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

Abstract

Tissue concentrations of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) and induction of ethoxyresorufin O-deethylase (EROD) were determined in female 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 compared with those following a single S.C. Administration of 300 ng/kg body wt 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD). Three days after the injection, approximately 93% of TBDD and 90% of TCDD had been absorbed. Fourteen days after S.C. Injection less than 1% of the administered dose of both substances remained at the injection site. Three days after 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, respectively. 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. Throughout the study, the concentration ratio in the TCDD-treated group was always at least twice as high as that in the TBDD-treated group. The 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 days). Tissue content of TBDD and TCDD in liver and adipose tissue increased dose-dependently and the linear regression in a double-logarithmic plot showed a straight line. Time course of the induction of hepatic 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/kg body wt. The induction of hepatic EROD activity was linearly correlated in a double-logarithmic plot to the hepatic concentrations of the congeners (both TBDD and TCDD). The slopes of the doseresponse curves after administration of TBDD and TCDD were almost parallel for tissue concentrations ranging from 0.1 to 30 ng/g wet weight.