The absorption, distribution, excretion, and metabolism of a single oral dose of O-ethyl O-4-nitrophenyl phenylphosphonothioate in hens

Details

• Personal Author:
  Abou-Donia MB ; Ashry MA ; Reichert BL
• Description:
  The pharmacokinetics and metabolism of a single oral 10mg/kg dose of carbon-14 labeled O-ethyl-O-4-nitrophenyl-phenylphosphonothioate (2104645) (EPN) were investigated in mature laying hens. Atropine- sulfate was administered immediately before EPN to protect the hens from acute toxicity. A single 10mg/kg dose was administered in a gelatine capsule. Hens were maintained in metabolism chambers. Hens were sacrificed at 0.5, 2, 4, 8, or 12 days after dosing. Most (74%) of the dose was excreted in the combined urinary and fecal excreta. Traces of radioactivity, 0.2%, were detected in expired carbon-dioxide. Most of the radioactive materials which were excreted were identified as phenylphosphonic-acid (1571331), O-ethyl- phenylphosphonic-acid, and O-ethyl-phenylphosphonothioic-acid. By 12 days after dosing, radioactivity in tissues reached a peak at 11.8%. The liver had the highest concentration of radioactivity, followed by the bile, kidney, adipose tissue, and muscle. The major compound identified in the brain, spinal cord, sciatic nerve, kidney and plasma was EPN. The half life of the elimination of EPN from plasma was 16.5 days, corresponding to a constant rate value of 0.04/day. This study indicated that a single oral toxic dose of EPN has a long elimination half life and exhibits high relative residence of EPN in tissues relative to plasma. The authors conclude that pharmacokinetics and metabolism of organophosphorus compounds may be important in species selectivity to organophosphorus ester induced delayed neurotoxicity. [Description provided by NIOSH]
• Subjects:
  Agriculture Energy Metabolism Insecticides Laboratories Nervous System Nervous System Diseases Occupational Health Organophosphates Safety
• Keywords:
  Agricultural-chemicals Body-burden Laboratory-animals Metabolic-study Nervous-system-disorders Neurotoxic-effects NIOSH-Grant NIOSH-Publication Organo-phosphorus-pesticides Tissue-distribution
• ISSN:
  0041-008X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  18-28
• Volume:
  70
• Issue:
  1
• NIOSHTIC Number:
  nn:00214018
• Citation:
  Toxicol Appl Pharmacol 1983 Aug; 70(1):18-28
• Contact Point Address:
  Pharmacology Duke University Department of Pharmacology Durham, N C 27710
• CAS Registry Number:
  O-Ethyl O-(4-nitrophenyl) phenylphosphonothioate (CAS RN 2104-64-5) ; Phenylphosphonic acid (CAS RN 1571-33-1)
• Federal Fiscal Year:
  1983
• NORA Priority Area:
  Neurotoxic Disorders ; Neurotoxic Effects
• Performing Organization:
  Duke University, Durham, North Carolina
• Peer Reviewed:
  True
• Start Date:
  19790401
• Source Full Name:
  Toxicology and Applied Pharmacology
• End Date:
  19980331
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:399beb1dbb5c5b4bc5b0c6499b194bb0d2fdb2a0411039b4feeef2ca8246f9940e665ecfdfff955aaf13152dec0f882a4fe9928c73428b43e243950ffbab6764
• Download URL:
  https://stacks.cdc.gov/view/cdc/205682/cdc_205682_DS1.pdf
• File Type:
  [PDF - 892.77 KB ]