ABSTRACT
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.
Subject(s)
Carboxylic Ester Hydrolases/antagonists & inhibitors , Isoflurophate/toxicity , Animals , Axons/drug effects , Chickens , Female , Nerve Degeneration/drug effects , Nervous System/drug effects , Time FactorsABSTRACT
Delayed neurotoxicity in hens was reported after the administration of several chlorinated alkyl phosphates. Neurotoxicity increased in a homologous series with the size and/or hydrophobic nature of substituents. In the present study the neurotoxicities of two commercial flame retardants, Fyrol PCF [tri(2-chloropropyl) phosphate] and Fyrol CEF [tri)beta-chloroethyl) phosphate], were compared in adult White Leghorn hens. When Fyrol PCF (10 ml/kg neat) was administered orally to four hens, no inhibition of plasma cholinesterase or brain neurotoxic esterase was evident 24 h later. Fyrol CEF (10 ml/kg neat) produced significantly greater inhibition of plasma cholinesterase (87.1%) and brain neurotoxic esterase (30.0%). Since neither compound produced greater than 75% neurotoxic esterase inhibition, they were not expected to produce delayed neurotoxicity in hens. This was verified in hens treated twice with Fyrol PCF (10 ml/kg neat) or Fyrol CEF (10 ml/kg neat) and observed for 6 wk. Neither group showed behavioral or histopathologic evidence of delayed neurotoxicity. Measurement of neurotoxic esterase correctly predicted the lack of potential of the two flame retardants to induce delayed neurotoxicity in hens.
