Dissertation
2,4-DICHLOROPHENOXYACETIC ACID (2,4-D) TRANSPORT ACROSS AN IN VITRO SALIVARY ACINAR CELL SYSTEM: A NOVEL APPROACH TO BIOMONITORING
Doctor of Philosophy (PhD), Washington State University
01/2017
Handle:
https://hdl.handle.net/2376/117376
Abstract
The herbicide 2, 4–D is widely used and thus a good candidate for exposure assessment by biomonitoring. Its renal clearance mechanism involves both glomerular filtration and active organic ion transport through an organic anion transporter (OAT 1). Thus, 2,4-D exposure has most often been assessed by analysis of urine. Xenobiotic detection in saliva has many advantages and can be influenced by a number of parameters, including protein binding characteristics and pH which can be evaluated in vitro. In the present study, we have considered the clearance of 2, 4-D in saliva for application to non-invasive biomonitoring strategies.
Using a recently developed salivary gland epithelial cell (SGEC) Transwell model we have evaluated the transport of 2,4-D across salivary serous-acinar cells in vitro. The basolateral to apical transfer of 2,4-D was investigated using non-physiological and physiological media (additional protein to simulate the plasma to saliva protein gradient). 2,4-D did not display directional transfer differences nor was the transport affected by a competitive substrate. In the physiological experiment the transfer of 2,4-D was much slower in the presence of a protein gradient, and equilibrium concentrations were different in the apical and basolateral compartments.
Protein binding significantly affected the transfer of 2,4-D, indicating only unbound 2,4-D is able to cross the SGEC. These results were used to parameterize a cellular transport computational model and it was able to simulate the transfer of 2,4-D reasonably well using different permeability coefficients (0.04 and 0.03 cm/h) for the non-physiological and physiological conditions, respectively. These experiments indicate that the primary mechanism of 2,4-D transport across the SGEC monolayer is passive diffusion under these conditions. In addition, protein binding plays a significant role in this transfer and may also play a critical role in the salivary clearance of 2,4-D. These data will further the aim of expanding a current salivary computational model to be predictive of salivary 2,4-D clearance in rats that could be extrapolated to humans. Once established, this approach can be extended to a variety of chemicals of toxicological interest to identify ideal candidates for non-invasive biomonitoring.
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Details
- Title
- 2,4-DICHLOROPHENOXYACETIC ACID (2,4-D) TRANSPORT ACROSS AN IN VITRO SALIVARY ACINAR CELL SYSTEM: A NOVEL APPROACH TO BIOMONITORING
- Creators
- Zana A. Carver
- Contributors
- Allan Felsot (Advisor)Vincent Hebert (Committee Member)Charles Timchalk (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- School of the Environment (CAHNRS)
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 98
- Identifiers
- 99900581826401842
- Language
- English
- Resource Type
- Dissertation