Use of physiologically-based pharmacokinetic modeling to predict the disposition and metabolic fate of trichloroethylene

Conference · Sun Dec 31 04:00:00 EST 1995

OSTI ID:458283

Greenberg, M S; Burton, Jr, G A ^[1]; Fisher, J W ^[2]

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1. Wright State Univ., Dayton, OH (United States)
2. Tri-Service Toxicology, Wright-Patterson AFB, Dayton, OH (United States)

Due to its carcinogenic potential, the kinetics of TCE metabolism to its primary oxidative products was studied in B6C3F1 mice exposed to TCE vapor concentrations of 100, 300 and 600 ppm in inhalation chambers. TCE and its metabolites were quantified in the blood, liver, kidney, fat and lungs by GC analysis. A physiologically-based pharmacokinetic (PB-PK) model was used to simulate the distribution and metabolism of TCE in the body using SIMUSOLV. The PB-PK model structure consisted of liver, kidney, lung, richly and slowly perfused tissues, and fat that were interconnected by arterial and venous blood pools. Tissue:blood partition coefficients for fat, liver, lung and slowly and rapidly perfused tissues and a blood:air partition coefficient were measured in the laboratory for TCE and its metabolites. The in vivo Michaelis-Menten metabolic constants, Vmaxc and Km, were determined for TCE in gas uptake studies. These values were Km = 0.2 mg/L and Vmaxc = 31.4 mg/hr-kg and they were used in the current PB-PK model to describe the metabolism of TCE to its primary oxidative metabolites. The results suggest that such models can be a useful tool in the evaluation of the impacts of environmental contaminants in any species for which adequate physiological data are available.

• OSTI ID: 458283
• Report Number(s): CONF-961149--
• Country of Publication: United States
• Language: English

Related Subjects

54 ENVIRONMENTAL SCIENCES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
AIR POLLUTION
BIOLOGICAL INDICATORS
BIOLOGICAL MARKERS
CHLORINATED ALIPHATIC HYDROCARBONS
METABOLISM
S CODES
TOXICITY