Delayed toxicity and delayed neurotoxicity of phosphonothioate and phosphonothioate esters

The delayed neurotoxicity to hens and delayed toxicity to rats of the isomeric trimethyl phosphonothioates, trimethyl phosphate, and a series of the methyl and ethyl esters of methyl-, ethyl-, and phenylphosphonate and phosphonothioates were examined. All the O,O-dialkyl phosphonothioates, phosphorothioates, and their corresponding oxons were relatively nontoxic to rats, with oral LD50 values greater than the 150-450 mg/kg tested. The O,S-dialkyl phosphorothioate esters were highly acutely toxic. The rat acute LD50 values for O,S-dimethyl methylphosphonothioate and O,S-diethyl ethylphosphonothioate were 3 and 8 mg/kg. O,S-Diethyl ethylphosphonothioate and O,O, S-trimethyl phosphorothioate were the only compounds tested that showed delayed toxicity to rats. The delayed LD50 values for these two compounds were 7 and 15-20 mg/kg, respectively, with rats dying 3-22 d after treatment The delayed toxic effects were associated with continual loss of weight, reaching 18-46% at the time of death. Of this series of compounds, only O,O-diethyl phenylphosphonothioate and its oxon showed delayed neurotoxicity to hens 45 d after treatment. The minimum effective dose for these two compounds was 25 mg/kg.d administered ip for 10 d. These findings suggest that delayed neurotoxicity in hens is not due to the same mechanism as delayed toxicity in rats.