Pretreatment with thiouracil provided significant protection to mice treated subsequently with the organophosphorus insecticide EPN. Uracil did not share the protective properties of thiouracil. Although other mechanisms are possible, the protective action of thiouracil is explained best by the working hypothesis that the oxidative desulfuration of thiouracil to form uracil interferes with a similar desulfuration of EPN and the formation of its pharmacologically active oxygen reaction product. Thiouracil also afforded some protection to mice against the acute toxicity of parathion. On the other hand, it had no protective action against the acute toxicity of the irreversible anticholinesterase compound, 217 AO. Treatment of mice with the metabolic inhibitor SKF 525A enhanced the lethal actions of EPN.
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