Comparative studies on distribution and covalent tissue binding of 2,4,2',4'- and 3,4,3',4'-tetrachlorobiphenyl isomers in the rat.

The 14C-labeled tetrachlorobiphenyl (TCB) isomers 2,4,2',4'-tetrachlorobiphenyl (2,4,2',4'-TCB) and 3,4,3',4'-tetrachlorobiphenyl (3,4,3'4'-TCB) were administered orally to rats, and distribution and covalent binding were measured in several organs. Marked differences in distribution and covalent binding of the two TCBs were observed. The accumulation and retention of 2,4,2',4'-TCB in adipose tissue were much higher than those of 3,4,3',4'-TCB, although the level of radioactivity in the blood was consistently higher in 3,4,3',4'-TCB treated rats. The radioactivity bound in covalent linkages with cellular macromolecules in several tissues was also measured. The data obtained indicated that covalent binding was higher in 3,4,3',4'-TCB treated rats than in those treated with 2,4,2',4'-TCB, particularly in liver and blood components. These results suggest that the two TCB isomers have different pharmacokinetic properties in rats, and the association of covalent binding with 3,4,3',4'-TCB-induced toxicities might be important. In addition, we found that repeated oral dosing with the two TCB isomers caused an increase in in vitro liver microsomal generation of reactive metabolites of TCBs, indicating that the microsomal enzyme system is likely to play an important role in the in vivo covalent binding of TCB.