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) Unties 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 (C) 2010 Elsevier Ltd All rights reserved