Direct measurements of exposure represent the most accurate assessment of a subject’s true exposure. The clearance of many drugs and chemicals, including pesticides such as chlorpyrifos (CPF), can be detected non-invasively in saliva. Here we have developed a serous-acinar transwell model system as an in vitro screening platform to prioritize chemicals for non-invasive biomonitoring through salivary clearance mechanisms. Rat primary serous-acinar cells express both α-amylase and aquaporin-5 proteins and develop significant tight junctions at postconfluence — a feature necessary for chemical transport studies in vitro. CPF exhibited bidirectional passage across the serous-acinar barrier that was disproportional to the passage of a cell impermeable chemical (lucifer yellow), consistent with a hypothesized passive diffusion process. CPF was metabolized to trichlorpyridinol (TCPy) by serous-acinar cells, and TCPy also displayed bidirectional diffusion in the transwell assay. This model system should prove useful as an in vitro screening platform to support the non-invasive monitoring of toxicons and pharmacons in human saliva and provide guidance for development of advanced in vitro screening platforms utilizing primary human salivary gland epithelial cells.
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salivary amylase alpha
transepithelial electrical resistance
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This work was supported by a grant from the CDC/NIOSH (RO1 OH008173-06). Chlorpyrifos and its major metabolite trichlorpyridinol (TCPy) were kindly provided by the Dow Chemical Company (Midland, MI, USA).
The authors declare no conflict of interest.
Supplementary Information accompanies the paper on the Journal of Exposure Science and Environmental Epidemiology website
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Weber, T., Smith, J., Carver, Z. et al. Non-invasive saliva human biomonitoring: development of an in vitro platform. J Expo Sci Environ Epidemiol 27, 72–77 (2017). https://doi.org/10.1038/jes.2015.74