Age-Related Brain Cholinesterase Inhibition Kinetics Following In Vitro Incubation with Chlorpyrifos-Oxon and Diazinon-Oxon

Details

• Personal Author:
  Kousba AA ; Poet TS ; Timchalk C
• Description:
  Chlorpyrifos and diazinon are two commonly used organophosphorus insecticides (OPs), and their primary mechanism of action involves the inhibition of acetylcholinesterase by their metabolites chlorpyrifos-oxon (CPO) and diazinon-oxon (DZO), respectively. The study objectives were to assess the in vitro age-related inhibition kinetics of neonatal rat brain cholinesterase (ChE) for CPO and DZO by estimating the bimolecular inhibitory rate constant (k(i)) values. Brain ChE inhibition and k(i) values following CPO and DZO incubation with neonatal Sprague-Dawley rat brain homogenates were determined at postnatal day (PND) 5, 12, and 17 and compared with the corresponding inhibition and k(i) values obtained in the adult rat. A modified Ellman method was utilized for measuring the ChE activity. CPO caused a greater ChE inhibition than DZO as evidenced from the estimated k(i) values of both compounds. Neonatal brain ChE inhibition kinetics exhibited a marked age-related sensitivity to CPO, with the order of ChE inhibition being PND 5 > PND 7 > PND 17 with k(i) values of 0.95, 0.50, and 0.22 nM(-1)hr(-1), respectively. In contrast, DZO ChE inhibition was not age related in the neonatal brain, and the estimated k(i) value at all PND ages was 0.02 nM(-1)hr(-1). These results demonstrated an age- and OP-selective inhibition of rat brain ChE, which may be critically important in understanding the potential sensitivity of juveniles to specific OPs exposures. [Description provided by NIOSH]
• Subjects:
  Aging Animals Environmental Monitoring Hazardous Substances Insecticides Laboratories Nervous System Occupational Health Organophosphates Safety
• Keywords:
  Age-groups Animal-studies Brain-function Exposure-assessment Exposure-levels Laboratory-animals Organo-phosphorus-pesticides Pharmacodynamics Toxic-effects
• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 10 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  147-155
• Volume:
  95
• Issue:
  1
• NIOSHTIC Number:
  nn:20031530
• Citation:
  Toxicol Sci 2007 Jan; 95(1):147-155
• Contact Point Address:
  Department of Pharmaceutical Property Assessments, TargeGen Inc., San Diego, California 92121
• Email:
  akousba@targegen.com
• CAS Registry Number:
  Chlorpyrifos (CAS RN 2921-88-2) ; Diazinon (CAS RN 333-41-5)
• Federal Fiscal Year:
  2007
• NORA Priority Area:
  Research Tools and Approaches: Exposure Assessment Methods
• Performing Organization:
  Battelle Memorial Institute, Richland, Washington
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  Toxicological Sciences
• End Date:
  20050929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:83b877b4f274e6377beed27d85dc3d51fcc2b539b21a7ea899ace6bf931a13681c53a5c9ccca0f73761aa4ee6cf2d5ead7da757b7ebf557c1753405e65a65093
• Download URL:
  https://stacks.cdc.gov/view/cdc/185788/cdc_185788_DS1.pdf
• File Type:
  [PDF - 274.36 KB ]