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Physiologically-based pharmacokinetic modeling of a mixture of toluene and xylene in humans.
Risk Anal. 1995 Jun; 15(3):335-42.RA

Abstract

A physiologically-based pharmacokinetic (PBPK) model for a mixture of toluene (TOL) and xylene (XYL), developed and validated in the rat, was used to predict the uptake and disposition kinetics of TOL/XYL mixture in humans. This was accomplished by substituting the rat physiological parameters and the blood:air partition coefficient with those of humans, scaling the maximal velocity for hepatic metabolism on the basis of body weight0.75, and keeping all other model parameters species-invariant. The human TOL/XYL mixture PBPK model, developed based on the quantitative biochemical mechanism of interaction elucidated in the rat (i.e., competitive metabolic inhibition), simulated adequately the kinetics of TOL and XYL during combined exposures in humans. The simulations with this PBPK model indicate that an eight hour co-exposure to concentrations that remain within the current threshold limit values of TOL (50 ppm) and XYL (100 ppm) would not result in significant pharmacokinetic interferences, thus implying that data on biological monitoring of worker exposure to these solvents would be unaffected during co-exposures.

Authors+Show Affiliations

Département de médecine du travail et d'hygiène du milieu, Faculté de médecine, Université de Montréal, Québec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7604167

Citation

Tardif, R, et al. "Physiologically-based Pharmacokinetic Modeling of a Mixture of Toluene and Xylene in Humans." Risk Analysis : an Official Publication of the Society for Risk Analysis, vol. 15, no. 3, 1995, pp. 335-42.
Tardif R, Laparé S, Charest-Tardif G, et al. Physiologically-based pharmacokinetic modeling of a mixture of toluene and xylene in humans. Risk Anal. 1995;15(3):335-42.
Tardif, R., Laparé, S., Charest-Tardif, G., Brodeur, J., & Krishnan, K. (1995). Physiologically-based pharmacokinetic modeling of a mixture of toluene and xylene in humans. Risk Analysis : an Official Publication of the Society for Risk Analysis, 15(3), 335-42.
Tardif R, et al. Physiologically-based Pharmacokinetic Modeling of a Mixture of Toluene and Xylene in Humans. Risk Anal. 1995;15(3):335-42. PubMed PMID: 7604167.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Physiologically-based pharmacokinetic modeling of a mixture of toluene and xylene in humans. AU - Tardif,R, AU - Laparé,S, AU - Charest-Tardif,G, AU - Brodeur,J, AU - Krishnan,K, PY - 1995/6/1/pubmed PY - 1995/6/1/medline PY - 1995/6/1/entrez SP - 335 EP - 42 JF - Risk analysis : an official publication of the Society for Risk Analysis JO - Risk Anal VL - 15 IS - 3 N2 - A physiologically-based pharmacokinetic (PBPK) model for a mixture of toluene (TOL) and xylene (XYL), developed and validated in the rat, was used to predict the uptake and disposition kinetics of TOL/XYL mixture in humans. This was accomplished by substituting the rat physiological parameters and the blood:air partition coefficient with those of humans, scaling the maximal velocity for hepatic metabolism on the basis of body weight0.75, and keeping all other model parameters species-invariant. The human TOL/XYL mixture PBPK model, developed based on the quantitative biochemical mechanism of interaction elucidated in the rat (i.e., competitive metabolic inhibition), simulated adequately the kinetics of TOL and XYL during combined exposures in humans. The simulations with this PBPK model indicate that an eight hour co-exposure to concentrations that remain within the current threshold limit values of TOL (50 ppm) and XYL (100 ppm) would not result in significant pharmacokinetic interferences, thus implying that data on biological monitoring of worker exposure to these solvents would be unaffected during co-exposures. SN - 0272-4332 UR - https://www.unboundmedicine.com/medline/citation/7604167/Physiologically_based_pharmacokinetic_modeling_of_a_mixture_of_toluene_and_xylene_in_humans_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0272-4332&date=1995&volume=15&issue=3&spage=335 DB - PRIME DP - Unbound Medicine ER -