Coupling In Vitro and Computational Methods to Investigate the Transport of Herbicide/Insecticide Mixtures into Saliva

Details

• Personal Author:
  Carver ZA ; Han AA ; Smith JN ; Timchalk C ; Weber TJ
• Description:
  Portable sensors and PBPK models have previously been developed to describe the relationship between salivary and plasma concentrations of a commonly applied herbicide and insecticide metabolite: 2,4-Dichlorophenoxyacetic acid (2,4-D) and 3,5,6-trichloro-2-pyridinol (TCPy). These efforts not only offer a better understanding of potential adverse health effects elicited by common household chemicals but further provide justification for biomonitoring saliva to assess risks associated with chemical exposures. While understanding the pharmacokinetics of a single chemical is necessary, chemical mixtures are more reflective of the reality of everyday exposures. An in vitro system was employed to evaluate the chemical transport of a simultaneous dosing of 2,4-D and TCPy across a monolayer of serous-acinar cells cultured from the submaxillary saliva gland of Sprague-Dawley rats. The transport of chemicals across the cell layer (via passive diffusion) was influenced by the binding of proteins (i.e. unbound chemicals were able to pass through the cell layer). At a constant concentration of TCPy (200 microM), levels of protein bound to TCPy in cell culture media (Advanced DMEM:F12 supplemented with 2% fetal bovine serum) decreased as much as 52% with an increasing co-exposure to 2,4-D (0-2300 microM), indicating that these chemicals compete for common binding sites on proteins. This suggests that exposure to chemical mixtures may influence measureable levels of herbicides/insecticides in saliva samples. Additional protein binding (at physiological conditions) and kinetic cellular transport experiments quantifying chemical transport and binding rates were conducted to further explore implications of chemical mixtures transport. [Description provided by NIOSH]
• Subjects:
  Cells, Cultured Energy Metabolism Environmental Exposure Hazardous Substances Herbicides Insecticides Laboratories Occupational Health Safety Toxicology
• Keywords:
  2,4-D 2,4-Dichlorophenoxyacetic Acid Analytical Methods Biological Monitoring Cell Cultures Cellular Transport Mechanism Chemical Binding Chemical Hazards Chemicals Exposure Assessment Exposure Levels In Vitro Study Laboratory Animals Laboratory Testing Mathematical Models Metabolites Mixed Exposures Proteins Risk Assessment Salivary Glands Sensors

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 10 ; OSHA Region 6 ; Texas ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  162
• Issue:
  1
• NIOSHTIC Number:
  nn:20051197
• Citation:
  Toxicologist 2018 Mar; 162(1):264
• CAS Registry Number:
  (2,4-Dichlorophenoxy)acetic acid (CAS RN 94-75-7) ; 3,5,6-Trichloro-2-pyridinol (CAS RN 6515-38-4)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  Battelle Pacific Northwest Laboratories, Richland, Washington
• Peer Reviewed:
  False
• Start Date:
  20160901
• Source Full Name:
  The Toxicologist. Society of Toxicology 57th Annual Meeting and ToxExpo, March 11-15, 2018, San Antonio, Texas
• End Date:
  20200831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6a0837cf1c63103be77c2b9751e36dc7fae1e216ec5250c89c0e3e9761352fe949476e19d7fdd5b248e278b493527e954a04a49e4b8e4e63dd0ef03a19e0a726
• Download URL:
  https://stacks.cdc.gov/view/cdc/211280/cdc_211280_DS1.pdf
• File Type:
  [PDF - 840.27 KB ]