Glutathione pathway in ethylbenzene metabolism: Novel biomarkers of exposure in the rat

• Published in: Chemosphere (Oxford) Vol. 81; no. 10; pp. 1334 - 1341
• Main Authors: Cossec, Benoît, Cosnier, Frédéric, Burgart, Manuella, Nunge, Hervé, Grossmann, Stéphane
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.11.2010; Elsevier
• Subjects: Animal, plant and microbial ecology; Animals; Applied ecology; Benzene Derivatives - pharmacokinetics; Benzene Derivatives - toxicity; Benzene Derivatives - urine; Biological and medical sciences; Biomarkers; Biomarkers - metabolism; Biomarkers - urine; Ecotoxicology, biological effects of pollution; Ethylbenzene; Fundamental and applied biological sciences. Psychology; General aspects; Glutathione - metabolism; Glutathione - urine; Glutathione pathway; Inhalation Exposure - analysis; Male; Mercapturic acids; Metabolic Networks and Pathways - drug effects; Rats; Rats, Sprague-Dawley; Techniques; Biomarkers; Ethylbenzene; Glutathione pathway; Mercapturic acids; Vertebrata; Mammalia; Rat; Rodentia; Biological marker; Metabolism; Glutathione
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2010.08.025

Glutathione pathway was specifically studied in rats exposed by inhalation to a range of ethylbenzene vapours (5–2000 ppm). Urines were collected during exposure (6 h) and over the 18 h following the exposure. The potential metabolites coming from either side-chain or ring oxidation were synthesized: 1-, 2-phenylethylmercapturic acids (1-, and 2-PEMA) and 2-, 3- and 4-ethylphenylmercapturic acids (2-, 3-, and 4-EPMA). Their synthesis was fully described and the molecules characterized. Urine samples were analysed using a selective HPLC–fluorescence method. Among the five metabolites, 2-PEMA was never observed in any urine sample. By contrast, 1-PEMA was discovered in its two diastereomeric forms, and it was shown that one of them was mainly present. 2-EPMA, 3-EPMA and 4-EPMA (in the ratio 1:2:6) were also found, and their combined excretion levels were similar to that of 1-PEMA. The atmospheric concentrations and urinary excretions yielded very close correlations which allow us to consider these mercapturic acids as novel ethylbenzene exposure biomarkers.