Organophosphate pesticide inhibition of cholinesterase in laboratory animals and man and effects of oxime reactivators.

The responses of rabbit whole blood cholinesterase following intravenous infusion or percutaneous application of dialkylphosphate inhibitors and injection of oxime enzyme reactivators. The experiments were conducted to determine the structure-activity relationships of the inhibitors and the reactivators, establish the mechanisms of enzyme inhibition, and investigate other factors affecting the toxicity of organophosphate esters including percutaneous absorption and conversion of dithioates to the more reactive respective ozones. Intravenous infusion of dialkylphosphate esters produced dose and time dependent inhibition, followed by a spontaneous, but incomplete recovery. The lack of complete recovery was not totally due to the "aging" phenomona as measurable enzyme reactivation could be induced subsequent to the spontaneous recovery. The need for revision of the enzyme inhibition model is discussed.