Page 183 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

150 SECTION | I General

VetBooks.ir (OECD, 1997c; EPA, 1998d,e). However, an important Immunotoxicity
issue related to the selection of animal model in neurotox-
Immunotoxicity tests are designed to detect adverse
icity testing is the delayed onset of effects manifested by
toxic agents. For example, in the case of assessment of effects of xenobiotics on the immune system including all
the relevant cells, organs and mechanisms of immune
the potential of OPs to produce delayed neuropathy
response, whether or not there is a measurable disturbance
induced by organophosphates, as rodents are not the most
in host resistance. Toxic substances can directly or indi-
sensitive models, the use of the hen model is recom-
rectly cause immunotoxicity, either by inhibiting the
mended (OECD, 1995a,b). The two protocols used in the
enzymatic activity of esterases and serine hydrolases in
hen model involve either acute or repeated dosing for up
the immune system or by chronic alteration in metabolism
to 28 days and determination of the enzymes acetylcholin-
of organs in the immune and nervous system, respec-
esterase and neuropathy target esterase, clinical observa-
tively. Some of the approaches, tests, and endpoints used
tion, and histopathology of the CNS (OECD, 1995a,b).
to assess in vivo immunotoxicity are presented in
Furthermore, the need to address the specific risks of
Table 9.4 (EPA, 1998g; Barlow et al., 2002; Galloway
the developing nervous system has led to the application
and Handy, 2003; OECD, 2008).
of more specific developmental neurotoxicity testing
Laboratory rodents, especially mice, are used in toxi-
guidelines in rats (EPA, 1998f; OECD, 2007). Although
cological tests because basic immunological studies were
rodents are the animal model of choice, the main prob-
mainly conducted in this species. The immune elements
lem using them in developmental studies is that the
and interactions in rodents and humans are very similar
period of enhanced brain growth takes place during the
and if the toxicokinetic properties of tested chemicals are
first 10 days after birth, whereas in humans, dogs,
close, then the use of mice or rats is recommended (IPCS,
guinea, and minipigs, this period is completed prena-
1996; EPA, 1998g).
tally. In conclusion, for predicting developmental neuro-
toxicity risk in humans, the rat is the recognized model.
However, due to the limitations of the rodent model, Transgenic Animals in Toxicity Testing
dogs, guinea, and minipigs are also widely used to
test pharmaceutical compounds that target children. The recent advances in genetic engineering techniques led
(Kaufmann, 2003). to the development of a number of transgenic in vivo
TABLE 9.4 Immunotoxicity Endpoints, Methods and Approaches Used for In Vivo Toxicity Testing
Tests Methods Endpoints
Nonfunctional tests of Immunopathology Lymphoid organ weight
immunotoxic response
Histopathology of lymphoid tissues, including bone marrow
Routine hematology Immunocyte viability/differential count
Immunoglobulin levels
Functional tests of immunotoxic Measurement of humoral Antibody response
response immunity
Antibody plaque forming
Measurement of nonspecific Neutrophil and monocyte numbers
immunity
Phagocytic activity of macrophages
Measurement of cell mediated Mitogen-induced cell proliferation
immunity
Natural killer cell activity
Mixed lymphocyte reaction
Delayed hypersensitivity
Host resistance assays Mortality and organ histopathology due to bacterial, virus,
and parasitic infection