TY - JOUR T1 - Metabolism, distribution, and excretion of the carcinogenic aromatic amine, 3,3'-dimethoxybenzidine in the rat. Formation of mutagenic urinary and biliary metabolites. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 293 LP - 300 VL - 11 IS - 4 AU - R M Rodgers AU - C Garvie-Gould AU - K F Scott AU - D F Milam AU - R K Lynn Y1 - 1983/07/01 UR - http://dmd.aspetjournals.org/content/11/4/293.abstract N2 - 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. ER -