Non-Invasive Biomonitoring of Pesticides

Details

• Personal Author:
  Campbell JA ; Lin Y ; Timchalk C
• Description:
  This research project established a non-invasive biomonitoring capability to evaluate exposure to organophosphorus (OP) insecticides utilizing a sensitive, non-invasive, micro-analytical instrument for real-time analysis of biomarkers of exposure and response in saliva. This project created a miniaturized nanobioelectronic biosensor that is highly selective and sensitive for the target analyte(s). In addition, a physiologically based pharmacokinetic and pharmacodynamic model (PBPK/PD) for the OP insecticide chlorpyrifos (CPF) was modified to incorporate a salivary gland compartment to quantitatively predict blood CPF concentration and saliva cholinesterase (ChE) inhibition to estimate exposure based on a saliva specimen. The utilization of saliva for biomonitoring, coupled to real-time monitoring and modeling is a novel approach with broad application for evaluating occupational exposures to insecticides. An OP sensor was developed based on a new biosensing principle of antigen-induced formation of nanoparticle-immuno complex nanostructure. A ChE sensor was also developed based on the electrodetection of the ChE hydrolyzed reaction products. In addition, immunoassays capable of sensitive detection of phosphorylated acetylcholinesterase (AChE) and butyrlcholinesterase (BuChE) in biological samples were also developed into a sensor platform. Hence, the sensor systems developed within this project enabled detection of chemical metabolites, enzymatic activity and protein modifications within the same sample matrix. Subsequently, the sensors were transformed to a "lab-on-a-chip", and the sensors performance was characterized, optimized and validated. To validate this approach the in vivo pharmacokinetics of CPF and ChE inhibition in rat saliva under various physiological conditions and dose levels was assessed to ensure that these endpoints are accurate predictors of internal dose. Finally, the sensor platform has undergone further evaluation initially utilizing human samples (blood & saliva) that were spiked with known concentrations of the target analyte and more recently in saliva samples obtained from chemical plant workers who were exposed to low concentrations of chlorpyrifos during their normal work routines. These data in both animal models and humans provides strong support for the use of saliva as a non-invasive biomonitoring matrix and demonstrates the potential utility of a novel sensor platform that could be broadly utilized for human biomonitoring. The development of a real-time saliva analysis coupled to a predictive pharmacokinetic model represents a significant advancement over current biomonitoring strategies. This model system represents the next generation of biomonitoring tools and approaches that can be utilized to assess worker exposure to insecticides under a wide range of occupational situations. [Description provided by NIOSH]
• Subjects:
  Animals Antigens Biomarkers Blood Chemistry Energy Metabolism Environmental Exposure Enzymes Insecticides Laboratories Men Occupational Health Organophosphates Risk Assessment Risk Factors Safety Women

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• Keywords:
  Acetylcholinesterase Biological Agents Biomonitoring Biosensors Chemical Properties Chemicals Chlorpyrifos Enzyme Activity Exposure Levels Humans In Vivo Study Laboratory Animals Metabolites Monitoring Systems Nanotechnology Organophosphorus Compounds Organophosphorus Insecticides Organophosphorus Pesticides Pesticides Pharmacodynamics Physiological Effects Physiological Function Physiology Proteins Risk Factors Sampling

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• Series:
  Grant Final Reports
• Publisher:
  National Institute for Occupational Safety and Health
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Final Grant Report
• Place as Subject:
  OSHA Region 10 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  OEP - Office of Extramural Programs
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-25
• NIOSHTIC Number:
  nn:20050522
• NTIS Accession Number:
  PB2018-100586
• Citation:
  Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, R01-OH-008173, 2012 Aug; :1-25
• Contact Point Address:
  Charles Timchalk, Battelle Pacific Northwest Laboratory, 902 Battelle Blvd., PO Box 999, Richland, WA 99352
• Email:
  charles.timchalk@pnnl.gov
• Federal Fiscal Year:
  2012
• Performing Organization:
  Battelle Pacific Northwest Laboratory
• Peer Reviewed:
  False
• Start Date:
  20060901
• Source Full Name:
  National Institute for Occupational Safety and Health
• End Date:
  20170831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:40e328af3c399468ce81a637a56f57a930b19402b1c61c32139872f8dcb8a2b19fab4db8a0dde51b975f6dd640232d48797e705bd03ff30f53719cd717de1125
• Download URL:
  https://stacks.cdc.gov/view/cdc/218674/cdc_218674_DS1.pdf
• File Type:
  [PDF - 707.69 KB ]