Toluene and methylethylketone: effect of combined exposure on their metabolism in rat
| Autor: | Aurélie Thomas, Elodie Bonfanti, Stéphane Grossmann, Samuel Muller, Pierre Campo, Laurent Gaté, Anne-Marie Lambert-Xollin, Sylvie Sébillaud, Frédéric Cosnier, Hervé Nunge |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Health Toxicology and Mutagenesis 010501 environmental sciences Toxicology 01 natural sciences Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Rats Inbred BN Organic chemistry Animals 0105 earth and related environmental sciences Pharmacology Inhalation Exposure Chemistry Body Weight Brain General Medicine Metabolism Organ Size 030210 environmental & occupational health Toluene Butanones Liver Biological Assay |
| DOI: | 10.6084/m9.figshare.5357527 |
| Popis: | 1. Multiple exposures are ubiquitous in industrial environments. In this article, we highlight the risks faced by workers and complete the data available on the metabolic impact of a common mixture: toluene (TOL) and methylethylketone (MEK). 2. Rats were exposed by inhalation under controlled conditions either to each solvent individually, or to mixtures of the two. How the interaction between the two solvents affected their fate in the blood and brain, their main relevant urinary metabolites (o-cresol, benzylmercapturic acid for TOL and 2,3-butanediols for MEK) and their hepatic metabolism were investigated. 3. Although the cytochrome P450 concentration was unchanged, and the activities of CYP1A2 and CYP2E1 isoforms were not additively or synergistically induced by co-exposure, TOL metabolism was inhibited by the presence of MEK (and vice versa). Depending on the relative proportions of each compound in the mixture, this sometimes resulted in a large increase in blood and brain concentrations. Apart from extreme cases (unbalanced mixtures), the amount of o-cresol and benzylmercapturic acid (and to a lesser extent 2,3-butanediols) excreted were proportional to the blood solvent concentrations. 4. In a co-exposure context, ortho-cresol and benzylmercapturic acid can be used as urinary biomarkers in biomonitoring for employees to relatively accurately assess TOL exposure. |
| Databáze: | OpenAIRE |
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