Current problems in the evaluation of chemical safety.

Current problems in the safety evaluation of chemicals, including species differences in chemical toxicity, the difficulty in predicting whether metabolism will result in detoxication or activation, the different metabolic roles of tissue cytochromes P-450, and the significance of oxygen radical formation, are reviewed. A number of specific chemical problems are discussed, including the safety evaluation of benzene, methylene dichloride, DDT, dieldrin, TCDD, the PCBs, and the hepatotoxic drugs: benoxaprofen and tienilic acid. Two novel methods for the prospective evaluation of chemical toxicity are described, namely (i) computer optimized parametric analysis for chemical toxicity (COMPACT) based on the computer graphic determination of chemical structure and its relationship to specific cytochromes P-450 and hence toxicity, and (ii) enzyme activation in chemical toxicity (ENACT) based on the induction of specific cytochromes P-450 by the chemical, from which toxicity can be predicted.