The historical development of the safety evaluation of drugs and chemicals is critically reviewed, and failures of the present approach using experimental animals are examined. The roles of the cytochromes P450 in the detoxication of drugs and chemicals, and in their activation to mutagens, carcinogens and neoantigens, are described, and the importance of the selective induction of the cytochromes P450 in the manifestation of chemical toxicity/carcinogenicity is highlighted. The computer graphic procedure of COMPACT, which relates chemical structures to metabolism by individual cytochromes P450, and hence to their potential toxicity/carcinogenicity, is described, and the advantages and disadvantages of this method of safety evaluation, which does not use experimental animals, are considered.
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