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

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Abstract
The acute toxicity of O,O-diethyl O-(4-methylthio-m-tolyl) phosphorothioate (DMP; Bayer 29492) was measured and factors responsible for a marked sex difference in susceptibility of rats to this cholinergic organic phosphate were investigated. The approximate LD50 values for DMP in mg/kg given intraperitoneally were as follows female rats 22, male rats 200, female mice 25, male mice 35, male guinea pigs 30. By the oral route the LD50 values were 14 mg/kg for female rats and 95 mg/kg for male rats. The intraperitoneal LD50 value for the oxygen analogue of DMP (O,O-diethyl O-(4-methylthio-m-tolyl) phosphate, was 5.8 mg/kg for male rats and there was no sex difference in susceptibility. Studies aimed at elucidating the reason for the sex difference in susceptibility to DMP revealed that the 10-fold resistance of male rats was absent at 2 days after partial hepatectomy but at 14 days when the liver had regenerated they regained their resistance unless the animals were castrated prior to hepatectomy. Injection of testosterone caused redevelopment of the resistance in hepatectomized, castrated rats. The results suggest that the liver contains some system responsible for the resistance of male rats to DMP and that androgens govern the development of this system.

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