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Issues in the Pharmacokinetics of Trichloroethylene and Its Metabolites

Much progress has been made in understanding the complex pharmacokinetics of trichloroethylene (TCE). Qualitatively, it is clear that TCE is metabolized to multiple metabolites either locally or into systemic circulation. Many of these metabolites are thought to have toxicologic importance. In addit...

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Detalles Bibliográficos
Autores principales: Chiu, Weihsueh A., Okino, Miles S., Lipscomb, John C., Evans, Marina V.
Formato: Texto
Lenguaje:English
Publicado: National Institute of Environmental Health Sciences 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570093/
https://www.ncbi.nlm.nih.gov/pubmed/16966104
http://dx.doi.org/10.1289/ehp.8691
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author Chiu, Weihsueh A.
Okino, Miles S.
Lipscomb, John C.
Evans, Marina V.
author_facet Chiu, Weihsueh A.
Okino, Miles S.
Lipscomb, John C.
Evans, Marina V.
author_sort Chiu, Weihsueh A.
collection PubMed
description Much progress has been made in understanding the complex pharmacokinetics of trichloroethylene (TCE). Qualitatively, it is clear that TCE is metabolized to multiple metabolites either locally or into systemic circulation. Many of these metabolites are thought to have toxicologic importance. In addition, efforts to develop physiologically based pharmacokinetic (PBPK) models have led to a better quantitative assessment of the dosimetry of TCE and several of its metabolites. As part of a mini-monograph on key issues in the health risk assessment of TCE, this article is a review of a number of the current scientific issues in TCE pharmacokinetics and recent PBPK modeling efforts with a focus on literature published since 2000. Particular attention is paid to factors affecting PBPK modeling for application to risk assessment. Recent TCE PBPK modeling efforts, coupled with methodologic advances in characterizing uncertainty and variability, suggest that rigorous application of PBPK modeling to TCE risk assessment appears feasible at least for TCE and its major oxidative metabolites trichloroacetic acid and trichloroethanol. However, a number of basic structural hypotheses such as enterohepatic recirculation, plasma binding, and flow- or diffusion-limited treatment of tissue distribution require additional evaluation and analysis. Moreover, there are a number of metabolites of potential toxicologic interest, such as chloral, dichloroacetic acid, and those derived from glutathione conjugation, for which reliable pharmacokinetic data is sparse because of analytical difficulties or low concentrations in systemic circulation. It will be a challenge to develop reliable dosimetry for such cases.
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spelling pubmed-15700932006-09-25 Issues in the Pharmacokinetics of Trichloroethylene and Its Metabolites Chiu, Weihsueh A. Okino, Miles S. Lipscomb, John C. Evans, Marina V. Environ Health Perspect Research Much progress has been made in understanding the complex pharmacokinetics of trichloroethylene (TCE). Qualitatively, it is clear that TCE is metabolized to multiple metabolites either locally or into systemic circulation. Many of these metabolites are thought to have toxicologic importance. In addition, efforts to develop physiologically based pharmacokinetic (PBPK) models have led to a better quantitative assessment of the dosimetry of TCE and several of its metabolites. As part of a mini-monograph on key issues in the health risk assessment of TCE, this article is a review of a number of the current scientific issues in TCE pharmacokinetics and recent PBPK modeling efforts with a focus on literature published since 2000. Particular attention is paid to factors affecting PBPK modeling for application to risk assessment. Recent TCE PBPK modeling efforts, coupled with methodologic advances in characterizing uncertainty and variability, suggest that rigorous application of PBPK modeling to TCE risk assessment appears feasible at least for TCE and its major oxidative metabolites trichloroacetic acid and trichloroethanol. However, a number of basic structural hypotheses such as enterohepatic recirculation, plasma binding, and flow- or diffusion-limited treatment of tissue distribution require additional evaluation and analysis. Moreover, there are a number of metabolites of potential toxicologic interest, such as chloral, dichloroacetic acid, and those derived from glutathione conjugation, for which reliable pharmacokinetic data is sparse because of analytical difficulties or low concentrations in systemic circulation. It will be a challenge to develop reliable dosimetry for such cases. National Institute of Environmental Health Sciences 2006-09 2006-05-09 /pmc/articles/PMC1570093/ /pubmed/16966104 http://dx.doi.org/10.1289/ehp.8691 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.
spellingShingle Research
Chiu, Weihsueh A.
Okino, Miles S.
Lipscomb, John C.
Evans, Marina V.
Issues in the Pharmacokinetics of Trichloroethylene and Its Metabolites
title Issues in the Pharmacokinetics of Trichloroethylene and Its Metabolites
title_full Issues in the Pharmacokinetics of Trichloroethylene and Its Metabolites
title_fullStr Issues in the Pharmacokinetics of Trichloroethylene and Its Metabolites
title_full_unstemmed Issues in the Pharmacokinetics of Trichloroethylene and Its Metabolites
title_short Issues in the Pharmacokinetics of Trichloroethylene and Its Metabolites
title_sort issues in the pharmacokinetics of trichloroethylene and its metabolites
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570093/
https://www.ncbi.nlm.nih.gov/pubmed/16966104
http://dx.doi.org/10.1289/ehp.8691
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