Glutathione pathway in ethylbenzene metabolism: novel biomarkers of exposure in the rat.
Glutathione pathway was specifically studied in rats exposed by inhalation to a range of ethylbenzene vapours (5-2000 ppm). Urines were collected during exposure (6h) 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.
Cossec
Benoît
B
Institut National de Recherche et de Sécurité (INRS), Rue du Morvan CS 60027, Vandoeuvre, 54519 Cedex, France. Benoit.cossec@inrs.fr
Cosnier
Frédéric
F
Burgart
Manuella
M
Nunge
Hervé
H
Grossmann
Stéphane
S
D000818:Animals; D001555:Benzene Derivatives / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D005978:Glutathione / Q000378:metabolism* / Q000652:urine; D019570:Inhalation Exposure / Q000032:analysis*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001555:Benzene Derivatives; D015415:Biomarkers; D005978:Glutathione; C004912:ethylbenzene