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

Excretion of mercapturic acids in the urine is indicative of the forma tion of electrophiles in the metabolism of xenobiotics. The determinat ion of these mercapturic acids thus may be a useful method to estimate the exposure. We identified the nephrotoxic and mutagenic mercapturic adds N-acetYl-S-(1,2-dichlorovinyl)-L-cysteine and N-acetyl-S- (2,2-d ichloro-vinyl)-L-cysteine in the urine of workers exposed to 1,1,2-tri chloroethene. A method to quantify these mercapturic acids by gas chro matography-mass spectrometry-selected ion monitoring was developed and appreciable amounts (2.8-3.8 mumole/L were found in human urine sampl es. Because deacetylation determines notably the amount of the excrete d mercapturic acids, the formation of the resulting cysteine S-conjuga tes was comparably measured in subcellular fractions of rodent and hum an kidneys; significant species differences in acylase activity were f ound. The formation of mutagenic and nephrotoxic metabolites during 1, 1,2-trichloroethene metabolism mandates a revision of the risk assessm ent of trichloroethene exposure.