Xenobiotic Kinetics and Toxicity among Fish and Mammals
Annual progress rept. 1 Aug 1990-29 Feb 1992
OHIO STATE UNIV COLUMBUS COLL OF PHARMACY
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The purpose of this project is to develop techniques that account for interspecies differences in the pharmacokinetics of xenobiotics. The hypothesis proposed is that toxicity occurs after exposure of the target organ to a characteristic concentration of toxicant for a particular period of time. To test the hypothesis, experiments are proposed to characterize the pharmacokinetics of three representative chemicals lindane, pentachlorophenol and paraoxon in small trout via water exposure, and large trout and rats via intravascular injection. Compartmental pharmacokinetic models will be used. The fraction of a dose of each test compound converted to each of its metabolites by the test animals will be determined to accounts for possible metabolic differences that might contribute to interspecies differences in toxicity. Binding of the test substances in blood to formed elements and plasma proteins will also be characterized.