title: 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.
authors.affiliation: Pacific Northwest National Laboratory, Health Impacts and Exposure Science Group, Richland, WA, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Weber
authors.affiliation: Pacific Northwest National Laboratory, Health Impacts and Exposure Science Group, Richland, WA, USA.
authors.forename: Jordan N
authors.initials: JN
authors.lastname: Smith
authors.affiliation: Pacific Northwest National Laboratory, Health Impacts and Exposure Science Group, Richland, WA, USA.
authors.forename: Zana A
authors.initials: ZA
authors.lastname: Carver
authors.affiliation: Pacific Northwest National Laboratory, Health Impacts and Exposure Science Group, Richland, WA, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Timchalk
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001681:Biological Assay; D015415:Biomarkers / Q000378:metabolism; D004390:Chlorpyrifos / Q000032:analysis* / Q000378:metabolism; D004784:Environmental Monitoring; D004847:Epithelial Cells / Q000378:metabolism; D066298:In Vitro Techniques; D007306:Insecticides / Q000032:analysis* / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D012463:Saliva / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D007306:Insecticides; D004390:Chlorpyrifos