Toxicity of toxaphene in the rat and beagle dog.

Residues of the insecticidal mixture, toxaphene, have been found in Great Lakes fish. The purpose of the present study was to assess the subchronic toxicity of toxaphene in the rat and beagle dog. In the rat study, groups of 10 male and 10 female animals were fed diets containing 0, 4, 20, 100, or 500 ppm of the test compound for 13 weeks. No clinical signs of toxicity or spontaneous deaths were observed. Toxaphene treatment up to 500 ppm had no effects on weight gain or food consumption. The liver/body weight ratio and hepatic microsomal enzyme activities (phenobarbital type) were increased in both sexes fed 500 ppm of the test compound. Toxaphene at the highest dose also caused kidney enlargement in male but not in female rats. Dose-dependent histological changes were seen in the kidney, thyroid, and liver. Changes in the liver and thyroid were considered to be adaptative but the injury in the proximal tubules of the kidney was focally severe. Groups of six male and six female beagle dogs were fed toxaphene in gelatin capsules at 0, 0.2, 2.0, and 5.0 mg/kg body wt/kg body wt/day for 13 weeks. Food consumption and growth rate were not affected. All animals survived the entire treatment period. No clinical signs of toxicity were observed. The liver/body weight ratio and serum alkaline phosphatase were increased in dogs of both sexes fed 5.0 mg/kg. Mild to moderate dose-dependent histological changes were observed in the liver and thyroid. Toxaphene was accumulated in a dose-dependent manner in the fat and liver of dogs and rats. Based on the biochemical, histological, and residue data, it was concluded that the no-adverse-effect levels of the pesticide were 4.0 ppm (0.35 mg/kg) for the rat and 0.2 mg/kg for the dog.