Physiologically-Based Parmacokinetic Model For Trichloroethylene Considering Enterohepatic Recirculation of Major Metabolites

Journal Article · Mon Jun 01 00:00:00 EDT 1998 · Risk Analysis

DOI:https://doi.org/10.1111/j.1539-6924.1998.tb01293.x· OSTI ID:1601807

Stenner, Robert D. ^[1]; Merdink, James L. ^[2]; Fisher, J.W ^[3]; Bull, Richard J. ^[4]

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1. BATTELLE (PACIFIC NW LAB)
2. Washington State University Tri-Cities
3. .
4. SELF-EMPLOYED CONSULTANTS

Trichloroacetic acid (TCA) is a major metabolite of trichloroethylene (TRI) thought to contribute to its hepatocarcinogenic effects in mice. Recent studies have shown that peak blood concentrations of TCA in rats do not occur until approximately twelve hours following an oral dose of TRI. However, blood concentrations of TRI reach a maximum within an hour and are non-detectable after two hours (1). The results of a study which examined the enterohepatic recirculation (EHC) of the principle TRI metabolites (2) was used to develop a physiologically-based pharmacokinetic model for TRI, which includes enterohepatic recirculation of its metabolites. The model quantitatively predicts the uptake, distribution and elimination of TRI, trichloroethanol, trichloroethanol-glucuronide, and TCA and includes production of metabolites through the enterohepatic recirculation pathway. Physiologic parameters used in the model were obtained from the literature (3 & 4). Parameters for TRI metabolism were taken from Fisher et al. (5). Other kinetic parameters were found in the literature or estimated from experimental data (2). The model was calibrated to data from experiments of an earlier study where TRI was orally administered (2). Verification of the model was conducted using data on the enterohepatic recirculation of TCEOH and TCA (2), chloral hydrate data (infusion doses) from Merdink (6), and TRI data from Templin (1) and Larson and Bull (7).

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1601807
• Report Number(s): PNWD-SA-4670
• Journal Information: Risk Analysis, Journal Name: Risk Analysis Journal Issue: 3 Vol. 18; ISSN 0272-4332
• Publisher: Wiley
• Country of Publication: United States
• Language: English