Delayed toxicity and delayed neurotoxicity of phosphorothioate and phosphonothioate esters

Abstract

The delayed neurotoxicity to hens and delayed toxicity to rats of the isomeric trimethyl phosphorothioates, 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 LD ₅₀ values greater than the 150–450 mg/kg tested. The O,S‐dialkyl phosphonothioate esters were highly acutely toxic. The rat acute LD ₅₀ 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 LD ₅₀ 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 mis 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.