Antifertility Action and Metabolism of Hexamethylphosphoramide

Abstract

A RECENT report on the toxicology of technical hexamethylphosphoramide¹ (HMPA; Fig. 1) prompts us to present a brief account of the antifertility effects and metabolism of this compound which have been under investigation here for some time. Following the initial report of the chemosterilant action of this substance in male houseflies², we examined the action of a commercial sample of the phosphoramide on the fertility of male rats. A short course of treatment by mouth (6 daily doses of 500 mg/kg) soon caused sterility with aspermia, which was prolonged and perhaps permanent (Table 1). One animal died during the 12 weeks of mating and the others followed suit during the ensuing few weeks. In mice, the same dose rate was better tolerated because no animal died, although the antifertility effect was less marked. By reducing the dose, it was possible to devise courses of treatment which produced reversible episodes of sterility, the minimum effective dose level being, for the rat, 100 mg/kg daily (Table 1). Biweekly sperm counts in treated rabbits showed that this species was also susceptible, besides confirming that inhibition of spermatogenesis with aspermia by the phosphoramide did not involve impairment of libido (Fig. 2).