Page 52 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Concepts in Veterinary Toxicology Chapter | 1 19

VetBooks.ir Characterization of hazard and estimation a pharmaceutical or a consumer product, various postmar-
keting surveillance systems should be put in place in an
of potency
attempt to detecting any unexpected adverse outcomes.
Extrapolation across
across species
species not required Extrapolation required
Clinical case Studies in laboratory Epidemiological/Epizootiological Studies
observations in animals
species of interest If a particular chemical has been used for an extended
Extrapolation to intact
organism, may require period of time, and human exposure has occurred previ-
cross species ously either in the workplace or from the environment,
extrapolation it may be feasible to conduct epidemiological studies.
Controlled exposure
studies in species Studies with cells and Epidemiology is the study of how disease is distributed in
of interest tissues from species of a population and the factors that influence or determine
interest and other this distribution. The design of a particular epidemiologi-
species
cal study will be guided by the hypothesis being tested
Multiple extrapolations and the nature of the population(s) available for study. As
Epidemiological or
epizootiological studies Structure – activity an aside, the term epidemiology (epi for across, dem for
in species of interest analyses people, and ology for scientific study) is applicable to
people while the more appropriate related term for studies
FIGURE 1.6 Sources of information for evaluating potential toxicants. on animals would be epizootiology (epa for across, zoo
for animal, and ology for scientific study). However, in
a particular toxicant causes disease have been elucidated common practice studies of the occurrence of disease
to a variable extent. When the toxicant is exclusively of in populations of species other than humans are frequently
concern in veterinary medicine and has no implications referred to as epidemiological studies. The details of
for human health, there has frequently been limited impe- conducting epidemiological or epizootiological studies are
tus for developing a detailed mechanistic understanding beyond the scope of this chapter. A relevant reference
of how a toxicant causes disease. Concern for human for basic concepts in epidemiology can be found in the
health has been a major driver of the biomedical research text by Gordis (2008).
agenda. An obvious exception is when the toxicoses A classic paper by Austin Bradford Hill (1965),
observed in veterinary medicine have large economic a British medical statistician, provides guidance on
impact or toxicants can reach people via animal products. the interpretation of epidemiological evidence for a given
There are many circumstances where observational agent or factor causing a health effect (Table 1.1).
knowledge is not adequate and it is necessary to conduct Although developed for interpreting epidemiological data,
experiments to characterize the toxicology of an agent. i.e., data acquired on human populations, the guidance
It is obvious that if concern for the potential toxic is also highly relevant to interpreting data acquired on
response is in a nonhuman species, controlled experiments animal populations. The framework needs to be used
can be conducted using the species of interest. This is intelligently rather than slavishly: it is a guide and not
obviously the case for domestic livestock as well as com- a checklist.
panion animals. Retrospective epidemiological studies may be feasible
A much more common situation is when concern for previously introduced agents for which prior exposure
focuses on potential toxicity of a newly developed agent has occurred or prospectively for a newly introduced
for use in people or animals. For example, it is necessary agent. If the agent is new it is obvious that it is not feasi-
to establish the safety of a potential new pharmaceutical ble to conduct epidemiological studies to retrospectively
or consumer product before it is introduced into com- evaluate the potential safety/hazard of the agent. If the
merce. In these instances studies in laboratory animals are ultimate interest is in the effects on people, it may be fea-
conducted to provide “first approximation” of the safety sible to conduct controlled exposure studies with human
of the new compounds to humans prior to administration volunteers. It is advisable for the planning of such studies
of the agent to humans. In the case of products intended to be based on a solid database on the potential toxicity of
for use in animals, studies on both efficacy and safety can the agent acquired from studies in laboratory animals.
be conducted in the species of interest. This remains an The design and conduct of such human studies must be
imperative step in the safety evaluation of new products. guided first and foremost by ethical considerations (NRC,
There are also circumstances in which it is desirable to 2004). If a nonhuman species is the target species
extend limited observations from opportunistic studies on of concern, then it is obvious that the most relevant
people or animals that have been inadvertently exposed. information is the information acquired from studies
When a new product is developed and marketed, either conducted in that species.