Characterization of Delayed Neurotoxicity in the Mouse Following Chronic Oral Administration of Tri-O-Cresyl Phosphate

Details

• Personal Author:
  Abou-Donia MB ; Campbell GA ; Lapadula DM ; Patton SE
• Description:
  The sensitivity of the mouse to organophosphorus-induced delayed neurotoxicity (OPIDN) has been investigated. One group of five mice received two single 1000-mg/kg po doses of tri-o-cresyl phosphate (TOCP) at a 21-day interval (on Days 1 and 21 of the study); a second group of five mice was given 225 mg/kg of TOCP daily for 270 days. A third group of five animals served as an untreated control. All animals were killed 270 days after the start of the experiment. Daily po dosing of 225 mg/kg TOCP caused a decrease in body weight gain, muscle wasting, weakness, and ataxia which progressed to severe hindlimb paralysis at termination. On the other hand, po administration of two single 1000-mg/kg doses of TOCP at a 21-day interval produced no observable adverse effects. Brain acetylcholinesterase (AChE) and neurotoxic esterase (NTE) activity were 35 and 10% of the control, respectively, in daily dosed animals while AChE and NTE in mice receiving two single 1000-mg/kg doses of TOCP were not significantly altered from the control group. Plasma butyrylcholinesterase activity was 12% of the control group in daily dosed animals. Hepatic microsomal enzyme activities of aniline hydroxylase and p-chloro-N-methylaniline demethylase and NADPH-cytochrome P-450 content in daily dosed animals were increased (141 to 161% of the control group) when compared to controls and mice receiving two single 1000-mg/kg doses of TOCP; the latter being not significantly different from each other. Degeneration of the axon and myelin of the spinal cord and sciatic fasicle were observed and were consistent with OPIDN. This study demonstrates that chronic dosing of TOCP produces OPIDN and induces hepatic microsomal enzyme activity in mice. It is concluded that while the mouse is susceptible to OPIDN, it is a less sensitive and a less appropriate test animal for studying this effect when compared to the adult hen. [Description provided by NIOSH]
• Subjects:
  Animals Energy Metabolism Enzymes Nervous System Occupational Health Safety
• Keywords:
  Animal Studies Enzyme Activity Metabolism Neurotoxic Effects Neurotoxicity Organophosphorus Compounds Triorthocresyl Phosphate
• 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:
  83-90
• Volume:
  79
• Issue:
  1
• NIOSHTIC Number:
  nn:20060496
• Citation:
  Toxicol Appl Pharmacol 1985 Jun; 79(1):83-90
• Contact Point Address:
  Mohamed B. Abou-Donia, Laboratory of Neurotoxicology, Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710 USA
• CAS Registry Number:
  o-Cresyl phosphate (CAS RN 78-30-8)
• Federal Fiscal Year:
  1985
• Performing Organization:
  Duke University, Durham, North Carolina
• Peer Reviewed:
  True
• Start Date:
  19840601
• Source Full Name:
  Toxicology and Applied Pharmacology
• End Date:
  19881031
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9655bac0ff1310bde4e1250bea996e1045a796d6a130e5e180d3e48853cabb7ad68eb3c53b5460405457e9af0720aebf5c3082bc312f8b90dd369c3276cafe4d
• Download URL:
  https://stacks.cdc.gov/view/cdc/224371/cdc_224371_DS1.pdf
• File Type:
  [PDF - 544.13 KB ]