Studies on the Sex Difference in Toxicity of a Cholinergic Phosphorothioate. ∗

Abstract

Summary

Measurements of the acute toxicity of DMP, a new cholinergic phosphorothioate, demonstrated that it has a high toxicity to female rats, male and female mice and male guinea pigs as evidenced by intraperitoneal LD₅₀ values ranging from 22 to 35 mg/kg. An exception was noted in the case of male rats to which the intraperitoneal LD₅₀ was 200 mg/kg. DMP inhibits cholinesterase activity of brain and peripheral tissues in vivo. The LD₅₀ of the oxygen analogue of DMP was 5.8 mg/kg to male rats and there was no sex difference in susceptibility. The 10-fold resistance of male rats to the toxicity of DMP was absent at 2 days after partial hepatectomy. At 14 days after partial hepatectomy males regained their resistance unless they were castrated before hepatectomy. Injection of testosterone caused redevelopment of resistance in hepatectomized, castrated rats. The results of these experiments indicate that some system in the liver is responsible for the resistance of male rats to DMP and that androgens govern the development of this system.