Evaluation of non-invasive biomonitoring of 2,4-Dichlorophenoxyacetic acid (2,4-D) in saliva

Details

• Journal Article:
  Toxicology
• Personal Author:
  Carver, Zana A. ; Han, Alice A. ; Timchalk, Charles ; Weber, Thomas J. ; Tyrrell, Kimberly J. ; Sontag, Ryan L. ; Luders, Teresa ; Chrisler, William B. ; Weitz, Karl K. ; Smith, Jordan N.
• 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.
• Subjects:
  2,4-Dichlorophenoxyacetic Acid Article Biological Modeling Biomonitoring Exposure Assessment In Vitro And Alternatives
• Source:
  Toxicology. 410:171-181
• DOI:
  http://dx.doi.org/10.1016/j.tox.2018.08.003
• Pubmed ID:
  30118794
• Pubmed Central ID:
  PMC6482822
• Document Type:
  Text ; Journal Article
• Funding:
  R01 OH008173/OH/NIOSH CDC HHS/United States ; R01 OH011023/OH/NIOSH CDC HHS/United States ; R01OH011023/ACL HHS/United States
• Genre:
  Journal Article
• Volume:
  410
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:1c2865cb35f3030c15bab375fdf0da6fac42d658d4139760b1312b65dc90870ce6cf0e18d18cf34ca668973ba76e65d0cb33f0d64b4301f805e5626fb6fd9cbf
• Download URL:
  https://stacks.cdc.gov/view/cdc/77855/cdc_77855_DS1.pdf
• File Type:
  [PDF - 834.19 KB ]