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.
Klos
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C
Toxicology Institute, University of Würzburg, Germany.
Dekant
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W
D000111:Acetylcysteine / Q000652:urine; D000818:Animals; D001711:Biotransformation; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000378:metabolism*; D002722:Chlorobenzenes / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006873:Hydroquinones / Q000652:urine; D007680:Kidney Neoplasms / Q000139:chemically induced*; D007700:Kinetics; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D002273:Carcinogens; D002722:Chlorobenzenes; D006873:Hydroquinones; C018511:4-dichlorobenzene; C069879:2,5-dichlorohydroquinone; D000111:Acetylcysteine