Metabolism of 1,2,4-trichlorobenzene in rats: examination of thiol formation

Abstract

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).