F P CLEVELAND’s research while affiliated with University of Cincinnati and other places

The level of Phosdrin insecticide in the diet that induced fatal intoxication in rats was 400 p.p.m. over a period of 13 weeks; in dogs, 200 p.p.m. over a period of 14 weeks. Nonspecific toxic degeneration and necrosis of the liver and renal tubular epithelium were noted. Characteristic alterations in exocrine glands of the animals were observed and could be correlated with the quantity of the insecticide in the diet. At dietary levels below 25 p.p.m., there was no gross effect on rats or dogs. At levels of 2 to 5 p.p.m. in the diets of rats, there was moderate depression of the cholinesterase in the erythrocytes, slight depression of the cholinesterase in the plasma, and no effect on the cholinesterase of the brain. Slight inhibition of the cholinesterase activity of erythrocytes and plasma of dogs was noted at dietary levels of 2.5 and 5 p.p.m.

When endrin was given orally in one dose, young female rats were more susceptible to its toxic effects than were young male rats. Female rats 6 months of age were more susceptible than younger females, but the reverse and more normal relationship between age and susceptibility prevailed in the case of male rats. Corresponding results were obtained with isodrin, which has the corresponding spatial configuration. Female rabbits were about as susceptible as female rats 6 months of age. Monkeys and cats were more susceptible than most groups of rats, whereas guinea pigs were more resistant than rats. The results of the oral administration of multiple doses of endrin to rats and rabbits, application of the material upon the skin of rabbits, and inhalation of the sublimed vapor of the compound by several species of animals over considerable periods of time, are described. The effects sustained by rats and dogs during and following prolonged consumption of diets contaminated with endrin are described, with particular reference to mortality, rate of growth, apparent influence upon the relative weights of specific organs, and gross and microscopic abnormalities in the viscera.

The immediate toxicity of four polychlorinated dimethanonaphthalenes-aldrin, isodrin, dieldrin, and endrin-compared on the basis of oral administration to rats or rabbits or as applied and maintained upon the skin of rabbits, depends more directly upon their spatial configuration than their empirical composition. Repetitive applications of aldrin, dieldrin, or DDT upon the skin of rabbits exerted toxic effects decreasingly, according to the use or type of a vehicle, in the following order: in Ultrasene, in a vegetable oil (aldrin and DDT in olive oil and dieldrin in peanut oil), and as dry powders (no vehicle). When fed for 2 years to rats of either sex at levels of 2.5, 12.5, or 25.0 p.p.m., aldrin, dieldrin, and DDT do not appear to shorten the lives of the animals, the rate of mortality among the test groups being comparable statistically to that in corresponding control groups. The rates of growth of the test groups were equal to or in excess of that of the controls. The weights of the livers of the test rats, in relation to their body weights, were somewhat on the high side. Dogs are more susceptible than rats to the toxic effects of aldrin or dieldrin. In prolonged periods of feeding on diets containing aldrin or dieldrin at 1 or 3 p.p.m., dogs of either sex do not appear to be affected adversely. In the reproduction of rats, the feeding of a diet containing dieldrin in the concentration of 2.5 p.p.m. reduced the number of pregnancies, but had no effect upon the number of off-spring per delivery and only a slight effect on the mortality of the suckling rats. At this level, aldrin had little or no effect.