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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

Overview
Journal Arch Toxicol
Specialty Toxicology
Date 1989 Jan 1
PMID 2818199
Citations 6
Authors
R Krowke
I Chahoud
D Neubert
Affiliations
Soon will be listed here.
Abstract

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.

Citing Articles

Four generation reproductive toxicity study with 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD) in rats. I. Toxicokinetic variations in dams and offspring.

Koch E, Thiel E, Chahoud E, Neubert D Arch Toxicol. 1995; 69(4):271-9.

PMID: 7755489 DOI: 10.1007/s002040050170.

Peri- and postnatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: effects on physiological development, reflexes, locomotor activity and learning behaviour in Wistar rats.

Thiel R, Koch E, Ulbrich B, Chahoud I Arch Toxicol. 1994; 69(2):79-86.

PMID: 7717865 DOI: 10.1007/s002040050141.

Reproductive toxicity and pharmacokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin. 1. Effects of high doses on the fertility of male rats.

Chahoud I, Krowke R, SCHIMMEL A, Merker H, Neubert D Arch Toxicol. 1989; 63(6):432-9.

PMID: 2619556 DOI: 10.1007/BF00316444.

Transfer of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) via placenta and through milk in a marmoset monkey.

Hagenmaier H, Wiesmuller T, Golor G, Krowke R, Helge H, Neubert D Arch Toxicol. 1990; 64(8):601-15.

PMID: 2128593 DOI: 10.1007/BF01974688.

Reproductive toxicity and toxicokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin. 2. Problem of paternally-mediated abnormalities in the progeny of rat.

Chahoud I, Krowke R, Bochert G, Burkle B, Neubert D Arch Toxicol. 1991; 65(1):27-31.

PMID: 2043047 DOI: 10.1007/BF01973499.

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