TISSUE DISTRIBUTION AFTER A SINGLE SUBCUTANEOUS ADMINISTRATION OF 2,3,7,8-TETRABROMODIBENZO-P-DIOXIN IN COMPARISON WITH TOXICOKINETICS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN FEMALE WISTAR RATS

Tissue concentrations of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) and induction of ethoxyresorufin O-deethylase (EROD) were determined in f emale Wistar rats following a single subcutaneous (s.c.) injection of TBDD. Two sets of experiments were performed in order to study (a) the time course after a single s.c. administration of 600 ng TBDD/kg body wt up to 78 days, and (b) the dose-response seven days after a single s.c. injection of different doses of TBDD (3 to 3,000 ng/kg body wt). The results obtained on toxicokinetics and enzyme induction were comp ared with those following a single s.c. administration of 300 ng/kg bo dy wt 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Three days after the injection, approximately 93% of TBDD and 90% of TCDD had been absorbe d. Fourteen days after s.c. injection less than 1% of the administered dose of both substances remained at the injection site. Three days af ter a single s.c. injection of 600 ng TBDD/kg body wt and 300 ng TCDD/ kg body wt, the maximum tissue concentrations in the liver amounted to (M +/- S.D.) 5.7 +/- 0.8 and 4.7 +/- 0.9 ng/g wet weight, respectivel y. In adipose tissue, the peak concentration was 3.2 +/- 0.2 ng/g wet weight for TBDD on day 14, and 0.8 +/- 0.1 ng/g for TCDD on day 7. Thr oughout the study, the concentration ratio in the TCDD-treated group w as always at least twice as high as that in the TBDD-treated group. Th e elimination half-life (t(1/2)) of TBDD and of TCDD in the liver was 13.3 and 13.6 days, respectively. In the adipose tissue the t(1/2) of TCDD was 24.5 days but no reliable t(1/2) could be calculated for TBDD (t(1/2) = 39.4 days with a 95% confidence interval of 25.9 to 82.4 da ys). Tissue content of TBDD and TCDD in liver and adipose tissue incre ased dose-dependently, and the linear regression in a double-logarithm ic plot showed a straight line. Time course of the induction of hepati c EROD activity after treatment with 600 ng TBDD/kg body wt was almost identical with that observed following a single dose of 300 ng TCDD/k g body wt. The induction of hepatic EROD activity was linearly correla ted in a double-logarithmic plot to the hepatic concentrations of the congeners (both TBDD and TCDD). The slopes of the dose-response curves after administration of TBDD and TCDD were almost parallel for tissue concentrations ranging from 0.1 to 30 ng/g wet weight.