Page 178 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

VetBooks.ir Chapter 9

Toxicological Testing:

In Vivo and In Vitro Models

Magda Sachana and Alan J. Hargreaves

INTRODUCTION More specifically, a named veterinary surgeon is
responsible not only for the health and well-being of
The large number of new chemical entities in the human
laboratory animals but also to advise on the selection of
and veterinary pharmaceutical industry has led to an
adequate in vivo models and ensure that priority is
increased demand for safety screening to ensure success-
given to the use of alternative methods during the local
ful drug development. Part of this screening process
ethical review process. Furthermore, the refinement of
includes the determination of the toxic potential of these
experimental techniques and husbandry approaches
new compounds by applying internationally recognized
should be one of the priorities of a veterinary surgeon
in vivo or in vitro toxicological tests. The importance of
working in animal units, especially where regulated pro-
toxicological testing is critical, as many pharmaceutical
cedures take place, and distressed animals should be kept
agents, industrial chemicals and agrochemical products
under very close supervision by a veterinarian. A similar
must be assessed for their safety, before they become
approach is used in the United States, where all institutes
available for general use. Furthermore, in some cases,
are also obliged to establish an Institutional Animal Care
basic research can produce data that eventually leads to
and Use Committee, where the participation of a trained
the ban of certain chemicals because they proved to be
and experienced veterinary surgeon is essential to ensure
unsafe.
that all aspects of the three Rs (replacement, reduction,
Animal studies and validated in vitro models are
and refinement) (Russell and Burch, 1959) have been fol-
extensively used for screening of agents in order to iden-
lowed before approving animal use for toxicological
tify and predict potential ill effects to humans, domestic
studies.
pets, and farm animals. Although the detection of adverse
A veterinarian with specific professional or scientific
health effects of xenobiotics is the main objective of
interest in toxicology should be aware of the alternative
toxicity testing, it can be complemented by more sophisti-
methods in toxicity testing, advise on replacement and
cated biomolecular approaches aimed at the elucidation of
refinement of laboratory animals used in toxicological stud-
the mechanisms of action of certain chemicals.
ies and safeguard animal welfare. The main aims of this
Another area of veterinary interest regarding toxico-
chapter are to outline the major aspects of in vivo and
logical testing is the evaluation of the safety of veterinary
in vitro models in toxicity testing and to give a brief over-
drugs for food animals as well as the safety assessment of
view of endpoint determination. The principal focus will be
veterinary drug residues in human food of animal origin,
to highlight some of the current in vivo and in vitro models
in order to determine the doses that cause nonobserved
available in toxicity testing and provide information on new
effect level and consequently to establish the
technologies and approaches used in this field.
acceptable daily intake in the human diet.
Toxicological testing laboratories now have to comply
with strict official controls and inspections on animal use IN VIVO MODELS IN TOXICITY TESTING
at any time that can be reinforced by relevant legislation. Introduction
In most European countries, veterinarians play a pivotal
role in toxicity testing and are required by law to be With the continuous development of new chemicals and
employed by designated establishments that undertake pharmaceutical products, laboratory animals have become
experiments on animals, including toxicological studies. important and well-established tools for the generation of
Veterinary Toxicology. DOI: http://dx.doi.org/10.1016/B978-0-12-811410-0.00009-X
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