Enzymatic and antidotal studies on the neurotoxic effect of certain organophosphates

Abstract

The antiesterase activity of tri- o-cresyl phosphate (TOCP) and its cyclic phosphate metabolite (SM-1) was examined. Administration of TOCP and SM-1 to hens in ataxia-inducing doses resulted in selective rather than prolonged inhibition of the nerve esterases hydrolyzing butyryl esters of choline, glycerol, and phenols. Nerve esterase inhibition was more persistent with TOCP than with SM-1. Selective inhibition of esterases hydrolyzing butyryl esters was also evident in studies in vitro with spinal cord homogenates and SM-1 or di isopropyl fluorophosphate (DFP). TOCP and SM-1 did not affect succinate, α-ketoglutarate, or pyruvate oxidation by preparations of nerve and liver from treated birds, nor was the response of the pyruvate oxidation by brain homogenates to thiamine pyrophosphate affected by TOCP. Many compounds tested as possible antidotes for the neurotoxicity induced by TOCP, SM-1, and DFP proved ineffective. Cortisone acetate gave limited improvement in the condition of the birds, thiamine and oxythiamine appeared to be detrimental, and many potential cholinesterase reactivators and other materials were without effect on the neurotoxicity.