Toxicological properties of phosphorothioate and related esters present as impurities in technical organophosphorus insecticides

Abstract

O,O,S‐Trimethyl phosphorothioate, an impurity in several technical organophosphorus insecticides, when administered orally to rats at single doses as low as 15 mg/kg caused delayed mortality, with death occurring 4–22 d after treatment. Delayed toxic signs were also observed in mice, but mice were generally less sensitive than rats. O,O,S‐Triethyl phosphorothioate and O,S,S‐trimethyl phosphorodithioate induced the same signs of intoxication at slightly higher doses. Rats treated with O,O,S‐trimethyl phosphorothioate refused food and water within 24 h after treatment and did not eat or drink until the time of death. Neither injection of nutrient solution nor atropine served to reduce or block intoxication. However, the isomeric O,O,O‐trimethyl phosphorothioate was a potent antagonist of the toxicity of O,O,S‐trimethyl phosphorothioate. As little as 1% of the O,O,O‐trimethyl isomer protected rats from the intoxicating effects of the O,O,S‐trimethyl isomer at doses as high as 200 mg/kg. Rat serum carboxylesterase and cholinesterase were inhibited for prolonged periods after a single oral dose of O,O,S‐trimethyl phosphorothioate, but the duration of inhibition was significantly less when the toxicant contained 1% O,O,O‐trimethyl isomer.