TOXICOLOGY AND PHARMACODYNAMICS OF DIELDRIN (HEOD) - 2-YEAR ORAL EXPOSURES OF RATS AND DOGS

Dieldrin, purity >99% HEOD, has been given for 2 years to CFE rats at dietary concentrations of 0, 0.1, 1.0, and 10.0 ppm and to beagle hounds at oral doses of 0, 0.005, and 0.05 mg/kg/day (equivalent to 0, 0.1, and 1.0 ppm). The health, body weight, food intake, and hematologic values of both rats and dogs and the clinical chemistry and mortality incidence in rats were unaffected. Rats fed 10.0 ppm became irritable and after 3 months feeding exhibited occasional convulsions on handling. In dogs an increased plasma alkaline phosphatase activity, not associated with other laboratory or clinical evidence of hepatic dysfunction, was observed after about 4 months dosing at 0.05 mg/kg; the reduced serum total protein in the males during the last 6 months of the experiment was without change in electrophoretic pattern and thus was considered of no toxicologic importance. Liver weight and liver: body weight ratio were increased in the 1.0 and 10.0 ppm groups of female rats and in female dogs dosed with 0.05 mg/kg. Histopathologic liver lesions attributable to dieldrin were observed in the rats (10 ppm) but not in dogs. No increase in the incidence of tumors was seen in rats; no tumors were seen in dogs. Significant relationships were found in both rats and dogs between the concentrations of HEOD in blood, brain, liver, or adipose tissue and the amounts of HEOD ingested daily, and between the concentrations of HEOD in brain, liver or adipose tissue and the concentrations in the blood. The changes in the tissue HEOD concentration of rats, and in the dogs given 0.005 mg/kg per day, in relation to the time of exposure were consistent with the concept of an upper limit of storage characteristic of the daily intake. The blood HEOD concentrations of the dogs given 0.05 mg/kg per day were also consistent with this concept for the first 18 months of the trial, but an unexplained significant increase in HEOD concentration occurred later in this group. An explanation of the dynamics of HEOD in rats and dogs is suggested on the basis of a compartmental model. © 1969.