A Random Walk Model of Skin Permeation

Details

• Personal Author:
  Frasch, H. Fredrick
• Description:
  A new mathematical model for permeability of chemicals in aqueous vehicle through skin is presented. The rationale for this model is to represent diffusion by its fundamental molecular mechanism, i.e., random thermal motion. Diffusion is modeled as a two-dimensional random walk through the biphasic (lipid and corneocyte) stratum corneum (SC). This approach permits calculations of diffusion phenomena in a morphologically realistic SC structure. Two concepts are key in the application of the model to the prediction of steady-state skin permeability coefficients: "effective diffusivity'' and "effective path length,'' meaning the diffusivity and thickness of a homogeneous membrane having identical permeation properties as the stratum corneum. Algebraic expressions for these two variables are developed as functions of the molecular weight and octanol-water partition coefficient of the diffusing substance. Combining these with expressions for membrane-vehicle partition coefficient and permeability of the aqueous epidermis enables the calculation of steady-state skin permeability coefficients. The resulting four-parameter algebraic model was regressed against the "Flynn data base'' with excellent results (R 2=0.84; SE=0.0076; F=154; N=94). The model provides insight into the contributions of stratum corneum diffusivity and effective path lengths to overall skin permeability and may prove useful in the prediction of non-steady-state diffusion phenomena. [Description provided by NIOSH]
• Subjects:
  Chemistry Lipids Occupational Health Risk Assessment Risk Factors Safety Skin Skin Absorption
• Keywords:
  Cell-wall-permeability Cellular-function Cellular-transport-mechanism Chemical-properties Diffusion-analysis Exposure-methods In-vitro-study Mathematical-models Molecular-biology Molecular-structure Protein-chemistry Proteins Quantitative-analysis Risk-analysis Risk-factors Skin-absorption Skin-exposure Skin-tests

  More +
• ISSN:
  0272-4332
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  265-276
• Volume:
  22
• Issue:
  2
• NIOSHTIC Number:
  nn:20022345
• Citation:
  Risk Anal 2002 Apr; 22(2):265-276
• Contact Point Address:
  Fred Frasch, Ph.D., NIOSH, MS L-3030, 1095 Willowdale Rd., Morgantown, WV 26505
• Email:
  hbf9@cdc.gov
• Federal Fiscal Year:
  2002
• NORA Priority Area:
  Research Tools and Approaches: Exposure Assessment Methods
• Peer Reviewed:
  True
• Source Full Name:
  Risk Analysis
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:482c3d1380a1b15daf54ccad6358047180ec97d5ab5f77ea513309967ba3e178b0f41b6e3757f47edef92a3cd8f686d961b78ba2b92108736cdac3a15c22381c
• Download URL:
  https://stacks.cdc.gov/view/cdc/199153/cdc_199153_DS1.pdf
• File Type:
  [PDF - 385.80 KB ]