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DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR PERCHLOROETHYLENE USING TISSUE CONCENTRATION-TIME DATA
Citation:
Dallas, C., X. Chen, K. O'Barr, S. Muralidhara, P. Varkonyi, AND J. Bruckner. DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR PERCHLOROETHYLENE USING TISSUE CONCENTRATION-TIME DATA. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/553.
Description:
The tissue disposition of perchloroethylene (PCE) was characterized experimentally in rats in order to: 1) btain input parameters from in vivo data for the development of a physiologically-based pharmacokinetic (PBPK) model; and 2) use the PBPK model to predict the deposition of PCE in a variety of tissues following inhalation exposure. or the derivation of model input parameters, male Sprague-Dawley rats received a single bolus of 10 mg PCE/kg bw in polyethylene glycol 400 by ia injection through an indwelling carotid arterial cannula. ther male Sprague-Dawley rats inhaled 500 ppm PCE for 2 hr in dynamic exposure inhalation chambers. erial samples of brain, liver, kidney, lung, heart, skeletal muscle, perirenal fat and blood were taken for up to 72 hr following ia injection, and during the 2-hr inhalation exposure and for up to 72 hr post-exposure. ollowing ia administration, the tissues exhibited similar terminal elimination half-lives (t 1/2). s comparable tissue t 1/2s are consistent with a blood-flow limited model, tissue-blood partition coefficients were calculated for non-eliminating compartments by division of the area under the tissue concentration-time curve (AUC) by the blood AUC. iver PCE concentration versus time data were employed in the calculation of in vivo metabolic rate constants. BPK model was developed using these parameters derived from the ia data set, and used to predict tissue PCE concentrations during and following PCE inhalation.