chapter  5
80 Pages

Comparative Metabolism: The Principal Cause of Differential Susceptibility to Toxic and Carcinogenic Agents

ByEdward J. Calabrese

The selection of animal models for toxicological studies, whose primary intention is to predict potential human responses, is often based on practical considerations such as cost, availability, and the susceptibility of the animal to infection. To what extent the animal model may actually be a good simulator of human responses is frequently not even considered. However, when it became apparent that initial teratogenicity studies with the rat model did not effectively predict the occurrence of thalidomide-induced birth defects—whereas subsequent investigations with nonhuman higher primates did—the need for accurate predictability as well as practicality became overwhelmingly evident. In fact, the capacity of nonhuman primates to reproduce many of the thalidomide-induced human birth defects revived the logical assertion that those species that are more closely related from a phylogenetic or evolutionary perspective should respond with 204greater similarity than more distant relatives. Being phylogenetically closer to the human than the rat, the monkey would be expected to metabolize compounds more like humans and therefore be a better predictor of human responses than rodent models.