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 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 (t1/2) of TBDD and of TCDD in the liver was 13.3 and 13.6 days, respectively. In the adipose tissue the t1/2 of TCDD was 24.5 days but no reliable t1/2 could be calculated for TBDD (t1/2 = 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 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.
Institute of Toxicology and Embryopharmacology, Free University Berlin, Germany.
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T
Nagao
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K
Yamashita
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G
Golor
H
H
Bittmann
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W
Körner
H
H
Hagenmaier
D
D
Neubert
D000042:Absorption; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004147:Dioxins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005260:Female; D006207:Half-Life; D007279:Injections, Subcutaneous; D008099:Liver / Q000378:metabolism; D010088:Oxidoreductases / Q000096:biosynthesis; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013723:Teratogens / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D013723:Teratogens; C066841:2,3,7,8-tetrabromodibenzo-4-dioxin; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1