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Sensitivity of the cat to delayed neurotoxicity induced by O-ethyl O-4-nitrophenyl phenylphosphonothioate.

Abstract
Delayed neurotoxicity was produced in cats following the administration of either a single dermal dose of 22.5 to 225 mg/kg (0.2 to 5.0 times the LD50) or subchronic (90 days) administration of 0.5 to 2.0 mg/kg of technical grade O-ethyl O-4-nitrophenyl phenylphosphonothioate (EPN). The study showed three differences from the condition produced in the chicken: difficulty to protect from acute poisoning, slower progression of delayed neurotoxicity, and propensity for improvement. These animals received atropine sulfate and pyridine-2-aldoxime methyl chloride (PAM) to protect them against acute poisoning, but most developed signs of acute cholinergic neurotoxicity, the degree of severity being dose dependent. Also cats given small single doses of EPN showed only leg weakness, while those treated with large doses progressed to severe ataxia and death. In cats treated with subchronic dermal daily doses of EPN, the extent and permanence of injury and progression or improvement of neurologic deficit also depended on the dose size and duration of exposure. Histopathologic changes were present in the most distal portion of the longest tracts in both the central and peripheral nervous system. Ascending tracts were most affected in the cervical spinal cord, while change in the descending tracts was concentrated in the lumbosacral spinal cord. Recovery to a varying degree from delayed neurotoxicity was seen in all surviving cats. The recovery was demonstrated as improvement in clinical signs, increase in body weight, and regeneration of peripheral nerves.
AuthorsM B Abou-Donia, D G Graham, C G Kinnes
JournalToxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 68 Issue 1 Pg. 54-65 (Mar 30 1983) ISSN: 0041-008X [Print] United States
PMID6845375 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Insecticides
  • Tritolyl Phosphates
  • Phenylphosphonothioic Acid, 2-Ethyl 2-(4-Nitrophenyl) Ester
  • tri-o-cresyl phosphate
Topics
  • Animals
  • Ataxia (chemically induced)
  • Body Weight (drug effects)
  • Cats
  • Female
  • Insecticides (toxicity)
  • Lethal Dose 50
  • Male
  • Nerve Degeneration (drug effects)
  • Nervous System (drug effects)
  • Paresis (chemically induced)
  • Peripheral Nerves (pathology)
  • Phenylphosphonothioic Acid, 2-Ethyl 2-(4-Nitrophenyl) Ester (toxicity)
  • Spinal Cord (pathology)
  • Tritolyl Phosphates (toxicity)

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