Page 190 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicological Testing: In Vivo and In Vitro Models Chapter | 9 157

VetBooks.ir approach is recommended to get an accurate overall pic- recent developments in the area of in vitro toxicity testing
have contributed significantly to the gradual reduction in
ture of the chain of events following exposure to toxin.
animal use for toxicity screening and have helped to
CONCLUDING REMARKS improve knowledge relating to mechanisms of cell- or
organ-specific toxicity. Veterinarians have played an
AND FUTURE DIRECTIONS
important role in the development of legislation and
A major issue facing toxicological science today is how guidelines relating to the use and replacement of labora-
to convert experimental data from in vivo and in vitro tory animals in toxicity assessment.
models into knowledge about molecular mechanisms of The generally accepted approach to screening com-
toxicity and safe levels of exposure to the agents tested. pounds for toxicity is to use a multitiered system starting
A number of animal models that have been used for many with simple monocultures of specific cell types, followed
years for screening purposes have been gradually refined by cocultures that simulate metabolic effects and/or
with increasing emphasis on improved experimental cell cell interactions in the whole organism, before car-
design, animal welfare, and reduced animal use. More rying out final testing on animals (Fig. 9.3). In this way,

FIGURE 9.3 Flow chart showing principles of multitiered approach to toxicity testing.