Pharmacokinetics of 3,3',5,5'-tetrachlorobiphenyl in the male rat

Abstract

The pharmacokinetics of 3,3',5,5'-tetrachlorobiphenyl (4-CB) was studied to determine the importance of chlorine position to the kinetics of polychlorinated biphenyl (PCB) distribution, metabolism, and excretion by the rat. Tissue samples and excreta were collected at times ranging from 2 hr to 42 days after intravenous 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-hr 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 the individual pharmacokinetics of 4-CB compared to several other PBC's. 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 five other differently chlorinated biphenyls could be ordered according to the number of adjacent unsubstituted carbon-atom pairs they contained. It appears that chlorine 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.