EPA/450/3-88/016
March 1989
Glossary of Terms Related to Health,
Exposure, and Risk Assessment
by
Air Risk Information Support Center (Air RISC)
U.S. Environmental Protection Agency
Sponsored by:
Office of Air Quality Planning and Standards
Research Triangle Park, NC 27711
Office of Health and Environmental Assessment
Research Triangle Park, NC 27711
Cincinnati, OH 45268
Washington, DC 20460
Center for Environmental Research Information
Cincinnati, OH 45268
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Disclaimer
This report has been reviewed by the Office of Air Quality Planning and Standards of
the Office of Air and Radiation, and by the Office of Health and Environmental
Assessment and the Center for Environmental Research Information of the Office of
Research and Development and approved for publication. Approval does not signify
that the contents necessarily reflect the views and policies of the U.S. Environmental
Protection Agency, nor does mention of trade names or commercial products
constitute endorsement or recommendation for use.
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Contents
Page
Introduction iv
1. Glossary of Health, Exposure, and Risk Assessment Terms 1
2. Discussion of Related Terms Frequently Encountered in Health, Exposure, and
Risk Assessment
Cohort Compared with Case-control Studies 17
Cohort Studies Compared with Clinical Studies 17
Epidemiology Compared with Toxicology 18
Parameters: Most Sensitive Compared with Most Critical Compared
with Most Selective 19
LOAEL Compared with NOAEL 19
LD Compared with LC 19
Additive, Synergistic, and Antagonistic Effects . 20
Mitosis and Meiosis 20
Threshold Compared with Non-Threshold 20
Benign Compared with Malignant 20
Exposure Compared with Dose 21
Sensitive Compared with Sensitization 21
Quantal Dose-response Compared with Graded Dose-Response 21
Epigenetic (Nonmutagenic) Carcinogens Compared with Mutagenic
Carcinogens 21
Initiators and Promoters 21
Qualitative Compared with Quantitative Risk Assessment . 22
Risk Assessment Compared with Risk Management 22
Population Threshold Compared with Individual Threshold 22
Measurement Compared with Modeling 23
Aggregate Compared with Individual Risk 23
3. References 25
in
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Introduction
Many state and local agencies are developing or implementing programs to control
emissions of toxic air pollutants. To successfully carry out these programs, agency
personnel must be familiar with a wide range of issues and terms related to health,
exposure, and risk assessment for toxic air pollutants. Understanding these issues and
terms is not always an easy task. This glossary has been prepared by the U.S. EPA's
Air Risk Information Support Center (Air RISC) as a resource tool for State and local air
pollution control agencies and U.S. EPA Regional Offices. The purpose of the glossary
is to define terms that are commonly used in health, exposure, and risk assessments
for toxic air pollutants.
The Air RISC is operated by the U.S. EPA's Office of Air Quality Planning and
Standards (OAQPS), Office of Health and Environmental Assessment (OHEA), and
Center for Environmental Research Information (CERI). The key goal of Air RISC is to
provide technical assistance to State and local air pollution control agencies and U.S.
EPA Regional Offices in obtaining, reviewing, and interpreting air toxics data related to
health, exposure, and risk assessment. Through Air RISC, Regional, State, and local
agency personnel can obtain expert guidance and information on health, exposure, and
risk assessment issues and methodologies.
This glossary is divided into three sections:
• Section 1 provides brief definitions of commonly used risk assessment, exposure
assessment, and biological terms.
• Section 2 provides more detailed discussions of related terms frequently
encountered in health, risk and exposure assessments.
• Section 3 lists key references concerning health, exposure, and risk assessment
for air toxics. These resources include general texts on toxicology,
carcinogenicity, and risk assessment, as well as certain U.S. EPA references
relating to health and exposure assessment.
The terms included in the glossary were selected by expectations of their commonality
of usage relative to the elements of the risk assessment process for inhaled chemicals.
The conceptual framework for risk assessment as it is currently practiced, was defined
by the National Academy of Science in 1983 as a four-phase process. The elements
in this process, as well as the interrelationships between research, risk assessment
and risk management are shown in the following figure.
IV
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Introduction (continued)
Research
Risk Assessment
Risk Management
Laboratory and field
observations of
adverse health
effects and exposures
to particular agents
Information on
extrapolation methods
for high to low dose
and animal to human
Field measurements,
estimated exposures,
characterization of
populations
\
Hazard identification
(Does the agent
cause the adverse
effect?)
I
Dose-Response
Assessment (What is
the relationship
between dose and
incidence in humans?)^
Exposure Assessment
(What exposures are
currently experienced
or anticipated under
different conditions?)
>
\
Risk Characterization
(What is the estimated
incidence of the
adverse effect in a
given population?)
Development of
regulatory options
I
Evaluation of public
health, economic,
social, political
consequences of
regulatory options
Agency decisions
and actions
Elements of Risk Assessment and Risk Management (From: National Academy of Sciences, [NAS] 1983
As indicated by the figure, a number of types of information are used in health risk
assessment. Hazard identification is a qualitative determination that a given agent is
causally linked to particular health effects. Data evaluated in this process may include
epidemiologic, animal studies, short-term assays and structure activity comparisons.
The exposure assessment component uses information on environmental levels, fate
and transport, ecologic analyses, applied exposures at the point of contact, any
pharmacokinetic modeling of the data, and demographic characteristics. A dose-
response assessment is performed by staff trained in biomedical and/or physical
sciences, who use available data on health endpoints, both for human and animal
studies. The assessment includes evaluation of how data from the human and animal
studies is influenced by the level of exposure to the chemical agent, as well as
differences between species or in target organ toxicologic responses. The final
component, termed risk characterization, is the formal application of mathematical
analysis to the data to estimate the individual and population risks or whether there is a
threshold in dose level which is exceeded. The Risk Characterization also contains a
discussion and interpretation of the numerical estimates and the degree to which the
quantitative estimates are likely to reflect the true magnitude of human risk.
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Introduction (continued)
The glossary is intended as a handy reference source, and should be used as a
starting point for accessing technical assistance and information relative to health,
exposure, and risk assessments for toxic air pollutants. The terms and comparisons
presented in this directory can provide an initial, quick response to your questions. For
more detailed information, consult the references listed in Section Three or call the Air
RISC Hotline at (919) 541-0888; FTS 629-0888.
VI
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Section 1
Glossary of Health, Exposure, and Risk Assessment Terms
This section provides brief definitions of terms that
are frequently encountered in discussions of health,
exposure, and risk assessments for toxic air
pollutants.
Absorbed dose. The amount of a substance
penetrating across the exchange boundaries of
an organism, via either physical or biological
processes, after contact (exposure).
Absorption. To take in a substance through a
body surface such as the lungs,
gastrointestinal tract, or skin and, ultimately
into body fluids and tissues.
Acute exposure. One or a series of short-
term exposures generally lasting less than 24
hours.
Administered dose. The amount of a
substance given to a human or test animal in
determining dose-response relationships,
especially through ingestion or inhalation (see
applied dose). Even though this term is
frequently encountered in the literature,
administered dose is actually a measure of
exposure, because even though the substance
is "inside" the organism once ingested or
inhaled, administered dose does not account
for absorption (see absorbed dose).
Adverse effect. A biochemical change,
functional impairment, or pathological lesion
that either singly or in combination adversely
affects the performance of the whole organism,
or reduces an organism's ability to respond to
an additional environmental challenge.
Adenoma. A benign tumor originating in the
covering tissue (epithelium) of a gland.
Additivity. A pharmacologic or toxicologic
interaction in which the combined effect of two
or more chemicals is approximately equal to
the sum of the effect of each chemical alone.
(Compare with: antagonism, synergism.)
Aerodynamic diameter. A measurement of
the diameter of a particle expressed as the
diameter of a unit density sphere with identical
inertial properties.
Aerosol. A suspension of liquid or solid
particles in a gaseous medium.
Aggregate risk. The sum of individual
increased risks of an adverse health effect in
an exposed population.
Airway. Any conducting segment of the
respiratory tract through which air passes
during breathing. The bronchial tubes are
examples of airways.
Airway resistance (Raw). The functional
resistance to air flow afforded by the airways
between the mouth and the alveoli.
Alkylation. The substitution of an alkyl radical
for a hydrogen atom in a chemical molecule.
An alkyl radical follows the general formula
CnH2n +1. Alkylation is viewed as an event that
may lead to toxicity.
Allergen. An antigenic substance capable of
eliciting an allergic response.
Altered growth. A change in offspring, organ,
or body weight or size. Altered growth can be
induced at any stage of development, may be
reversible, or may result in a permanent
change.
Alveolar. Pertaining to the air sacs (alveoli) of
the lung where gas exchange occurs.
Alveolar macrophage. A cell within the lung
that contributes to immunological activities of
the lung by phagocytosing (engulfing) and
killing microbes, phagocytosing inhaled
particles, secreting/excreting antimicrobial
substances, and performing other activities.
Under some conditions, it also can secrete/
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excrete enzymes capable of digesting lung
tissue.
Alveolar ventilation. The volume of air
entering the alveoli each minute.
Ambient. Encompassing or surrounding area.
Ames test. An in vitro bacterial test for
detecting point mutations in a group of
histidine-requiring strains of Salmonella
typhimurium. An Ames test is usually
conducted with an exogenous source of
metabolic activation by adding, for example,
enzymes obtained from mammalian liver cells
(S9 liver fraction), to the S. typhimurium assay
system.
Anaphylaxis. An exaggerated reaction to an
antigen to which an organism has been
previously sensitized.
Anemia. A condition characterized by a
reduction in the number of circulating red blood
cells and/or the number of hemoglobin
molecules in red blood cells.
Anergy. Diminished reactivity to specific
antigens.
Aneuploidy. A condition in which the
chromosome number is not an exact multiple
of the usual number of chromosomes for that
species. For example, a "normal" human has
46 chromosomes; an individual with 47
chromosomes would be described as
aneuploid.
Annual incidence. The number of new cases
of a disease occurring or predicted to occur in
a population over a year.
Anoxia. Absence/lack of or significant
reduction in oxygen.
Antagonism. A pharmacologic or toxicologic
interaction in which the combined effect of two
chemicals is less than the sum of the effect of
each chemical alone; the chemicals either
interfere with each other's actions, or one
interferes with the action of the other.
(Compare with: additivity, synergism.)
Antibody. A protein substance developed in
response to, and interacting specifically with,
an antigen. The antibody-antigen reaction
forms a major basis for immunity.
Antigen. A substance that induces the
formation of antibodies and interacts with its
specific antibody. Antigens may be introduced
into the body or may be formed within the
body. The antigen-antibody reaction forms a
basis for immunity.
Apnea. Temporary cessation of breathing.
Applied Dose. The amount of a substance
given to a human or test animal in determining
dose-response relationships, esp. through
dermal contact (see administered dose). Even
though this term is encountered in the
literature, applied dose is actually a measure of
exposure, since it does not take absorption into
account.
Arrhythmia. Any variation from the normal
rhythm of the heartbeat.
Asthma. A condition marked by recurrent
attacks of difficult or labored breathing and
wheezing resulting from spasmodic contraction
and hypersecretion of the bronchi resulting
from exposure to allergens such as drugs,
foods, environmental pollutants, or intrinsic
factors.
Atmospheric half-life. The time required for
one-half of the quantity of an air pollutant to
react and/or break down in the atmosphere.
Atmospheric residence time. The time
required for removal of a substance from the
atmosphere to the extent that l/e
(approximately 37%) of the original material
remains.
Atrophy. Reduction in the size of a structure
or organ resulting from lack of nourishment or
functional activity, death and reabsorption of
cells, diminished cellular proliferation, pressure,
ischemia or hormone changes.
Averaging time. The time period over which a
function (e.g., average concentration of an air
pollutant) is measured, yielding a time-
weighted average.
Benign. A condition of a neoplasm (tumor) in
which the morphological and behavioral
characteristics of the tumor differ minimally
from the tissue from which it originates. A
benign neoplasm (as distinct from malignant)
may expand, but remains encapsulated, and
has limited potential to invade local structure
and proliferate.
Bioaccumulation. Progressive increase in
amount of a chemical in an organism or part of
an organism that occurs because the rate of
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intake exceeds the organism's ability to
remove the substance from the body.
Bioassay. A test conducted in living organisms
to determine the hazard or potency of a
chemical by its effect on animals, isolated
tissues, or microorganisms.
Bioavailability. A measure of the degree to
which a dose of a substance becomes
physiologically available to the body tissues
depending upon absorption, distribution,
metabolism and excretion rates.
Bioconcentration. Same as bioaccumulation;
refers to the increase in concentration of a
chemical in an organism.
Biological half-life. The time required for the
concentration of a chemical present in the
body or in a particular body compartment to
decrease by one-half through biological
processes such as metabolism and excretion.
Biological markers/monitoring. Measuring
chemicals or their metabolites in biological
materials (e.g., blood, urine, breath) to estimate
exposure, or to detect biochemical changes in
the exposed subject before or during the onset
of adverse health effects. Sometimes refers to
a specific indicator for a particular
disease/functional disturbance.
Biologically significant effect. A response in
an organism or other biological system that is
considered to have a substantial or noteworthy
effect (positive or negative) on the well-being
of the biological system. Used to distinguish
statistically significant effects or changes,
which may or may not be meaningful to the
general state of health of the system.
Biotransformation. An enzymatic chemical
alteration of a substance within the body that
generally leads to a more excretable
metabolite, sometimes producing a more toxic
form of the substance.
Block group/enumeration district (BG/ED).
The smallest geographic areas used by the
Bureau of Census in conducting the population
census. Block groups are designated for urban
areas, while enumeration districts are
designated for rural areas. BG/EDs data are
frequently incorporated into exposure models
to estimate population exposure to-
environmental pollutants.
Bronchial. Pertaining to the airways of the
lung below the larynx that lead to the alveolar
region of the lungs. Bronchial airways provide a
passageway for air movement.
Bronchiectasis. Pathological ;dilation of a
bronchus or of the bronchial tubes.
Bronchitis. Inflammation of the
membrane of the bronchial tubes.
mucous
Cancer. A malignant new growth. Cancers are
divided into two broad categories: carcinoma
and sarcoma.
Carcinogenic. Able to produce malignant
tumor growth. Operationally most benign
tumors are usually included also.
Carcinogenic process. A series of stages at
the cellular level after whichcancer will develop
in an organism. Some believe there are at least
3 stages: initiation, promotion, and
progression.While hypothesized as staged
process, little is known about specific
mechanisms of action.
Carcinoma. A malignant tumor of epithelial cell
origin (e.g., skin, lung, breast), tending to
infiltrate the surrounding tissue and give rise to
metastases.
Case-control study: A retrospective
epidemiologic study in which individuals with
the disease under study (cases) are compared
with individuals without the disease (controls)
in order to contrast the extent of exposure in
the diseased group with the extent of exposure
in the controls.
Ceiling limit. A concentration limit in the work
place that should not be exceeded, even for a
short time, to protect workers against frank
health effects.
Central nervous system. The portion of the
nervous system that includes the brain and
spinal cord, and their connecting nerves.
Chemical mixture. Any combination of two or
more substances regardless of source or.of
spatial or temporal proximity.
Chromosome. A very long molecule of DNA
complexed with protein, containing genetic
information arranged in a linear sequence.
Chromosome abnormality. A group of
conditions associated with abnormalities in the
number or structure of chromosomes. These
can be produced by insertion, deletion, or
rearrangement of chromosomal segments.
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Chronic exposure. Long-term exposure
usually lasting six months to a lifetime.
Chronic obstructive pulmonary disease
(COPD). A disease of the lung, involving
increased resistance to air flow in the bronchial
airways and loss of tissue elasticity, that leads
to decreased ability of the lungs to perform
ventilation. The pathological changes that lead
to COPD can be caused by chronic bronchitis,
pulmonary emphysema, chronic asthma, and
chronic bronchiolitis.
Cirrhosis. A liver disease characterized by
increased fibrous tissue, accompanied by other
abnormal physiological changes. Clinical signs
of cirrhosis include the loss of functional liver
cells and increased resistance to blood flow
through the liver.
Ciliated epithelial cell. A cell with cilia that
lines the tracheobronchial region of the lung.
The beating of the cilia moves mucus and
substances (such as inhaled particles trapped
on/in the mucus) upwards and out of the lung,
thereby contributing significantly to lung
clearance.
Clastogenic. Able to break chromosomes and
thereby produce chromosome abnormalities, a
form of genotoxicity. This results in the gain,
loss, or rearrangement of pieces of
chromosomes.
Clearance. The disappearance of a compound
from a specific organ or body compartment or
the whole body. In pulmonary toxicology,
clearance refers specifically to removal of an
inhaled substance that deposits on the lung
surface.
Cohort study. A study of a group of persons
sharing a common experience (e.g., exposure
to a substance) within a defined time period;
this experiment is used to determine if an
increased risk of a health effect (disease) is
associated with that exposure.
Complete carcinogen. Chemicals that are
capable of inducing tumors in animals or
humans without supplemental exposure to
other agents. Complete refers to the three
stages of carcinogenesis, initiation, promotion,
and progression which need to be present in
order to induce a cancer.
Compliance. Pulmonary compliance. The
volume change per unit of pressure change for
the lungs, the thorax, or the lungs-thorax
system. The distensibility of the lungs or
thorax.
Confidence limit. The confidence interval is a
range of values that has a specified probability
(e.g., 95 percent) of containing a given
parameter or characteristic. The confidence
limit refers to the upper value of the range (e.g.
upper confidence limit).
Control group. A group of subjects observed
in the absence of the exposure agent for
comparison with exposed groups.
Critical Endpoint. A chemical may elicit more
than one toxic effect (endpoint), even'in one
test animal, in tests of the same or different
duration (acute, subchronic, and chronic
exposure studies). The doses that cause these
effects may differ. The critical endpoint used in
the dose-response assessment is the one
that occurs at the lowest dose. In the event
that data from multiple species are available, it
is often the most sensitive species that
determines the critical endpoint. This term is
applied in the derivation of risk reference
doses.
Cross-sectional study. An epidemiologic
study assessing the prevalence of a disease in
a population. These studies are most useful for
conditions or diseases that are not expected to
have a long latent period and do not cause
death or withdrawal from the study population.
Potential bias in case ascertainment and
exposure duration must be addressed when
considering cross-sectional studies.
Cyanosis. Bluish discoloration, especially of
the skin and mucous membranes and fingernail
beds caused by deficient oxygenation of the
blood.
Cytochrome P-448 and P-450. Enzymes
which are important in the detoxification by
biotransformation of many chemical
substances. Cytochrome P-448 and P-450
enzymes, integral in the metabolic activation
and detoxification of many compounds, are
found primarily in the liver and, to a lesser
extent, in the lung and other tissues.
Cytotoxicity. Producing a specific toxic action
upon cells.
DNA. Deoxyribonucleic acid. The nucleic acid
molecule in chromosomes that contains the
genetic information. The molecule is double
stranded, with a "backbone" of phosphate and
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sugar (deoxyribose) to which the nucleotide
bases are attached. The nucleotides form a
ladder-like structure by hydrogen bonds such
that adenine (A) pairs with thymine (T) and
guanine (G) pairs with cytosine (C). The
specific sequence of nucleotide bases defines
the gene.
DNA adduct. A lesion in the DNA formed by
the covalent binding of an exogenous chemical
to one of the nucleotide bases. DNA adducts
are frequently the precursors to changes in the
sequence of nucleotides (mutations).
DNA crosslink. A lesion in the DNA formed by
the covalent binding of an exogenous chemical
to two nucleotide bases, one each on opposing
strands of the DNA. DNA crosslinks usually
prevent DNA replication and are lethal to cells
attempting to divide.
Deposition. Specific to, air toxics, the
adsorption on the respiratory tract surface of
inhaled, gaseous, or particulate pollutants.
Also, adsorption of a gaseous or particulate air
pollutant at the surface of the ground,
vegetation, or water.
Dermatitis. Inflammation of the skin.
Detoxification. Reduction of a chemical's toxic
properties by means of biotransformation
processes, to form a more readily excreted, or
a less toxic chemical than the parent
compound.
Developmental toxicity. Adverse effects on
the developing organism that may result from
exposure prior to conception (either parent),
during prenatal development, or postnatally to
the time of sexual maturation. Adverse
developmental effects may be detected at any
point in the life span of the organism. Major
manifestations of developmental toxicity
include: death of the developing organism;
induction of structural abnormalities
(teratogenicity); altered growth; and functional
deficiency.
Diffusion. Movement of a chemical substance
from areas of high concentration to areas of
low concentration. Biologically, diffusion is an
important means for toxicant deposition for
gases and very small particles in the
pulmonary region of the lungs.
Diploid. The chromosome state in which each
homologous chromosome is present in pairs.
Normal human somatic (non-reproductive)
cells are diploid (i.e., they have 46
chromosomes), whereas reproductive cells,
with 23 chromosomes are haploid.
Dispersion model. A mathematical model or
computer simulation used to predict the
movement of airborne pollution. Models take
into account a variety of mixing mechanisms
which dilute effluents and transport them away
from the point of emission.
Disposition. The movement and fate of
chemicals in the body, including absorption,
distribution, biotransformation, and excretion.
Distribution. Transport of a substance through
the body by physical means (e.g., active
transport or diffusion). Distribution is dependent
on the chemical properties of the toxicant or its
metabolites and, to some extent, the route of
exposure as well as physiologic variables.
Diuresis. Increased production of urine.
Dose-response relationship. A relationship
between: (1) the dose, often actually based on
"administered dose" (i.e., exposure), rather
than absorbed dose, and (2) the extent of toxic
injury produced by that chemical. Response
can be expressed either as the severity of
injury or proportion of exposed subjects
affected. A dose-response assessment is one
of the four steps in a risk assessment.
Dosimetry. In general, the measurement or
modeling of the amount, rate, and distribution
of a drug or toxicant especially as it pertains to
producing a particular biological effect.
Dyspnea. Difficult or labored breathing.
Edema. An accumulation of an excessive
amount of fluid in cells, tissues, or serous
cavity. Lung edema is the accumulation of fluid
in the lung.
Embryo. In mammals, the stage in the
developing organism at which organs and
organ systems are developing. For humans,
this involves the stage of development
between the second through eighth weeks
(inclusive) post conception.
Embryotoxicity. Any toxic effect on the
conceptus as a result of prenatal exposure
during the embryonic stages of development.
These effects may include malformations and
variations, altered growth, in utero death, and
altered postnatal function.
Emphysema. Chronic pulmonary disease
characterized by loss of lung function due to
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destruction of many of the alveolar walls with
resulting enlargement of the air spaces. The
total epithelial area for gas exchange in the
lungs is reduced in emphysema patients.
Endemic. Present in a community or among a
group of people; said of a disease prevailing
continually in a region.
Endocrine. Pertaining to hormones or to the
glands that secrete hormones into the blood.
Endothelial. Pertaining to the layer of flat cells
lining the inner surface of blood and lymphatic
blood vessels, and the surface lining of serosa
and synovial membranes.
Endpoint. An observable or measurable
biological or chemical event used an an index
of the effect of a chemical on a cell, tissue,
organ, organism, etc.
Environmental Fate. The destiny of a
chemical or biological pollutant after release
into the environment. Environmental fate
involves temporal and spatial considerations of
transport, transfer, storage, and transformation.
Epidemiology. The study of the occurrence
and distribution of a disease or physiological
condition in human populations and of the
factors that influence this distribution.
Epigenetic. Alterations in the expression of
genes by mechanisms other than changes in
the nucleotide sequence of DNA. The term has
historically been used in the area of embryonic
differentiation, but more recently has been
used in describing a component of the
formation of cancer.
Epithelial. Pertaining to the cell layer that
covers all internal and external surfaces of the
body, including the gastrointestinal, respiratory,
and urinary tracts.
Equilibrium. The state in which opposing
forces are exactly counteracted or balanced.
Types of equilibrium include acid-base,
colloid, dynamic, homeostatic, and chemical.
Used in risk assessment of toxic air pollutants
to generally describe the chemical equilibrium
between a pollutant in the inhaled air and the
level in the body.
Excess risk. An increased risk of disease
above the normal background rate.
Excretion. Elimination or discharge of excess
and waste chemicals from the body. Chemicals
may be excreted through feces, urine, exhaled
breath, etc..
Exposure. Contact of an organism with a
chemical, physical, or biological agent.
Exposure is quantified as the amount of the
agent available at the exchange boundaries of
the organism (e.g., skin, lungs, digestive tract)
and available for absorption.
Exposure assessment. Measurement or
estimation of the magnitude, frequency,
duration and route of exposure of animals or
ecological components to substances in the
environment. The exposure assessment also
describes the nature of exposure and the size
and nature of the exposed populations, and is
one of four steps in risk assessment.
Extrapolation. An estimate of response or
quantity at a point outside the range of the
experimental data. Also refers to the estimation
of a measured response in a different species
or by a different route than that used in the
experimental study of interest (i.e., species-
to-species, route-to-route, acute-to-
chronic, high-to-low).
Extrathoracic. Situated or occurring outside
the thorax (the part of the respiratory tract
above the trachea).
Fence Line Concentration. Modeled or
measured concentrations of air pollutants found
at the boundaries of a property on which a
pollution source is located. Usually assumed to
be the nearest location at which an exposure
of the general population could occur.
Fertility. The ability to achieve conception and
to produce offspring. For litter-bearing
species, the number of offspring per litter is
also used as a measure of fertility. Reduced
fertility is sometimes referred to as subfertility.
Fetus. The post-embryonic stage of the
developing young. In humans, from the end of
the second month of pregnancy up to birth.
Fibrosis. Formation of scar tissue in the lung
or other tissues, usually as a result of
inflammation occurring over a long period of
time.
First pass effect. Reduction in a substance's
systemic availability resulting from metabolism
or excretion by the first major organ of contact
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with such capability after the absorption
process. This phenomenon of removing
chemicals after absorption before entering the
general systemic circulation can occur in the
lung or liver.
Flash point. The lowest temperature at which
a chemical will ignite.
Forced expiratory volume (FEV). The amount
of air that can be forcefully exhaled in a
specified time, usually one second (FEVi). A
forced expiratory volume test provides an index
of lung function.
Forced vital capacity (FVC). The greatest
amount of air that can be forcefully exhaled
following maximum inhalation.
Frank effect level (PEL). Related to biological
responses to chemical exposures (compare
with NOAEL and LOEL); the exposure level
that produces an unmistakable adverse health
effect (such as inflammation, severe
convulsions, or death).
Gamma multi-hit model. A dose-response
model that can be derived under the
assumption that the response is induced if the
target site has undergone some number of
independent biological events (hits).
Functional developmental toxicity. The study
of the causes, mechanisms, and manifestations
of alterations or delays in functional
competence of the organism or organ system
following exposure to an agent during critical
periods of development pre- and/or
postnatally. This is a subset of development
toxicity.
Gamete. A mature male or female germ cell
[sperm or ovum (egg)] usually possessing a
haploid chromosome set and capable of
initiating formation of a new diploid individual
by fusion with a gamete from the opposite sex.
Gastrointestinal. Pertaining to the intestines
and stomach.
Gavage. Experimental exposure regimen in
which a substance is administered to an animal
into the stomach via a tube.
Gene. The simplest complete functional unit in
a DNA molecule. A linear sequence of
nucleotides in DNA that is needed to
synthesize a protein and/or regulate cell
function. A mutation in one or more of the
nucleotides in a genemay lead to abnormalities
in the structure of the gene product or in the
amount of gene product synthesized.
Genome. A term used to refer to all the
genetic material carried by a single gamete.
Genotoxic. A broad term that usually refers to
a chemical which has the ability to damage
DNA or the chromosomes. This can be
determined directly by measuring mutations or
chromosome abnormalities or indirectly by
measuring DNA repair, sister-chromated
exchange, etc. Mutagenicity is a subset of
genotoxicity.
GEMS (Graphical Exposure Modeling
System). An interactive computerized
management tool developed by the U.S. EPA
that ties together several previously discrete
tools into a coordinated system, allowing for
multiple types of analyses. These tools include
environmental fate and transport models,
chemical property estimation techniques,
statistical analysis, and graphical and modeling
programs.
Germ cell. A cell capable of developing into a
gamete [ovum (egg) or sperm].
Glomerulus. Part of the nephron, the basic
structure of the kidney.
Half-life. See atmospheric half-life and
biological half-life. Also, the period of time
characteristic of a radionuclide in which one-
half of the activity has decayed.
Haploid. Containing a single set of unpaired
chromosomes. Gametes (specialized
reproductive cells) are characterized as
haploid. (Compare with: diploid.)
Hazard identification. The process of
determining whether exposure to a substance
is causally related to the incidence and/or
severity of an adverse health effect .(e.g.,
cancer, birth defects, etc.). Hazard
identification involves gathering and evaluating
data on the types of health injury or disease
that may be produced by a chemical and on
the conditions of exposure under which injury
or disease is produced. It may also involve
characterization of the behavior of a chemical
within the body and the interactions it
undergoes within organs, cells, or even parts
of cells. Hazard identification is the first step in
the risk assessment process.
Hemangiosarcoma. A malignant neoplasm
characterized by rapidly proliferating,
extensively infiltrating, anaplastic cells derived
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from blood vessels and lining blood-filled
spaces.
Hema or We/no. Prefix, pertaining to blood.
Hemoglobin. The oxygen-carrying protein in
red blood cells.
Hepato. Prefix, pertaining to the liver.
Histology. The discipline that deals with the
structure of cells, tissues, and organs in
relation to their function.
Homeostasis. Maintenance of normal, internal
stability in an organism by coordinated
responses of the organ systems.
Hormone. A chemical substance, formed in
one organ or part of the body and carried in
the blood to another organ or part where it
alters the functional activity, and sometimes
the structure, of one or more organs by its
specific chemical activity.
Host defenses/systems. A complex system
that defends the body against biological or
chemical agents. Often referred to with respect
to the lungs where the system clears the lungs
of microbes and particulate pollutants. Also
refers to chemical defenses such as
antioxidant substances that defend against
oxidants such as ozone or nitrogen dioxide.
Human equivalent dose. The human dose of
an agent expected to induce the same type
and severity of toxic effect that an animal dose
has induced.
Human Exposure Model (HEM). A
mathematical model used in exposure
assessments for toxic air pollutants to quantify
the number of people exposed to pollutants
emitted by stationary sources and the pollutant
concentrations they are exposed to. Input data
include plant characteristics such as location,
emission, parameters, etc. as well as Bureau
of Census data used in the estimation of
persons exposed and appropriate
meteorological data.
Hygroscopic. Absorbing moisture from the air.
Hyper. Prefix, pertaining to a higher than
normal value.
Hyperplasia. The abnormal multiplication or
increase in the number of normal cells in
normal arrangement in a tissue.
Hypersensitivity. Exaggerated response by
the immune system to an allergen. Sometimes
used incorrectly in a non-immune sense to
indicate increased susceptibility to the effects
of a pollutant.
Hypertension. Abnormally elevated arterial
blood pressure.
Hypertrophy. Enlargement of an organ due to
increase in cell size with no change in the cell
number. For example, liver hypertrophy occurs
in mice exposed to chlorinated hydrocarbons
or to phenobarbital.
Hyperventilation. Overventilation; increased
rate of air exchange relative to metabolic
carbon dioxide production so that alveolar
carbon dioxide pressure tends to fall below
normal.
Hypo. Prefix, pertaining to a less than normal
value.
Hypox/a. Low oxygen content in a body
tissue(s); below physiologic levels.
Immediately dangerous to life and health
(IDLH). A concentration representing the
maximum level of a pollutant from which an
individual could escape within 30 minutes
without escape-impairing symptoms, or
irreversible health effects.
Immune system. All internal structures and
processes providing defense against disease
causing organisms (viruses, bacteria, fungi,
parasites). Includes nonspecific defense
mechanisms, such as interferon production,
epithelialmembranes and phagocytic cells, as
well as specific immune responses of cells
producing antibodies in response to antigens
entering the body.
Immunodeficiency. A condition resulting from
ineffective functioning of the immunological
system. Immunodeficiency may be primary
(due to a defect in the immune mechanism per
se) or secondary (dependent upon another
disease process or toxicant exposure).
Immunosuppression. Decrease of
immunologic response, usually resulting from
exposure to chemical, pharmacologic, physical,
or immunologic agents.
Incidence. The number of new cases of a
disease within a specified time period. It is
frequently presented as the number of new
cases per 1,000, 10,000, or 100,000. The
incidence rate is a direct estimate of the
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probability or risk of developing a disease
during a specified time period.
Individual risk. The increased risk for a
person exposed to a specific concentration of a
toxicant.
Indoor/outdoor ratio. The ratio of the indoor
concentration of an air pollutant to the outdoor
concentration of that pollutant.
Industrial Source Complex (ISC) model. A
Gaussian dispersion model used to predict the
movement of a plume of air pollution and
concentrations the general population may be
exposed to near a facility. There are two
versions of the ISC model, short-term and
long-term. This is a standard model used by
the U.S.EPA and incorporates detailed source
and emissions characteristics and appropriate
meteorological data.
Infertile. Lacking fertility, inability to conceive
offspring. Infertility may be temporary or
permanent; permanent infertility is termed
sterility.
Inflammation. A protective tissue response to
injury that serves to destroy, dilute, or wall off
both the injurious agent and the injured tissue.
It is characterized by symptoms such as pain,
heat, redness, swelling and loss of function.
Under some circumstances, it can be a toxic
response due to local accumulations of cells
and mediators.
Initiator. An agent capable of starting but not
necessarily completing the process of
producing an abnormal, uncontrolled growth of
tissue usually by altering a cell's genetic
material. Initiated cells may or may not be
transformed into tumors.
Interspecies. Between different species.
Interspecies scaling factors. Numerical
values used in the determination of the
equivalent doses between species, (e.g.
frequently a known animal dose is scaled to
estimate an equivalent human dose.) The U.S.
EPA's cancer risk assessment guidelines (50
FR 33992) note that commonly used dosage
scales include milligram per kilogram body
weight per day, parts per million in soil or water
or air, milligram per square meter body surface
area per day, and milligram per kilogram body
weight per lifetime. The guidelines for
carcinogen assessment generally recommend
using the surface area approach unless there
is evidence to the contrary. The dose as mg/kg
of body weight/day is generally used to scale
between species for non-cancer effects of
chemicals after dermal, oral, or parenteral
exposure.
Intramuscular. Within the muscle; refers to
injection.
Intraperitoneal. Within the membrane
surrounding the organs of the abdominal
cavity; refers to injection.
Intraspecies. Within a particular species.
Intravascular. Within the blood vessels; refers
to injection, usually into the veins (intravenous
or i.v.).
in vitro. Tests conducted outside the whole
body in an artificially maintained environment,
as in a test tube, culture dish, or bottle.
in vivo. Tests conducted within the whole
living body.
Lacrimation. Secretion and discharge of tears.
Larynx. The enlarged upper end of the
trachea, below the root of the tongue
commonly referred to as the voice box.
Latency. The period of time between exposure
to an injurious agent and the manifestation of a
response.
Lavage. A technique used to wash out a cavity
such as the stomach or a portion of the lungs
via a tube. This technique is commonly used
clinically to remove toxic substances from the
stomach. This procedure may also be used to
obtain cell populations and fluids from the iung
for experimental manipulation.
Lesion. A pathologic or traumatic discontinuity
of tissue or loss of function.
Lethal. Deadly; fatal.
L.CLQ (Lethal Concentration Low). The
lowest concentration of a chemical required to
cause death in some of the population after
exposure for a specified period of time and
observed for a specified period of time after
exposure. Refers to inhalation time exposure in
the context of air toxics (may refer to , water
concentration for tests of aquatic organisms, or
systems).
(Median Lethal Concentration). The
concentration of a chemical required to cause
death in 50% of the exposed population when
exposed for a specified time period, and
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observed for a specified period of time after
exposure. Refers to inhalation exposure
concentration in the context of air toxics (may
refer to water concentration for tests of aquatic
organisms or systems).
LDi_o (Lethal Dose Low). The lowest dose of
a chemical required to cause death in some of
the population after noninhalation exposure,
e.g., injection, ingestion, for a specified
observation period after exposure.
(Median Lethal Dose). The dose of a
chemical required to cause death in 50% of
the exposed population after noninhalation
exposure, e.g., injection, ingestion, for a
specified observation period after exposure.
Leukemia. A progressive, malignant disease of
the blood-forming tissues, marked by an
excessive number of white blood cells and
their precursors.
Lifetime. Covering the lifespan of an organism
(generally considered 70 years for humans).
Limited evidence. According to the U.S. EPA
carcinogen risk assessment guidelines, limited
evidence is a collection of facts and accepted
scientific inferences that suggests the agent
may be causing an effect but the suggestion is
not strong enough to be an established fact.
Local effect. A biological response occurring
at the site of first contact between the toxic
substance and the organism.
Logit model. A dose-response model that
can be derived under the assumption that the
individual tolerance level is a random variable
following the logit distribution.
Lower respiratory tract. That part of the
respiratory tract below the larynx.
/.owesf-oJbserved-acfverse-ef/ect level
(LOAEL). The lowest dose or exposure level of
a chemical in a study at which there is a
statistically or biologically significant increase in
the frequency or severity of an adverse effect
in the exposed population as compared with an
appropriate, unexposed control group.
Lowest-observed effect level (LOEL). In a
study, the lowest dose or exposure level at
which a statistically or biologically significant
effect is observed in the exposed population
compared with an appropriate unexposed
control group.
Lymphoma. Any abnormal growth (neoplasm)
of the lymphoid tissues. Lymphoma usually
refers to a malignant growth and thus is a
cancer.
Macrophage. A specialized cell of the immune
system capable of engulfing and digesting
foreign particles.
Male reproductive toxicity. The occurrence
of adverse effects on the male reproductive
system, which may result from exposure to
environmental agents. The toxicity may be
expressed as alterations to the male
reproductive organs and/or the related
endocrine system. The manifestation of such
toxicity may include alteration in sexual
behavior, fertility, pregnancy outcomes, or
modifications in other functions that are
dependent on the integrity of the male
reproductive system.
Malformation. A permanent structural change
in a developing organism that may adversely
affect survival, development, or function.
Compare with variation.
Malignant. A condition of a neoplasm (tumor)
in which it has escaped normal growth
regulation and has demonstrated the ability to
invade local or distant structures, thereby
disrupting the normal architecture or functional
relationships of the tissue system.
Margin of exposure (MOE). The ratio of the
no-observed-adverse-effect level (NOAEL)
to the estimated human exposure. The MOE
was formerly referred to asthe margin of safety
(MOS).
Margin of safety (MOS). The term formerly
applied to the margin of exposure concept.
Mass median aerodynamic diameter
(MMAD). Median of the distribution of mass
with respect to the aerodynamic diameter of a
particle.
Maximum individual risk (MIR). The
increased risk for a person exposed to the
highest measured or predicted concentration of
a toxicant.
Maximum likelihood estimate (MLE). A
statistical best estimate of the value of a
parameter from a given data set.
Maximum tolerated dose (MTD). The highest
dose of a toxicant that causes toxic effects
without causing death during a chronic
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exposure and that does not decrease the body
weight by more than 10%.
Meiosis. Cell and nuclear division in which the
number of chromosomes is reduced from
diploid (2n) to haploid (n). This process is
characteristic of germ cells (spermatocyte or
oocyte) division in which two successive
divisions of the nucleus produce four cells that
contain half the number of chromosomes
present in the somatic cells. Each of the four
daughter cells .obtain, at random, any one of
,the two copies of each chromosome from
parent cell. These cells may mature to sperm
or egg cells.
Metabolism. The biochemical reactions by
which energy is made available for the use of
an organism. Metabolism includes all,chemical
transformations occurring in an organism from
the time a nutrient substance enters, until it
has been utilized and the waste products
eliminated. In toxicology, metabolism of a
toxicant consists of a series of chemical
transformations that take place within an
organism. A wide range of enzymes act on
toxicants, that may increase water solubility,
and facilitate elimination from the organism. In
some cases, however, metabolites may be
more toxic than their parent compound.
Metaplasia. The abnormal transformation of an
adult, fully differentiated tissue of one kind into
a differentiated tissue of another kind.
Metastasis. The transfer of a disease, or its
local manifestations, from one part of the body
to another. In cancer, this relates to the
appearance of neoplasms in parts of the body
remote from the site of the primary tumor. This
is a characteristic of malignancy.
Microbe/microorganism. A single-cell
organism such as a virus or a bacterium.
Microenvironment. The immediate local
environment of an organism.
Minute volume. Volume of air breathed per
minute, usually liters/minute. The product of
the tidal volume (the normal volume of air
moved into and out of the lungs with each
breath) and the respiratory rate.
Mitosis. Cellular and nuclear division that
involves duplication of the chromosomes of a
parent cell, and formation of two daughter
cells. This type of cell division occurs in most
somatic cells.
MLE. See maximum likelihood estimate.
Model. A mathematical representation of a
natural system intended to mimic the behavior
of the real system, allowing description of
empirical data, and predictions about untested
states of the system.
Modifying factor (MF). A factor that is greater
than zero and less than or equal, to 10; used in
the operational derivation of a reference dose.
Its magnitude depends upon an assessment of
the scientific uncertainties of the toxicological
data base not explicitly treated with standard
uncertainty factors (e.g., number of animals
tested). The default value for the MF is 1.
Morbidity. The number of sick individuals or
cases of disease in a population.
Morphology. Study of the form or structure of
cells, tissues, organs, or organisms.
Morphometry. Quantitative measure of
morphology.
Mortality. The number of individual deaths in a
population.
Multistage model. A mathematical function
used to extrapolate the probability of incidence
of disease from a bioassay in animals using
high doses, to that expected to be observed at
the low doses that are likely to be found in
chronic human exposure. This model is
commonly used in quantitative carcinogenic
risk assessments where the chemical agent is
assumed to be a complete carcinogen and the
risk is assumed to be proportional to the dose
in the low region.
Mutagenic. Ability to cause a permanent
change in the structure of DNA. More specific
than, but often used interchangeably with,
genotoxic.
Mutation. Changes in the composition of DNA,
generally divided according to size into "gene
mutations" (changes within a single gene) and
"chromosome mutations" (affecting larger
portions of the chromosome, or the loss or
addition of an entire chromosome). A "heritable
mutation" is a mutation that is passed from
parent to offspring and therefore was present
in the germ cell of one of the parents. Somatic
cell mutations may result in cancer.
Narcosis. A disorder characterized by
drowsiness or unconsciousness, caused by the
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action of a toxicant on the central nervous
system.
Nasopharyngeal region. The area including
the nasopharynx, oropharynx, and nose. The
pharynx is the cavity situated between the
nasal cavities, mouth, and larynx, where it
divides to form the trachea and esophagus,
which accept air and food, respectively.
Necrosis. Death of areas of tissue or bone,
usually as individual cells, as groups of cells,
or in localized areas. Necrosis can be caused
by cessation of blood supply, physical agents
such as radiation, or chemical agents.
Neonatal. Newly born; in humans, up to 6
weeks of age.
A/eop/as/a. The pathologic process that results
in the formation and growth of a tumor, i.e., a
neoplasm.
Neoplasm. A new and abnormal growth of
tissue, such as a tumor.
Nephritis. Inflammation of the kidney.
Nephron. The structural and functional unit of
the kidney, consisting of capillaries and tubes
that adjust the composition of blood and form
urine.
Nephro-. Prefix, pertaining to the kidney.
Neuropathy. Functional disturbances and/or
pathological changes in the peripheral nervous
system.
Neurotoxicity. Ability to damage nervous
tissue.
Nonthreshold toxicant. An agent considered
to produce a toxic effect from any dose; any
level of exposure is deemed to involve some
risk. Usually used only in regard to
carcinogenesis.
No-observed-adverse-effect level
(NOAEL). The highest experimental dose at
which there is no statistically or biologically
significant increases in frequency or severity of
adverse health effects, as seen in the exposed
population compared with an appropriate,
unexposed population. Effects may be
produced at this level, but they are not
considered to be adverse.
No-observed-effect level (NOEL). The
highest experimental dose at which there is no
statistically or biologically significant increases
in frequency or severity of toxic effects seen in
the exposed compared with an appropriate,
unexposed population.
Nucleus. The structure within the cell that
contains the chromosomes and the nucleolus.
The nucleus controls cellular function, both
chemical reactions that occur in the cell, and
reproduction of the cell. Also, the part of an
atom containing protons and neutrons.
Obligate nose breathers. Animals that must
breathe through the nose rather than through
the mouth. Beyond the infant stage, humans
may breathe either through the nose or mouth
but this difference is significant when
comparing effects between obligate nose
breathers (e.g., rats, mice) and humans as the
nasopharyngeal region can remove a
proportion (often significant) of inhaled
toxicants before they reach the lungs. When
humans breathe through the mouth, this early
removal does not occur. Infant humans are
obligate nose breathers.
Occupational exposure limit (OEL). A
generic term denoting a variety of values and
standards, generally time-weighted average
concentrations of airborne substances to which
a worker can be exposed during defined work
periods.
Oocyte. The immature ovum.
Oncogene. A naturally occurring gene that
specifies the synthesis of a protein which is
involved in normal cellular processes.
Alterations in the structure or function of
oncogenes are associated with the
development of some cancers.
Oncogenesis. The origin and growth of a
neoplasm.
One-hit model. A mathematical model that
assumes a single biological event can initiate a
response.
Organogenesis. The development of specific
body structures or organs from undifferentiated
tissue. In humans, this relates primarily to
weeks 2 through 8 (inclusive) post conception.
Organoleptic. Affecting or involving an organ,
especially a sense organ as of taste, smell, or
sight.
Ovum. The female sex cell or gamete (egg).
Peripheral nervous system. The portion of
the nervous system outside of the brain and
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spinal cord, which includes sense organs and
the nerves controlling the body.
Pharmacokinetics. The field of study
concerned with defining, through measurement
or modeling, the absorption, distribution,
metabolism, and excretion of drugs or
chemicals in a biological system as a function
of time.
Pharynx. Passageway for air from the nasal
cavity to the larynx and for food from the
mouth to the esophagus.
Physiologically based pharmacokinetics.
Pharmacokinetics (see above) based on
measured physiological variables such as blood
flows through organs, etc.
Population variability. The concept of
differences in susceptibility of individuals
within a population to toxicants due to
variations such as genetic differences in
metabolism and response of biological tissue to
chemicals.
Portal of entry effects. Biological response at
the site of entry (e.g., the lungs, stomach) of a
toxicant into the body.
Potency. A comparative expression of
chemical or drug activity measured in terms of
the relationship between the incidence or
intensity of a particular effect and the
associated dose of a chemical, to a given or
implied standard or reference.
Prevalence. The percentage of a population
that is affected with a particular disease at a
given time.
Probit model. A dose-response model that
can be derived under the assumption that
individual tolerance is a random variable
following log normal distribution.
Promotion. The second hypothesized stage in
a multistage process of cancer development.
The conversion of initiated cells into
tumorigenic cells.
Proteinuria. An excess of serum proteins in
the urine.
Pulmonary region. The area of the respiratory
system consisting of respiratory bronchioles
and alveoli where gas exchange occurs.
gj*The symbol used to denote the 95% upper
bound estimate of the linearized slope of the
dose-response curve in the low dose region
as determined by the multistage model. ,
Reactivity. Tendency of
undergo chemical change.
a substance to
Reference dose (RfD). An estimate (with
uncertainty spanning perhaps an order of
magnitude) of the daily exposure to the human
population (including sensitive subpopulations)
that is likely to be without deleterious effects
during a lifetime. The RfD is reported in units
of mg of substance/kg body weight/day for oral
exposures, or mg of substance/m3 of air
breathed for inhalation exposures.
Renal toxicity. Ability to damage kidney cells;
kidney toxicity.
Reportable quantity. The quantity of a
hazardous substance that is considered
reportable under CERCLA. Reportable
quantities are: (1) one pound, or (2) for
selected substances, an amount established by
regulation either under CERCLA or under
Section 311 of the Clean Water Act.
Reportable quantities are measured over a
24-hour period.
Reproductive toxicity. Harmful effects on
fertility, gestation, or offspring, caused by
exposure of either parent to a substance.
Residual volume. The volume of air remaining
in the lungs after a maximal forceful exhalation.
Respiratory rate. The frequency of a
complete cycle of a breath (inhalation and
exhalation).
Restrictive lung disease Lung disease in
which the expansion of the lung is restricted
either because of alterations in the supportive
structures of the lung (parenchyma) or
because of disease of the pleura, the chest
wall, or the neuromuscular apparatus. An
example is fibrosis.
Retention. The state of being held in a
specific location. Used to refer to the amount
of an inhaled material that remains in the lung
(pulmonary retention) or to the amount of a
toxicant dose that remains in the body or body
compartment for a specified period of time.
RfD. See reference dose.
Risk. The probability of injury, disease, or
death under specific circumstances. In
quantitative terms, risk is expressed in values
ranging from zero (representing the certainty
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that harm will not occur) to one (representing
the certainty that harm will occur).
Risk assessment. The scientific activity of
evaluating the toxic properties of a chemical
and the conditions of human exposure to it in
order both to ascertain the likelihood that
exposed humans will be adversely affected,
and to characterize the nature of the effects
they may experience. May contain some or all
of the following four steps:
Hazard identification - The determination
of whether a particular chemical is or is not
causally linked to particular health effect(s).
Dose-response assessment - The
determination of the relation between the
magnitude of exposure and the probability
of occurrence of the health effects in
question.
Exposure assessment - The
determination of the extent of human
exposure.
Risk characterization - The description
of the nature and often the magnitude of
human risk, including attendant uncertainty.
Risk characterization. The final step of a risk
assessment, which is a description of the
nature and often the magnitude of human risk,
including attendant uncertainty.
Risk management. The decision-making
process that uses the results of risk
assessment to produce a decision about
environmental action. Risk management
includes consideration of technical, scientific,
social, economic, and political information.
Risk-specific dose. The dose corresponding
to a specified level of risk.
Route of exposure. The means by which
toxic agents gain access to an organism (e.g.,
ingestion, inhalation, dermal exposure,
intravenous, subcutaneous, intramuscular,
intraperitoneal administration).
Sarcoma. A malignant tumor arising in
connective tissue and composed primarily of
anaplastic cells resembling supportive tissue.
SCE. See sister chromatid exchange.
Sedimentation. Deposition of particles in the
small airways of the lungs which occurs as
gravity acts on particles in a downward
direction and buoyancy and air resistance act
in an upward direction. Also, the settling out of
particles in the atmosphere due to their
gravitational fall.
Sensitization. An allergic condition that usually
effects the skin or lungs. Once exposure to a
substance has caused a reaction, the individual
may be sensitized to that substance and
further exposure even at low levels may elicit
an adverse reaction.
Serosa. A membrane producing a serous
secretion, or containing serum or a serumlike
substance.
Short-term exposure limit (STEL). A time-
weighted average OEL that the American
Conference of Government and Industrial
Hygienists (ACGIH) indicates should not be
exceeded any time during the work day.
Exposures at the STEL should not be longer
than 15 minutes and should not be repeated
more than 4 times per day. There should be at
least 60 minutes between successive exposure
at the STEL.
Sister chromatid exchange (SCE). The
reciprocal exchange of chromosomal material
between two chromatids (longitudinal subunits
of a replicated chromosome). Increased SCE is
indicative of genotoxic effects.
Somatic cells. All cells other than germ cells
or gametes.
Spermatozoa/7. Sperm. The male sex cell or
gamete.
Spirometry. The measurement of air volumes
of the lungs. (Example, tidal volume, reserve
volume, etc.).
Squamous cell carcinoma. A malignant
neoplasm derived from squamous epithelium.
Standardized Mortality Ratio. The number of
deaths, either total or cause-specific, in a
given group expressed as a percentage of the
number of deaths that could have been
expected if the group has the same age and
sex specific rates as the general population.
Used in epidemiologic studies to adjust
mortality rates to a common standard so that
comparisons can be made among groups.
Statistically significant effect. In statistical
analysis of data, a health effect that exhibits
differences between a study population and a
control group that are unlikely to have arisen
by chance alone.
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STEL. See short-term exposure limit.
Structure-activity relationship. Relationships
of biological activity or toxicity of a chemical to
its chemical structure or substructure.
Subcutaneous. A method of exposure where
the substance is injected beneath the skin.
Subchronic exposure. Exposure to a
substance spanning approximately 10% of the
lifetime of an organism.
Surface area scaling factor. The intra- and
interspecies scaling factor most commonly
used for cancer risk assessment by the U.S.
EPA to convert an animal dose to a human
equivalent dose; milligrams per square meter
surface area per day. Body surface area is
proportional to basal metabolic rate; the ratio of
surface area to metabolic rate tends to be
constant from one species to another. Since
body surface area is approximately proportional
to an animal's body weight to the 2/3 power,
the scaling factor can be reduced to milligrams
per (body weight)2''3.
Synergism. A pharmacologic or toxicologic
interaction in which the combined effect of two
or more chemicals is greater than the sum of
the effect of each chemical alone. (Compare
with: additivity, antagonism.)
Systemic. Pertaining to or affecting the body
as a whole or acting in a portion of the body
other than the site of entry. Used to refer
generally to non-cancer effects. (Compare
with portal-of-entry effects.)
Target organ/system. An organ or functional
system (e.g., respiratory, immune, excretory,
reproductive systems) which demonstrates
toxicity to a specific chemical; not necessarily
the organ/system with the highest
accumulation of the chemical, but rather that
which elicits a toxic response(s) of concern.
(Toxic dose low). The lowest dose of a
substance required to cause a toxic-effect in
some of the exposed population.
Teratogenicity. The property of a chemical to
cause structural or functional defects during
the development of an organism.
Threshold Limit Value (TLV). The
concentration of a substance below which no
adverse health effects are expected to occur
for workers assuming exposure for 8 hours per
day, 40 hours per week. TLVs are published by
the American Conference of Governmental
Industrial Hygienists (ACGIH). This listing may
be useful in identifying substances used in the
workplace and having the potential to be
emitted into the ambient air.
Threshold toxicant. A substance showing an
apparent level of effect that is a minimally
effective dose, above which a response
occurs; below that dose no response is
expected.
Tidal volume. The amount of air that is inhaled
or exhaled during one breath; in humans,
approximately 0.5 liter.
Time-weighted average (TWA). An
approach to calculating the average exposure
over a specified time period.
Toxicology. The multidisciplinary study of
toxicants, their harmful effects on biological
systems and the conditions under which these
harmful effects occur. The mechanisms of
action, detection, and treatment of the
conditions produced by toxicants are studied.
Tracheobronchial region. The area of the
lungs including the trachea (windpipe) and
conducting airways (bronchi, bronchioles, and
terminal bronchioles).
Tumor. An abnormal growth of tissue; a
neoplasm.
Uncertainty. In the conduct of risk assessment
(hazard identification, dose-response
assessment, exposure assessment, risk
characterization) the need to make
assumptions or best judgments in the absence
of precise scientific data creates uncertainties.
These uncertainties, expressed qualitatively
and sometimes quantitatively, attempt to define
the usefulness of a particular evaluation in
making a decision based upon the available
data.
Uncertainty factor (UF). One of several,
generally 10-fold factors, applied to a NOAEL
or a LOAEL to derive a reference dose (RfD)
from experimental data. UFs are intended to
account for (a) the variation in the sensitivity
among the members of the human population;
(b) the uncertainty in extrapolating animal data
to humans; (c) the uncertainty in extrapolating
from data obtained in a less-than-lifetime
exposure study to chronic exposure; and (d)
the uncertainty in using a LOAEL rather than a
NOAEL for estimating the threshold region.
Unit cancer risk. A measure of the probability
of an individual's developing cancer as a result
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of exposure to a specified unit ambient
concentration. For example, an inhalation unit
cancer risk of 3.0 x 1(H near a point source
implies that if 10,000 people breathe a given
concentration of a carcinogenic agent (e.g., u1
g/m3) for 70 years, three of the 10,000 will
develop cancer as a result of this exposure. In
water the exposure unit is usually 1 pg/l, while
in air it is 1 ug/m3.
Upper Bound Cancer Risk-assessment. A
qualifying statement indicating that the cancer
risk estimate is not a true value in that the
dose-response modeling used provides a
value which is not likely to be an underestimate
of the true value. The true value may be lower
than the upper bound cancer risk estimate and
it may even be close to zero. This results from
the use of a statistical upper confidence limit
and from the use of conservative assumptions
in deriving the cancer risk estimate.
Upper respiratory tract. The structures that
conduct air into the lungs, including the nasal
cavity, mouth, pharynx, and larynx.
Variation. A divergency in the developing
organism beyond the usual range of structural
constitution that may not adversely affect
survival or health. A specific category in the
evaluation of developmental effects. (Compare
with malformation.)
Vasoconstriction. Narrowing of a blood vessel
resulting in decreased blood flow.
Ventilation. The movement of air between the
lungs and the ambient air.
Vital capacity. The maximal volume of air
exhaled after the deepest inspiration without
forced or rapid effort. In adult humans,
generally 5 liters.
Weibull model. A dose-response model of
the form:
P(d) = 1 - exp(-bdm)
where P(d) is the probability of
cancer due to a continuous
dose rate d, and b and m are
constants.
Weight-of-evidence. The extent to which
the available biomedical data support the
hypothesis that a substance causes an effect
in humans. For example, the following factors
increase the weight-of-evidence that a
chemical poses a hazard to humans; an
increase in the number of tissue sites affected
by the agent; an increase in the number of
animal species, strains, sexes, and number of
experiments and doses showing a response;
the occurrence of a clear-cut dose-response
relationship as well as a high level of statistical
significance in the occurrence of the adverse
effect in treated subjects compared with
untreated controls; a dose related shortening of
thetime of occurrence of the adverse effect;
etc.
Xenobiotic. A substance not normally present
in the environment, such as a pesticide or
pollutant.
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Section 2
Discussion of Related Terms Frequently Encountered in Health, Exposure, and
Risk Assessments
This section presents comparisons of related' risk
assessment, exposure assessment, and biological
terms. Each comparison provides detailed definitions
of the terms and explains how they are used in
health, exposure or risk assessment.
Cohort Compared with Case-control Studies
Cohort studies are a direct approach to determining
whether a given exposure increases the risk of
disease. Groups that are free of the disease in
question, both exposed and unexposed, but
comparable in every respect that could influence risk
estimation are followed through time for observation
of the, development of disease. Difficulties can arise
from the choice of the exposed and unexposed
cohorts, e.g., whether they are representative of the
population from which they are selected; the expense
of the undertaking and the time necessary to observe
an effect, especially that of a chronic disease such as
cancer. Frequently, the time to conduct the study can
be shortened by proper selection of a population with
documented past exposure sufficiently antecedent
that the health consequences are manifest in the
present.
Case-control studies are an indirect approach to
evaluation of exposure versus enhanced risk of
disease. Persons who have been identified as having
a disease are matched with persons who are
healthy, but comparable with respect to factors that
might be related to the disease or the exposure.
Case-control studies, intrinsically retrospective, are
relatively inexpensive, quick, and most often useful
for identifying suspect risk factors. The results
provide direct measurement of the frequency of
exposure in the diseased group versus that of the
healthy controls. In some instances, the calculated
exposure rates can be employed to estimate the risk
of disease attributable to the suspect agent.
Thus, an individual enters a case-control study on
the basis of having or not having a disease or health
effect, while an individual enters a cohort study on the
basis of having or not having an exposure or risk
factor. The case-control study is always retro-
spective, while the cohort study may be either
retrospective or prospective. Both types of studies
use control groups.
Case-control and cohort studies each have distinct
advantages and disadvantages. The cohort study can
provide accurate information on exposure, can assess
multiple health effects from a particular exposure, and
is useful when the exposure under study can be
successfully isolated. However, the cohort study is
often lengthy, expensive, and may require large
samples or long follow-up to observe health effects.
The case-control study is useful when the health
effect under study is rare or can otherwise be isolated
from other diseases, when there is a long latency
period for the disease in question, and when there
are multiple exposures that contribute to the disease
under study. Disadvantages of the case-control
study include the difficulties of reconstructing an
accurate exposure history for the cases and problems
in proper selection of controls.
Cohort Studies Compared with Clinical Studies
A cohort study is an epidemiologic study in which
individuals are characterized by their risk factors or
exposure status, and are followed forward in time to
identify subsequent cases of disease or death. For
example, a cohort study might follow a cohort of
Vietnam veterans exposed to Agent Orange, and a
control group (veterans not exposed to Agent
Orange), to determine if there is an increased
incidence of disease or adverse health effects in the
exposed group. A cohort study may be prospective,
starting from the present and going forward to a
future date, or retrospective, when both the exposure
and the health effect have occurred in the past.
A clinical study (also called an experimental or
intervention study) has objectives that are analogous
to a cohort study, except that the investigator controls
or adjusts the dose (exposure) or selects the risk
factor under study, and assigns the subjects, usually
at random, to be either exposed to the agent under
test or to a sham (control). The biological effects in
the exposed group and the control group are then
statistically compared; depending on the study,
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individual comparisons may be made or post-
exposure values may be compared with pre-
exposure values for the same individual. Clinical
studies are usually undertaken when there is a large
body of other clinical, toxicologic, and epidemiologic
evidence that points to an association between an
exposure and a health outcome. Clinical studies are
considered the best basis for establishing a statistical
association between dose or exposure and effect in
humans, since the study groups are selected
randomly and the level of exposure is controlled.
Epidemiology Compared with Toxicology
Epidemiology is the study of the distribution and
determinants of health and diseases in a population.
A basic tenet of epidemiology is that diseases do not
occur randomly, but are associated with risk factors,
such as exposure to pathogens or toxicants.
Historically, epidemiology developed as a way to
reveal the causes of epidemics of infectious disease,
such as outbreaks of cholera linked to unsanitary
water supplies. Today, epidemiology is also used to
discover associations between noninfectious disease
or health effects (cancer, heart disease, injuries) and
exposure to risk factors (e.g., environmental, occu-
pational, diet, heredity, etc.).
Descriptive epidemiology looks at differences in
disease rates among different groups, in different
places, and over time to generate hypotheses about
disease causation. Analytic epidemiologic studies
compare two groups of people who are alike except
for either (1) their exposure to a risk factor, or (2) the
presence of a disease or health effect. Statistical
methods are then used to determine whether an
association exists between a risk factor and a disease
or other health outcome. Epidemiologic studies must
attempt to take into account any confounding
variables of effect modifiers, which are factors that
are associated with both the exposure and the health
effect under study. For example, a study to determine
the association between radon exposure in homes
and lung cancer should take into account the smoking
habits of the study populations.
While properly designed and conducted epidemiologic
studies may be expensive and lengthy, they are an
important source of data for risk assessments
because they provide human data. Positive
epidemiologic studies are generally treated as the
most conclusive evidence for a particular disease. A
negative result in a particular study does not mean
there is no human health risk, particularly if there is
evidence of the disease from animal studies.
Toxicology is the science that studies the harmful
effects of substances on an organism. In toxicologic
studies, scientists examine the responses of
microorganisms, cells, plants, animals, or humans
that have been exposed to a measured dose of a
substance. Toxicologic studies provide precise
information on how health effects vary with exposure
levels because the exposure levels, the study
population, and other experimental conditions are
carefully controlled. Toxicology draws from the fields
of chemistry, biochemistry, and pharmacology to
investigate the metabolism and modes of action of
toxic substances.
In vitro toxicologic tests, which assess the effects of
toxicants on microorganisms or living cells, are a
rapid and less expensive means of assessing some of
the effects of a toxicant in a test system other than
an intact animal or human.. In vitro studies make use
of cell culture systems, cell homogenates, perfused
organs, subcellular fractions, and microorganisms. In
vivo tests examine the effects of toxicants on intact
living beings, including humans. In vivo studies can
provide dose-response information about biological
processes that involve complex metabolic pathways
and interactions, endocrine and immune regulation,
and multiple tissues or organs, and can help
determine whether a substance can cause genetic
and/or long-term effects. Both in vitro and in vivo
studies are important in determining mechanisms of
toxicity, that is, how a substance is absorbed into a
tissue, how it interacts with tissues or other
substances, and how it is metabolized and eliminated.
In vitro studies allow the understanding of the
mechanism of action in some phases of the overall
metabolism and disposal of a substance.
Data from both epidemiologic and toxicologic studies
are assessed qualitatively to determine the overall
weight-of-evidence as to whether or not a
particular chemical is potentially hazardous to
humans. The qualitative assessment, also referred to
as the hazard identification step of a risk assessment,
should include an evaluation of the strength of the
association between exposure to a toxicant and
elicitation of a response (e.g., high statistical signif-
icance in relevant studies, a clear dose-response
relationship, etc.), consistency (e.g., multiple species,
multiple routes of exposure, etc.); and biological
plausibility. This includes consideration of supportive
evidence (e.g., structure activity relationships, in vitro
tests, pharmacokinetic data, etc.). In addition to a
qualitative assessment, data from epidemiologic and
toxicologic studies may be Used in a quantitative
analysis, also referred to as the dose-response
assessment step of a risk assessment.
The use of epidemiologic and toxicologic studies have
limitations that must be considered. While
epidemiology provides valuable data on response in
human groups, it cannot assess how toxicants affect
individuals, or explain individual variation within a
population. In vivo toxicologic studies may provide
information on the response of organisms to
toxicants, but extrapolation from the test species to
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humans is required, with all the inherent uncertainties
such extrapolation implies.
Parameters: Most Sensitive Compared with Most
Critical Compared with Most Selective
Changes in physiologic and biologic parameters are
used by scientists to detect adverse effects resulting
from exposure to toxicants. These parameters can be
used to screen individuals who may be at risk due to
exposure to specific toxicants. The following
parameters are frequently identified:
* The mosf sensitive parameter is the effect that
is first detectable following the exposure, or the
effect that occurs at the lowest exposure level.
• The most critical parameters are indicators of
the most serious health effects.
• The mosf selective parameters give scientists
the most information about specific effects.
LOAEL Compared with NOAEL
The lowest-observed-adverse-effect level
(LOAEL) is the lowest dose or exposure level to a
chemical at which there is a statistically or biologically
significant increase in the frequency or severity of
adverse effects in the exposed population as
compared with an appropriate control group.
The no-observed-adverse-effect level (NOAEL) is
the highest dose or exposure level to a chemical at
which there is no statistically or biologically significant
increase in the frequency or severity of an adverse
effect observed between the exposed population and
its appropriate control group. Effects may be
produced at this level, but, based on scientific
judgment, they are not considered to be adverse
(such as the appearance of a dull coat on a
laboratory rat or the change of an enzyme activity in
blood).
The NOAEL is often used to obtain a quantitative
estimate of exposure levels at which no adverse
effects are expected to occur in humans. Generally,
more than one species is studied, and the highest
dose at which the most sensitive species shows no
adverse effect is divided by appropriate uncertainty
factors to derive a reference dose (RfD). It should be
noted that the NOAEL gives no quantitative or
qualitative indication of toxicity that occurs above the
NOAEL. In the absence of an identifiable NOAEL, a
LOAEL may be used to derive an RfD. In this case,
an additional uncertainty factor would be used to
account for calculating from a LOAEL versus a
NOAEL.
LD Compared with LC
The LDso (Median Lethal Dose) is the single dose
(i.e., mg/kg) of a toxicant that will cause death in 50%
of the exposed animals over a specified observation
period. This test is generally used when the route of
administration is oral, dermal, or parenteral (e.g.,
intravenous, subcutaneous, intramuscular), and is
usually the first experiment performed with a new
chemical. Different doses that are estimated to
produce between 10 and 90% mortality are
administered to test groups of animals. A dose-
response curve is derived plotting the chemical
concentration given (dose) versus the death rate
(response). The LDso is obtained from this curve
using statistical procedures.
The LCso (Median Lethal Concentration) is the
concentration (i.e., parts per million) of a toxicant that
will cause death in 50% of the exposed animals over
a specified exposure and observation period. This test
is generally used when the route of exposure is
inhalation, but is also used for aquatic toxicity testing
(when the exposure route is water). As with the LDso,
different concentrations that are estimated to produce
between 10 and 90% mortality are administered to
test groups of animals. A dose-response curve is
generated and the LCso is obtained from this curve
using statistical procedures.
These tests have been used to determine the relative
toxicity of various substances, i.e., categorizing
chemicals in order from "extremely toxic" to
"relatively harmless." For example, the LDso of an
"extremely toxic" substance might be 1 milligram or
less per kilogram of body weight (mg/kg), while the
LDso °f a "relatively harmless" substance might be
more than 15 grams per kilogram (g/kg). However,
the LDso and LCso are of limited usefulness for
several reasons: (1) effects other than lethality (i.e.,
chronic effects) may be more important to consider
for a particular chemical; (2) LDso ar|d LCso levels
are amounts that are rarely encountered in the
environment; (3) LDsp and LCso levels do not
necessarily allow predictions of relative toxicity at
lower doses (depending on the slope of the dose-
response curve); and (4) LDso and l-Cso levels can
vary widely from species to species. ;
The LD[_o (Lethal Dose Low) is the lowest dose of a
substance introduced by any route other than
inhalation, over any given period of time, that causes
death in humans or animals over a specified
observation period. The LC|_o (Lethal Concentration
Low) is the lowest concentration of a substance In air
that causes death in humans or animals. The
exposure period for calculating the LC may be less
than 24 hours (acute exposure) or greater than 24
hours (subchronic or chronic exposure).
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Additive, Synergistic, and Antagonistic Effects
An additive effect is a pharmacologic or toxicologic
interaction in which the combined effect of two
chemicals is equal to the sum of the effect of each
chemical given alone.
A synergistic effect occurs when the combined effect
of two chemicals is greater than the sum of the effect
of each chemical given alone. For example, the
solvent carbon tetrachloride and ethanol each
produce liver damage, but this effect is greatly
enhanced if these two substances are present
together.
An antagonistic effect occurs when two chemicals
given together interfere with each other's actions, or
one interferes with the action of the other chemical.
Thus, the combined effect of two chemicals is less
than the sum of the effect of each chemical given
alone. Mechanisms that produce antagonistic effects
include (1) change in the disposition of a toxicant; (2)
interaction of two chemicals to produce a less toxic
substance; (3) counterbalancing of physiologic
effects; and (4) binding of two chemicals at the same
receptor. The production of antagonistic effects is the
basis for antidotes.
Mitosis and Meiosis
Mitosis is the division of a somatic cell into two
daughter cells, which have the same chromosomal
composition as the parent cell (a pair of each
chromosome, or the diploid number). Mitosis is the
basis for the perpetuation of genetic material in
somatic cells.
Meiosis occurs when primitive germ cells (oocytes
and spermatocytes) undergo two successive divisions
resulting in four cells with half the normal number of
chromosomes (the haploid number). Each of these
cells contains, at random, only one of the two copies
of each chromosome from the parent cell. These
cells may mature to sperm or egg cells. The random
assortment and recombination of chromosomes are
responsible for the normally observed variability of
individuals in a population.
Toxicants can act on the genetic material during both
mitosis and. meiosis. Mutations that occur during
mitosis in somatic cells are not inherited by offspring
but may result in cell death, or other illness, or non-
hereditary developmental defects if they occur in the
early embryo. Mutations that occur during meiosis
can be passed on to future generations. Meiosis and
mitosis are very susceptible stages for chemical
toxicity.
Threshold Compared with Nonthreshold
A threshold dose is the minimally effective dose of
any chemical that is observed to produce a response,
(e.g., enzyme change, liver toxicity, death). For most
toxic effects, except possibly for carcinogenesis,
there appear to be threshold doses. The lack of
observable toxic effects following exposure to
concentrations below the threshold dose may be
related to (1) physiologic adaptations or homeostatic
mechanisms that compensate for any slight effects;
(2) failure of a sufficient dose to reach the target
organ; (3) normal repair processes that rapidly correct
any damage that does occur; or (4) lack of sensitivity
of the measurement method. ., • .
Nonthreshold substances are those substances that
are known or assumed to have some risk of response
at any dose above zero. While some scientists
believe that thresholds exist for some carcinogens, in
general, carcinogens and mutagens are classified as
nonthreshold substances. This is because (1-) if an
effect is caused by a single, irreversible molecular
interaction of a toxicant with a target cell, there would
be no threshold for that toxicant. It is believed that
cancer can arise from a single cell in which the DNA
has been irreversibly altered (a mutagenic effect) by a
very small amount of a carcinogenic substance; (2)
dose-response data from many epidemiologic
studies of carcinogens fit mathematical models that
are linear with no apparent threshold; and (3) even if
thresholds could be determined for individuals,
genetic variation within a population would make it
difficult to determine a no-effect threshold for a
population.
Benign Compared with Malignant
A benign tumor is a neoplasm whose morphological
and behavioral characteristics, differ only minimally
from the tissue from which it originates. A benign
tumor may expand but remains encapsulated and
does not invade neighboring tissues or metastasize
(produce secondary growths far away from the
original tumor). The presence of benign tumors may
be life threatening, but not to the degree associated
with malignant tumors. Experimentally, it has been
argued that some benign tumors in animals may
actually be an intermediate stage in the natural
progression towards cancer development.
A malignant tumor is a neoplasm that shows marked
cellular atypia and marked deficiency of
differentiation. The cells have the properties of
anaplasia, invasiveness, and metastasis. The term
cancer is equated with malignant tumors.
It has not yet been definitely established whether the
development of benign tumors represents a risk
factor for carcinogenicity. However, EPA generally
adopts the policy that the presence of benign tumors
can be taken as an indication that a cancer hazard
exists, unless there is evidence to the contrary.
Toxicants that produce either benign or malignant
tumors in laboratory animals tend to be designated as
potential human carcinogens. • '
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Exposure Coir;parecs with Dose
Exposure is an event in which an organism comes
into contact with a chemical or "physical agent
Exposure can occur through ingestlon, inhalation,
dermal absorption, or injection.
Dose is the amount of a chemical substance taken in
the body. The route of exposure generally impacts
the extent of absorption and therefore the absorbed
dose. The quantity can be further defined in several
terms of quantity, including per unit body weight, per
body-surface-area of the test animal, and per
region of the lung per minute.
Dose as well as exposure, must be considered in
assessing risk, because (1) a toxicant must reach
biologic receptors to elicit a rosponse; (2) ihe
production of a response and the degree of response
are related to the dose of the toxicant at the receptor;
and (3) the exposure concentration and the route of
exposure significantly affect the dose of the toxicant
at the receptors.
Sensitive Compared with Sensitization
An individual is sensitive to a toxicant if he or, she
shows a biologic response following exposure to that
substance. Sensi'cization is an allergic response
involving the immune system. Sensitization reactions
can range from minor skin irritation to death.
Quanta! Dose-response Compared with Graded
Dose-Response
The dose-response relationship is the relationship
between the degree of response by an organism or
population to a toxicant and the amount of the
toxicant administered. Quantal dose-response
involves those responses that are "all-or-none,"
such as death or development 'of cancer. Most
animals respond in the middle portion of the dose
range, with smaller numbers at the low and high
extremes of the dose range.
Graded dose-responses are those responses that
occur continuously over a range, such as blood
pressure, enzyme level, and pathologic changes.
Some graded responses can be transformed into
qUantal responses. The responses of a large number
of test animals can be quantified and the standard
deviation (measure of variability) determined.
Epigenetic {Nonmutagenic) Carcinogens
Compared with Mutsgenic Carcinogens
As more chemical carcinogens (usually as determined
in rodent bioassays) have been tested and found
negative in short-term mutagenicity tests, it has
been suggested that carcinogens be classified as
either rnutagenic or nonmutagenic. iVIutagenic
carcinogens interact with and alter the primary
structure of DNA, causing a heritable alteration. This
includes both direct-acting chemicals which can
react directly with DNA, and indirect-acting
chemicals, which must be metabolically converted to
a reactive form that alters the DNA, as well as other
(often, inorganic) chemicals, which cause incorrect
replication of DNA. Somatic mutation is generally
considered the first step in the carcinogenic process
and rnutagenic agents are often referred to as
initiators.
Nonmutagenic carcinogens include .those chemicals
that act initially through mechanisms such as
hormonal imbalance or suppression of the immune
system. Ultimately, however, the effect of these
nonmutagenic agents would have to become fixed as
a heritable alteration for cells to progress to cancer.
Also included as non-mutagenic carcinogens are
chemicals referred to as promoters. These chemicals
are thought to act on pre-existing genetically altered
(mutated) cells (i.e. those cells having altered DNA)
to complete the cancer progress.
It should be recognized that many scientists do not
believe that the dichotomous classification of
carcinogens into rnutagenic and nonmutagenic is
really indicative of mechanism of action. Indeed, there
does not exist a precise set of criteria for defining
nonmutagenic. The number of available genotoxicity
tests is extremely large and the probability of a
common data base for any but a few is very small.
initiators and Promoters
The cancer process is now widely accepted as being
a multistage process,, although the precise
demonstration of this remains a research pursuit. The
basic components of the stages are thought to
involve: Initiation, Promotion, and Progression. The
evidence for multiple stages is based on many
experimental in vivo and in vitro observations since
the 1920'Si Initiators (I) are chemical substances
which can start the cancer process. Effects caused
by initiators, e.g., mutagenieity, are not reversible in
nature, so that once exposed a tissue is committed to
possible oncogenesis. Promoters (P) are chemicals
which enhance the chances that cancer can happen.
This enhancement occurs in initiated tissues, but not
in non-initiated tissues. Promoter effects seem, to be
reversible, require (relative to I's) large exposures to
exert their promoting effects and operationally exhibit
dose thresholds, i and P can happen at different
times in the life history of the tissue. Progressors (M)
are compounds which interact with , initiated and
promoted tissue to bring about (M)alignancy from
benign tumors. A compound possessing I + P + M
is called a complete carcinogen. A complete
carcinogen is of greatest concern usually because np
other factors need be present in normal tissue in
order to start and carry through the oncogenic
process. The current practice is to assume no dose,
no matter how small, is safe for complete
carcinogens.. Current carcinogenesis models include
temporal sequence: I + P + M = cancer. It should
be kept in mind that each of these gross stages (I, P
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and M) are further divisible by hypothesis into a
number of cellular responses in the progressive loss
of cellular control characteristic of cancer.
While the multistage process can be grossly
observed, primarily from biomarker studies, the exact
nature of the carcinogenic process is relatively
unknown. The ability to clearly demonstrate that a
compound has one and only one of the I, P or M
characteristics is the subject of scientific research.
The conventional chronic animal bioassay program,
(i.e., 2 year rat or mouse bioassay) can only
demonstrate that an agent is or is not carcinogenic.
Also, it has been suggested that regulatory
distinctions can be made based on these
carcinogenic mechanisms. However, this proposal
remains controversial. Some scientists argue, for
example, that many carcinogens affect both initiation
and promotion, and promoters (such as dioxin) may
themselves be very potent. U.S. EPA generally
considers substances found to be carcinogenic in
animal tests to be complete carcinogens "unless
there is definitive evidence to the contrary."
Qualitative Compared with Quantitative Risk
Assessment
A qualitative risk assessment, also referred to as
hazard identification, attempts to answer the question:
Does exposure to a specified hazard cause adverse
health effects (such as cancer)? A qualitative
determination of risk may entail some interpretation,
such as whether animal carcinogens are presumed to
be human carcinogens, or whether benign tumors in
animals represent potential human carcinogenicity.
A quantitative risk assessment begins with the
assessment that a hazard does cause adverse health
effects, and asks the question: What is the magnitude
of the risk posed by that hazard? The quantitative
assessment includes development of a mathematical
description of the dose-response curve, extra-
polation, where necessary, from animal data to
humans, estimation of human exposurelevels, and,
uses all this information for estimating individual and
population risks.
Like the qualitative assessment, the quantitative
assessment often involves making choices among
different scientifically plausible hypotheses. For
example, judgments may be made as to what dose-
response models should be used to extrapolate from
doses used in animal tests to lower doses generally
encountered by humans; or inferences may be made
as to how to extrapolate exposure measurements
from a small segment of a population to the entire
population.
Risk Assessment Compared with Risk
Management
Risk assessment is the process of determining the
potential adverse health effects of human exposure to
environmental hazards. Risk assessment includes
four steps:
(1) Hazard Identification. This is the process of
determining whether exposure to an agent can
cause an increased incidence of adverse health
effects. It involves the use of epidemiologic data,
in vitro studies, animal studies, and comparison
of molecular structure with known chemical
hazards.
(2) Dose-response Assessment. This is the
process of characterizing the relationship
between the dose of a toxicant received and the
incidence of adverse health effects in exposed
populations. This step usually requires extra-
polation of data from animal studies to humans
and from high doses to low doses.
(3) Exposure Assessment. This is the process of
measuring or estimating the intensity, duration,
and frequency of human exposure to a toxicant.
(4) Risk Characterization. This is the final step of
risk assessment and is the process of estimating
the magnitude of the public health problem that
results from the hazard. It involves the com-
bination of the hazard identification, dose-
response assessment, and the exposure
assessment. Thus, the final expressions of
health risks are derived in this step.
Risk management is the decision-making process in
which an action is taken or a policy developed once a
risk has been determined to exist. It integrates the
risk assessment with technical, political, social, and
economic issues. Risk management is also a means
of setting priorities among possible actions for a
toxicant or source. Risk management must take into
account the uncertainties associated with various
assumptions and judgments made in each step of the
risk assessment process.
Population Threshold Compared with Individual
Threshold
An individual threshold is the dose of a toxicant below
which no health effects occur in a given individual.
The population threshold is the dose of a toxicant
below which no effect will occur throughout a
population. The individual and population thresholds
can be quite different due to genetic variability in a
population, differences in age, sex, and other factors
associated with differing responses to a toxicant (e.g.,
health status or genetic makeup). [ For carcinogens,
many scientists believe that even if a threshold effect
could be determined for individuals, it would be
difficult to demonstrate a threshold for a population
because of genetic differences among individuals and
because of the multiplicity of human exposures.
22
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Measurement Compared with Modeling
Measurement (monitoring may also be used to
describe this process) is the process of directly
ascertaining the amount or concentration of a toxicant
in the environment, whereas modeling involves the
use of mathematical and/or computer simulation to
predict the movement and fate of environmental
toxicants. Because with direct measurement (i.e.,
monitoring) it is often difficult to fully assess
exposure, or because there are no available
measurement methods, models are frequently used in
environmental risk assessment to estimate exposure.
The results of exposure models may be used in
regulatory decision-making. However, the use of
models introduces numerous uncertainties and
assumptions that are not present with measurement,
including use of average meteorological data and
emission estimates.
Aggregate Compared with Individual Risk
The individual risk is the probability of adverse health
effects occurring in a given individual as a result of
exposure to a toxicant, while the aggregate risk is the
probability of an increased incidence of adverse
health effects in a population or specific sub-
populations exposed to a toxicant. It is difficult to
determine accurately individual risk from the
aggregate risk because of factors such as genetic
variability, age, sex, multiplicity of exposures, and
other factors that affect individual response to
toxicants.
23
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Section 3
References
This section presents brief descriptions and ordering information for references that are useful in understanding
health, exposure, and risk assessments for toxic air pollutants. It includes textbooks, handbooks, EPA
documents, and other reference books.
Air Pollution Assessment Methodology and Modeling, Erich Weber, ed. New York: Plenum
Press, 1982.
Plenum Publishers
233 Spring Street
New York, NY 10013
212-620-8000
Plenum: $65.00; no quantity discount; S&H approximately $2.00 ea/copy
Report of a NATO Committee on the Challenges of Modern Society (CCMS) pilot study
on air pollution. Discusses air quality management systems, air quality modeling, and
assessment methodology.
Carcinogens: Identification and Mechanisms of Action, Griffin, C. and C. Shaw, eds. Raven
Press: New York, 1978.
Raven Press
1185 Avenue of the Americas
New York, NY 10036
212-930-9500
Raven: $82.50; no quantity discounts; S&H $2.00 ea/copy
A compilation of reports from the 31st Annual Symposium on Fundamental Cancer
Research. Emphasis is on the identification of environmental carcinogens; mechanisms
of carcinogenesis; genetics of carcinogenesis; and cellular and molecular markers of
the carcinogenic process.
Casarett and Doull's Toxicology: the Basic Science of Poisons, 3rd ed. Curtis D. Klassen,
Mary O. Amdur and John Doull, eds. Riverside, New Jersey: Macmillan Publishing
Co., 1986.
ISBN: 0-02-364650-0
Macmillan Publishing Co.
Front and Brown St.
Riverside, NJ 08075
212-702-2000
Macmillan: $54.95/ea; no quantity discount; S&H (UPS) 6% of order
A textbook that covers the general principles of toxicology, the types of injury produced
by toxins in specific organs and organ systems, specific classes of toxins,
environmental toxicology, and applications of toxicology in the health sciences.
25
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Catalog of Teratogenic Agents, 5th ed. Thomas H. Shepard. Baltimore, Maryland: Johns
Hopkins University Press, 1986.
ISBN: 0-8018-3350-7
Johns Hopkins University Press
701 W. 40th Street, Suite 275
Baltimore, MD21211
301-338-6960
Johns Hopkins: $45/ea; no quantity discount; S&H $2.50/ea copy
Lists information on teratogenicity for over 600 agents. Included in the listing are
chemicals, drugs, physical factors, and viruses. Presents information on experimental
data and selected literature references for each substance.
Clinical Toxicology of Commercial Products, 5th ed. Robert E. Gosselin, Harold C. Hodge,
Roger Smith, and Marion N. Gleason. Baltimore, Maryland: Williams and Wilkins Co.,
1984.
ISBN: 0-683-03632-7
Williams and Wilkins
428 E. Preston St.
Baltimore, MD 21201
800-638-0672
W&W: $120/ea; 10+ copies 20% discount; S&H (UPS) $3/ea copy
Provides information necessary for dealing quickly with acute chemical poisonings
arising from misuse of commercial products. Provides a list of trade name products and
their ingredients; addresses and phone numbers of companies for use when product
descriptions are not available; sample formulas with an estimate of toxicity of each
formula; toxicologic information; and recommendations for treatment and care. Also
provides some information on chronic toxicity and teratogenic, mutagenic and
carcinogenic effects.
Concepts of Genetics, William S. Klug and Michael R. Cummings. Columbus.Ohio: Charles
E. Merrill Publishing Company, 1983.
ISBN: 0-673-18680-6
Scott Foresman
1900 East Lake Ave.
Glenview, IL 60025
312-729-3000
Scott Foresman: $41.00 each, S&H (UPS) 6% of order
A textbook presenting the basic concepts of genetics, including heredity; DNA; genetic
variation; gene structure, function and regulation; and genetics of organisms and
populations.
Determining Risks to Health: Federal Policy and Practice, U.S. Department of Health and
Human Services, Task Force on Health Risk Assessment, 1986,
Auburn House Publ. Co. 508-785-2220
14 Dedham St. 800-223-2665
Dover, MA 02030-0658
Auburn House: Trade $32/ea; paper $16.95/ea copy
Provides description of risk assessment process and activities as practiced by the
Department of Health and Human Services. Includes comparisons to framework for risk
assessment defined by the National Academy of Sciences.
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norlands Illustrated Medical Dictionary, 27th ed. W. B. Saunders, Philadelphia
ISBN: 0-7216-3154-1
Saunders 800-545-2522
218 W. Washington Square
Philadelphia, PA 19105
Saunders $38.95/ea.; S&H 6%
A widely used, comprehensive medical dictionary.
Foundations of Epidemiology, 2nd ed. A. Lilienfeld and D.E. Lilienfeld, eds. New York:
Oxford University Press, 1980.
ISBN 0-19-502723-X
Oxford University Press
200 Madison Ave.
New York, NY 10016
212-679-7300
Oxford University Press, $18.95/ea., no quantity discount, S&H free if prepaid.
An introductory textbook of epidemiology with a thorough discussion of basic concepts,
study design, and interpretation.
Fundamentals of Air Pollution, Arthur C. Stern, Henry C. Wohlers, Richard W.Boubel,
William P. Lowry. 2nd ed. New York: Academic Press, 1984.
Academic Press, Inc. 800-321-5068
465 S. Lincoln Drive
Troy, MO 63379
Academic: $49.95; no quantity discount; no S&H charge on prepaid order
A textbook covering the elements, effects, meteorology, and control of air pollution.
Guideline on Air Quality Models (Revised). U.S. EPA Office of Air Quality Planning and
Standards, Research Triangle Park, NC 27711. July 1986. Supplement A, 1988.
EPA-450/2-78-027A.
Order from:
U.S. EPA Library
MD-35
Research Triangle Park, NC 27711
(919) 541-2777
FTS 629-2777
Recommends air quality modeling techniques that may be applied to air pollution
control strategy evaluations and new source reviews. Intended for use by U.S. EPA
regional offices in judging the adequacy of modeling analysis performed by the U.S.
EPA, state and local agencies, and by industry and its consultants. Also identifies
modeling techniques and data bases that the U.S. EPA considers acceptable. Makes
specific recommendations concerning air quality models, data bases and general
requirements for concentration estimates.
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Handbook of Emergency Toxicology: A Guide for the Identification, Diagnosis, and
Treatment of Poisoning, 5th ed. Sidney Kaye. Springfield, Illinois: Charles C. Thomas,
1988.
ISBN: 0-398-05403-7
Charles C. Thomas 217-789-8980
2600 S. 1st Street
P.O. Box 19265
Springfield, IL 62794-9265
CCT: $85.00/ea; 10+ copies 10% discount; 25+ copies 15%; S&H (UPS) $2/ea copy
Discusses symptoms and signs of poisoning, lethal doses, antidotes and treatment, and
analyses. Includes a listing of information about approximately 170 poisons.
Handbook of Industrial Toxicology, 3rd ed. E.R. Plunkett, ed. New York: Chemical,..'..
Publishing Co., Inc., 1987.
ISBN: 0-8306-0321-X
Chemical Publishing Co., Inc.
80 Eightieth Ave.
New York, NY 10011
212-255-1950
Chem Pub: $75/ea; 10+ copies 10% discount; S&H $4.50/ea copy
A quick reference source on industrial toxicology. Lists substances under commonly-
used names, along with synonyms; descriptions; occupational exposure; threshold limit
values; toxicity; and preventive measures.
Handbook of Poisoning, 12th ed. Robert H. Dreisbach. Los Altos, California: Lange
Medical Publications, 1987.
ISBN: 0-9395-3643-3
Learning Trends
200 Old Tappan Road
Old Tappan, NJ 07675-7095
800-922-0579
(Division of Lange)
Learning Trends: §16.50/ea; 15+ copies 15% discount; S&H included
Provides a concise summary of the diagnosis and treatment of clinically important
poisons, with other poisons included in tabular form.
Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2nd ed. Marshall Sittig.
Park Ridge, New Jersey: Noyes Data Corp., 1985.
ISBN: 0-8155-1009-8
Noyes Publications 201-391-8484
Mill Road at Grand Avenue
Park Ridge, NJ 07656
Noyes: $96.00/ea; quantity discount available; no S&H charge on prepaid order, if not
prepaid 1st copy $3, each additional copy $1 per copy
Presents concise chemical and safety information on nearly 800 toxic and hazardous
chemicals. Provides information such as synonyms; potential exposure;
incompatibilities; permissible exposure limits; routes of entry; harmful effects;
symptoms; medical surveillance; personal protection; first aid; and disposal methods.
28
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Human Physiology, 2nd ed. Stuart Ira Fox. Dubeque, Iowa: William C. Brown, Publishers, 1987.
ISBN: 0-697-08232-6
Wm. C. Brown 800-338-5578
2460 Kerper Blvd.
Dubeque, IA 52001
Wm. C. Brown: $52.00 each
An introductory text on the physiology of the human cardiovascular, pulmonary, renal,
digestive, immune, reproductive, and endocrine systems. Presents basic information in
biology and chemistry for readers who lack a science background.
Identifying and Regulating Carcinogens.
U.S. Government Printing Office
Superintendent of Documents
Washington, DC 20402
U.S. G.P.O. #052-003-01080-1 $11/ea
Office of Technology Assessment.
202-783-3238
FTS 783-3238
Describes policies issued by Federal agencies concerning the identification,
assessment, and regulation of carcinogenic chemicals; the chemicals that have been
regulated because of carcinogenic risk; the Federal government's carcinogenicity
testing program; and the extent of agency action for chemicals determined to be
carcinogenic.
Integrated Risk Information System, Volume I. Supportive documentation.
U.S. Environmental Protection Agency. March 1987.
EPA 600/8-86/032a
Order from:
The National Technical Information Service
5285 Port Royal Road
Springfield, VA 22161
703-487-4600
Contains a user's guide to the Integrated Risk Information System (IRIS), a computer-
housed catalog of the U.S. EPA's risk assessment and risk management information for
chemical substances. The guide also contains appendices on the use of reference
dose in risk assessments; the U.S. EPA's approach to risk assessment for
environmental carcinogens; drinking water health advisories; and other supplementary
information.
Merck Index: An Encyclopedia of Chemicals and Drugs, 10th ed. Martha Windholz, ed.
Rahway, New Jersey: Merck and Co., Inc., 1983.
ISBN: 0-911910-27-1
Merck and Co., Inc. 201-750-7482
Professional Handbook Dept. WBC-220
P.O. Box 2000
Rahway, NJ 07065-0901
Merck: $28.50/ea; 1-9 20% discount; 10+ copies 25% discount; S&H (UPS) $3/ea
copy, $15 for 20 copies
Gives concise information on over 10,000 chemicals. Includes discussion of isolation,
preparation, biosynthesis, physical and biological properties, pharmacological actions,
uses and toxicity.
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National Air Toxics Information Clearinghouse: Qualitative and Quantitative Carcinogenic
Risk Assessment, U.S. Environmental Protection Agency. U.S. EPA Office of Air
Quality Planning and Standards, Research Triangle Park, North Carolina, 1987b.
EPA-450/5-87-003
Federal, State, and local agencies may receive free copies by calling the Clearinghouse
staff at 919-541-0850; FTS 629-0850.
Describes the basic principles and assumptions associated with a qualitative and
quantitative carcinogenic risk assessment. Uses several examples of quantitative risk
assessments done by state and local agencies. Aimed at managers and staff members
in state and local agencies concerned with the use of risk assessment for evaluating
emissions of toxic air pollutants.
National Air Toxics Information Clearinghouse: How the Clearinghouse Can Help to
Answer Your Air Toxics Questions, U.S. Environmental Protection Agency. Office of
Air Quality Planning and Standards, Research Triangle Park, North Carolina, 1986a.
EPA-450/5-86-009
Federal, State, and local agencies may receive free copies by calling the Clearinghouse
staff at 919-541-0850; FTS 629-0850.
Illustrates how the National Air Toxics Information Clearinghouse can help to answer
questions commonly asked by state and local agencies involved with air toxics
assessment and control. Includes discussion of several problem scenarios that may be
encountered by state and local agencies.
National Air Toxics Information Clearinghouse: Bibliography of Selected Reports
and Federal Register Notices Related to Air Toxics. July 1988.
Federal, State, and local agencies may receive free copies by calling the Clearinghouse
staff at 919-541-0850; FTS 629-0850.
Provides citations to reports and Federal Register notices useful in developing and
operating air toxics control programs. Reports selected are published by: U.S. EPA;
National Academy of Sciences; National Cancer Institute; National Institute of
Environmental Health Sciences; National Toxicology Program; National Institute for
Occupational Safety and Health; World Health Organization; and various state and local
agencies.
NIOSHIOSHA Occupational Health Guidelines for Chemical Hazards. U.S. Dept. HHS/Public
Health Service/CDC/NIOSH, U.S. Department of Labor/ OSHA. January 1981. DHHS
(NIOSH) Publication No. 81-123.
For sale by the Superintendent of Documents, U.S. Government Printing Office,
Washington, DC 20402.
Occupational guidelines on 397 chemicals and metals are compiled. Information on
permissible exposure limits, chemical and physical properties, and health hazards is
summarized. Recommendations for medical surveillance, respiratory protection,
personal protection, and sanitary practices for specific chemicals that are federally
regulated are provided.
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Patty's Industrial Hygiene and Toxicology, 6 Part 3 Vol. Set, 3rd ed. G.D.Clayton and
F.E. Clayton, eds. New York: John Wiley and Sons, 1985.
ISBN: 0-471-86137-5
201-469-4400
John Wiley & Sons, Inc.
1 Wiley Drive
Somerset, NJ 08875 Attn: Order Dept.
Wiley: $680/set; no quantity discount; S&H (UPS) $30
NOTE: This set includes Vols. 1, 2A, 2B, 2C, 3A, and 3B; ordering information for the
six individual books is listed below.
A comprehensive and detailed text on industrial hygiene and toxicology. Volume 1
covers general principles, Volumes 2A, 2B and 2C cover toxicology, and Volumes 3A
and 3B cover the theory and rationale of industrial hygiene practice.
Patty's Industrial Hygiene and Toxicology, General Principles, Vol. 1, 3rd ed. G.D. Clayton
and.F.E. Clayton, eds. New York: John Wiley and Sons, 1978.
ISBN: 0-471-16046-6
Wiley: $172/ea; no quantity discount; S&H (UPS) $5/ea book
Patty's Industrial Hygiene and Toxicology, Vol. 2A, 3rd ed. G.D. Clayton and F.E. Clayton, eds.
New York: John Wiley and Sons, 1978.
ISBN: 0-471-16042-3
Wiley: $162/ea; no quantity discount; S&H (UPS) $5/ea book
Patty's Industrial Hygiene and Toxicology, Vol. 2B, 3rd ed. G.D. Clayton and F.E. Clayton, eds.
New York: John Wiley and Sons, 1981.
ISBN: 0-471-07943-X
Wiley: $115/ea; no quantity discount; S&H (UPS) $5/ea book
Patty's Industrial Hygiene and Toxicology, Vol. 2C, 3rd ed. G.C.Clayton and F.E. Clayton, eds.
New York: John Wiley and Sons, 1982.
ISBN: 0-471-09258-4
Wiley: $147/ea; no quantity discount; S&H (UPS) $5/ea book
Patty's Industrial Hygiene and Toxicology, The Work Environment. Vol. 3A, 2nd
ed. Lewis J. Cralley and Lester J. Cralley, eds. New York: John Wiley and Sons, 1985.
ISBN: 0-471-86137-5
Wiley: $105/ea; no quantity discount; S&H (UPS) $5/ea book
Patty's Industrial Hygiene and Toxicology, The Work Environment. Vol. 3B, 2nd
ed. Lewis J. Cralley and Lester J. Cralley, eds. New York: John Wiley and Sons, 1985.
ISBN: 0-471-82333-3
Wiley;,$100/ea; no quantity discount; S&H (UPS) $5/ea book
Principles of Biochemistry, Albert Lehninger. New York: Worth Publishers, Inc. 1982.
Worth Publishers, Inc. " 212-475-6000
33 Irving Place
New York, NY 10003
Worth: $45.95; no quantity discount, S&H $2.95 ea/copy
A textbook written for students taking their first course in biochemistry. Covers
biomolecules (including the rudiments of organic chemistry relevant to biomolecules),
bioenergetics and metabolism, aspects of human biochemistry, and the fundamentals of
molecular genetics.
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Principles of Genetic Toxicology, 2nd ed. David Brusick. New York: Plenum Press, 1987.
ISBN: 0-306-42532-7
Plenum Publishers 212-620-8000
233 Spring Street
New York, NY 10013
Plenum: $35.00/ea.
A textbook presenting basic concepts of genetics and a thorough discussion of all
aspects of genetic toxicology.
Quantitative Risk Assessment for Environment and Occupational Health. William
H. Hallenbeck and Kathleen M. Cunningham-Burns. Chelsea, Michigan:
Lewis Publications, Inc., 1986.
ISBN: 0-87371-055-X
Lewis Publications, Inc. 800-525-7894
121 S. Main St.
P.O. Drawer 519
Chelsea, Ml 48118
Lewis: $35.95/ea; quantity discounts available; no S&H charges if prepaid, if not
prepaid S&H depends on quantity ordered
Presents a methodology for quantifying the health risks associated with exposure to
environmental and occupational toxins. Covers the characterization of exposure of a
risk group; evaluation of experimental studies; calculation of risk and cases; and
calculation of acceptable concentrations of toxins. Also contains examples of risk
assessments. Requires only a basic knowledge of biology and algebra to use the
methodology presented.
Registry of Toxic Effects of Chemical Substances, 1985-86 Edition. National Institute for
Occupational Safety and Health. Washington, DC: G.P.O., 1988.
202-783-3238
FTS 783-3238
U.S. Government Printing Office
Superintendent of Documents
Washington, DC 20402
U.S. G.P.O. #017-033-00431-5 $85.00
Lists prime chemical name substances with their associated toxicity data; includes all
substances for which regulatory or consensus group information is cited. This edition
replaces and updates the older printed versions of RTECS.
Research to Improve Health Risk Assessments (RIHRA) Program. U.S. EPA, Office of
Research and Development, Washington, D.C. 20460.
EPA/600/8-88/089
Center for Environmental Research Information 513-569-7562
U.S. EPA
26 West Martin Luther King Drive
Cincinnati, OH 45268
Presents plan for integrated and systematic research program to reduce uncertainties,
due to deficiencies in the quality and quantity of appropriate data, in health risk
assessments. Describes targeted laboratory and field research to improve health risk
assessments.
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Risk Assessment in the Federal Government: Managing the Process. Committee on the
Institutional Means for Assessment of Risks to Public Health, Commission on Life
Sciences, and National Research Council. Washington, DC: National Academy Press,
1983.
National Academy Press 202-334-331 3
2101 Constitution Avenue
Washington, DC 20418
National Academy: $14.50; 15% discount over 4 copies; S&H (book rate) included in
price
A Congressionally-mandated study by the National Academy of Sciences to determine
institutional mechanisms for strengthening risk assessment as the basis for federal
regulatory policies. Explores the relationship between science and policy in risk
assessment. Discusses the current practice of risk assessment and its relationship to
the process of regulation; past efforts to develop risk assessment guidelines;
experiences of regulatory agencies with different administrative arrangements for risk
assessment; and various proposals to modify risk assessment procedures.
The Risk Assessment Guidelines of 1986. U.S. EPA, Office of Health and
Environmental Assessment, Washington, DC 20460.
EPA-600/8-87-045
NTIS PB88-123997/AS.
Center for Environmental Research Information 513-569-7562
U.S. EPA
26 West Martin Luther King Drive
Cincinnati, OH 45268
Presents the U.S. EPA's risk assessment guidelines relating to five areas:
carcinogenicity, mutagenicity, chemical mixtures, suspect developmental toxicants, and
estimating exposure. Presents the five guidelines as they originally appeared in the
Federal Register (51 FR 33992-34054) but in a format that is easier to read.
Stedmans Medical Dictionary, 24th ed. Williams and Wilkins Co., Baltimore.
ISBN:0-683-07915-8
Williams and Wilkins Co.
428 E. Preston Street
Baltimore, MD 21202
301-528-4000
Williams and Wilkins: $36.95 ea; no quantity discounts, S&H $7.34/copy.
A widely used, comprehensive medical dictionary.
Superfund Public Health Evaluation Manual, U.S. Environmental Protection Agency.
U.S. EPA Office of Emergency and Remedial Response, Washington, DC, 1986b.
EPA-540/1-86/060.
Order from EPA Public Information Center 202-382-2080
(Note: This document is currently being revised; new edition will be available Fall 1989.)
Establishes a framework for public health evaluation at Superfund sites and for
development of health-based performance goals for remedial alternatives based on
applicable laws or risk analysis techniques.
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Threshold Limit Values and Biological Exposure Indices, 1986-1987 ed.
American Conference of Governmental Industrial Hygienists (ACGIH).
American Conference of Governmental 513-661-7881
Industrial Hygienists
6500 Glenway, Bldg. D-7
Cincinnati, OH 45211
ACGIH: $4.50/1-4 copies; $3.50/5-9 copies, $3.00/10-49 copies, $2.75/50-199
copies; S&H depends on quantity ordered
A pocket-sized listing of chemical specific exposure limits for the workplace
recommended by the ACGIH. Contains over 400 chemical listings for Threshold Limit
Values (TLVs) and approximately 16 chemical listings for Biological Exposure Limits
(BELs).
Also see:
Documentation of Threshold Limit Values and Biological Exposure Limits, 5th ed.,
1986. ACGIH.
American Conference of Governmental 513-661-7881
Industrial Hygienists
6500 Glenway, Bldg. D-7
Cincinnati, OH 45211
ACGIH: $110/1 copy, $99/5-15 copies; $88/16 or more copies; no S&H charges if
prepaid
Provides detailed documentation for chemical-specific exposure limits recommended
by the ACGIH. Gives the chemical formula, statement on toxicity and hazards,
explanation of the basis for selection of the TLV, and references for each substance.
Toxicology: A Primer on Toxicology Principles and Applications, Michael Kamrin.
Chelsea, Michigan: Lewis Publishers, Inc., 1988.
ISBN:0-87371-133-5
Lewis Publishers, Inc. 800-525-7894
121 S. Main Street
P.O. Drawer 512
Chelsea, Ml 48114
Lewis: $27.50; no quantity discount; S&H $3.00 to $5.00
Discussion of the general principles of toxicology; toxicology in risk assessment and
risk management; and analysis of four case studies.
User's Manual for the Human Exposure Model (HEM), U.S. Environmental Protection Agency,
Office of Air Quality Planning and Standards, Research Triangle Park, NC, 1986.
Federal, State, and local agencies can obtain free copies by contacting the Pollutant
Assessment Branch, Office of Air Quality Planning and Standards at 919-541-5647;
FTS 629-5647.
Describes the Human Exposure Model (HEM), a general model designed to estimate
the population exposed to air pollutants emitted from stationary sources and the
carcinogenic risk associated with this exposure. Explains the use of the two basic
models within HEM, the System Applications Human Exposure and Dosage (SHED)
model and the Systems Application Human Exposure and Risk (SHEAR) model.
*U.S. GOVERNMENT PRINTING OFFICE: 1989-648-163/87084
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