Kinetics of distribution and elimination of DDE in rats

Abstract

1. Rats were given single i.v. doses of ¹⁴C-DDE, and total drug (¹⁴C) and unchanged DDE (g.l.c.) were measured for up to 14 days in blood, tissues, and excreta. The ¹⁴C recoveries amounted to 90±0±10±8 (SD) % dose.

2. DDE underwent redistribution from blood to liver, muscle, skin and, ultimately, adipose tissue. The tissue/blood concentration ratios were 6 for liver and muscle, 35 for skin, 400 for adipose tissue. Concentrations in blood and lean tissues declined biphasically with β-half-lives of 8-12 days. The half-lives for adipose tissue and total body burden were larger by one order of magnitude. However, due to the increase of adipose tissue mass with time, the amount of DDE stored therein remained constant at almost 60% dose.

3. Except for liver, no substantial metabolite concentrations in tissues were found. In particular, lipophilic metabolites were clearly absent. Thus, tissue kinetics and storage are controlled by unchanged DDE.

4. Of a given dose of DDE, 31% was excreted in the faeces as polar metabolites within 14 days, and 3-4% dose as DDE. Urinary excretion was negligible. The β-half-life of faecal excretion was equal to the one in blood and lean tissues. It is concluded that excretion is limited by the slow formation of polar metabolites of DDE.