||Physiological Pharmacokinetic Modeling of Inhaled Trichloroethylene in Rats.
Dallas, C. E. ;
Gallo, J. M. ;
Ramanathan, R. ;
Muralidhara, S. ;
Bruckner, J. V. ;
||Georgia Univ., Athens. Dept. of Pharmacology and Toxicology.;Health Effects Research Lab., Research Triangle Park, NC.
Environmental pollutants ;
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The pharmacokinetics of trichloroethylene (TCE) was characterized during and following inhalation exposures of male Sprague-Dawley rats. The blood and exhaled breath TCE time-course data were used to formulate and assess the accuracy of predictions of a physiologically based pharmacokinetic (PB-PK) model for TCE inhalation. Fifty or 500 ppm TCE was inhaled by unanesthetized rates of 325-375g for 2 hrs through a miniaturized one-way breathing valve. Repetitive samples of the inhaled and exhaled breath streams, as well as arterial blood, were collected concurrently during and for 3 hrs following the exposures and analyzed fo TCE by headspace gas chromatography. Respiratory rates and volumes were continuously monitored and used in conjunction with the pharmacokinetic data to delineate uptake and elimination profiles. Levels of TCE in the exhaled breath attained near steady-state soon after the beginning of exposures, and were then directly proportional to the inhaled concentration. Exhaled breath levels of TCE in rats were similar in magnitude to values previously published for TCE inhalation exposures of humans. The uptake and elimination profiles were accurately simulated by the PB-PK model for both the 50 and 500 ppm TCE exposure levels. Such a model may be quite useful in risk assessments in predicting internal (i.e., systemically absorbed) doses of TCE and other volatile organics under a variety of exposure scenarios.