Metabolism, distribution, and excretion of the carcinogenic aromatic amine, 3,3'-dimethoxybenzidine in the rat. Formation of mutagenic urinary and biliary metabolites.
The carcinogenic aromatic amine 3,3'-dimethoxybenzidine (DMOB) was rapidly metabolized in the rat. Thirty minutes after iv administration of 14C-DMOB, less than 2% of the dose could be recovered from the animal as the parent compound. Extensive biliary excretion (70% of the dose) resulted in the accumulation of approximately 50% of the dose in the intestinal tract. Three days after either oral or iv dosing, 50% of the administered radiolabel had been excreted in the feces and 30-40% excreted in the urine while 45% of the radiolabel remaining in the animal was present in the liver in the form of covalently bound metabolites. GC/MS studies of urine and bile demonstrated the presence of eight previously unidentified metabolites formed via N-acetylation, hydroxylation, O-demethylation, and glucuronidation. DMOB was mutagenic to Salmonella typhimurium strain TA98 only after metabolic activation by liver enzymes. N-Acetyl-DMOB was a more potent bacterial mutagen than either DMOB, N,N'-diacetyl-DMOB, or other biliary metabolites.
D000818:Animals; D001560:Benzidines / Q000378:metabolism* / Q000652:urine; D001646:Bile / Q000378:metabolism*; D001711:Biotransformation; D003962:Dianisidine / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D013058:Mass Spectrometry; D009153:Mutagens / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D001560:Benzidines; D009153:Mutagens; D003962:Dianisidine