Chemical disease in humans: problems in comparative toxicology

Difficulties in assessment of the comparative pharmacology of drugs now apply to the effects on humans of foreign compounds from the environment (xenobiotics). Perhaps the most striking change in perspective has been the recognition that a latency of several decades may precede the development of toxic effects. Xenobiotics may persist and accumulate in tissue stores, and estimates of biologically active doses are sometimes complicated by the presence of highly toxic trace contaminants and homologues that have varying biological activity. The effects of chemical exposure on the tissues may be obscured by the absence of the pathognomonic symptoms normally associated with the structural changes of disease. Interactions between two or more xenobiotics or between xenobiotics and genetic and metabolic variables may explain the lack of coherence between carefully defined laboratory observations and the clinical effects of enzyme-inducing xenobiotics. Since we have considerable evidence that biological processes are strikingly similar in different mammalian species, the toxicological significance to humans of enzyme induction and related processes requires careful evaluation.