PHARMACOKINETICS AND MOLECULAR DETOXICATION

This paper presents a comprehensive overview of the pharmacokinetic pa rameters used from in vivo and in vitro studies that are important in order to understand the major conceptual approaches of toxicokinetics and the disposition of environmental chemicals. In vitro biochemical i nformation concerning the detoxication of environmental chemicals is a lso presented. The discussion leads to a more complete appreciation fo r the use of in vitro measurements for in vivo correlations. The conce pt of interspecies scaling in the interpolation and extrapolation of f undamental biochemical metabolic processes is illustrated with a numbe r of examples. Additional examples of in vitro-in vivo correlations ar e presented in the evaluation of the impact of chemical exposure to hu mans. Finally, several important metabolic detoxication enzymes are pr esented, including the mammalian microsomal cytochrome P450 and flavin -containing monooxygenases as well as carboxylesterases and glucuronos yltransferases, to provide insight into the processes of chemical deto xication in mammalian tissue and blood. Because interspecies scaling a nd the pharmacokinetics of chemical disposition have already shown the ir usefulness in understanding some examples of chemical disposition, our summary focuses on showing the usefulness of the pharmacokinetic e quations and providing confidence in using the approach for in vitro-i n vivo correlations. Ultimately, the presentation may provide the read er with a conceptual framework for future evaluation of the human heal th risks associated with environmental toxicants.