Biological monitoring of mixed exposures in the workplace: Development of models to facilitate the interpretation of exposure data

Abstract

Given the virtually unlimited number of products, it is for all practical purposes impossible to test every product and combination of products. An alternate solution to this problem is the use of computer models that mimic the behaviour of specific substances in the human body. Using validated models of this type, it is possible to test multiple exposure scenarios and predict the effects of these scenarios on the results of biological monitoring of workers.

The objective of this project was to develop models that simulate exposure to solvent mixtures, predict the effect of such exposures on biological monitoring end-points, and facilitate the interpretation of data obtained from the biological monitoring of mixed exposures.

The models developed simulate the interaction of human metabolites produced by exposure to ten solvent mixtures and shed light on the influence of several factors on metabolic interactions. In addition, the study demonstrated the utility of modelling to predict the influence of metabolic interactions on the level of biological markers and establish exposure limits for solvent mixtures.

Produced Under this Project

Scientific Reports

Biological monitoring of mixed occupational exposure. Development of models for interpreting biological exposure monitoring data Research Report: R-150

Scientific Publications

Un modèle de simulation utile à la surveillance biologique de l'exposition à des solvants organiques hydrosolubles en milieu de travail
Laparé S., Tardif R., Brodeur J.
Source :
in Le partenariat en santé et sécurité du travail: une approche à développer : Congrès de l'Association québécoise pour l'hygiène, la santé et la sécurité du travail / AQHSST, (18e : mai, 1996 : Hull, Canada), 1996, p. 79-85
Modélisation toxicocinéthiques des interactions toxicocinétiques résultant de l'exposition à des mélanges de solvants
Tardif R., Charest-Tardif G., Laparé S., Brodeur J.
Source :
in Le partenariat en santé et sécurité du travail: une approche à développer : Congrès de l'Association québécoise pour l'hygiène, la santé et la sécurité du travail / AQHSST, (18e : mai, 1996 : Hull, Canada), 1996, p. 292
Use of kinetic modeling to predict metabolic interaction for binary mixtures of industrial solvents
Brodeur J., Tardif R., Laparé S., Charest-Tardif G., Krishnan K.
Source :
Archives of Complex Environment Studies, vol. 8, no 1-2, 1996, p. 17-24
Comparison of the influence of binary mixtures versus a ternary mixture of inhalated aromatic hydrocarbons on their blood kinetics in rat
Tardif R., Charest-Tardif G., Brodeur J.
Source :
Archives of Toxicology, vol. 70, no7, 1996, p. 405-413
Use of kinetic modeling to predict metabolic interaction for combinations of binary mixtures of industrial solvents
Brodeur J., Tardif R., Laparé S., Charest-Tardif G., Krishnan K.
Source :
International Conference on the Combined Effects of Environmental Factors (ICCEF) (6e, 1994, Toyama, Japon), Proceeding, 1994, p. 72
Predicting the magnitude of toxicokinetic interactions at low doses with physiologically-based models: Implications for chemical mixtures risk assessment
Pelekis M., Charest-Tardif G., Brodeur J., Krishnan K.
Source :
in Symposium of the United States Environmental Protection Agency : Chemical mixtures and quantitative risk assessment, Research Triangle Park, Proceeding, 1994, p. 28
Physiologically-based pharmacokinetic modeling of a ternary mixture of aromatic hydrocarbons in the rat
Tardif R., Charest-Tardif G., Brodeur J., Krishnan K.
Source :
in Symposium of the United States Environmental Protection Agency: Chemical mixtures and quantitative risk assessment, Research Triangle Park, Proceedings, novembre 1994, p. 34
Utilisation de modèles cinétiques à base physiologique pour la prédiction des interactions métaboliques consécutives aux expositions à des mélanges binaires de solvants
Tardif R., Laparé S., Charest-Tardif G., Brodeur J., Krishnan K.
Source :
in Colloque de l'Université de Montréal sur l'environnement : analyse et intervention (1er : 1994 : Montréal, Québec), 1994, p. 72
Statistical approaches for the validation of physiologically based pharmacokinetic (PBPK) models
Haddad S., Gad S. C., Tardif R., Krishnan K.
Source :
Society of Toxicology, Annual Meeting (34e, 1995, Baltimore, Mar.), The Toxicologist, vol. 15, mars 1995, p. 48
In vitro data based physiological pharmacokinetic model for methyl-t butyl ether in the rat
Tardif R., Charest-Tardif G., Brodeur J., Krishnan K.
Source :
Society of Toxicology, Annual Meeting (34e, 1995, Baltimore, Mar.), The Toxicologist, vol. 15, mars 1995, p. 270
Physiologically based pharmacokinetic (PBPK) modeling of a temary mixture of alkyl benzenes in the rat
Tardif R., Charest-Tardif G., Brodeur J., Krishnan K.
Source :
Society of Toxicology, Annual Meeting (34e, 1995, Baltimore, Mar.), The Toxicologist, vol. 15, mars 1995, p. 269
Physiologically based pharmacokinetic (PBPK) modeling of toxicokinetic interactions among industrial solvents
Tardif R., Charest-Tardif G., Laparé S., Pelekis M., Krishnan K., Brodeur J.
Source :
in International Congress of Toxicology (1995 : Seattle, Washington), Proceeding, 1995, p. 18-P-3
Physiologically based pharmacokinetic modeling of a mixture of toluence and xylene in humans
Tardif R., Laparé S., Charest-Tardif G., Brodeur J., Krishnan K.
Source :
Risk Analysis, vol. 15, no 3, 1995, p. 335-342
Utilisation des modèles cinétiques à base physiologique pour la prédiction des interactions métaboliques consécutives aux expositions à des mélanges binaires de solvants
Tardif R., Laparé S., Charest-Tardif G., Krishnan K., Brodeur J.
Source :
Colloque en environnement, Université de Montréal (1995, Montréal, Québec), vol. 18, 1995, p. 582-590
Physiologically-based pharmacokenetic modeling of a ternarty mixture of alkylbenzenes in rats and humans
Brodeur J., Charest-Tardif G., Krishnan K., Tardif R.
Source :
in International Symposium on Biological Monitoring in Occupational and Environmental Health (September 11-13, 1996 : Espoo, Finlande), Aitio, A., K. Engström, M. Kiilunen, J. Liesivuori et L. Pyy (eds), Book of abstracts, 1996, p. 31-32
Physiologically-based pharmacokinetic modeling of a ternary mixture of alkyl benzenes in the rat
Tardif R., Charest-Tardif G., Brodeur J., Krishnan K.
Source :
Toxicology and Applied Pharmacology, vol. 144, 1990, p. 120-134

Additional Information

Type: Project

Number: 0092-0090

Status: Completed

Research Field: Chemical and Biological Hazard Prevention

Team:

Robert Tardif (Université de Montréal)
Jules Brodeur (Université de Montréal)