Distribution and metabolism of O-ethyl O-4-nitrophenyl phenylphosphonothioate after a single oral dose in one-week old chicks

Details

• Personal Author:
  Abou-Donia MB ; Abou-Donia SA ; Ahmed NS ; Hernandez YM
• Description:
  The metabolism and tissue distribution of O-ethyl-O-4-nitrophenyl- phosphonothioate (2104645) (EPN) were studied in chicks. One week old Leghorn-chicks were given 1mg/kg carbon-14 (C-14) labeled EPN orally. They had been pretreated with 15mg/kg atropine-sulfate to prevent cholinergic symptoms. Expired air, feces, and urine samples were collected periodically for 12 days and assayed for C-14 activity. Selected birds were killed 0.5, 2, 4, 8, or 12 days post dosing to determine the tissue distribution of EPN derived C-14 activity. The excreta and tissues were analyzed for EPN metabolites. No radioactivity was detected in the expired air. Cumulative urinary and fecal excretion of C-14 activity amounted to 91.3% of the dose after 4 days and 93.9% after 7 days. Total tissue EPN burdens peaked at 16.9% of the dose after 0.5 days and decreased to 0.6% of the dose after 4 days. Most of the radiolabel was found in the gastrointestinal tract contents at these time points. Smaller amounts were found in the bile and liver. Among the nervous tissues, the highest level of radioactivity was found in the peripheral nerves followed by the spinal cord and brain in that order. No radioactivity was detected in the gastrointestinal tract contents or tissues by day 12. Elimination of the total EPN body burden showed first order kinetics with a halflife of 16 hours. The authors conclude that following oral dosing to chicks, EPN is readily absorbed from the gastrointestinal tract and distributed to the tissues. The faster rate of metabolism and clearance of neurotoxic organophosphates in young animals may contribute to their resistance to organophosphate induced delayed neurotoxicity. [Description provided by NIOSH]
• Subjects:
  Energy Metabolism Laboratories Nervous System Occupational Health Organophosphates Safety
• Keywords:
  Author Keywords: O-ethyl O-4-nitrophenyl Phenylphosphonothioate Biotransformation Chick Delayed Neurotoxicity EPN In-vivo-studies Laboratory-animals Metabolism Neurotoxic-effects NIOSH-Grant NIOSH-Publication Organo-phosphorus-compounds Pharmacodynamics Tissue-distribution

  More +
• ISSN:
  0340-5761
• 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:
  83-96
• Volume:
  54
• Issue:
  1
• NIOSHTIC Number:
  nn:00213643
• Citation:
  Arch Toxicol 1983 Sep; 54(1):83-96
• 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)
• 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:
  Archives of Toxicology
• End Date:
  19980331
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d7b14b9e52292b9294d05b51dbef92fb61655f603779f68d1a1a807f16b55b7803ae6b07b65eba7f7dc64e8cc388dd8973755c8ab6f086777734dafd06219201
• Download URL:
  https://stacks.cdc.gov/view/cdc/204507/cdc_204507_DS1.pdf
• File Type:
  [PDF - 749.18 KB ]