Non-invasive saliva human biomonitoring: development of a transwell assay to support exposure science assessment and health impacts

Details

• Personal Author:
  Carver ZA ; Smith JN ; Timchalk C ; Weber TJ
• Description:
  The use of saliva as a biomonitoring matrix can significantly advance quantitative dosimetry as an integral component of epidemiology. A major limitation has been an inability to identify which chemicals are readily cleared in saliva, at levels that can be quantified. To address this limitation, we have developed a primary salivary gland serous-acinar cell model that can be used for chemical transport studies in vitro. Serousacinar biomarkers detected by Western blot include alpha amylase and aquaporin 5 which are uniformly expressed in confluent cultures. Serous-acinar cells express the tight junction marker zona occludens-1 and measurements of transepithelial electrical resistance (TEER) demonstrate exceptional tight junction formation [routinely >2000 omega(ohms)/cm2] in a relatively short period of time (6-8 days) in Transwell inserts. When TEER values are > 2000 omega(ohms)/cm2, lucifer yellow transport from apical to basolateral chambers is approximately 0.1%/hr. The insecticide chlorpyrifos (CPF) and its primary metabolite trichlorpyridinol (TCPy) can be quantified in saliva at concentrations that are less than, but parallel to blood levels. Results from the Transwell assay indicate that chlorpyrifos transports by diffusion with transport rates that are linear among doses tested. Lucifer yellow passage across the epithelial barrier was clearly disproportional to chlorpyrifos transport. Primary serous-acinar cells showed a low level of CPF metabolism to TCPy, which subsequently localized to both apical and basolateral chambers, consistent with a diffusional process and lack of TCPy concentration gradient. These experiments establish 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. Future studies will begin linking the transwell assay to higher content chemical screening capabilities to increase throughput. [Description provided by NIOSH]
• Subjects:
  Biological Assay Biomarkers Cells, Cultured Epidemiology Insecticides Occupational Health Radiation Dosimeters Safety Toxicology
• Keywords:
  Acinar-glands Analytical-models Bioassays Biological-monitoring Cell-culture-techniques Cellular-reactions Cellular-transport-mechanism Cellular-uptake Chemical-kinetics Dosimetry In-vitro-study Pesticides Pharmacodynamics Protein-chemistry Proteins Quantitative-analysis Salivary-glands

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; OSHA Region 10 ; OSHA Region 6 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  30
• Volume:
  150
• Issue:
  1
• NIOSHTIC Number:
  nn:20047580
• Citation:
  Toxicologist 2016 Mar; 150(1):30
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  Battelle Pacific Northwest Laboratories
• Peer Reviewed:
  False
• Start Date:
  20060901
• Source Full Name:
  The Toxicologist. Society of Toxicology 55th Annual Meeting and ToxExpo, March 13-17, 2016, New Orleans, Louisiana
• End Date:
  20170831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:81a42b9f6b7fe38cf4e507cda6d9b84c9225eec692f89d35ed8b4a3b484188a53a76116596b41bb5cf40aa3ce54e5aca8f9b578f0109d61e1ea8520218de3c8d
• Download URL:
  https://stacks.cdc.gov/view/cdc/202597/cdc_202597_DS1.pdf
• File Type:
  [PDF - 2.16 MB ]