Toxicity Assessment
 the process of determining the
relationship between the exposure to a
contaminant and the increased
likelihood of the occurrence or severity
of adverse effects
Toxicological Terms
Acute toxicity
Cancer
Procedures Included in Toxicity Assessment
 Hazard
identification
determines
whether exposure to a contaminant
causes increased adverse effects for
humans and to what level of severity.
 Dose-response
evaluation
uses
quantitative information on the dose of
the contaminant and relates it to the
incidence of adverse reactions in an
exposed population.
Carcinogen
Carcinomas
Chronic Toxicity
The single factor that determines the degree of
harmfulness of a compound is the dose of that
compound (Loomis, 1978).
Dose
 defined as the mass of chemical received
by the animal or exposed individual
 usually expressed in units of milligrams
per kilogram of body mass (mg · kg−1)
 Some authors use parts per million
(ppm) instead of mg · kg−1. Where the
dose is administered over time, the units
may be mg · kg−1 · day−1. It should be
noted that dose differs from the
concentration of the compound in the
medium (air, water, or soil) to which the
animal or individual is exposed.
The statistical relationship of organism response
to dose is commonly expressed as a cumulativefrequency distribution known as a dose-response
curve.
(Insert graph here)
Genotoxic
Initiator
Leukemias
Lymphomas
Metastasis
Definition
An adverse effect
that has a rapid
onset, short course,
and pronounced
symptoms.
An abnormal growth
process in which cells
begin a phase of
uncontrolled growth
and spread
A cancer-producing
substance
Cancers of epithelial
tissues. Lung cancer
and skin cancer are
examples of
carcinomas
An adverse effect
that frequently takes
a long time to run its
course and initial
onset of symptoms
may go undetected.
Toxic to the genetic
material (DNA)
A chemical that starts
the change in a cell
that irreversibly
converts the cell into
a cancerous or
precancerous state.
Needs to have a
promoter to develop
cancer.
Cancers of white
blood cells and the
tissue from which
they are derived.
Cancers of the
lymphatic system. An
example is Hodgkin’s
disease.
Process of spreading
or migration of
cancer cells
throughout the body
Neoplasm
Oncogenic
Promoter
Reproductive Toxicity
Sarcoma
Subacute Toxicity
Teratogenesis
A new growth.
Usually an
abnormally fastgrowing tissue
Causing cancers to
form.
A chemical that
increases the
incidence to a
previous carcinogen
exposure
Decreases in fertility,
increases in
miscarriages, and
fetal or embryonic
toxicity as manifested
in reduced birth
weight or size
Cancer of
mesodermal tissue
such as fat and
muscle.
Subacute toxicity is
measured using daily
dosing during the
first 10% of the
organism’s normal
life expectancy and
checking for effects
throughout the
normal lifetime.
Production of a birth
defect in the
offspring after
maternal or paternal
exposure
Example 6.1
EPA has selected a modification of the multistage
model for toxicological assessment, called the
linearized multistage model. This model
assumes that we can extrapolate from high doses
to low doses with a straight line. At low doses,
the slope of the dose-response curve is
represented by a slope factor (SF) expressed in
units of risk per unit dose, or risk (kg · day ·
mg−1).
The EPA maintains a toxicological data base
called IRIS (the Integrated Risk Information
System) that provides background information
on potential carcinogens. IRIS includes suggested
values for the slope factor.
Limitations of Animal Studies. No species
provides an exact duplicate of human response.
Certain effects that occur in common lab animals
generally occur in people. Many effects produced
in people can, in retrospect, be produced in some
species. Notable exceptions are toxicities
dependent on immunogenic mechanisms. Most
sensitization reactions are difficult if not
impossible to induce in lab animals. The
procedure in transferring animal data to people
is then to find the “proper” species and study it
in context. Observed differences are then often
quantitative rather than qualitative.
Carcinogenicity as a result of application
or administration to lab animals is often assumed
to be transposable to people because of the
seriousness of the consequence of ignoring such
evidence. However, slowly induced, subtle
toxicity—because of the effects of ancillary
factors (environment, age, etc.)—is difficult at
best to transfer. This becomes even more difficult
when the incidence of toxicity is restricted to a
small hypersensitive subset of the population.
Limitations of Epidemiological Studies.
Epidemiological studies of toxicity in human
populations present four difficulties. The first is
that large populations are required to detect a
low frequency of occurrence of a toxicological
effect. Second, a long or highly variable latency
period may be needed between the exposure to
the toxicant and a measurable effect. Third,
competing causes of the observed toxicological
response make it difficult to attribute a direct
cause and effect. For example, cigarette smoking;
the use of alcohol or drugs; and personal
characteristics such as gender, race, age, and
prior disease states tend to mask environmental
exposures. Fourth, epidemiological studies are
often based on data collected in specific political
boundaries that do not necessarily coincide with
environmental boundaries such as those defined
by an aquifer or the prevailing wind patterns.