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Non-Invasive Biological Monitoring of Pesticides



Details

  • Personal Author:
  • Description:
    Our overarching research strategy has been to establish a non-invasive biomonitoring capability to evaluate exposure to pesticides utilizing a sensitive, non-invasive, micro-analytical instrumentation for real-time analysis of biomarkers of exposure and response in saliva. Our previously completed research resulted in the development of pesticide sensor platforms, an in vivo animal model system for rapid characterization of saliva pesticide uptake and clearance, and an in vivo dosimetry model to predict systemic dose based upon a 'spot' saliva measurement. Since human exposure is rarely to single agents but rather to complex mixtures, there is a need to develop biomonitoring strategies capable of measuring multiple analytes. This is particularly true in agriculture where multiple pesticides are routinely utilized on crops. Hence there is a need to extend the strategy to other important pesticides; however, a major limitation is the inability to a priori identify which chemicals are adequately cleared in saliva, hampering our ability to easily develop a multiplex screening platform. To address this challenge, this recently completed project evaluated the hypothesis that chemical uptake and clearance in saliva can readily be predicted based upon limited in vitro experiments which are integrated into a pharmacokinetic model. To test this hypothesis this project exploited a previously developed in vivo rat model for salivary gland uptake and clearance and established in vitro cell and sub-cellular based approaches to evaluate salivary gland uptake and clearance. More specifically, a serous-acinar Transwell model system was developed as an in vitro screening platform to prioritize chemicals for non-invasive biomonitoring through salivary clearance mechanisms. Rat primary serous-acinar cells express both a-amylase and aquaporin-5 proteins and develop significant tight junctions at post-confluence - a feature necessary for chemical transport studies in vitro. This model system provides a useful in vitro screening platform to support the non-invasive monitoring using human saliva and provide guidance for development of advanced in vitro screening platforms utilizing primary human salivary gland epithelial cells. Secondly, computational modeling approaches have been developed that couple in vivo and in vitro experiments to predict salivary uptake and clearance of xenobiotics and provides additional insight on species-dependent differences in partitioning that are of key importance for extrapolation. Specifically, a cellular transport computational model was developed using experimentally derived transport parameters based upon the in vitro serous-acinar cell system. Furthermore, the cellular transport computational model was integrated into an existing physiologically based pharmacokinetic (PBPK) model to enable accurate simulation of target metabolite concentrations in saliva of rats that were exposed to selected pesticides in vivo. Overall, this approach demonstrates the utility of a combination experimental and computational approach to predict chemical transport in saliva potentially increasing the utility of salivary biomonitoring in the future. 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:
  • Keywords:
  • Series:
    Grant Final Reports
  • Publisher:
    National Institute for Occupational Safety and Health
  • Document Type:
    Text
  • Funding:
    Grant
  • Genre:
    Final Grant Report
  • Place as Subject:
  • 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:
    1-22
  • NIOSHTIC Number:
    nn:20050997
  • NTIS Accession Number:
    PB2018-100664
  • 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, 2017 Nov; :1-22
  • Contact Point Address:
    Jordan Ned Smith, PhD, Pacific Northwest National Laboratory, 902 Battelle Blvd., PO Box 999, Richland, WA 99352
  • Email:
    jordan.smith@pnnl.gov
  • Federal Fiscal Year:
    2018
  • NORA Priority Area:
    Agriculture, Forestry and Fishing
  • 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):
  • Main Document Checksum:
    urn:sha-512:b36cdc5db35177dfbd401fe257f825c919721a89a8d4fd716f70c82094016ef5598ec4dc4f0fb8cea6976a551a2596595a7d35ab905b58d95a4e3f463949988d
  • Download URL:
  • File Type:
    Filetype[PDF - 2.61 MB ]
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