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.


Journal Details

This article was published in the following journal.

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


DeepDyve research library

PubMed Articles [4558 Associated PubMed Articles listed on BioPortfolio]

Postmortem distribution of chlorpyrifos-methyl, fenitrothion, and their metabolites in body fluids and organ tissues of an intoxication case.

We herein report a fatal intoxication case caused by the ingestion of the insecticides chlorpyrifos-methyl (CPFM) and fenitrothion (MEP). A 70-year-old man was found dead in his house and a cup contai...

The impact of repeated organophosphorus pesticide exposure on biomarkers and neurobehavioral outcomes among adolescent pesticide applicators.

Egyptian adolescents are hired as seasonal workers to apply pesticides to the cotton crop and may perform this occupation for several years. However, few studies examined the effects of repeated pesti...

Associations of maternal exposure to organophosphate and pyrethroid insecticides and the herbicide 2,4-D with birth outcomes and anogenital distance at 3 months in the Odense Child Cohort.

In Odense Child Cohort (OCC), concentrations of the pesticide metabolites 3-phenoxybenzoic acid (3-PBA), 3,5,6-trichloro-2-pyridinol (TCPY), 2,4-Dichlorophenoxyacetic acid (2,4-D) and dialkyl phosphat...

Effects of chlorpyrifos and trichloropyridinol on HEK 293 human embryonic kidney cells.

Chlorpyrifos (CPF) [O, O-diethyl -O-3, 5, 6-trichloro-2-pyridyl phosphorothioate] is an organophosphate insecticide widely used for agricultural and urban pest control. Trichloropyridinol (TCP; 3,5,6-...

Human saliva as a diagnostic material.

Today blood biochemical laboratory tests are essential elements to the diagnosis and monitoring of the treatment of diseases. However, many researchers have suggested saliva as an preferable diagnosti...

Clinical Trials [1151 Associated Clinical Trials listed on BioPortfolio]

Evaluation of the Versamed iVent in the Transport of Patients Receiving Mechanical Ventilation

The purpose of this study is to evaluate the use of the VersaMed iVent ventilator in the acute care setting, hypothesizing that, in comparison to the standard approach, the use of the Vers...

Measurements of Water in Breath and Saliva

This study proposes to demonstrate the feasibility of measuring 2H:1H and 18O:16O in saliva and breath by comparing the natural abundances of 2H:1H and 18O:16O in saliva and urine of un-do...

Occurrence of Selected Vitamins in Saliva and Blood

There is an interest to assess nutritional status of vitamins in humans in a non-invasive way, i.e. by avoiding taking blood samples. Saliva could potentially be an alternative to blood fo...

Transport PLUS Intervention

Hypothesis: 'Transport PLUS,' a low cost, easily generalizable intervention performed by Emergency Medical Technicians while transporting a patient home from the hospital, can improve tran...

Measurement of Substance P in Saliva of Low Back Pain Patients

The purpose of this study is to compare the levels of Substance P in saliva, in patients with severe chronic low back pain and in subjects without it. In addition, to explore a possible cu...

Medical and Biotech [MESH] Definitions

A solution used for irrigating the mouth in xerostomia and as a substitute for saliva.

Any of the ducts which transport saliva. Salivary ducts include the parotid duct, the major and minor sublingual ducts, and the submandibular duct.

The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.

A broad category of proteins involved in the formation, transport and dissolution of TRANSPORT VESICLES. They play a role in the intracellular transport of molecules contained within membrane vesicles. Vesicular transport proteins are distinguished from MEMBRANE TRANSPORT PROTEINS, which move molecules across membranes, by the mode in which the molecules are transported.

Membrane transport proteins found predominately in NEURONS and neuroendocrine cells that facilitate neurotransmitter transport. They include two distinct families of proteins that transport NEUROTRANSMITTERS across the PLASMA MEMBRANE and that transport NEUROTRANSMITTERS into SECRETORY VESICLES.

Quick Search


DeepDyve research library

Relevant Topics

An assay is an analytic procedure for qualitatively assessing or quantitatively measuring the presence or amount or the functional activity of a target entity.  This can be a drug or biochemical substance or a cell in an organism or organic sample. ...

Cell Culture
Types of Cell Culture Open to view video on cell culture basics. Four catagories of cell culture techniques are listed below: Adherent cells Cells shown to require attachment for growth are sa...

Searches Linking to this Article