title: Nephrotoxic and genotoxic N-acetyl-S-dichlorovinyl-L-cysteine is a urinary metabolite after occupational 1,1,2-trichloroethene exposure in humans: implications for the risk of trichloroethene exposure.
abstract: Excretion of mercapturic acids in the urine is indicative of the formation of electrophiles in the metabolism of xenobiotics. The determination of these mercapturic acids thus may be a useful method to estimate the exposure. We identified the nephrotoxic and mutagenic mercapturic acids N-acetyl-S-(1,2-dichlorovinyl)-L- cysteine and N-acetyl-S-(2,2-dichlorovinyl)-L-cysteine in the urine of workers exposed to 1,1,2-trichloroethene. A method to quantify these mercapturic acids by gas chromatography-mass spectrometry-selected ion monitoring was developed and appreciable amounts (2.8-3.8 mumole/L were found in human urine samples. Because deacetylation determines notably the amount of the excreted mercapturic acids, the formation of the resulting cysteine S-conjugates was comparably measured in subcellular fractions of rodent and human kidneys; significant species differences in acylase activity were found. The formation of mutagenic and nephrotoxic metabolites during 1,1,2-trichloroethene metabolism mandates a revision of the risk assessment of trichloroethene exposure.
authors.affiliation: Institut für Toxikologie, Universität Würzburg, Federal Republic of Germany.
authors.forename: G
authors.initials: G
authors.lastname: Birner
authors.forename: S
authors.initials: S
authors.lastname: Vamvakas
authors.forename: W
authors.initials: W
authors.lastname: Dekant
authors.forename: D
authors.initials: D
authors.lastname: Henschler
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000652:urine; D000818:Animals; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009153:Mutagens / Q000009:adverse effects; D016273:Occupational Exposure; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D014241:Trichloroethylene / Q000009:adverse effects* / Q000378:metabolism*
chemical_list: D009153:Mutagens; C049705:S-1,2-dichlorovinyl-N-acetylcysteine; D014241:Trichloroethylene; D000111:Acetylcysteine