Evaluation of Non-Invasive Biomonitoring of 2,4-Dichlorophenoxyacetic Acid (2,4-D) in Saliva

Details

• Personal Author:
  Carver ZA ; Chrisler WB ; Han AA ; Luders T ; Smith JN ; Sontag RL ; Timchalk C ; Tyrrell KJ ; Weber TJ ; Weitz KK
• Description:
  The objective of this study was to evaluate the potential for non-invasive biomonitoring of 2,4-Dichlorophenoxyacetic acid (2,4-D) in saliva. Using an in vitro rat salivary gland epithelial cell (SGEC) system, a collection of experiments investigating chemical protein binding, temporal and directional transport, as well as competitive transport with para-aminohippuric acid (PAH), a substrate for renal organic anion transporters, was conducted to identify cellular transport parameters required to computationally model salivary transport of 2,4-D. Additionally, a physiological protein gradient was implemented to mimic physiologically relevant concentrations of protein in rat plasma and saliva, and under these conditions the transfer of 2,4-D was markedly slower, driven by increased protein binding (i.e. reduced free 2,4-D species available to cross salivary barrier). The rate of transfer was directly proportional to the amount of unbound 2,4-D and demonstrated no indication of active transport. An in vivo assessment of 2,4-D exposure in rats revealed non-linear protein binding in plasma, indicating saturated protein binding and increased levels of unbound 2,4-D species at higher doses. A strong correlation between 2,4-D concentrations in saliva and unbound 2,4-D in plasma was observed (Pearson correlation coefficient = 0.95). Saliva:plasma 2,4-D ratios measured in vivo (0.0079) were consistent within the linear protein binding range and expected 2,4-D levels from occupational exposures but were significantly different than ratios measured in vitro (physiological conditions) (0.034), possibly due to 2,4-D concentrations in saliva not being at equilibrium with 2,4-D concentrations in blood, as well as physiological features absent in in vitro settings (e.g. blood flow). We demonstrated that 2,4-D is consistently transported into saliva using both in vitro and in vivo models, making 2,4-D a potential candidate for human non-invasive salivary biomonitoring. Further work is needed to understand whether current sensor limits of detection are sufficient to measure occupationally relevant exposures. [Description provided by NIOSH]
• Subjects:
  Animals Blood Environmental Exposure Laboratories Occupational Health Risk Assessment Risk Factors Safety
• Keywords:
  2,4-Dichlorophenoxyacetic Acid Author Keywords: 2,4-Dichlorophenoxyacetic Acid Biological Function Biological Modeling Biomonitoring Exposure Assessment Exposure Levels In Vitro And Alternatives In Vitro Study Laboratory Animals Models Protein Chemistry Proteins Risk Factors

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• 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:
  171-181
• Volume:
  410
• NIOSHTIC Number:
  nn:20055698
• Citation:
  Toxicology 2018 Dec; 410:171-181
• Contact Point Address:
  Jordan N. Smith, P.O. Box 999, Richland, WA
• Email:
  Jordan.Smith@pnnl.gov
• CAS Registry Number:
  (2,4-Dichlorophenoxy)acetic acid (CAS RN 94-75-7)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  Battelle Pacific Northwest Laboratories
• Peer Reviewed:
  True
• Start Date:
  20060901
• Source Full Name:
  Toxicology
• End Date:
  20170831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e38c0e112d3d78365baf8871bfca920255c1c844007238cd00d7575ce8c5cccca82df6693aa09a69015ebc1aa254acf0bf22d084c5d2de81cc6a941cf95dc13d
• Download URL:
  https://stacks.cdc.gov/view/cdc/213486/cdc_213486_DS1.pdf
• File Type:
  [PDF - 2.87 MB ]