Membrane-Coated Fiber Array Approach for Predicting Skin Permeability of Chemical Mixtures from Different Vehicles

Details

• Personal Author:
  Baynes RE ; Riviere JE ; Xia XR
• Description:
  A membrane-coated fiber (MCF) array approach was developed for quantitative assessment of skin absorption from chemical mixtures, which was based on the similarity in the absorption mechanisms of the MCF membrane and the stratum corneum of the skin. A set of probe compounds were used to detect the relative molecular interaction strengths of chemicals with the vehicle and the membranes, which provided a linkage between the skin permeability (log k) and MCF partition coefficients (log KF). A predictive model was established via multiple linear regression analysis of the data matrix of experimentally measured log k value and log KFm values; log k=a0+a1 log KF1+a2 log KF2+...+an log KFm, where m is the number of diverse MCFs. Twenty-five probe compounds and three MCFs (polydimethylsiloxane for lipophilic, polyacrylate for polarizable, and CarboWax for polar interactions) were used to demonstrate the model development processes in the MCF array approach. The skin permeability of the probe compounds was measured with conventional diffusion cell experiments using dermatomed porcine skin. Three predictive models were established for skin permeability prediction from chemical mixtures in water, 50% ethanol, and 1% sodium lauryl sulfate (SLS) with R2 values of 93, 91, and 83, respectively. The log k and log KF values were considerably altered by the addition of ethanol or SLS into the dose vehicle; however, their correlations to skin permeability remained strong under various conditions. These results suggested that the experimentally based MCF array approach can be used to predict skin absorption from chemical mixtures in different vehicles or formulations. [Description provided by NIOSH]
• Subjects:
  Coal Coal Mining Mining Occupational Health Safety Safety Management
• Keywords:
  Absorption-rates Chemical-composition Chemical-properties Chemical-structure Models Qualitative-analysis Quantitative-analysis Risk-analysis Skin-absorption Skin-exposure Statistical-analysis Statistical-quality-control Toxic-effects Toxins

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• ISSN:
  1096-6080
• 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:
  153-161
• Volume:
  99
• Issue:
  1
• NIOSHTIC Number:
  nn:20032681
• Citation:
  Toxicol Sci 2007 Sep; 99(1):153-161
• Contact Point Address:
  Jim E. Riviere, Center for Chemical Toxicology Research and Pharmacokinetics (CCTRP), College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606
• Email:
  jim_riviere@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:
  Toxicological Sciences
• End Date:
  20100331
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e95882ad1f714be9c0c35f48be71dde8636e72fd12c7eb7ee288a047706611195d96addc8708caf00635b236c248ae006ca75424a30a026a03f9417dc675ade0
• Download URL:
  https://stacks.cdc.gov/view/cdc/186569/cdc_186569_DS1.pdf
• File Type:
  [PDF - 311.20 KB ]