THE CHRONIC ORAL TOXICITY OF DDT (2,2-BIS (p-CHLOROPHENYL-1,1,1-TRICHLOROETHANE)

¹ From the Division of Pharmacology, Food and Drug Administration, Federal Security Agency, Washington, D. C.

In rats fed diets containing from 100 to 800 p.p.m. DDT for a period of 2 years, the following effects were noted.

1. DDT produced chronic toxicity in rats at all concentrations.

2. The outstanding and characteristic histopathological lesion caused by DDT under the conditions of this experiment was a hypertrophy of the centrolobular hepatic cells with an increased cytoplasmic oxyphilia, plus increased basophilia and margination of the cytoplasmic granules, and a tendency to hyalinization of the remainder of the cytoplasm. Frequently there was superimposed more or less of centrolobular hepatic cell necrosis, much of which had an appearance of being recent.

3. Slight focal necrosis of hind leg muscles was found frequently. This was a much less prominent lesion than liver damage.

4. DDT showed a minimal tendency to cause formation of hepatic cell tumors. This tendency did not operate until after 18 months of feeding.

5. In the later months of the experimental period the ovarian stroma underwent fibrosis and cellular proliferation.

6. The microscopic lesions observed, except for focal necrosis of the hind leg muscles, showed a fairly distinct gradation with dosage level. They varied from slight at 100 p.p.m. to marked at 800 p.p.m. DDT.

7. An increased intake of DDT-containing diet per kgm. of body weight during the fast growing period of the rat produced an increase in toxicity.

8. The greater intake of DDT per kgm. of body weight by female rats than that by male rats on similar concentrations produced an increased toxicity in the females.

9. At concentrations of 400 to 800 p.p.m. DDT, rats showed characteristic nervous symptoms of poisoning. Lower dosages produced an increased irritability. Muscle tremors were more pronounced in female rats than males.

10. Concentrations of 400 to 800 p.p.m. DDT in the diet retarded growth of female rats. In male rats only 800 p.p.m. DDT retarded growth.

11. The livers, and to a lesser extent the kidneys of experimental animals, were larger than those of the controls. These differences were more pronounced in the groups on 600 and 800 p.p.. DDT.

12. At concentrations of 400 to 800 p.p.m. DDT in the diet, female rats showed an increased mortality rate. DDT at concentrations used in this experiment did not produce any effect on mortality rate of male rats.

13. DDT did not affect the food consumption of rats.

14. The withdrawal of all food from the chronically fed rats on 400 to 800 p.p.m. DDT produced characteristic tremors within 24 hours.

15. No difference in incidence or degree of changes occurred between animals given DDT in dry form and those given DDT in corn oil solutions.

In rats sacrificed at intervals after cessation of feeding 1000 p.p.m. DDT in the diet for 12 weeks, those sacrificed at 1 and 2 weeks afterwards showed damaged livers, while at 4 and 6 there was little change. The livers of rats sacrificed after withdrawal of DDT for 8 and 10 weeks exhibited a normal appearance.

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