ABSTRACT

The significance of nitrogen oxidation in the metabolic activation of xenobiotics has been discussed earlier, and it appears that the metabolites responsible for the toxicity and carcinogenicity of many aromatic amines are of intermediate oxidation states, i.e., hydroxylamines and nitroso compounds. In the majority of cases, glucuronidation results in the detoxication and facile elimination of the compound in question, with the consequence that glucuronidation capacity, which is determined by factors such as dose size, drug interactions, and species, strain and genetic differences in enzyme activity, is an important determinant of toxicity. Metabolic activation is often the result of more than one reaction acting in concert to produce a reactive intermediate. The importance of metabolic activation in toxicity, and it is important to understand how metabolism relates to target organ toxicity. The organs affected are generally referred to as the target organs of toxicity, and the differences between these and the other organs of the body may be quantitative or qualitative.