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Cluster Analysis of the Dermal Permeability and Stratum Corneum/Solvent Partitioning of Ten Chemicals in Twenty-Four Chemical Mixtures in Porcine Skin



Details

  • Personal Author:
  • Description:
    Assumptions based on absorption from single solvent systems may be inappropriate for risk assessment when chemical mixtures are involved. We used K-means and hierarchical cluster analyses to identify clusters in stratum corneum partitioning and porcine skin permeability datasets that are distinct from each other based on mathematical indices of similarity and dissimilarity. Twenty-four solvent systems consisting of combinations of water, ethanol, propylene glycol, methyl nicotinate and sodium lauryl sulfate were used with 10 solutes, including phenol, p-nitrophenol, pentachlorophenol, methyl parathion, ethyl parathion, chlorpyrifos, fenthion, simazine, atrazine and propazine. Identifying the relationships between solvent systems that have similar effects on dermal absorption formed the bases for hypotheses generation. The determining influence of solvent polarity on the partitioning data structure supported the hypothesis that solvent polarity drives the partitioning of non-polar solutes. Solvent polarity could not be used to predict permeability because solvent effects on diffusivity masked the effects of partitioning on permeability. The consistent influence of the inclusion of propylene glycol in the solvent system supports the hypothesis that over-saturation due to solvent evaporation has a marked effect on permeability. These results demonstrated the potential of using cluster analysis of large datasets to identify consistent solvent and chemical mixture effects. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    1660-5527
  • Document Type:
    Text
  • Funding:
    Grant
  • Genre:
    Journal Article
  • Place as Subject:
  • CIO:
    National Institute for Occupational Safety and Health (NIOSH)
  • Topic:
    Workplace Safety & Health
  • Location:
    North America
  • Pages in Document:
    198-206
  • Volume:
    19
  • Issue:
    4
  • NIOSHTIC Number:
    nn:20031336
  • Citation:
    Skin Pharmacol Physiol 2006 Jul; 19(4):198-206
  • Contact Point Address:
    J.E. Riviere, Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC 27606
  • Email:
    Jim_Riviere@ncsu.edu
  • Federal Fiscal Year:
    2006
  • 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:
    Skin Pharmacology and Physiology
  • End Date:
    20100331
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:7457972d5a94dc8b7ca8fdeb075d8d2db4bd01c1163713c725f5a86f757fd7e94a08553bbbe3659cf401f228fc7594a4961a48904663a391bead05cd977ae54d
  • Download URL:
  • File Type:
    Filetype[PDF - 127.38 KB ]
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