DELAYED NEUROTOXICITY OF O-ETHYL O-4-NITROPHENYL PHENYLPHOSPHONOTHIOATE - TOXIC EFFECTS OF A SINGLE ORAL DOSE ON THE NERVOUS-SYSTEM OF HENS

Delayed neurotoxicity was produced in hens, following the administration of a single oral dose of technical (85%) EPN (O-ethyl O-4-nitrophenyl phenylphosphonothioate) in a gelatin capsule. Doses ranged from 25 to 500 mg/kg (2.5-50 times the LD50). These hens also received multiple doses of atropine sulfate to protect them against acute toxicity. Hens given the smaller doses of EPN showed only ataxia, while a few of those treated with the larger doses progressed to paralysis and death. Histologic examination showed marked axon and myelin degeneration in the sciatic nerve and spinal cord of some hens. The lesions in the peripheral nerves were generally observed earlier than those in the spinal cord. Hens given only 10 mg/kg of EPN (LD50 value) and small doses of atropine sulfate did not show neurologic signs of delayed neurotoxicity nor histological changes. Controls consisted of four groups of hens given a single dose of 500 mg/kg of tri-o-cresyl phosphate (TOCP), 10 mg/kg of parathion (O,O-diethyl O-4-nitrophenyl phosphorothioate), 300 mg/kg of atropine sulfate, or an empty gelatin capsule. TOCP-Treated hens developed delayed neurotoxicity while those given parathion showed initially leg weakness but subsequently recovered without developing delayed neurotoxicity. Controls receiving atropine sulfate and gelatin capsule remained normal. Plasma cholinesterase activity was significantly reduced in all surviving hens 90 days after the administration of a single dose of TOCP or EPN, except in birds given 10 mg/kg of EPN. This enzyme was not affected in atropine sulfate or parathion control hens. © 1979 Academic Press, Inc. All rights reserved.