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• W2037290401 abstract "The mutagenic and carcinogenic aromatic amine, benzidine (BZ), underwent extensive biotransformation in the rat. Three days after po (5.0 mg/kg) or iv (2.5 mg/kg administration of [14C]BZ, 90% of the radiolabel had been excreted in the urine (25%) and feces (65%); 7% was recovered in the animal. As the dose was increased from 0.5 to 50 mg/kg, the percentage of the dose excreted in urine increased twofold. In distribution studies, a major portion of the iv dose accumulated in the intestinal tract due to the excretion of 71% of the administered radiolabel in bile. The liver, which is a primary target organ of BZ carcinogenicity in rats, contained a higher concentration of radiolabel than other tissues studied. A minimum of 17 urinary and/or biliary metabolites were separated by HPLC. The major metabolites were N-acetyl-BZ(ABZ), N,N'-diacetyl-BZ(DABZ), BZ-N-glucuronide, ABZ-glucuronide, N-OH-DABZ glucuronide, 3-OH-DABZ glucuronide, and a glutathione conjugate of DABZ (3-GSH-DABZ). At low doses (0.5 to 5 mg/kg), 3-OH-DABZ glucuronide, 3-GSH-DABZ, and DABZ were the major urinary or biliary metabolites. However, at higher doses (50 mg/kg), N-OH-DABZ glucuronide, which was a minor metabolite at low doses, became a major urinary and biliary metabolite. Several urinary and biliary metabolites displayed significant mutagenicity in the Salmonella typhimurium (strain TA98)-liver S9-beta-glucuronidase assay. However, N-OH-DABZ glucuronide exhibited a mutagenic potency 10X greater than the other urinary metabolites. Results of these studies demonstrate that BZ is rapidly metabolized via N-acetylation, N-hydroxylation, and aromatic hydroxylation to a variety of mutagenic metabolites which are excreted in urine or bile primarily as glucuronide and/or glutathione conjugates. The most potent mutagen studied was also a major urinary and biliary metabolite." @default.
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• W2037290401 date "1984-01-01" @default.
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• W2037290401 title "Disposition of the aromatic amine, benzidine, in the rat: Characterization of mutagenic urinary and biliary metabolites" @default.
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• W2037290401 doi "https://doi.org/10.1016/0041-008x(84)90244-8" @default.
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