The pharmacokinetics of 2,2',5,5'-tetrachlorobiphenyl and 3,3',4,4'-tetrachlorobiphenyl and its relationship to toxicity.
The pharmacokinetics of two toxicologically diverse tetrachlorobiphenyls (TCBs) were measured in mice. After dosing to apparent steady-state conditions, 2,2',5,5'-TCB was found to have a tissue elimination half-life of between 1.64 and 2.90 days. The half-life of 3,3',4,4'-TCB was similar, ranging from 1.07 to 2.60 days. Systemic clearance and volume of distribution estimates were also similar for the two TCB isomers. The 3,3',4,4'-isomer had a substantially greater partitioning from serum into adipose, liver, and thymic tissues. With dosing regimens developed using these measured pharmacokinetic parameters, experiments were undertaken to compare toxic potency of these two TCBs when similar tissue concentrations of the two isomers were achieved in target and storage tissues. These studies demonstrated that thymic atrophy occurs at lower 3,3',4,4'-TCB doses and tissue concentrations than those required to produce hepatotoxicity. These two organ toxicities were produced only by 3,3',4,4'-TCB despite the fact that equivalent or higher tissue concentrations of 2,2',5,5'-TCB were achieved in vivo in all tissues. We conclude that the in vivo difference in the toxic potency of these two TCB isomers does not result from the significant differences in their tissue disposition, elimination, and ultimate bioaccumulation.
Clevenger
M A
MA
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock 72205.
Roberts
S M
SM
Lattin
D L
DL
Harbison
R D
RD
James
R C
RC
D000273:Adipose Tissue / Q000032:analysis; D000818:Animals; D006207:Half-Life; D008099:Liver / Q000032:analysis; D008297:Male; D008433:Mathematics; D008657:Metabolic Clearance Rate; D051379:Mice; D008813:Mice, Inbred ICR; D011078:Polychlorinated Biphenyls / Q000032:analysis / Q000493:pharmacokinetics* / Q000633:toxicity; D013950:Thymus Gland / Q000032:analysis; D014018:Tissue Distribution
C009407:2,5,2',5'-tetrachlorobiphenyl; D011078:Polychlorinated Biphenyls; C028451:3,4,3',4'-tetrachlorobiphenyl