2, 4 - Dichlorophenoxyacetic acid (2, 4-D) transport across an in vitro salivary acinar cell system: a novel approach to biomonitoring

Details

• Personal Author:
  Carver ZA ; Smith JN ; Timchalk C ; Weber TJ
• Description:
  The non-invasive use of saliva for biomonitoring has the potential to significantly advance quantitative dosimetry as an integral component of public health. A major limitation for this approach has been an inability to identify which chemicals are readily cleared in saliva, at levels that can be quantified at relevant exposure levels. 2, 4-D is a widely used herbicide and its renal clearance mechanism involves both glomerular filtration and active organic ion transport. 2, 4-D was dosed in the basolateral chamber at 2 different concentrations (10 or 100 microg/mL), and both chambers were sampled longitudinally up to 24 hr post dosing. At these doses and time-points cells were viable and maintained tight junction function based upon: transepithelial electrical resistance (TEER) and lucifer yellow permeability (LY) testing. 2, 4-D concentrations in the apical chambers increased over time, and 2, 4-D concentrations in both chambers were equivalent within 24 hours post dosing with the high dose; however with the low dose, basolateral 2, 4-D concentrations remained higher than apical 2, 4-D concentrations (p=0.04) at 24 hr. To evaluate the potential role of active transport, a competitive substrate experiment with the OAT substrate para-aminohippuric acid (PAH), was conducted (0, 0.515, 5.15, or 51.5 microg/ml PAH + 10 microg/ml 2, 4-D) at 4 hr post-dose. Preliminary evaluations suggest that PAH did not significantly alter the concentration of 2, 4-D transported across the SGEC monolayer at 4 hours, suggesting that passive processes may predominate under these conditions. Once the salivary transport mechanism and kinetic parameters of 2, 4-D have been fully characterized, results will be incorporated into a mechanistic computational cellular transport model and used to further inform a PBPK for 2, 4-D. This approach, once established, can be exploited for human biomonitoring without the need to conduct more challenging in vivo saliva clearance studies. [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 Ion Transport Organic Chemicals 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:
  30-31
• Volume:
  150
• Issue:
  1
• NIOSHTIC Number:
  nn:20047581
• Citation:
  Toxicologist 2016 Mar; 150(1):30-31
• CAS Registry Number:
  (2,4-Dichlorophenoxy)acetic acid (CAS RN 94-75-7)
• 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-512:54d131fbd370aaa51411de455c402806f42f6dbfbe4696e7d9eaec2916edf5afb2e2a5d76b672f83ddde7e9eddc20aabbe3119f0fe607bc9826d471d9d6d9acb
• Download URL:
  https://stacks.cdc.gov/view/cdc/202598/cdc_202598_DS1.pdf
• File Type:
  [PDF - 2.17 MB ]