Drug metabolism and the safety evaluation of drugs and chemicals

Abstract

In the safety evaluation of drugs and chemicals tests are carried out in laboratory animals before man is exposed to the compounds. This procedure has been successful in identifying chemicals which directly cause serious lesions to major organs. Prediction of likely risk to man by these tests is less good when the lesions have a biochemical, rather than a morphological manifestation, or when toxicity is mediated not by the parent compound but by a chemically reactive metabolite. In the latter case species and strain differences in toxicity complicate safety assessment. Additionally, the occasional failure to predict serious toxicity in man with tests in animals suggests that there is a need to reappraise the safety assessment procedure. There is also pressure, some of it justified, to reduce man’s exploitation of animals in toxicity testing. This latter objective might be achieved by adopting a more rational approach to toxicity testing.