1. 1. Kelthane (2,2-bis-(chlorophenyl)-2,2,2-trichloroethanol), referred to below as K, was studied from the standpoints of its acute, subacute, and chronic toxicity, its storage in body fat when fed in the diet, and its effect on the ability of the adrenals to elaborate 17-hydroxycorticosteroids in response to ACTH administration. 2. 2. Oral LD 50's (mg/kg) of the technical grade material were: male and female rats, 809 ± 33 and 684 ± 16, respectively; male rabbits, 1810 ± 350; dogs of mixed sex, >4000. 3. 3. Percutaneous LD 50's in male rabbits were: technical grade K, 30% in dimethyl phthalate, 2.1 ± 0.3 g/kg; K emulsion concentrate (18.5% active ingredient), >10 ml/kg. 4. 4. Subacute percutaneous toxicity (minimal lethal dose) in male rabbits, as indicated by deaths occurring after the inunction of the test materials once daily, 5 days a week for 13 weeks, was found to be: technical grade K, 30% in dimethyl phthalate, 1.0 ml/kg; K emulsion concentrate, 18.5% active ingredient, 0.1 ml/kg; K wettable powder, 18.5% active ingredient, mixed with 2 parts of water, 0.5 g/kg. Technical grade K in dimethyl phthalate and the K emulsion concentrate were both irritating to the skin, the latter being markedly more destructive than the former. The K wettable powder was only mildly irritating. 5. 5. In the dog, K in sufficient dosage depresses the ability of the adrenals to elaborate 17-OH-corticosteroids in response to ACTH stimulation. 6. 6. Dogs fed 300 ppm or less of K in their diets for one year were unaffected. Deaths occurred at a dietary level of 900 ppm, but no signs of toxicity were observed in other animals which survived this feeding level. 7. 7. When rats were fed various concentrations of K in their diets for three months, survival was affected at 1250 ppm in both sexes. Growth was inhibited at the 100 ppm and higher levels in females, but only at 1250 ppm and higher in males. 8. 8. When rats were fed K in their diets for longer periods up to two years, survival was unaffected at levels below 1000 ppm. Females fed 250 ppm and higher levels and males 500 ppm and higher levels suffered a depression of growth. 9. 9. Lesions in the liver constituted the only treatment-related histopathologic changes seen in rats fed K containing diets. These changes varied in frequency and intensity with the dietary levels fed, with only a scattered incidence at levels below 1250 ppm. Increased liver-body weight ratios were observed. No histopathologic changes were seen in the dogs. There were no significant variations in hematological findings in treated animals as compared with controls. 10. 10. K is stored in the body fat of rats, but disappears after cessation of administration.
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