Disposition of 3,3'-dichlorobenzidine in the rat
Hsu, R.S.; Sikka, H.C.
Toxicology and Applied Pharmacology 64(2): 306-316
1982
ISSN/ISBN: 0041-008X PMID: 7123557 Document Number: 185127
The disposition of the carcinogen 3,3'-dichlorobenzidine (DCB) was studied in the male rat following oral administration. [14C]DCB was well absorbed by the rat with the maximum plasma radioactivity levels being found within 8 h after dosing. The radioactivity was well distributed in the tissues 24 h after administration with the highest levels found in the liver, followed by kidney, lung, and spleen. Repeated administration (6 doses) of [14C]DCB to animals did not result in a substantial accumulation of 14C in the tissues. The elimination of radioactivity from the plasma, liver, kidney and lung was biphasic, showing an initial rapid decline (half-lives 1.68, 5.78, 7.14, and 3.85 h, respectively) followed by a slower disappearance phase (half-lives 33.0, 77.0, 138.6, and 43.3 h, respectively). Approximately half of the total 14C in the liver and kidney was covalently bound to cellular macromolecules 72 h after dosing. [14C]DCB-derived radioactivity was extensively excreted by rats, mainly via the feces. Approximately 23-33% of the administered dose was recovered in the urine and 58-72% in the feces of rats within 96 h. More than 65% of the administered 14C was eliminated in the bile of bile duct-cannulated rats within 24 h after dosing. The radioactivity excreted in the urine and bile was primarily in the form of free (urine 71.2%, bile 25.5%) and conjugated (urine 19.6%, bile 57.9%) metabolites of DCB. DCB is readily absorbed following oral administration, and then metabolized and excreted mainly via the feces.