Predicting skin permeability from complex chemical mixtures: incorporation of an expanded QSAR model

Details

• Personal Author:
  Baynes RE ; Brooks JD ; Hughes-Oliver JM ; Xu G
• Description:
  Quantitative structure-activity relationship (QSAR) models have been widely used to study the permeability of chemicals or solutes through skin. Among the various QSAR models, Abraham's linear free-energy relationship (LFER) model is often employed. However, when the experimental conditions are complex, it is not always appropriate to use Abraham's LFER model with a single set of regression coefficients. In this paper, we propose an expanded model in which one set of partial slopes is defined for each experimental condition, where conditions are defined according to solvent: water, synthetic oil, semi-synthetic oil, or soluble oil. This model not only accounts for experimental conditions but also improves the ability to conduct rigorous hypothesis testing. To more adequately evaluate the predictive power of the QSAR model, we modified the usual leave-one-out internal validation strategy to employ a leave-one-solute-out strategy and accordingly adjust the Q(2) LOO statistic. Skin permeability was shown to have the rank order: water > synthetic > semi-synthetic > soluble oil. In addition, fitted relationships between permeability and solute characteristics differ according to solvents. We demonstrated that the expanded model (r(2) = 0.70) improved both the model fit and the predictive power when compared with the simple model (r(2) = 0.21). [Description provided by NIOSH]
• Subjects:
  Chemistry Chemistry, Analytic Laboratories Occupational Health Safety Skin Skin Absorption Solvents
• Keywords:
  Adjusted Q2 LOO Analytical-chemistry Analytical-models Analytical-processes Author Keywords: Abraham's LFER Model Chemical-analysis Chemical-kinetics Chemical-properties Chemical-reactions Chemical-structure Expanded LFER Model Laboratory-testing Leave-one-solute-out Mathematical-models Models Molecular-structure Oils Pharmacodynamics QSAR Quantitative-analysis Skin-absorption Synthetic-materials Synthetics

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• ISSN:
  1062-936X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 3 ; OSHA Region 4 ; Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  24
• Issue:
  9
• NIOSHTIC Number:
  nn:20043958
• Citation:
  SAR QSAR Environ Res 2013 Sep; 24(9):711-731
• Contact Point Address:
  R.E. Baynes, Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University College of Veterinary Medicine, Raleigh, NC 27606, USA
• Email:
  rebaynes@ncsu.edu
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  North Carolina State University, Raleigh, North Carolina
• Peer Reviewed:
  True
• Start Date:
  20000801
• Source Full Name:
  SAR and QSAR in Environmental Research
• End Date:
  20150731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:fe1c9f4f6aa926e3a9fa7390b03081a03b48e864963698d53613275d75569f753cbd9b6e4807c96589635c436bd272c65190a1a7d79c39a090c64ae62d5c8a9f
• Download URL:
  https://stacks.cdc.gov/view/cdc/199820/cdc_199820_DS1.pdf
• File Type:
  [PDF - 639.94 KB ]