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USE OF A PHYSIOLOGICALLY BASED MODEL TO PREDICT SYSTEMIC UPTAKE AND RESPIRATORY ELIMINATION OF PERCHLOROETHYLENE
Citation:
Dallas, C., S. Muralidhara, X. Chen, R. Ramanathan, P. Varkonyi, J. Gallo, AND J. Bruckner. USE OF A PHYSIOLOGICALLY BASED MODEL TO PREDICT SYSTEMIC UPTAKE AND RESPIRATORY ELIMINATION OF PERCHLOROETHYLENE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/555.
Description:
The pharmacokinetics of inhaled perchloroethylene (PCE) were studied in male Sprague-Dawley rats to characterize pulmonary absorption and elimination. irect measurements of the time-course of PCE in the blood and breath were used to evaluate the ability of a physiologically-based pharmacokinetic (PBPK) model to predict its systemic uptake and elimination. ifty or 500 ppm PCE were inhaled for 2 hr through a miniaturized one-way breathing valve by unanesthetized male Sprague-Dawley rats. erial samples of the inhaled and exhaled breath streams, as well as arterial blood, were collected during and following PCE inhalation. CE exhaled breath concentrations increased rapidly to near steady-state (i.e., within 20 min), and were directly proportional to the inhaled concentration. ptake of PCE into the blood was also rapid, but blood levels continued to increase progressively over the course of the 2-hr exposure at both exposure levels. umulative uptake, or total absorbed dose was not proportional to the exposure level. BPK model was developed from in vivo parameters determined from tissue concentration-time data in a comparison in study (Dallas et al, 1993). CE concentrations in the blood and exhaled breath during the following PCE inhalation were well predicted by the PBPK model. he model accurately simulated percentage uptake and cumulative uptake of PCE over time.