PMID: 6109607Nov 1, 1980Paper

Use of a physiological compartmental model for the rat to describe the pharmacokinetics of several chlorinated biphenyls in the mouse

Drug Metabolism and Disposition : the Biological Fate of Chemicals
D B Tuey, H B Matthews

Abstract

The feasibility of extrapolating the pharmacokinetics of some chlorinated biphenyl congeners (PCB's) from one animal species to another was investigated. The fate of four differently chlorinated biphenyls previously studied in the rat was determined in the mouse The experimental tissue level, metabolism, and excretion data were then used to evaluate results predicted for each PCB after a physiological compartmental model for the rat was scaled to the mouse. Pharmacokinetic parameter values were also obtained from data in the mouse for further evaluations, and to determine whether the congener-dependent relationships previously observed in the rat were present in the mouse. The pharmacokinetics predicted by the scaled model and the results obtained when model parameters were derived from mouse data were equally descriptive of the experimental tissue distribution and excretion kinetics of the PCB's studied. Congener-dependent relationships among the PCB model parameters for the mouse were more varied than for the rat. The accuracy of the pharmacokinetic model predictions extrapolated from the rat to the mouse was primarily a function of their similar congener-dependent rates of PCB metabolism.

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