Studies on the mechanism of absorption and distribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the toxic contaminant of Agent Orange, is absorbed essentially by the lymphatic route and is transported predominantly by chylomicrons after intestinal absorption. Plasma disappearance of [3H]TCDD-labeled chylomicrons followed first-order decay kinetics, with two exponential components having half-lives of 0.8 and 30 min, respectively. Liver and adipose tissues together accounted for 74 to 81% of the total radioactivity distributed among various tissues. The i.p. route of administration was as effective as the oral route for uptake in 24 h by the adipose and liver tissues, whereas the s.c. route was less efficient. Adipose tissue exhibited a progressive accumulation of labeled TCDD during the first 24 h, whereas the liver showed an exponential disappearance of the newly absorbed TCDD with a half-life of 21.3 h. In contrast, long-term pharmacokinetics of TCDD in the adipose and liver tissues revealed exponential decay patterns with half-lives of 7.6 and 5.3 weeks, respectively. These results show that the adipose tissue and the liver are the major sites of TCDD storage.