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.

Wistar rats were treated initially with very high single doses of 14C-2,3,7,8-TCDD (either 75 or 25 micrograms/kg body wt) followed by weekly maintenance doses of 15 and 5 micrograms/kg body wt, respectively. 14C-radioactivity was measured in various organs over a period of 22 weeks. 1) 75 micrograms 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 micrograms TCDD/kg body wt (followed by weekly doses of 5 micrograms/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.