Chronic Oral Toxicity and Related Studies on Animals with the Insecticide and Pyrethrum Synergist, Piperonyl Butoxide

Publisher Website
Google Scholar
Abstract
Summary and Conclusions 1. The biologic and pathologic effects of Piperonyl butoxide, a synthetic organic insecticidal material used synergistically with pyrethrins, were studied by an acute toxicity test on rats, by subacute toxicity tests on rats, by graded-dosage chronic toxicity tests on rats and dogs, by a low-dosage chronic test on a goat and by a short term experiment of low and moderate dosages on monkeys. 2. Piperonyl butoxide was found to be a material of a relatively low order of toxicity for the tested warm-blooded animals. There was relatively little difference between sexes and between species of animals (rats, dogs, monkeys, goat) in susceptibility to this material, and no indication of cumulative toxic effect upon the second and third generations of rats fed food containing up to 10,000 parts per million of Piperonyl butoxide. 3. The outstanding biologic findings of moderate toxicity caused by chronic ingestion of relatively large doses of Piperonyl butoxide (10,000 and 25,000 p.p.m.) were anorexia, wasting, reduced food consumption, reduced or lost ability to reproduce and accentuation of concomitant natural disease. 4. Biologic and pathologic findings in a two-year, graded dosage, paired-rat experiment, in which Piperonyl butoxide was added to a standard diet and fed ad libitum, indicated the following degrees of toxicity: a) 100 p.p.m. were nontoxic. b) 1000 p.p.m. were tolerated in good health. c) The addition of one-sixth as much pyrethrins to a ration containing 1000 p.p.m. Piperonyl butoxide produced no additional toxicity. d) 10,000 p.p.m. were tolerated with moderate toxicity. e) 25,000 p.p.m. were fatal to a group of 24 rats during a period of 4 to 68 weeks. 5. Biologic and pathologic findings in a one-year graded-dosage dog experiment, in which Piperonyl butoxide was fed six times a week by capsule, indicated the following converted degrees of toxicity: a) Approximately 80 p.p.m. were nontoxic. b) Approximately 700 p.p.m. were tolerated in good health. c) Approximately 3000 p.p.m. were tolerated with moderate toxic effect. d) Approximately 11,000 p.p.m. were fatal in 4 to 15 weeks. 6. Subbiologic toxic lesions observed in the livers of rat, dog, goat and monkey in good health were acidophil and hyalin-necrosis cells, hydropic swelling and slight dystrophy and dysplasia. These lesions were nonspecific and no significant change occurred in incidence and degree, as compared to lesions in the livers of the control rats and dogs. 7. In moderate biologic toxicity, the outstanding lesions of rat and dog were moderate numbers of acidophil and hyalin-necrosis cells, moderate dystrophy and dysplasia and advanced hydropic swelling; the lesions were accentuated in instances of concomitant natural disease. 8. Biochemical Balance studies on a dog indicated that when a large dose of Piperonyl butoxide is fed by stomach-tube it is quickly eliminated in the feces, and that only traces appear in the urine. 9. Piperonyl butoxide was not carcinogenic for the liver. It did not exert a malignant tumorogenic effect upon the general tissues, nor upon the endocrine glands and breasts, and did not have an indirect general tumorogenic effect through disturbance of the endocrine glands. 10. The safe human tolerance for chronic ingestion of Piperonyl butoxide was estimated, after allowing for a 100-fold safety factor, to be 42 parts per million in all the food eaten.