A cellular model to evaluate salivary gland uptake and clearance of pesticides: a novel non-invasive biomonitoring strategy.
Timchalk-C; Smith-JN; Weber-TJ
Toxicologist 2014 Mar; 138(1):411
The use of saliva as a biomonitoring matrix has potential to significantly advance quantitative dosimetry as an integral component within epidemiology studies. A major limitation for saliva biomonitoring has been an inability to identify which chemicals are readily cleared in saliva, at levels that can be detected analytically. To address this limitation, immortalized Par C10 cells (parotid gland origin) grown on a TranswellŽ insert (3 mm pore) were used to quantify the uptake and clearance of trichloropyridinol (TCPy) the metabolite of the insecticide chlorpyrifos. Cells seeded on Transwell inserts were maintained until 7-days post-confluence at which time they displayed expression of parotic acinar cell proteins and localization of tight junction proteins at points of cell-cell contact. For uptake/clearance studies a range of TCPy concentrations (0.2-10 u/mL) were evaluated. TCPy was added to the basolateral chamber (lower chamber) and sampled from the apical chamber (upper chamber) longitudinally for 4 hours. In the absence of cells, TCPy rapidly diffused across the transwell; whereas, the transport rate was substantially reduced with cells, and apical concentrations of TCPy were proportional to dose. These in vitro results are consistent with in vivo pharmacokinetic model predictions where TCPy salivary gland clearance is described with a 1-compartment model and transfer from blood to saliva is via passive transcellular diffusion. These experiments have established the feasibility of utilizing an in vitro cell based uptake/clearance assay coupled with pharmacokinetic modeling as a novel chemical screening strategy to identify ideal chemical candidates for saliva biomonitoring. This approach will be further evaluated using a broader range of pesticides with varying physical and chemical properties. Once established, this approach can be exploited for biomonitoring without the need to conduct more challenging in vivo saliva clearance studies.
Toxicology; Exposure-levels; Workers; Work-environment; Environmental-exposure; Biomarkers; Personal-protective-equipment; Dosimetry; Epidemiology; Insecticides; Pesticides; Metabolites; Cell-cultures; Proteins
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona
Battelle Pacific Northwest Laboratories