title: Use of physiologically-based pharmacokinetic modeling to simulate the profiles of 3-hydroxybenzo(a)pyrene in workers exposed to polycyclic aromatic hydrocarbons.
abstract: 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.
authors.affiliation: Département de santé environnementale et santé au travail, Chaire d'analyse et de gestion des risques toxicologiques and Institut de recherche en santé publique de l'Université de Montréal, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Roberto
authors.initials: R
authors.lastname: Heredia Ortiz
authors.affiliation: Equipe environnement et prédiction de la santé des populations, Laboratoire TIMC (UMR 5525), CHU de Grenoble, Université Joseph Fourier, La Tronche, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Maître
authors.affiliation: Equipe environnement et prédiction de la santé des populations, Laboratoire TIMC (UMR 5525), CHU de Grenoble, Université Joseph Fourier, La Tronche, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Barbeau
authors.affiliation: Institut national de recherche et de sécurité, Vandoeuvre, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Lafontaine
authors.affiliation: Département de santé environnementale et santé au travail, Chaire d'analyse et de gestion des risques toxicologiques and Institut de recherche en santé publique de l'Université de Montréal, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Michèle
authors.initials: M
authors.lastname: Bouchard
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000009:adverse effects / Q000493:pharmacokinetics*; D001580:Benzopyrenes / Q000009:adverse effects / Q000493:pharmacokinetics*; D004784:Environmental Monitoring; D006801:Humans; D008962:Models, Theoretical; D016273:Occupational Exposure / Q000032:analysis*; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000652:urine*; D051381:Rats
chemical_list: D001580:Benzopyrenes; D011084:Polycyclic Aromatic Hydrocarbons; D001564:Benzo(a)pyrene; C021338:3-hydroxybenzo(a)pyrene