Absorption, distribution, metabolism, and excretion of 1,3-diphenylguanidine in the male F344 rat

Abstract

1,3-Diphenylguanidine (DPG), a rubber accelerator, was readily absorbed from the gastrointestinal tract of the male Fischer rat and rapidly distributed throughout the body tissues. Absorption and disposition of DPG were not significantly affected by the route of administration or by the dose in the dose range studied, 1.5 to 150 μmol/kg. Most of the dose of DPG was excreted in the urine and feces at approximately equal amounts within 24 hr after oral or iv administration. Greater than 99% of the DPG dose was cleared into the urine and feces within 3 days after administration. Approximately 30% of the DPG-derived radioactivity excreted in urine was the parent compound, DPG, while the remainder was present in the form of two major and one minor metabolite. Close to 95% of the radioactivity excreted in bile was in the form of a single major metabolite. Administration of multiple doses resulted in a proportional increase of DPG-derived radioactivity in the liver as the number of doses increased. DPG-derived radioactivity did not increase in other tissues following multiple doses.