Biotransformation of trichloroethene : dose-dependent excretion of 2,2,2-trichloro-metabolites and mercapturic acids in rats and humans after inhalation.
Chronic bioassays with trichloroethene (TRI) demonstrated carcinogenicity in mice (hepatocellular carcinomas) and rats (renal tubular cell adenomas and carcinomas).
The chronic toxicity and carcinogenicity is due to bioactivation reactions.
TRI is metabolized by cytochrome P450 and by conjugation with glutathione.
Glutathione conjugation results in S- (dichlorovinyl) glutathione (DCVG) and is presumed to be the initial biotransformation step resulting in the formation of nephrotoxic metabolites.
Enzymes of the mercapturic acid pathway cleave DCVG to the corresponding cysteine S-conjugate, which is, after translocation to the kidney, cleaved by renal cysteine S-conjugate ï-lyase to the electrophile chlorothioketene.
After N-acetylation, cysteine S-conjugates are also excreted as mercapturic acids in urine.
The object of this study was the dose-dependent quantification of the two isomers of N-acetyl-S- (dichlorovinyl) - L-cysteine, trichloroethanol and trichloroacetic acid, as markers for the glutathione-and cytochrome P450-mediated metabolism, respectively, in the urine of humans and rats after exposure to TRI.
Three male volunteers and four rats were exposed to 40,80 and 160 ppm TRI for 6 h. A dose-dependent increase in the excretion of trichloroacetic acid, trichloroethanol and N-acetyl-S- (dichlorovinyl) - L-cysteine after exposure to TRI was found both in humans and rats.
Amounts of 3100 mol trichloroacetic acid+trichloroethanol and 0.45 mol mercaptur...
Mots-clés Pascal : Ethylène(trichloro), Solvant organique, Métabolisme, Métabolite, Inhalation, Excrétion, Exposition professionnelle, Homme, Surveillance biologique, Médecine travail, Rat, Rodentia, Mammalia, Vertebrata, Animal, Toxicité, Rein, Appareil urinaire pathologie
Mots-clés Pascal anglais : Ethylene(trichloro), Organic solvent, Metabolism, Metabolite, Inhalation, Excretion, Occupational exposure, Human, Biological monitoring, Occupational medicine, Rat, Rodentia, Mammalia, Vertebrata, Animal, Toxicity, Kidney, Urinary system disease
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 96-0156379
Code Inist : 002B03L04. Création : 199608.