An Experimentally Based Approach for Predicting Skin Permeability of Chemicals and Drugs Using a Membrane-Coated Fiber Array

Details

• Personal Author:
  Baynes RE ; Monteiro-Riviere NA ; Riviere JE ; Xia XR
• Description:
  A membrane-coated fiber (MCF) array approach is proposed for predicting the percutaneous absorption of chemicals and drugs from chemical or biological mixtures. Multiple MCFs were used to determine the partition coefficients of compounds (logKMCF). We hypothesized that one MCF will characterize one pattern of molecular interactions and therefore the skin absorption process can be simulated by a multiple MCF array having diverse patterns of molecular interactions. Three MCFs, polydimethylsiloxane (PDMS), polyacrylate (PA) and CarboWax (Wax), were used to determine the logKMCF values for a set of calibration compounds. The skin permeability log(kp) of the compounds was measured by diffusion experiments using porcine skin. The feasibility of the MCF array approach for predicting skin permeability was demonstrated with the three MCFs. A mathematical model was established by multiple linear regression analysis of the log(kp) and logKMCF data set: log(kp) = - 2.34-0.124 logKpdms + 1.91 logKpa - 1.17 logKwax (n = 25, R2 = 0.93). The MCF array approach is an alternative animal model for skin permeability measurement. It is an experimentally based, high throughput approach that provides high prediction confidence and does not require literature data nor molecular structure information in contrast to the existing predictive models. [Description provided by NIOSH]
• Subjects:
  Chemistry Occupational Health Safety Skin Skin Absorption
• Keywords:
  Chemical-composition Chemical-properties Chemical-reactions Chemoreceptors Mathematical-models Physical-chemistry Skin-absorption Skin-exposure Skin-irritants Skin-sensitivity Statistical-analysis

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• ISSN:
  0041-008X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  320-328
• Volume:
  221
• Issue:
  3
• NIOSHTIC Number:
  nn:20032454
• Citation:
  Toxicol Appl Pharmacol 2007 Jun; 221(3):320-328
• Contact Point Address:
  Center for Chemical Toxicology Research and Pharmacokinetics (CCTRP), North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606
• Email:
  xia@cctrp.ncsu.edu
• Federal Fiscal Year:
  2007
• NORA Priority Area:
  Work Environment and Workforce: Mixed Exposures
• Performing Organization:
  North Carolina State University, Raleigh, North Carolina
• Peer Reviewed:
  True
• Start Date:
  20010601
• Source Full Name:
  Toxicology and Applied Pharmacology
• End Date:
  20100331
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:afeb2effa1bcfd05de2ae8427981907cfa459fbb2e81e95b236f59e98ffae33c00135950500c60de7cadd043ae187aee8fe7e6fbf1463ceaa47ebda455beaffc
• Download URL:
  https://stacks.cdc.gov/view/cdc/186412/cdc_186412_DS1.pdf
• File Type:
  [PDF - 851.54 KB ]