Absorption, distribution, excretion and metabolism of a single oral dose of [14C]tri-o-cresyl phosphate (TOCP) in the male rat

Details

• Personal Author:
  Abou-Donia MB ; Bower JH ; Makkawy HA ; Nomeir AA
• Description:
  The distribution, excretion, and metabolism of tri-o-cresyl- phosphate (78308) (TOCP) were studied in rats. Male Sprague-Dawley- rats were given 50mg/kg carbon-14 (C-14) labeled TOCP orally. Urine, feces, and expired air were assayed for C-14 activity. Selected rats were killed 2, 6, or 12 hours or 1, 2, or 5 days after dosing to determine the tissue distribution of radiolabel. The plasma C-14 data were subjected to kinetic analysis. Plasma, liver, urine, and feces samples were analyzed for TOCP metabolites. TOCP was rapidly absorbed, TOCP derived C-14 activity being detected in all tissues within 2 hours of dosing. During the first 12 hours, most C-14 activity was found in the gastrointestinal tract and contents, plasma, urinary bladder, and liver. The least C-14 activity was found in the brain, spinal cord, muscles, and testes. Most tissue C-14 concentrations plateaued after 6 to 12 hours, decreasing thereafter. After 5 days, the highest C-14 concentrations were found in the liver, erythrocytes, skin, kidney, and lungs. Among the neural tissues, the most C-14 activity was found in the sciatic nerve. Approximately 63 and 36% of the dose was excreted in the urine and feces after 5 days, respectively. Very little C-14 activity was detected in the expired air. The decrease in activity in the plasma could be fitted to a two component exponential equation with a terminal halflife of 46 hours. Metabolites found in the plasma, liver, urine, and feces were identified. The authors conclude that after oral dosing TOCP is rapidly absorbed and distributed throughout the body and efficiently eliminated in male rats. The rapid metabolism and elimination of TOCP may be responsible, at least in part, for the lack of sensitivity of rats to organophosphate induced delayed neurotoxicity. [Description provided by NIOSH]
• Subjects:
  Blood Energy Metabolism Laboratories Occupational Health Organophosphates Safety
• Keywords:
  Author Keywords: Tri-o-cresyl Phosphate Biotransformation Blood-plasma Delayed Neurotoxicity In-vivo-studies Laboratory-animals Mathematical-models Metabolic-study Metabolism NIOSH-Grant NIOSH-Publication Organo-phosphorus-compounds Organophosphorus Compound-induced Delayed Neurotoxicity Pharmacodynamics Rat Tissue-distribution

  More +
• ISSN:
  0300-483X
• 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:
  61-74
• Volume:
  65
• Issue:
  1
• NIOSHTIC Number:
  nn:00200378
• Citation:
  Toxicology 1990 Dec; 65(1):61-74
• Contact Point Address:
  Pharmacology Duke University Department of Pharmacology Durham, N C 27710
• CAS Registry Number:
  o-Cresyl phosphate (CAS RN 78-30-8)
• Federal Fiscal Year:
  1991
• Performing Organization:
  Duke University, Durham, North Carolina
• Peer Reviewed:
  True
• Start Date:
  19790401
• Source Full Name:
  Toxicology
• End Date:
  19980331
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:327467cf1bc437f32ce9090bcf19135182f0c6d087a5e987b1ae73dcfcb4e27949d1beb7157c9f8fbd4ea70a752e5999c5e7aad11a3d849415c760050ce18677
• Download URL:
  https://stacks.cdc.gov/view/cdc/204064/cdc_204064_DS1.pdf
• File Type:
  [PDF - 689.50 KB ]