Physiologically Based Pharmacokinetic Modeling of Salivary Concentrations for Noninvasive Biomonitoring of 2,4-Dichlorophenoxyacetic Acid (2,4-D)

Details

• Personal Author:
  Carver ZA ; Chrisler WB ; Du D ; Gibbins T ; Han AA ; Lin Y ; Smith JN ; Sontag RL ; Timchalk C ; Tyrrell KJ ; Weber TJ ; Weitz KK
• Description:
  Saliva has become a favorable sample matrix for biomonitoring due to its noninvasive attributes and overall flexibility in collection. To ensure measured salivary concentrations reflect the exposure, a solid understanding of the salivary transport mechanism and relationships between salivary concentrations and other monitored matrices (ie, blood, urine) is needed. Salivary transport of a commonly applied herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), was observed in vitro and in vivo and a physiologically based pharmacokinetic (PBPK) model was developed to translate observations from the cell culture model to those in animal models and further evaluate 2,4-D kinetics in humans. Although apparent differences in experimental in vitro and in vivo saliva:plasma ratios (0.034 and 0.0079) were observed, simulations with the PBPK model demonstrated dynamic time and dose-dependent saliva:plasma ratios, elucidating key mechanisms affecting salivary transport. The model suggested that 2,4-D exhibited diffusion-limited transport to saliva and was additionally impacted by protein binding saturation and permeability across the salivary gland. Consideration of sampling times post-exposure and potential saturation of transport mechanisms are then critical aspects for interpreting salivary 2,4-D biomonitoring observations. This work utilized PBPK modeling in in vitro to in vivo translation to explore benefits and limitations of salivary analysis for occupational biomonitoring. [Description provided by NIOSH]
• Subjects:
  Herbicides Occupational Exposure Occupational Health Safety
• Keywords:
  2,4-Dichlorophenoxyacetic Acid Author Keywords: Salivary Biomonitoring Biological Monitoring Biomonitoring Detectors Exposure Assessment Occupational Exposure PBPK Modeling
• 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:
  330-343
• Volume:
  172
• Issue:
  2
• NIOSHTIC Number:
  nn:20059917
• Citation:
  Toxicol Sci 2019 Dec; 172(2):330-343
• Contact Point Address:
  Jordan N. Smith, Chemical Biology & Exposure Science, Pacific Northwest National Laboratory, PO Box 999, Richland, WA 99354
• Email:
  Jordan.Smith@pnnl.gov
• CAS Registry Number:
  (2,4-Dichlorophenoxy)acetic acid (CAS RN 94-75-7)
• Federal Fiscal Year:
  2020
• Performing Organization:
  Battelle Pacific Northwest Laboratories, Richland, Washington
• Peer Reviewed:
  True
• Start Date:
  20160901
• Source Full Name:
  Toxicological Sciences
• End Date:
  20200831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:296c5454b3d1c1bc91bea26dceb13c2096ff1f39665b991a6d2562fc331912a9f8e6aae118546fe62f968b84b74dfb9253f4cbd40bab742c12a98543395b1124
• Download URL:
  https://stacks.cdc.gov/view/cdc/223971/cdc_223971_DS1.pdf
• File Type:
  [PDF - 662.32 KB ]