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Health Effects Notebook
About Health Effects Fact Sheets
INTRODUCTION
The chemical fact sheets contained in this notebook provide a hazard summary for each of the hazardous air pollutants (except 2,3,7,8-tetrachlorodibenzo-p-dioxin and mineral fibers, which are under review by the U.S. Environmental Protection Agency [EPA]) specified in the Clean Air Act Amendments of 1990. These brief summaries are intended to provide a quick reference for pertinent toxicity information and to indicate where more comprehensive and primary information can be found. This information is targeted to those concerned with toxic air pollutants at the State and local levels. The information in the fact sheets is summarized from EPA databases, and, where EPA data are lacking, information from other sources has been added for a more complete picture of possible toxicity concerns. The fact sheets should be used as one of many information sources for understanding a pollutant's human health hazard potential. In the case of listed compound categories, one or more representative compounds have been selected for the fact sheet summary.The fact sheets do not represent EPA policy on health hazards and they should not be construed as constituting an EPA judgment about a hazard where a judgment does not already exist. In addition, they cannot be cited or quoted as a primary source of EPA health hazard information.
Appendix A, Section 1, contains a glossary of health, exposure, and risk assessment terms and the definitions of acronyms used in the graphs that accompany the fact sheets. Appendix A, Section 2, discusses related terms frequently encountered in health, exposure, and risk assessments. Appendix B (WordPerfect 5.1 file) is a hazardous air pollutants' Fact Sheet chemical cross reference, which contains an alphabetical listing of all the chemicals and their most common synonyms contained in this Notebook and the page number of the associated fact sheet.
This health effects notebook contains fact sheets on hazardous air pollutants. These chemicals include volatile organic chemicals, chemicals used as pesticides and herbicides, inorganic chemicals, and radionuclides. Many of these chemicals are used for a variety of purposes in the United States today. Other chemicals, although not in use today, were used extensively in the past and may still be found in the environment.
These fact sheets were developed based on available human and/or animal data. The human data consist primarily of epidemiological studies, which are studies that examine the incidence, distribution, and control of disease in the human population. The primary type of epidemiologic studies used in the development of these fact sheets were occupational studies, which examined the effects of a chemical on a group of workers over time. The animal data are from studies that experimentally exposed animals to chemicals to observe and measure toxicity and disease development. These studies include effects data related to acute (short-term) exposures, subchronic (medium-length) exposures, and chronic (long-term) exposures.
The primary sources of information used to develop the fact sheets were EPA's Integrated Risk Information System (IRIS),(http://www.epa.gov/ngispgm3/iris/index.html), a database that summarizes available toxicity data and contains EPA's assessment of the data, and secondary sources, such as EPA's Health Assessment Documents, EPA's Drinking Water Criteria Documents, EPA's Health Effects Assessment Summary Tables (HEAST), and the Agency for Toxic Substances and Disease Registry (ATSDR) Toxicological Profiles(http://atsdr1.atsdr.cdc.gov/toxfaq.html). In addition, databases such as the Hazardous Substances Data Bank (HSDB), which contains summaries of peer-reviewed literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), which lists toxic effects of chemicals and is not peer reviewed, were used.
Each bulleted piece of information on the fact sheet contains one or more reference numbers after it which correspond to the numbered references at the end of each fact sheet. Complete reference information is provided in the reference section of each fact sheet.
When available, numerical data are presented in the fact sheets. The numerical data presented are primarily those numbers that are found in the IRIS database. IRIS numbers are EPA- verified values; i.e, they have been subjected to extensive review by EPA scientists and a consensus was reached on their validity. These numbers include the Oral Reference Dose (RfD) and the Inhalation Reference Concentration (RfC) (see the Chronic Effects section) and the risk specific dose (see the Cancer Risk section). In addition, some numbers are presented that are not on the IRIS database; these numbers have not been subjected to the same degree of review and consensus as the IRIS values. These values are "provisional" RfDs and "provisional" RfCs (see the Chronic Effects section) and may be found in EPA's HEAST document. For some chemicals, numerical data are not available either on IRIS or in the HEAST document. The fact sheets for these chemicals simply present the available qualitative information.
The quality and decisiveness of the knowledge base underlying each of the agents portrayed in the fact sheets vary according to the abundance or paucity of high-quality health science data. The strength or confidence in particular hazard conclusions or inferences similarly varies according to the amount and quality of data and also according to the inherent methodologic generated uncertainties that go along with health hazard assessment. The overall effect of these circumstances is that each agent has its unique combination of uncertainty elements that are not explicitly listed in the fact sheets. A responsible user of these fact sheets must appreciate the implications of the underlying uncertainties, which take on more or less meaning depending on how the fact sheets are used.
The fact sheets focus on the health effects of each chemical in humans and laboratory animals (mammals). No information is presented on the ecological effects of the chemicals or the health effects in nonmammalian species. The ecological effects from exposure to toxic chemicals are an important area that EPA is currently addressing.
The fact sheets are organized as follows:
- Chemical name and CAS
number
- Hazard summary
- Environmental/occupational
exposure
- Assessing personal
exposure
- Health hazard
information
- Physical properties
- Uses
The chemical name and Chemical Abstract Service (CAS) registry number given on the fact sheet are the same as that used in the list of 189 hazardous air pollutants in the Clean Air Act Amendments of 1990. For listed compound categories, CAS numbers for one or more representative compounds have been selected.
The hazard summary is an overview of the key information provided in the Health Hazard Information section of the fact sheet. The major health effects of the chemical are presented in bold print.
Environmental/Occupational Exposure
This section contains information on how the general public may be exposed to the chemical, e.g., through water, food, or air, as well as information on occupational exposure. In addition, this section tells which chemicals have been listed as pollutants of concern to EPA's Great Waters Program and the reason for the listing. The purpose of the Great Waters Program is to evaluate the atmospheric deposition of air pollutants to the Great Lakes, Lake Champlain, Chesapeake Bay, and coastal waters. All of the pollutants of concern possess certain common characteristics, including persistence in the environment and the potential for long-distance transport.
This section describes the medical tests available to determine whether a person has been exposed to the chemical.
This section summarizes the key toxicology information on the chemical, emphasizing the inhalation (air) route of exposure. If available, oral and dermal (skin) exposure data are also presented.
Acute Effects
The results from acute animal tests and/or acute human studies are
presented in this section. Acute animal studies consist of LD50 and LC50
tests, which present the median lethal dose (or concentration) to the
animals. The results from these tests are divided into the toxicity
categories as shown in Table 1.
Acute human studies usually consist of case reports from accidental
poisonings or industrial accidents. These case reports often help to
define the levels at which acute toxic effects are seen in humans.
This section summarizes the major chronic noncarcinogenic effects seen
from exposure to the chemical. Chronic animal studies usually range from
90 days' to 2 years' duration. Human studies investigating effects
ranging from exposure of a few years to a lifetime are also included. In
addition, subchronic studies may be included in this section. Subchronic
studies are usually animal studies of several weeks' to 90 days'
duration.
The Inhalation RfC is presented in this section, with information on the
critical effect and species upon which it is based. The RfC is an
estimate (with uncertainty spanning perhaps an order of magnitude) of
the daily exposure of a chemical to the human population by inhalation
(including sensitive subpopulations) that is likely to be without
deleterious effects during a lifetime of exposure. The RfC is derived
based on the assumption that thresholds exist for noncancer effects;
i.e., there is a level below which no toxic effects would occur. It is
based on the available toxicological data, using uncertainty factors to
account for data gaps such as experimental animal-to-human extrapolation
and extrapolation to sensitive members of the population. The RfC is not
a direct or absolute estimator of risk, but rather a reference point to
gauge the potential effects. Doses at or below the RfC are not likely to
be associated with any adverse health effects. However, exceedance of
the RfC does not imply that an adverse health effect would necessarily
occur. As the amount and frequency of exposures exceeding the RfC
increase, the probability that adverse effects may be observed in the
human population also increases. If available, the oral RfD is also
presented in this section. The RfD is the oral equivalent of the RfC.
EPA's confidence in the RfC and/or RfD is also presented in this
section. EPA ranks each RfC and RfD as either low, medium, or high in
three areas: (1) confidence in the study on which the RfC or RfD was
based; (2) confidence in the database; (3) overall confidence in the RfC
or RfD. All three rankings are presented in this section.
This section also includes a "provisional" RfC or "provisional" RfD, if
available. A provisional RfC or RfD is generated in several ways. Often
they are determined in the course of developing an EPA document on a
chemical. Some have been generated through EPA's Work Group process and
have been reviewed extensively but have not yet been put on the IRIS
system. At the time each value was derived, all available information on
the chemical was evaluated and the value was calculated using the most
current methodology.
The results of a scoring system for chronic toxicity effects, termed the
Composite Score, are also included in this section. The Composite Score
was originally developed by EPA for the determination of relative hazard
to human health of chronically toxic pollutants in the Reportable
Quantities methodology under the Comprehensive Environmental Response,
Compensation, and Liability Act (CERCLA) or Superfund and has recently
been used by EPA's Office of Air Quality Planning and Standards (OAQPS)
for a hazard ranking under Section 112(g) of the Clean Air Act
Amendments. The Composite Score is a qualitative tool that reflects two
primary attributes of each pollutant: (1) minimum effective dose (MED)
levels, which are extrapolated for human exposure and which result in
adverse effects from chronic exposures, and (2) the severity of effect
(e.g., mortality, rated as the most severe effect and given the highest
score) resulting from the MED levels in animal or human studies. Of the
hazardous air pollutants summarized in this document, 47 chemicals have
been scored using this system. The composite scores range from 1 to 100,
with 100 being the most toxic. These scores are ordinal and do not give
an absolute number but rather present a perspective on the chemical in
terms of its relative hazard. Of the 47 chemicals scored, the highest
scoring (most toxic) was methylene diphenyl diisocyanate (MDI) with a
score of 46, the lowest scoring (least toxic) chemical was
1,1,1-trichloroethane with a score of 2, and the average score was 18
(calcium cyanamide had a score of 16, which was closest to the average
score).
Reproductive and Developmental Effects
This section presents the results of reproductive and developmental
studies on the effects of the chemical in animals and humans. Examples
of female reproductive effects include reduced fertility, a decrease in
the survival of offspring, and alterations in the reproductive cycle.
Male reproductive effects include a decrease in sperm count or an
increase in abnormal sperm morphology. Developmental effects are adverse
effects on the developing organism that result from exposure prior to
conception (either parent), during prenatal development, or postnatally
to the time of sexual maturation. Examples include altered growth, death
of the developing organism, and malformations or birth defects.
Reproductive and developmental effects may be observed after short-term
or long-term exposure to the chemical because some effects can be
attributed to one-time or short-term exposures during a critical
biological cycle.
The results of available cancer studies in animals and/or humans are
presented in this section. In addition, the ranking of the chemical in
EPA's cancer classification system is included. EPA uses a
weight-of-evidence three-step procedure to classify the likelihood that
the chemical causes cancer in humans. In the first step, the evidence is
characterized separately for human studies and for animal studies. The
human studies are examined for the validity and representativeness of
the populations studied, any possible confounding factors, and the
statistical significance of the results of the studies. The animal
studies are evaluated to decide whether biologically significant
responses have occurred and whether the responses are statistically
significantly increased in treated versus control animals. Next, the
human and animal evidence is combined into an overall classification.
This classification is based on an analysis of both the human and animal
evidence, considering the number and quality of both types of studies.
In the third step, the classification is adjusted upward or downward,
based on an analysis of the supporting evidence. Supporting evidence
includes structure-activity relationships (i.e., the structural
similarity of a chemical to another chemical with known carcinogenic
potential), studies on the metabolism and pharmacokinetics of a
chemical, and short-term genetic toxicity tests. The result is that each
chemical is placed into one of the following five categories:
The cancer risk section also includes the inhalation unit risk for a
chemical, which is the increased probability of a person developing
cancer from breathing air containing a specified concentration of the
chemical for 70 years. The inhalation unit risk is derived using
mathematical models that assume a nonthreshold approach; i.e., there is
some risk of cancer occurring at any level of exposure. The methods used
to derive these values result in an "upper bound" estimate; i.e., the
true risk is unlikely to exceed this value and may be much lower. The
risk-specific dose, an estimate of the chemical dose corresponding to a
specified level of cancer risk, is also presented in this section. The
risk-specific doses corresponding to a one-in-a-million,
one-in-a-hundred thousand, and one-in-ten thousand excess risk
attributed to exposure to the chemical are presented. This means that
EPA has estimated that, if an individual were to breathe air containing
these concentrations of the chemical over his or her entire lifetime,
that person would theoretically have no more than a one-in-a-million,
one-in-a-hundred thousand, or one-in-ten thousand increased chance of
developing cancer as a direct result of breathing air containing the
chemical. The use of the risk-specific dose should include recognition
of the weight-of-evidence.
A measure of the carcinogenic potency of a chemical, termed the ED10, is
also included in this section. These ED10s were used by EPA's OAQPS for
a hazard ranking under Section 112(g) of the Clean Air Act Amendments.
The ED10 is the estimated dose associated with an increased cancer
incidence of 10 percent over background.
A ranking system for relative carcinogenicity, developed by EPA for
Reportable Quantities provisions under CERCLA and used by EPA's OAQPS
for the hazard ranking cited above, is also included in this section.
Chemicals are ranked based on inhalation hazard as high, medium, or low
for potential carcinogenicity. This ranking system is intended to
present further perspective on the relative carcinogenicity of the
compound. Thus, a chemical ranked as high by this system could be
assumed to present more of a cancer risk than a chemical ranked in the
medium category. The following method is used to rank the chemicals:
The characterizations of cancer hazard presented in these fact sheets
are based on those proposed for the hazard ranking done by EPA's OAQPS
for Section 112(g) and may vary with those used for EPA's Reportable
Quantities. The focus of concern for Reportable Quantities was oral and
inhalation exposure, while that for Section 112(g) was inhalation
exposure.
This section provides the physical state (solid, liquid, or gas) of
the chemical at ambient conditions, as well as solubility information
and the odor threshold of the chemical (if available). The chemical
formula, molecular weight, vapor pressure, and octanol/water partition
coefficient are also provided in this section.
This section presents the major uses of the chemical in the United
States today. In addition, past uses of the chemical are summarized.
Following each fact sheet is a graph that visually presents the
available health numbers, showing the concentration (on a logarithmic
scale) at which effects have been noted. The numbers labeled as "health"
on the graph are LC50 and LD50 numbers; the RfC, RfD,
lowest-observed-adverse-effect level (LOAEL) and
no-observed-adverse-effect level (NOAEL), which are the basis for the
RfC or RfD; risk-specific dose levels, as cited in EPA's IRIS system;
and the "provisional" RfC or RfD, as cited in EPA's HEAST document. Even
though there may be other numbers cited in different sources, if there
are no numbers in IRIS or in the HEAST document, the only health numbers
included in the graph are LC50 or LD50 numbers. Relevant regulatory and
advisory numbers are also included on the graph. Regulatory numbers
consist of values that have been incorporated in government regulations,
such as EPA and State air regulations or the Occupational Safety and
Health Administration's (OSHA's) occupational standards. Advisory
numbers are nonregulatory values that are provided by the Federal
Government, State Government, or other groups as advice. Examples
include EPA's Health Advisories and the American Conference of
Governmental and Industrial Hygienist's (ACGIH's) threshold limit values
(TLVs). The graphs present health data for inhalation exposure only. For
those chemicals that lack inhalation data, a graph on health data from
oral exposure has been included.
As discussed at the beginning of this Introduction, the fact sheets were
developed using data presented in secondary sources and databases. Other
sources of information used were chemical information sheets, such as
the New Jersey Hazardous Substance Fact Sheets, and chemical textbooks,
such as The Merck Index or the Handbook of Toxic and Hazardous
Chemicals and Carcinogens. However, an exhaustive literature search
was not performed for each chemical.
There are many other data sources that may be used to find additional
information on a chemical. A few key sources are:
Definitions and discussion of terms that are frequently encountered in
risk assessments for air pollutants are contained in the document,
Glossary of Terms Related to Health, Exposure, and Risk
Assessment. An appendix to this document contains additional terms.
The Glossary of Terms document and the appendix may be used to
help clarify and expand upon information contained in the chemical fact
sheets. To obtain this document, as well as additional information on
air pollutants, please contact EPA's Air RISC Hotline at (919) 541-0888,
Monday-Thursday, 8 a.m. to 5 p.m., and Friday, 8 a.m. to 4 p.m., EST.
This Notebook was prepared under Contract No. 68-D2-0065 for the U.S.
Environmental Protection Agency, Air Risk Information Support Center,
Research Triangle Park, North Carolina, in response to requests by State
and local air agencies. Julie Andresen of the Office of Air Quality
Planning and Standards directed the work assignment, and the Notebook
was written by Susan Goldhaber, Susan Wolf, and Michael Laney of
Research Triangle Institute. The authors wish to thank Dr. Charles
Ris and Dr. Chon Shoaf, Office of Research and Development, and Dr. Jane
Caldwell and Dr. Carolyn Miller, Office of Air Quality Planning and
Standards, for their significant contributions throughout the
development of the Notebook (PB95503579; Year : 1995).
Lethality
Extreme
High
Moderate
Low
Oral LD50
<50 mg/kg
50-500 mg/kg
500-5,000 mg/kg
>5,000 mg/kg
Dermal LD50
<200 mg/kg
200-2,000 mg/kg
2000-20,000 mg/kg
>20,000 mg/kg
Inhalation LC50
<200 mg/m3
200-2,000 mg/m3
2,000-20,000 mg/m3
>20,000 mg/m3
Source: U.S. EPA. Office of Pesticide Programs, Registration and
Classification Procedures, Part II. Federal Register
40:28279.
Weight-of-evidence group
Potency group 1 (highest)
(1/ED10 >100)
Potency group 2
(1/ED10 1 - 100)
Potency group 3 (lowest)
(1/ED10 <1)
A
High
High
Medium
B1 or B2
High
Medium
Low
C
Medium
Low
Low
D
No hazard ranking
No hazard ranking
No hazard ranking
E
No hazard ranking
No hazard ranking
No hazard ranking
DATA SOURCES
Documents listed above with PB numbers can be ordered through the
National Technical Information Service (NTIS).
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