PMID: 5256Mar 1, 1976

Uptake and disposition of chlorinated biphenyls by isolated perfused rat liver

Drug Metabolism and Disposition : the Biological Fate of Chemicals
H M Mehendale


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 pe...Continue Reading

Related Concepts

Biliary Sludge
Biphenyl Compounds
Structure-Activity Relationship

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