Cellular responses to trialkylphosphorothioate-induced injury in rat lung
The acute toxicity of trimethyl and triethylphosphorothioates present as impurities in technical organophosphorus insecticides has been examined in rats. Although the majority of these compounds caused cholinergic signs, in some a second phase of toxicity affecting the lung was also seen. Rats after recovering from the cholinergic phase of poisoning showed respiratory distress and died 3–6 days after dosing with a massive increase in lung weight, associated with progressive diffuse interstitial thickening maximal on day 4. For two compounds no cholinergic toxicity was observed and narcosis was the predominant sign of poisoning. Pretreatment with phenobarbitone, piperonyl butoxide or SKF525A protected rats against lung toxicity caused by trimethylphosphorothioate and dithioate but only phenobarbitone was effective against OOS-triethylphosphorothioate lung toxicity. Direct intrabronchial instillation of OSS-trimethylphosphorodithioate and OOS-triethylphosphorothioate, both of which had been shown to cause lung damage after other routes of dosing, did not greatly increase the toxicity of these two compounds, suggesting that they are not directly toxic to the lung and probably require metabolism.