Predicting Skin Permeability of Molecules from Chemical Mixtures Using an Inert Membrane-Coated Fiber Array

Details

• Personal Author:
  Baynes RE ; Monteiro-Riviere NA ; Riviere JE ; Xia XR
• Description:
  Predicting skin permeability of compounds from chemical mixtures is required for transdermal drug delivery, safety evaluation of cosmetics and risk assessment of chemicals, where most exposure occurs in complicated chemical mixtures, not individual chemicals. We have developed a membrane-coated fiber technique that can be used to measure the partition coefficients of molecules from chemical mixtures with high precision and throughput. This novel approach predicts skin permeability based on its correlation with the partition coefficients from chemical mixtures determined in a fiber array. Each of the membrane-coated fibers represents a pattern of molecular interactions: polydimethylsiloxane (PDMS, lipophilic), polyacrylate (PA, polarizable) and CarboWax (Wax, polar). Molecular interactions occurring during percutaneous absorption can be simulated by the multiple fibers: log(kp) = c + a logKMCF1+ b logKMCF2 + - + logKMCFn. The feasibility of this approach was demonstrated with 25 diverse chemicals; their skin permeability [log(kp)] from chemical mixtures were measured by in vitro flow through diffusion experiments and partition coefficients of the chemicals (logKMCFn) were determined by the membrane-coated fiber technique. Multiple regression analysis was used to define equations linking log(kp) to logKMCFn for the three MCFs. A significant correlation equation was defined: Log(kp)= -2.73 - 1.31 logKwax - 0.31 logKpdms + 2.34 logKpa with a R 2 of 0.92. The correlation coefficients in the equation reflected the mixture-skin interactions in different vehicles. These data clearly demonstrate that dermal absorption of diverse chemicals can be estimated from data collected in the inert fiber array which reflect the physicochemical diversity of interactions seen when chemicals partition into the stratum corneum. [Description provided by NIOSH]
• Subjects:
  Chemistry Filtration Occupational Health Safety Skin Skin Absorption
• Keywords:
  Chemical-composition Chemical-properties Chemical-reactions Chemoreceptors Filter-fabrics Filter-materials Filter-membranes Mathematical-models Physical-chemistry Skin-absorption Skin-exposure Skin-irritants Skin-sensitivity Statistical-analysis

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• 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:
  433-434
• Volume:
  96
• Issue:
  1
• NIOSHTIC Number:
  nn:20031942
• Citation:
  Toxicologist 2007 Mar; 96(1):433-434
• Federal Fiscal Year:
  2007
• NORA Priority Area:
  Work Environment and Workforce: Mixed Exposures
• Performing Organization:
  North Carolina State University, Raleigh, North Carolina
• Peer Reviewed:
  False
• Start Date:
  20010601
• Source Full Name:
  The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina
• End Date:
  20100331
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:91937d201474ba6559c379878130c4515675177a04b1987b51bd7f6c0fee70345b69851f6cee274fca283974abfbc9be33df7331621dd6a91e99c5516dd11a89
• Download URL:
  https://stacks.cdc.gov/view/cdc/186052/cdc_186052_DS1.pdf
• File Type:
  [PDF - 179.69 KB ]