Time course for neurotoxic esterase inhibition in hens given multiple diisopropyl fluorophosphate injections

Neurotoxic esterase has been useful for predicting delayed neurotoxicity after acute administration of organophosphorus esters. The present study determined how it could be used to predict neurotoxicity after 20 daily sc injections of 0.05 mg/kg diisopropyl fluorophosphate (DFP) in adult hens. Brain neurotoxic esterase activities were measured during the course of intoxication. No significant occurred after a single DFP injection but the level of inhibition gradually increased to a maximum of 54.3% after 20 injections. The time courses for inhibition of plasma cholinesterase, brain pseudocholinesterase and brain acetylcholinesterase were distinctly different from that for neurotoxic esterase and the former 3 enzymes reached a plateau of inhibition after 1 or 5 DFP injections. Walking behavior was regularly measured in treated hens and distinct motor impairment was first noted after 5 daily DFP injections. Brains, spinal cords and sciatic nerves were removed 24 hr after the last injection and examined microscopically. All hens exhibited central-peripheral distal axonopathy that was characteristic for organophosphate delayed neurotoxicity. Neurotoxicity developed in the absence of a high level of inhibition of neurotoxic esterase following multiple injections of DFP and the "critical" level neurotoxic esterase inhibition used to predict subchronic neurotoxicity may be lower than that used after single treatments.