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

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.