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Predicting Transport of 3,5,6-Trichloro-2-pyridinol (TCPy) into Saliva Using a Combination Experimental and Computational Approach.

08:00 EDT 11th April 2017 | BioPortfolio

Summary of "Predicting Transport of 3,5,6-Trichloro-2-pyridinol (TCPy) into Saliva Using a Combination Experimental and Computational Approach."

A combination experimental and computational approach was developed to predict chemical transport into saliva. A serous-acinar chemical transport assay was established to measure chemical transport with non-physiological (standard cell culture medium) and physiological (using surrogate plasma and saliva medium) conditions using 3,5,6-trichloro-2-pyridinol (TCPy) a metabolite of the pesticide chlorpyrifos. High levels of TCPy protein binding were observed in cell culture medium and rat plasma resulting in different TCPy transport behaviors in the two experimental conditions. In the non-physiological transport experiment, TCPy reached equilibrium at equivalent concentrations in apical and basolateral chambers. At higher TCPy doses, increased unbound TCPy was observed, and TCPy concentrations in apical and basolateral chambers reached equilibrium faster than lower doses, suggesting only unbound TCPy is able to cross the cellular monolayer. In the physiological experiment, TCPy transport was slower than non-physiological conditions, and equilibrium was achieved at different concentrations in apical and basolateral chambers at a comparable ratio (0.034) to what was previously measured in rats dosed with TCPy (saliva:blood ratio: 0.049). A cellular transport computational model was developed based on TCPy protein binding kinetics and simulated all transport experiments reasonably well using different permeability coefficients for the two experimental conditions (1.14 vs 0.4 cm/hr for non-physiological and physiological experiments, respectively). The computational model was integrated into a physiologically based pharmacokinetic (PBPK) model and accurately predicted TCPy concentrations in saliva of rats dosed with TCPy. Overall, this study demonstrates an approach to predict chemical transport in saliva, potentially increasing the utility of salivary biomonitoring in the future.

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This article was published in the following journal.

Name: Toxicological sciences : an official journal of the Society of Toxicology
ISSN: 1096-0929
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