Disposition of [14C]tri-o-cresyl phosphate and its metabolites in various tissues of the male cat following a single dermal application.

Details

• Personal Author:
  Abou-Donia MB ; Nomier AA
• Description:
  Carbon-14 labeled tri-o-cresyl-phosphate (78308) (TOCP) was dermally applied to cats, and the disposition of TOCP and its metabolites was determined. The study examined this process in the brain, spinal cord, and sciatic nerve along with liver, kidneys, lungs and plasma of cats. Adult male cats received a single dermal dose of 50mg/kg and were sacrificed 0.5, 1, 2, 5, or 10 days after dosing. The highest plasma concentration of TOCP was recorded at 12 hours, with the metabolites peaking between 24 and 48 hours. TOCP had a half life of 1.2 days in the plasma and its disappearance followed a monoexponential kinetic. The major metabolites found in the plasma were di-o-cresyl-hydrogen-phosphate and o-cresyl-dihydrogen- phosphate. The dihydroxymethyl metabolite was noted in trace amounts. Saligenin-cyclic-o-tolyl-phosphate (1222873) was detected in the plasma at all times and is thought to be the active neurotoxic metabolite. The brain, spinal cord, and sciatic nerve contained predominantly TOCP itself. The liver, kidneys, and lungs contained primarily metabolites. The liver, kidneys and lungs contained o-hydroxybenzoic-acid as the major metabolite followed by di-o-cresyl-hydrogen-phosphate. The brain, spinal cord and sciatic nerve contained di-o-cresyl-hydrogen-phosphate and o-cresyl- dihydrogen-phosphate as the most predominant metabolites. Saligenin- cyclic-o-tolyl-phosphate was not found to any great degree due to its instability or high reactivity with many tissue enzymes. [Description provided by NIOSH]
• Subjects:
  Energy Metabolism Laboratories Nervous System Occupational Health Organophosphates Safety Skin
• Keywords:
  NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Metabolic-study; Metabolites; Laboratory-animals; Skin-exposure; Organo-phosphorus-compounds
• ISSN:
  0090-9556
• 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
• Volume:
  12
• Issue:
  6
• NIOSHTIC Number:
  nn:00232169
• Citation:
  Drug Metab Dispos 1984 Nov; 12(6):705-711
• Contact Point Address:
  Pharmacology Duke University Department of Pharmacology Durham, N C 27710
• CAS Registry Number:
  Cresyl saligenin phosphate (CAS RN 1222-87-3) ; o-Cresyl phosphate (CAS RN 78-30-8)
• Federal Fiscal Year:
  1985
• NORA Priority Area:
  Neurotoxic Disorders ; Neurotoxic Effects
• Performing Organization:
  Duke University, Durham, North Carolina
• Peer Reviewed:
  True
• Start Date:
  19790401
• Source Full Name:
  Drug Metabolism and Disposition
• End Date:
  19980331
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7dc847c09aedf140bc731323e8446b4703641ae07d6ad9e7b7238120dab30b8f7dcaa9b938d34d035f87873a0fe7fec262d5d13dcaf290925445e82b6de3b57d
• Download URL:
  https://stacks.cdc.gov/view/cdc/247842/cdc_247842_DS1.pdf
• File Type:
  [PDF - 168.02 KB ]