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

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.