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Archives of Toxicology

, Volume 63, Issue 5, pp 356–360 | Cite as

Pharmacokinetics and biological activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin

2. Pharmacokinetics in rats using a loading-dose/maintenance-dose regime with high doses
  • Ralf Krowke
  • Ibrahim Chahoud
  • Irmela Baumann-Wilschke
  • Diether Neubert
Original Articles

Abstract

Wistar rats were treated initially with very high single doses of 14C-2,3,7,8-TCDD (either 75 or 25 μg/kg body wt) followed by weekly maintenance doses of 15 and 5 μg/kg body wt, respectively. 14C-radioactivity was measured in various organs over a period of 22 weeks. 1) 75 μg TCDD/kg body wt (followed by the maintenance doses) was lethal for all the rats within a period of 9 weeks. While the concentration of 14C-TCDD equivalents in liver and thymus stayed reasonably constant during this period in the surviving rats, the concentration in adipose tissue and kidneys clearly increased in the same animals. 2) The dose of 25 μg TCDD/kg body wt (followed by weekly doses of 5 μg/kg body wt) proved to be a just tolerable dose over a period of 22 weeks for our strain of rats. 3) Within the individual variabilities the TCDD concentrations in the investigated organs showed no clear-cut decline, indicating that the animals were exposed to fairly constant levels of TCDD throughout the study. Thus, this dosing regime is suitable for maintaining constant TCDD exposure during long-term studies.

Key words

2,3,7,8-Tetrachlorodibenzo-p-dioxin TCDD Pharmacokinetics 

Abbreviations

TCDD

2,3,7,8-tetrachlorodibenzo-p-dioxin

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Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • Ralf Krowke
    • 1
  • Ibrahim Chahoud
    • 1
  • Irmela Baumann-Wilschke
    • 1
  • Diether Neubert
    • 1
  1. 1.Institut für Toxikologie und EmbryopharmakologieFreie Universität BerlinBerlin 33

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