| Environmental Health Issues John R. Cashman,1 Beatrice Y.T. Perotti,2 Clifford
E. Berkman,1 and Jing Lin1 1Seattle Biomedical Research Institute, Seattle, Washington;
2Pfizer Incorporated, Central Research Division, Groton,
Connecticut Abstract
In this paper we will present a comprehensive overview of the pharmacokinetic parameters 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 information concerning the detoxication of environmental chemicals will also be presented. The discussion will lead to a more complete appreciation for the use of in vitro measurements for in vivo correlations. The concept of interspecies scaling in the interpolation and extrapolation of fundamental biochemical metabolic processes will be illustrated with a number of examples. Additional examples of in vitro-in vivo correlations will be presented in the evaluation of the impact of chemical exposure to humans. Finally, several important metabolic detoxication enzymes will be presented including the mammalian microsomal cytochrome P450 and flavin-containing monooxygenases, as well as carboxylesterases and glucuronosyltransferases, to provide insight into the processes of chemical detoxication in mammalian tissue and blood. Because interspecies scaling and the pharmacokinetics of chemical disposition has already shown its usefulness in understanding some examples of chemical disposition, our summary will focus on showing the usefulness of the pharmacokinetic equations and providing confidence in using the approach for in vitro-in vivo correlations. Ultimately, the presentation may provide the reader with a conceptual framework for future evaluation of the human health risks associated with environmental toxicants. -- Environ Health Perspect 104(Suppl 1) :00-00 (1996) Key words: environmental chemicals, toxicokinetics, in vitro/in vivo correlations, interspecies allometric scaling, physiological modeling, (S) -nicotine, cytochrome P450, flavin-containing monooxygenase, carboxylesterases, organophosphates, glucuronidation
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