Species susceptibility to delayed toxic neuropathy in relation toin vivoinhibition of neurotoxic esterase by neurotoxic organophosphorus esters

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Abstract
Tri-o-cresyl phosphate (TOCP) and O-ethyl O-(4-cyanophenyl) phenylphosphonothioate (cyanofenphos, Surecide) were found to be delayed neurotoxicants. They were administered to chickens by gavage at 100 and 30 mg/kg per day for 15 days, respectively. In CD-1 mice TOCP or cyanophenphos did not induce any of the usually recognized clinical symptoms of neuropathy when administered daily by gavage at 262 or 31.25 mg/kg per day for 30 days, respectively. In the chickens, TOCP and cyanofenphos produced .apprx. 98 and 90% in vivo inhibition of brain neurotoxic esterase (NTE) activity. In the mice, 24 h after the last daily dose, TOCP and cyanofenphos produced only .apprx. 50 and 40% in vivo inhibition of the brain NTE activity. Parathion at 2 or 6.75 mg/kg per day for 15 or 30 days, did not induce neuropathy in chicken or mice and produced no significant in vivo inhibition of brain NTE activity at the end of the dosing regimen. The specific activity of NTE in control chicken brain crude homogenate was higher than that in mouse brain homogenate. The differences between chickens and mice in susceptibility to neurotoxic organophosphates may be attributed to inhibitor specificity of NTE forms in the brain in these 2 different animal species and/or inability of the active metabolites of these neurotoxic compounds to reach the site of action.