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Non-invasive saliva human biomonitoring: development of an in vitro platform

Abstract

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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Abbreviations

AQP5:

aquaporin 5

CPF:

chlorpyrifos

LY:

lucifer yellow

MTBSTFA:

N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide

Ω:

resistance

α-amylase:

salivary amylase alpha

TEER:

transepithelial electrical resistance

TCPy:

trichlorpyridinol

ZO-1:

zona occludin-1.

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Acknowledgements

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).

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Correspondence to Thomas J Weber.

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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

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Keywords

  • biomonitoring
  • pesticides
  • salivary gland
  • tight junction

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