Delayed neuropathy in hen by the insecticide synergist O-n-propyl O-(2-propynyl) phenylphosphonate (NIA-16388) and other phenylphosphonate esters

Abstract

O-n-Propyl O-(2-propynyl) phenylphosphonate (NIA-16388), which has been recommended for use as insecticide synergist, was synthesized and tested for acute and neurotoxicities in hens. The 24-h LD50 value of this compound in the hen was found to be about 340 mg/kg. Hens treated with this compound at 400 mg/kg with atropine sulfate as an antidote developed clear clinical signs of delayed neurotoxicity 12-17 d after single oral treatment. The signs of neurotoxicity gradually progressed from ataxia through paralysis. Biochemical tests indicated that at the tested dose level of this compound, the level of hen-brain neurotoxic esterase (NTE) was inhibited in vivo to less than 10% of the normal level 1 d after treatment. These clinical and biochemical signs of neurotoxicity are supported by histopathological findings. Degenerative lesions of axons were observed in the NIA-treated group of hens. The lesions in the spinal cord were seen most frequently and most prominently in the lateral columns, although they sometimes were observed in other areas, e.g., in the anterior columns (especially in thoracic and lumbar sections). Generally, the lesions were more apparent in the longitudinal sections than in the cross-sections. Two other phenylphosphonate derivatives, O-ethyl S-benzyl phenylphosphonothioate (ESBP) and O-methyl O-(4-benzylidenylphenylhydrazone) phenylphosphonothioate, were also synthesized and tested for neurotoxicity to hens. The LD50 values for these two compounds in the hen were more than 1000 mg/kg. No signs of delayed neuropathy were detected in hens given either ESBP or the hydrazone compound at single oral doses of 1000 mg/kg.