title: 3-Chloro-2-hydroxypropylmercapturic acid and α-chlorohydrin as biomarkers of occupational exposure to epichlorohydrin.
abstract: Until now no urinary biomarker of exposure was available to assess human exposure to epichlorohydrin (ECH). For this purpose the urinary excretion of mercapturic acids and α-chlorohydrin (α-CH), which are potential metabolites of ECH in humans was investigated. This study was undertaken in a chemical plant in which ECH is used in the production of glycidyl ethers. Urine samples were collected from 19 persons at the beginning and at the end of work-shifts and at the morning after the last work-shift. Respiratory air concentrations of ECH were determined by personal air monitoring (PAM) and were found to range from<0.03 to 1.1 mg/m(3) (8 h-TWA, median 0.09, n=23). The determined respiratory exposure to ECH was in all cases below the current occupational exposure limit of 4 mg/m(3) for ECH (8 h-TWA-OEL). In one additional case a dermal exposure to an unknown amount of technical ECH was noted. Urinary metabolites were isolated by ethyl acetate extraction or by lyophilization and determined by GC-MS. In ethyl acetate extracts of acidified urine samples of workers with potential occupational exposure to ECH, 3-chloro-2-hydroxypropylmercapturic acid (CHPMA) was identified with GC-MS and the concentrations measured ranged from<0.05 (detection limit) to 5.35 mmol/mol creatinine. The increase of the CHPMA excretion during the work-shifts, corrected for creatinine excretion, correlated well with the 8 h-TWA respiratory air concentrations of ECH (r(2)=0.94, n=7). For 8 individuals it was possible to assess an urinary half-life for the excretion of CHPMA (2.54±0.94 h). By extrapolating the relation between the ambient air concentrations of ECH and the urinary CHPMA excretions, an excretion of 6.2 mmol CHPMA/mol creatinine (tolerance levels of 95% C.I.: 5.1-7.3) is predicted if ECH exposure is at the level of the current OEL. The urinary excretion of two other known metabolites of ECH in rats, namely α-CH and 2,3-dihydroxypropylmercapturic acid (DHPMA) was also investigated. α-CH was identified in urine of workers exposed to low air concentrations of ECH but DHPMA could only be identified after the dermal exposure to technical ECH. In these latter samples CHPMA and α-CH were determined up to 167 and 6.3 mmol/mol creatinine, respectively. From this investigation it is concluded that urinary excretion of the mercapturic acid CHPMA is an appropriate biomarker of human exposure to ECH. A tentative biological exposure index (BEI) of 6 mmol CHPMA/mol creatinine for ECH during an 8 h work-shift is proposed.
authors.affiliation: Leiden-Amsterdam Center for Drug Research (LACDR), Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
authors.forename: B M
authors.initials: BM
authors.lastname: de Rooij
authors.forename: P J
authors.initials: PJ
authors.lastname: Boogaard
authors.forename: J N
authors.initials: JN
authors.lastname: Commandeur
authors.forename: N P
authors.initials: NP
authors.lastname: Vermeulen