PHARMACOKINETICS OF 3,3',5,5'-TETRACHLOROBIPHENYL IN MALE RAT

Abstract

The pharmacokinetics of 3,3'',5,5''-tetrachlorobiphenyl (4-CB) was studied to determine the importance of Cl position to the kinetics of polychlorinated biphenyl (PCB) distributio, metabolism and excretion by the rat. Tissue samples and excreta were collected at times ranging from 2 h-42 days after i.v. injection of a single 0.6 mg/kg dose of 14C-labeled 4-CB. The relative fractions of 4-CB and its metabolites were determined in selected samples, and 4 h bile cannulations were performed to establish the rate of biliary excretion. A mathematical model description of PCB kinetics in the rat was defined here for 4-CB and used to generate tissue and excretion concentration-time profiles for both the parent compound and its metabolites. Model predictions were in good agreement with the experimental data, and showed how theindividual pharmacokinetics of 4-CB compared to several other PCB. The rate of 4-CB metabolism and excretion was slower than would be predicted according to its degree of chlorination. The relative rates of metabolism for 4-CB and 5 other differently chlorinated biphenyls could be ordered according to the number of adjacent unsubstituted C-atom pairs they contained. It appears that Cl position is more important than degree of chlorination because the former can alter the availability of vicinal hydrogens thought to facilitate rapid PCB metabolism by mammals.