Effects of 2,3,7,8-tetrachlorodibenzo- p-dioxin on the distribution and biliary excretion of polychlorinated biphenyls in rats

Abstract

Plasma disappearance, biliary excretion, and tissue distribution of two polychlorinated biphenyls (PCBs), 2,5,2′,5′-[ 3H]tetrachlorobiphenyl (4-CB) and 2,4,5,2′,4′,5′-[ 3H]hexachlorobiphenyl (6-CB), was determined in rats 10 days after oral administration of a single 10 or 25 μg/kg dose of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD). Plasma disappearance of both PCBs was not altered by TCDD treatment, but biliary excretion was depressed. Associated with the depressed excretion was a reduction in bile flow and concentration of 4-CB- and 6-CB-derived 3H in bile. Treatment with TCDD resulted in less PCB being distributed to the skin and a greater percentage of the dose being accumulated in the liver. The content of PCB-derived 3H in skeletal muscle, adipose tissue, and urine was similar in control and TCDD-treated rats. Extraction of bile with hexane showed that the majority of biliary radioactivity was in the form of polar metabolites and that the proportion of parent PCB (hexane-extractable radioactivity) to polar metabolites was not altered by TCDD treatment. In rats given 4-CB and sacrificed 1 hr later, the majority of radioactivity in the liver was hexane extractable, and the smaller amount of hepatic radioactivity due to polar 4-CB metabolites was greater in the TCDD treatment group than in the control group. When biliary metabolites of 4-CB were administered, biliary excretion of the metabolites was depressed in TCDD-treated animals. Thus, TCDD treatment impairs the initial and main excretory pathway for PCB elimination in the rat—biliary excretion—and alters the distribution of PCBs to the skin and liver.