Uptake and disposition of chlorinated biphenyls by isolated perfused rat liver.
The hepatic disposition of four chlorinated biphenyls was studied in isolated perfused rat liver preparations perfused with 30% rat blood. Biliary excretion of 14C-labeled 4-chlorobiphenyl (1-CB): 4,4'-dichlorobiphenyl (2-CB): 2,4,5,2',5'-pentachlorobiphenyl (5-CB) and 2,4,5,2',5'-hexachlorobiphenyl (6-CB) appeared to be inversely related to increased chlorination. Each of the compounds was rapidly taken up by the liver from the circulating perfusate. After 4 hr of perfusion, biliary excretion of 14C from 1-CB, 2-CB, 5-CB, and 6-CB was 48.2, 29.6, 20.5, and 1.3% of total dose, respectively. For 1-CB, this rate of biliary elimination represents a maximum perfusate/bile ratio of 107. About 97% of the label in the bile from 1-CB experiments was in the form of metabolites. Biliary excretion of 1-CB was biphasic: an initial rapid phase (t 1/2 = 13 min) was followed by a slower second phase (t 1/2 = 122 min). When the metabolites of 1-CB were added to the perfusate, biliary excretion of these metabolites was monophasic; t 1/2 = 120 min, which corresponded to the slower phase observed when the parent compound was presented to the liver. 1-CB disappeared from the perfusate via a biphasic process. Metabolites of 1-CB effused into the perfusate immediately after the initial rapid uptake of 1-CB by the liver, and the recirculating pool of metabolites was eliminated in the bile by the slow postsynthetic phase of biliary elimination. Less than 2% of 1-CB was present as the parent compound in the perfusion system after 4 hr of perfusion. These findings indicate that the metabolism of 1-CB is not the limiting factor in the hepatic disposition of 1-CB and that the circulating metabolites of 1-CB effusing from the liver might be the major source for urinary excretion.
Uptake and disposition of chlorinated biphenyls by isolated perfused rat liver. The hepatic disposition of four chlorinated biphenyls was studied in isolated perfused rat liver preparations perfused with 30% rat blood. Biliary excretion of 14C-labeled 4-chlorobiphenyl (1-CB): 4,4'-dichlorobiphenyl (2-CB): 2,4,5,2',5'-pentachlorobiphenyl (5-CB) and 2,4,5,2',5'-hexachlorobiphenyl (6-CB) appeared to be inversely related to increased chlorination. Each of the compounds was rapidly taken up by the liver from the circulating perfusate. After 4 hr of perfusion, biliary excretion of 14C from 1-CB, 2-CB, 5-CB, and 6-CB was 48.2, 29.6, 20.5, and 1.3% of total dose, respectively. For 1-CB, this rate of biliary elimination represents a maximum perfusate/bile ratio of 107. About 97% of the label in the bile from 1-CB experiments was in the form of metabolites. Biliary excretion of 1-CB was biphasic: an initial rapid phase (t 1/2 = 13 min) was followed by a slower second phase (t 1/2 = 122 min). When the metabolites of 1-CB were added to the perfusate, biliary excretion of these metabolites was monophasic; t 1/2 = 120 min, which corresponded to the slower phase observed when the parent compound was presented to the liver. 1-CB disappeared from the perfusate via a biphasic process. Metabolites of 1-CB effused into the perfusate immediately after the initial rapid uptake of 1-CB by the liver, and the recirculating pool of metabolites was eliminated in the bile by the slow postsynthetic phase of biliary elimination. Less than 2% of 1-CB was present as the parent compound in the perfusion system after 4 hr of perfusion. These findings indicate that the metabolism of 1-CB is not the limiting factor in the hepatic disposition of 1-CB and that the circulating metabolites of 1-CB effusing from the liver might be the major source for urinary excretion.