Toxicology of hexamethylphosphoric triamide in rats and rabbits

Abstract

Hexamethylphosphoric triamide (HEMPA), an insect chemosterilant, was tested for acute and chronic toxicity in rats and rabbits. In rabbits, the estimated dermal LD50 was 2600 mg/kg. Clinical signs of systemic toxicity preceding death included alterations of nervous, gastrointestinal, and respiratory systems. Repeated application of HEMPA at 100 or 500 mg/kg to the skin of rabbits caused dose-related weight loss, altered gastrointestinal function and produced apparent nervous system dysfunction. Administration of HEMPA to rats at 50 (oral toxicity study) and 10 (reproductive study) mg/kg resulted in exacerbation of the chronic murine pneumonia complex when compared to lower-dosed and control animals. Morphologic differences in the oral toxicity study included imbibition of minimal amounts of proteinaceous material into renal tubular epithelium and increased splenic extramedullary hematopoietic activity in animals given 50 mg/kg when compared to control, 2 mg/kg and 10 mg/kg treated rats. No other compound-related pathologic or morphologic change was present in other tissues examined including the reproductive organs. No teratologic or unequivocal change that could be attributed directly to the compound was observed in the fertility, gestation, live birth, or lactation indices following administration of HEMPA at 2 or 10 mg/kg/day for a total of 169 days during which time the first (F1A) of 3 filial sets of pups were produced. Also, the reproductive activity and function of the offspring were normal.