Impact of coexposure on toluene biomarkers in rats

Abstract

1. Toluene (TOL) is widely used in industry. Occupational exposure to TOL is commonly assessed using TOL in blood, hippuric acid and ortho-cresol. Levels of these biomarkers may depend on factors potentially interfering with TOL biotransformation, such as the presence of other solvents in the workplace. Mercapturic acids (MAs) could be an alternative to the “traditional” TOL biomarkers.

2. This study aims (1) to investigate in rat the effects of an exposure to vapours mixtures on the TOL metabolism, and (2) to assess how well MAs performed in these contexts compared to the traditional TOL biomarkers.

3. Rats were exposed by inhalation to binary mixtures of TOL with n-butanol (BuOH), ethyl acetate (EtAc), methyl ethyl ketone (MEK) or xylenes (XYLs); biological exposure indicators were then measured.

4. Depending on the compounds in the mixture and their concentrations, TOL metabolism was accelerated (with BuOH), unchanged (with EtAc) or inhibited (with XYLs and MEK). Inhibition leads to an increase in blood TOL concentrations, even at authorized atmospheric concentrations, which may potentiate the effect of TOL.

5. MAs excretions are little affected by coexposure scenarios, their levels correlating well with atmospheric TOL levels. They could thus be suitable bioindicators of atmospheric TOL exposure.

• Binary mixture
• biological monitoring
• butanol
• inhalation
• mercapturic acid
• metabolic interaction
• methyl ethyl ketone
• toluene

Acknowledgements

The authors gratefully acknowledge Philippe Chaumont and Jean-Claude Gondrexon for their technical assistance and Lionel Dussoul and Sylvie Michaux from the laboratory animal facility for their help in rat handling and husbandry.