Effect of Dose, Time, and Pretreatement on the Biliary Excretion and Tissue Distribution of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in the Rat

Effect of Dose, Time, and Pretreatment on the Biliary Excretion and Tissue Distribution of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in the Rat. KEDDERIS, L. B., ANDERSEN, M. E., AND BIRNBAUM, L. S. (1993). Fundam. Appl. Toxicol. 21, 405–411. Previous studies of the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) pretreatment on the biliary excretion and hepatic disposition indicated that TCDD did not induce its own metabolic elimination. Pretreatment with TCDD did enhance its hepatic uptake. The present work was designed to further examine the effects of dose, time, and pretreatment on the tissue distribution and biliary elimination of [3H]TCDD. Adult male F-344 rats were administered 0 or 100 nmol [14C]TCDD or [3H]-TCDD/kg body weight po 3 days prior to bile duct cannulation and iv injection of 0 or 1 nmol [3H]TCDD or 1, 10, or 100 nmol [14C]TCDD/kg. Bile was collected for up to 8 hr while rats were maintained under pentobarbital anesthesia. Biliary TCDD and TCDD metabolites were quantified by liquid scintillation spectrometry. In naive animals which received no pretreatment, similar rates of excretion (% dose) were observed following iv administration of 1 nmol [3H]TCDD/kg or 10 or 100 nmol [14C-TCDD/kg. Metabolic elimination of highly purified [3H]TCDD (