Comparative metabolism of the renal carcinogen 1,4-dichlorobenzene in rat: identification and quantitation of novel metabolites.

1. The metabolism of 1,4-dichlorobenzene has been studied in the male and female Fisher 344 rat over 72 h after oral administration of 14C-1,4-dichlorobenzene (900 mg = 96.8 microCi/kg). No covalent binding of radioactivity could be detected in samples of liver, kidney, lung and spleen. The major route of excretion was with urine accounting for 41.3% of the dose for male and 37.8% of the dose for female rat within 72 h after dosing. 2. Urinary metabolites of 1,4-dichlorobenzene were identified and quantified. The major metabolites identified in the urine of both the male and female rat, were the sulphate and glucuronide of 2,5-dichlorophenol. Minor amounts of 2,5-dichlorohydroquinone were excreted as an unidentified conjugate. 3. 2-(N-acetyl-cysteine-S-yl)-1,4-dichlorobenzene and 2-(N-acetyl-cysteine-S-yl)-2,3-dihydro-3-hydroxy-1,3-hydroxy-1,4-dich lorobenzen e were minor metabolites excreted in the urine of both sexes. 4. A novel biotransformation pathway for 1,4-dichlorobenzene may be postulated, leading to the urinary excretion of a mercapturic acid of chlorophenol. 5. No marked differences in the distribution and excretion of metabolites of 1,4-dichlorobenzene were observed between the male and female Fisher 344 rat.