Effect of subchronic dermal application of O-ethyl O-4-nitrophenyl phenylphosphonothioate on producing delayed neurotoxicity in hens.
Daily dermal administration for 90 days of 0.01 to 10 mg/kg of O-ethyl O-4-nitrophenyl phenylphosphonothioate (EPN) technical grade (85%) in acetone (0.1 ml) on the unprotected back of the neck produced delayed neurotoxicity. Hens given 2.5 to 10 mg/kg daily doses also received daily doses of atropine sulfate for 5 or 6 days to protect against cholinergic acute toxicity. Severity of the clinical condition depended on the concentration of the daily dermal dose of EPN; i.e., while hens given small doses showed only ataxia, those treated with large doses progressed to paralysis and died. The most consistent histopathologic alteration was the degeneration of axons and myelin in the spinal cord which was identical to that found in positive control hens that received daily dermal doses of 5 or 10 mg/kg tri-o-cresyl phosphate (TOCP). Some of the hens treated daily with the smallest tested dose of EPN (0.001 mg/kg) which did not show clinical signs of delayed neurotoxicity showed equivocal histological changes in the spinal cord. EPN and TOCP treatments had a more profound effect on the activity of plasma butyrylcholinesterase than that of brain acetylcholinesterase (AchE). by contrast O,O,-diethyl O-4-nitrophenyl phosphorothioate (parathion) was more inhibitory to brain AChE. Negative control hens that were treated with 90 daily dermal doses of 1 mg/kg of parathion initially showed leg weakness followed by recovery. A group of hens that received the same volume of acetone (0.1 ml) daily remained normal.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D002645:Chickens; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D010525:Peripheral Nerves / Q000187:drug effects; D004849:Phenylphosphonothioic Acid, 2-Ethyl 2-(4-Nitrophenyl) Ester / Q000008:administration & dosage / Q000633:toxicity*; D012869:Skin Absorption; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
D007306:Insecticides; D004849:Phenylphosphonothioic Acid, 2-Ethyl 2-(4-Nitrophenyl) Ester