Impact of co-exposure on toluene biomarkers in rats

Toluene is widely used in industry, with an annual consumption close to 20 million tons. Occupational exposure to toluene is commonly assessed using hippuric acid and ortho-cresol despite their low specificity and poor sensitivity. Levels of these biomarkers may depend on factors potentially interfering with toluene biotransformation, such as the presence of other solvents in the workplace. An alternative to the "traditional" toluene biomarkers, mercapturic acids are sensitive and specific toluene metabolites. This study assessed how well mercapturic acids performed in multiple exposure contexts in rats. For these experiments, rats were exposed by inhalation to binary mixtures of toluene with n-butanol, ethyl acetate, methyl ethyl ketone (2-butanone) or xylenes; biological exposure indicators were then measured. Depending on the compounds in the mixture and their concentrations, toluene metabolism was accelerated (with n-butanol), unchanged (with ethyl acetate), or inhibited (with xylenes and 2-butanone). Inhibiting metabolism leads to an increase in blood toluene concentrations, even at authorized atmospheric concentrations, which may have an impact on employees' health. Mercapturic acids appear to be only slightly affected by co-exposure, their levels correlating well with atmospheric toluene levels. They could thus be a suitable substitute for ortho-cresol and hippuric acid for biomonitoring purposes.