Development of an in vitro screening assay for noninvasive biomonitoring

Details

• Personal Author:
  Smith JN ; Timchalk C ; Weber TJ
• Description:
  The use of saliva as a biomonitoring matrix has the potential to 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 undertaken efforts to develop a primary salivary gland epithelial cell model that can be used for chemical transport studies in vitro. Western blot analysis detected expression of alpha amylase and aquaporin 5 protein, suggesting that primary cells were acinar in origin. Cells strongly expressed the tight junction protein ZO-1 at points of cell-cell contact. A time-dependent increase in tight junction formation was confirmed by monitoring transepithelial electrical resistance (routinely reached > 2500 Omega/cm2). When resistance values were > 2000 Omega/cm2, lucifer yellow transport from apical to basolateral chambers was approximately 0.1%/hr (acceptable standards are < 2%/hr). These data demonstrate excellent tight junction formation. We have demonstrated that the insecticide chlorpyrifos can be quantified in saliva at concentrations that are less than but parallel blood levels. Results from the Transwell assay using primary salivary gland epithelial cells indicate that chlorpyrifos transports by diffusion with transport rates that are linear among doses tested. Lucifer yellow was included in transport studies and was clearly disproportional to chlorpyrifos transport. 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. This approach will be further evaluated using a broader range of pesticides with varying physical and chemical properties. Once established this approach can be exploited for biomonitoring. [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

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 10 ; OSHA Region 9 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  144
• Issue:
  1
• NIOSHTIC Number:
  nn:20046030
• Citation:
  Toxicologist 2015 Mar; 144(1):106
• CAS Registry Number:
  Chlorpyrifos (CAS RN 2921-88-2)
• Federal Fiscal Year:
  2015
• 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 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California
• End Date:
  20170831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2e06846bd1b7560dc77f7a4294cdde36412cda080a9e4dd2992d84f8cb356a967c45d239b75a67ef3baf6319b60871218c2e404b3b7ebd08fdbc3b12c92630af
• Download URL:
  https://stacks.cdc.gov/view/cdc/201219/cdc_201219_DS1.pdf
• File Type:
  [PDF - 1.07 MB ]