Characterization of the In Vitro Kinetic Interaction of Chlorpyrifos-Oxon with Rat Salivary Cholinesterase: A Potential Biomonitoring Matrix

Details

• Personal Author:
  Kousba AA ; Poet TS ; Timchalk C
• Description:
  The primary mechanism of action for organophosphorus (OP) insecticides such as chlorpyrifos (CPF) involves the inhibition of acetylcholinesterase (AChE) by their active oxon metabolites resulting in a wide range of neurotoxic effects. These oxons also inhibit other cholinesterases (ChE) such as butyrylcholinesterase (BuChE), which represents a detoxification mechanism and a potential biomarker for OP insecticide exposure/response. Salivary biomonitoring has recently been explored as a practical method for examination of chemical exposure, however, there are few studies exploring the use of saliva for OP insecticides. To evaluate the use of salivary ChE as a biological monitor for OP insecticide exposure, a modified Ellman assay in conjunction with a pharmacodynamic model was used to characterize salivary ChE in adult male Sprague-Dawley rats. Comparison of rat saliva, brain, and plasma ChE activity in the presence of selective inhibitors of AChE and BuChE (BW284C51 and iso-OMPA, respectively) with different ChE substrates indicated that rat salivary ChE activity is primarily associated with BuChE (>95%). Further characterization of rat salivary BuChE kinetics yielded an average total BuChE active site concentration of 1.20+/-0.13 fmol ml-1 saliva, an average reactivation rate constant (Kr) of 0.070+/-0.008 h-1, and an inhibitory rate constant (Ki) of 9 nM-1 h-1. The pharmacodynamic model successfully described the in vitro BuChE activity profile as well as the kinetic parameters. These results support the potential utility of saliva as a biomonitoring matrix for evaluating occupational and environmental exposure to CPF and other OP insecticides. [Description provided by NIOSH]
• Subjects:
  Animals Biochemistry Biomarkers Blood Cardiovascular Diseases Cardiovascular System Energy Metabolism Environmental Exposure Environmental Health Environmental Pollution Hematologic Tests Hypersensitivity Insecticides Laboratories Nervous System Nervous System Diseases Occupational Health Organophosphates Safety

  More +
• Keywords:
  Animal-studies Biochemical-analysis Biodynamics Blood-samples Blood-tests Brain-electrical-activity Brain-function Cerebrovascular-system Cerebrovascular-system-disorders Chemical-hypersensitivity Environmental-contamination Environmental-exposure Environmental-factors Laboratory-animals Metabolic-rate Metabolism Models Organo-phosphorus-pesticides Pesticides Pharmacodynamics Salivary-gland-disorders Salivary-glands

  More +
• ISSN:
  0300-483X
• 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:
  219-232
• Volume:
  188
• Issue:
  2
• NIOSHTIC Number:
  nn:20032916
• Citation:
  Toxicology 2007 Jun; 188(2-3):219-232
• Contact Point Address:
  Charles Timchalk, Pacific Northwest National Laboratory, 902 Battelle Blvd, PO Box 999, Richland, WA 99352
• Email:
  charles.timchalk@pnl.gov
• CAS Registry Number:
  O,O-Diethyl phosphorochloridothioate (CAS RN 2524-04-1)
• 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:
  Toxicology
• End Date:
  20050929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2af7f8eff6eeb8ab4ee5660baf4e9106c41fcc6c07c72231cdd0aaf927f3a6de22b829b3858d1c5479af0fdba47e67c9e1d9ce2acf14b974f16223209181f28a
• Download URL:
  https://stacks.cdc.gov/view/cdc/186703/cdc_186703_DS1.pdf
• File Type:
  [PDF - 320.61 KB ]