Use of physiologically-based pharmacokinetic modeling to simulate the profiles of 3-hydroxybenzo(a)pyrene in workers exposed to polycyclic aromatic hydrocarbons.

Biomathematical modeling has become an important tool to assess xenobiotic exposure in humans. In the present study, we have used a human physiologically-based pharmacokinetic (PBPK) model and an simple compartmental toxicokinetic model of benzo(a)pyrene (BaP) kinetics and its 3-hydroxybenzo(a)pyren...

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Autores principales:	Roberto Heredia Ortiz, Anne Maître, Damien Barbeau, Michel Lafontaine, Michèle Bouchard
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4a6e18c3e09c4d349a723660ce8219fa
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spelling	oai:doaj.org-article:4a6e18c3e09c4d349a723660ce8219fa2021-11-25T06:08:12ZUse of physiologically-based pharmacokinetic modeling to simulate the profiles of 3-hydroxybenzo(a)pyrene in workers exposed to polycyclic aromatic hydrocarbons.1932-620310.1371/journal.pone.0102570https://doaj.org/article/4a6e18c3e09c4d349a723660ce8219fa2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25032692/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Biomathematical modeling has become an important tool to assess xenobiotic exposure in humans. In the present study, we have used a human physiologically-based pharmacokinetic (PBPK) model and an simple compartmental toxicokinetic model of benzo(a)pyrene (BaP) kinetics and its 3-hydroxybenzo(a)pyrene (3-OHBaP) metabolite to reproduce the time-course of this biomarker of exposure in the urine of industrially exposed workers and in turn predict the most plausible exposure scenarios. The models were constructed from in vivo experimental data in rats and then extrapolated from animals to humans after assessing and adjusting the most sensitive model parameters as well as species specific physiological parameters. Repeated urinary voids from workers exposed to polycyclic aromatic hydrocarbons (PAHs) have been collected over the course of a typical workweek and during subsequent days off work; urinary concentrations of 3-OHBaP were then determined. Based on the information obtained for each worker (BaP air concentration, daily shift hours, tasks, protective equipment), the time courses of 3-OHBaP in the urine of the different workers have been simulated using the PBPK and toxicokinetic models, considering the various possible exposure routes, oral, dermal and inhalation. Both models were equally able to closely reproduce the observed time course of 3-OHBaP in the urine of workers and predicted similar exposure scenarios. Simulations of various scenarios suggest that the workers under study were exposed mainly by the dermal route. Comparison of measured air concentration levels of BaP with simulated values needed to obtain a good approximation of observed time course further pointed out that inhalation was not the main route of exposure for most of the studied workers. Both kinetic models appear as a useful tool to interpret biomonitoring data of PAH exposure on the basis of 3-OHBaP levels.Roberto Heredia OrtizAnne MaîtreDamien BarbeauMichel LafontaineMichèle BouchardPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e102570 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Roberto Heredia Ortiz Anne Maître Damien Barbeau Michel Lafontaine Michèle Bouchard Use of physiologically-based pharmacokinetic modeling to simulate the profiles of 3-hydroxybenzo(a)pyrene in workers exposed to polycyclic aromatic hydrocarbons.
description	Biomathematical modeling has become an important tool to assess xenobiotic exposure in humans. In the present study, we have used a human physiologically-based pharmacokinetic (PBPK) model and an simple compartmental toxicokinetic model of benzo(a)pyrene (BaP) kinetics and its 3-hydroxybenzo(a)pyrene (3-OHBaP) metabolite to reproduce the time-course of this biomarker of exposure in the urine of industrially exposed workers and in turn predict the most plausible exposure scenarios. The models were constructed from in vivo experimental data in rats and then extrapolated from animals to humans after assessing and adjusting the most sensitive model parameters as well as species specific physiological parameters. Repeated urinary voids from workers exposed to polycyclic aromatic hydrocarbons (PAHs) have been collected over the course of a typical workweek and during subsequent days off work; urinary concentrations of 3-OHBaP were then determined. Based on the information obtained for each worker (BaP air concentration, daily shift hours, tasks, protective equipment), the time courses of 3-OHBaP in the urine of the different workers have been simulated using the PBPK and toxicokinetic models, considering the various possible exposure routes, oral, dermal and inhalation. Both models were equally able to closely reproduce the observed time course of 3-OHBaP in the urine of workers and predicted similar exposure scenarios. Simulations of various scenarios suggest that the workers under study were exposed mainly by the dermal route. Comparison of measured air concentration levels of BaP with simulated values needed to obtain a good approximation of observed time course further pointed out that inhalation was not the main route of exposure for most of the studied workers. Both kinetic models appear as a useful tool to interpret biomonitoring data of PAH exposure on the basis of 3-OHBaP levels.
format	article
author	Roberto Heredia Ortiz Anne Maître Damien Barbeau Michel Lafontaine Michèle Bouchard
author_facet	Roberto Heredia Ortiz Anne Maître Damien Barbeau Michel Lafontaine Michèle Bouchard
author_sort	Roberto Heredia Ortiz
title	Use of physiologically-based pharmacokinetic modeling to simulate the profiles of 3-hydroxybenzo(a)pyrene in workers exposed to polycyclic aromatic hydrocarbons.
title_short	Use of physiologically-based pharmacokinetic modeling to simulate the profiles of 3-hydroxybenzo(a)pyrene in workers exposed to polycyclic aromatic hydrocarbons.
title_full	Use of physiologically-based pharmacokinetic modeling to simulate the profiles of 3-hydroxybenzo(a)pyrene in workers exposed to polycyclic aromatic hydrocarbons.
title_fullStr	Use of physiologically-based pharmacokinetic modeling to simulate the profiles of 3-hydroxybenzo(a)pyrene in workers exposed to polycyclic aromatic hydrocarbons.
title_full_unstemmed	Use of physiologically-based pharmacokinetic modeling to simulate the profiles of 3-hydroxybenzo(a)pyrene in workers exposed to polycyclic aromatic hydrocarbons.
title_sort	use of physiologically-based pharmacokinetic modeling to simulate the profiles of 3-hydroxybenzo(a)pyrene in workers exposed to polycyclic aromatic hydrocarbons.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/4a6e18c3e09c4d349a723660ce8219fa
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Use of physiologically-based pharmacokinetic modeling to simulate the profiles of 3-hydroxybenzo(a)pyrene in workers exposed to polycyclic aromatic hydrocarbons.

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