Sex differences in urinary levels of several biological indicators of exposure: a simulation study using a compartmental based toxicokinetic model

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Ressource 1Télécharger: BIB_A0CF19A6FE49.P001.pdf (1588.21 [Ko])
Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_A0CF19A6FE49
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Sex differences in urinary levels of several biological indicators of exposure: a simulation study using a compartmental based toxicokinetic model
Périodique
Journal of Occupational and Environmental Hygiene
Auteur⸱e⸱s
Tomicic Catherine, Vernez David
ISSN
1545-9632 (Electronic)
ISSN-L
1545-9624
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
11
Numéro
6
Pages
377-387
Langue
anglais
Résumé
Toxicokinetic modeling is a useful tool to describe or predict the behavior of a chemical agent in the human or animal organism. A general model based on four compartments was developed in a previous study in order to quantify the effect of human variability on a wide range of biological exposure indicators. The aim of this study was to adapt this existing general toxicokinetic model to three organic solvents, which were methyl ethyl ketone, 1-methoxy-2-propanol and 1,1,1,-trichloroethane, and to take into account sex differences. We assessed in a previous human volunteer study the impact of sex on different biomarkers of exposure corresponding to the three organic solvents mentioned above. Results from that study suggested that not only physiological differences between men and women but also differences due to sex hormones levels could influence the toxicokinetics of the solvents. In fact the use of hormonal contraceptive had an effect on the urinary levels of several biomarkers, suggesting that exogenous sex hormones could influence CYP2E1 enzyme activity. These experimental data were used to calibrate the toxicokinetic models developed in this study. Our results showed that it was possible to use an existing general toxicokinetic model for other compounds. In fact, most of the simulation results showed good agreement with the experimental data obtained for the studied solvents, with a percentage of model predictions that lies within the 95% confidence interval varying from 44.4 to 90%. Results pointed out that for same exposure conditions, men and women can show important differences in urinary levels of biological indicators of exposure. Moreover, when running the models by simulating industrial working conditions, these differences could even be more pronounced. In conclusion, a general and simple toxicokinetic model, adapted for three well known organic solvents, allowed us to show that metabolic parameters can have an important impact on the urinary levels of the corresponding biomarkers. These observations give evidence of an interindividual variablity, an aspect that should have its place in the approaches for setting limits of occupational exposure.
Mots-clé
Environmental Exposure , Biological Markers , Models, Biological , Pharmacokinetics , Sex Factors
Pubmed
Web of science
Open Access
Oui
Création de la notice
20/01/2014 9:32
Dernière modification de la notice
20/08/2019 15:06
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