Toxicological Sciences 70, 171-182 (2002)
Copyright © 2002 by the Society of Toxicology
BIOTRANSFORMATION AND TOXICOKINETICS |
Tissue Distribution and Half-Lives of Individual Polychlorinated Biphenyls and Serum Levels of 4-Hydroxy-2,3,3`,4`,5-pentachlorobiphenyl in the Rat
,1
* Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; and
Department of Environmental Chemistry, Stockholm University, Stockholm, Sweden
This study was done to generate kinetic data on individual congeners of chlorinated biphenyls in the low dose range, which could be of value in the risk assessment procedure. Male Sprague-Dawley rats were given a single oral dose of a mixture of polychlorinated biphenyls (CBs) containing either CBs 105, 118, 138, 153, 156, 157, 170, and 180 (A-mix) or CBs 28, 52, 77, 87, and 101 (B-mix). Liver, serum, and adipose tissue were collected after 6 h up to 135 days, from rats given the A-mix, and after 6 h up to 4 days from rats given the B-mix. CB concentrations were measured in liver, serum, and adipose tissue. In addition, this study provides kinetic data of one of the major CB metabolites, 4-hydroxy-2,3,3`,4`,5-pentachlorobiphenyl (4-OH-CB107). The low doses used resulted in serum CB concentrations similar to human background serum concentrations. In the A-mix experiment all CBs show high initial liver and serum concentrations followed by redistribution into adipose tissue. Differences between congeners were correlated to molecular weight. High molecular weight correlated to lower uptake and slower redistribution. During dynamic steady-state the tissue concentrations decreased with a calculated first order rate between 54–129 days for halving the concentrations (half-life). Most of the decrease in concentration was explained by the growth-related increase of tissue masses in general and adipose tissue in particular. In the B-mix experiment, the concentrations of CBs in adipose tissue decreased with between 25 and 59% from day 1 to day 4. These results show that the B-mix congeners, given at low dose, have longer half-lives than previously reported in high dose studies. Partition coefficients between body compartments are reported and for the first time a high and congener specific liver-to-serum ratio of CB 77 is observed.
Key Words: distribution; partition coefficient; half-life; polychlorinated biphenyls; PCB; liver; adipose tissue; serum; rat; 4-hydroxy-2,3,3`,4`,5-pentachlorobiphenyl.
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