEGLs, SPEGLS, and ERPGs. The methods eventually developed by
the NRC will allow exposure limits to be set on a chemical-by-chemical basis
using currently available data.
A dose-response approach for acute exposures and noncancer endpoints has
been developed by Clement and has been applied to the data for hydrogen
chloride. This method has undergone internal EPA review and may be useful in
establishing de minimis levels under Section 112(b). The model takes dose,
duration, and severity of the response into consideration and estimates the
probability that a response will occur at a specified level of severity (or
the no observed effect level if the lowest severity category is so defined)
for any dose-duration combination.
Recommended Approach
From che methods presented in this document, it would appear that on the
basis of flexibility and scientific validity, the approach of Calabrese and
Kenyon is most appropriate for setting de minimis levels for short-term acute
exposures as an interim method. This method is very well defined and is
flexible enough to incorporate the available data for any given chemical. By
allowing the use of either an occupational exposure limit or a NOAEL or LOAEL
based on animal or human data, an AALG may be derived for any chemical on the
Section 112(b) list. Calabrese and Kenyon provide guidance on selecting
appropriate uncertainty factors and determining whether a particular study
meets the criteria for scientific merit. ^Although they assume that the
ambient air levels are to be protective for long-term effects, their approach
is easily applicable to short-term, acute exposures. This may be done by not
extrapolating from acute exposures (which are often more readily available) to
Chronic exposures.In addition, AALGs and their rationales are provided for
nTany of the substances on the Section 112(b) list, which provides a convenient
starting point for deriving short-term, acute exposure limits.
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The following is a brief review of the scheme for deriving AALGs, as
presented by Calabrese and Kenyon, and which may be used for che development
of de minimis levels.
Step 1: Choosing Bndpoints of Concern for Each Chemical for Which an
AALG will be Derived
Calabrese and Kenyon use several approaches for deriving AALG values.
One approach is specific for carcinogens, and others are specific for either
(1) genotoxicity; (2) developmental, reproductive, and systemic toxicity; or
(3) skin and eye irritation. Data used to derive an AALG for a given chemical
should be categorized into one or more of these effects. Subsequently, the
endpoint of most concern would be used as the basis for the AALG. If more
than one endpoint applies, an AALG could be calculated for each endpoint and
the most conservative AALG could be chosen.
For the initial screening, the RTECS data base is used as a source of
information for determining which of the above categories apply to the
chemical of interest. From RTECS, health effects can be identified and the
chemicals can be categorized by the different effects. However, this is only
a preliminary step. The studies in RTECS that describe specific health
effects should be retrieved to confirm the cited information.
In addition, these effects should be confirmed using some or all of the
following secondary data sources:
IARC Monographs
ACGIH TLV documents
NIOSH Criteria Documents or Current Intelligence Bulletin (CIBs)
NTP Carcinogen Technical Report
EPA Gene Tox data base
Ambient Water Quality Criteria Documents
Drinking Water Criteria Documents
Drinking Water Health Advisories
ATSDR Health Profiles
EPA Health Assessment Documents
EPA Health Effects Documents
Integrated Risk Information System (IRIS)
Once the crucial endpoint(s) for a chemical are positively identified and
verified, the principal and supporting studies that confirm the health effects
should be used to derive the AALGs.
As mentioned previously, Calabrese and Kenyon present schemes for
deriving AALGs for each of the endpoints indicated above. However, only the
scheme for developmental, reproductive or systemic toxicants will be discussed
here as an example of how the schemes may be applied to a specific chemical.
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