Metabolism of 1,2,4-trichlorobenzene in rats: examination of thiol formation.
1. More than 60% of oral doses of 14C-1,2,4-trichlorobenzene (ca. 21 mg/kg) administered to rats were excreted in bile as S-trichlorophenyl-mercapturic acid pathway metabolites. 2. The biliary metabolites were ultimately excreted in urine mainly as the isomeric mercapturic acids. 3. An acetylated glutathione conjugate was isolated as a major metabolite in bile (8% dose). The acetyl group was shown by mass spectrometry to be on the glutamyl moiety. 4. A glutamylcysteine conjugate of trichlorobenzene was also isolated from bile as a major metabolite (8% dose). 5. Trichlorothiophenols were deduced not to be intermediates or end-products of enzymic metabolism of trichlorobenzene in rats because 14C-2,4,5-trichlorothiophenol dosed i.p. to rats was excreted as the S-glucuronide (17% dose) and as S-(methylsulphonyl-dichlorophenyl)-mercapturic acid (36% dose).
Bakke
J E
JE
Biosciences Research Laboratory, US Department of Agriculture, Fargo, ND 58105.
Huwe
J K
JK
Mulford
D J
DJ
Bergman
A
A
D000111:Acetylcysteine / Q000031:analogs & derivatives; D000818:Animals; D001646:Bile / Q000378:metabolism; D002722:Chlorobenzenes / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D010636:Phenols / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000378:metabolism* / Q000652:urine
D002722:Chlorobenzenes; D010636:Phenols; D013438:Sulfhydryl Compounds; C009947:1,2,4-trichlorobenzene; D000111:Acetylcysteine