Toxicity and Metabolism of Dieldrin in Rats.

The main constituent of the insecticide dieldrin has been studied in male and female rats. The LD50s depend on the route of injection and, after intravenous infusion, on the rate of infusion. After oral injection of a 4% solution in arachis oil, deaths take place within six hours or from two to seven days later; but the first convulsion occurs at 40 min. over a wide range of doses. For further studies 36CI-dieldrin was used. Absorption from the gastrointestinal tract varies with the vehicle and is via the portal vein, not the thoracic lymph duct. Distribution is initially general, but within a few hours of injection it is heavily in favour of fat. Excretion of 36C1 averages about 5% per day. It is markedly increased by a restriction of diet, which reduces the body fat. From the cannulated bile duct, excretion accelerates as the rat loses weight, exceeding 10% per day after a few days. Only 3% of the 3"Cl is excreted as dieldrin unless the bile is cannulated, when 10% may be excreted. The remainder is in metabolites, 90% in the faeces and 10% in the urine. Many metabolites have been demonstrated but not identified. The most important, containing about 60% of the total 36CI, is excreted in the bile, probably as a glucuronide, and reconstituted in the intestine before being excreted in the faeces. From these findings one can interpret many of the toxic effects of dieldrin, including the effects of starvation on toxicity and the prolonged sensitization to a second dose (Barnes and Heath, 1964) in terms of the low solubility of dieldrin in water, its high solubility in fat, and its mobilization when fat is utilized. Toxic effects are related to the dieldrin mobilized; there is no need to postulate that dieldrin produces a long-lasting lesion in the central nervous system. The findings and conclusions are shown to be relevant to the toxic effects of dieldrin in man.