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Fulden
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Physiologically-based pharmacokinetics of trichloroethylene

By Fulden
  • 5 Topics started
on 10 Oct 2018 (Edited)
Latest activity Edited by Hollis Potter on 7 Nov 2018

This project presents a SimBiology implementation of a physiologically-based pharmacokinetic (PBPK) model for trichloroethylene (TCE) and its metabolites. It is based on the article, “A human physiologically based pharmacokinetic model for trichloroethylene and its metabolites, trichloroacetic acid and free trichloroethanol” by Fisher et al. [1].

The human PBPK model for TCE and its metabolites presented here was developed by Fisher et al. [1] in order to assess human health risks associated with low level exposure to TCE. TCE is a commonly used solvent in the automotive and metal industries for vapor degreasing of metal parts. Exposure to TCE has been associated with toxic responses such as cancer formation and brain disorders in rodents and in humans [1]. In this PBPK model, TCE enters the systemic circulation through inhalation. Its disposition is described by a six-compartment model representing the liver, lung, kidney, fat, and slowly perfused and rapidly perfused tissues. In the liver, TCE is metabolized to trichloroacetic acid (TCA) and free trichloroethanol (TCOH-f) via P450-mediated metabolism where a fraction of TCOH-f is converted to TCA. For simplicity, a four-compartment submodel was used to describe the disposition of metabolites, TCA and TCOH-f, in the lung, liver, kidney, and body (muscle). Both metabolites are described to be excreted in the urine. TCOH-f is glucuronidated in the liver, forming glucuronide-bound TCOH (TCOH-b), and excreted in the urine via a saturable process whereas TCA is excreted by a first-order process by the kidney.

Reference: Fisher, J. W., Mahle, D., & Abbas, R. (1998). A human physiologically based pharmacokinetic model for trichloroethylene and its metabolites, trichloroacetic acid and free trichloroethanol. Toxicology and applied pharmacology, 152(2), 339-359.

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