Physical-Chemical and Solvent Considerations in Evaluating the Influence of Carbon Chain Length on the Skin Sensitization Activity of 1-Bromoalkanes

Details

• Personal Author:
  Anderson, Stacey E. ; Beezhold, Donald H. ; Butterworth L ; Fedorowicz A ; Law B ; Siegel, Paul D. ; Snyder J
• Description:
  The murine local lymph node assay (LLNA) is an internationally accepted assay for identification of contact allergens. The LLNA has also been used in research studies to evaluate contact allergen potency, as well as chemical structural-allergenic activity relationships. The 1-bromoalkanes have been used in such a manner as they represent a chemical series with generally the same chemical reactivity but differing in alkane carbon chain length-dependent lipid solubilities. Previous reports noted a biphasic LLNA response with increasing carbon chain length that peaked at the 16-carbon chain (C16) of 1-bromohexadecane (delivered in an acetone-olive oil [AOO] vehicle; 4:1). In the present study, this biphasic LLNA response was confirmed, and 1-bromoalkane chemical-physical factors were explored using both modeling tools and further laboratory studies to help understand this finding. Volatility and effect of vehicle on 1-bromoalkanes' sensitizations were assessed. Selected 1-bromoalkanes were tested in the LLNA using the polar, protic vehicle, tetrahydrofuran-butanol (THF-BuOH; 1:1), to compare to the nonpolar (aprotic) vehicle AOO 1-bromoalkanes-LLNA responses. Enhanced 1-bromoalkane LLNA responses were observed using the THF-BuOH vehicle but with the greatest activity still observed for 1-bromohexadecane (C16). The shorter 1-bromoalkanes were subject to volatile losses upon application with approximately 75% volatile loss from a surface of 1-bromohexane (C6) within 5 min at room temperature. It is concluded that multiple factors, in addition to lipid solubility, including vehicle, solvation, and retention on the skin surface contribute to the apparent potency of 1-bromoalkanes in the LLNA. [Description provided by NIOSH]
• Subjects:
  Biological Factors Hypersensitivity Laboratories Occupational Health Safety Skin
• Keywords:
  Allergic-reactions Author Keywords: Bromoalkane Biological-effects Biological-factors Biological-function Biological-monitoring Biological-transport Cell-biology Cellular-reactions Chemical-hypersensitivity Contact Allergen Laboratory-animals Murine Local Lymph Node Assay Skin-exposure Skin-irritants Skin-sensitivity Statistical-analysis Structure-activity Relationship

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• ISSN:
  1096-6080
• 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:
  78-84
• Volume:
  107
• Issue:
  1
• NIOSHTIC Number:
  nn:20034854
• Citation:
  Toxicol Sci 2009 Jan; 107(1):78-84
• Contact Point Address:
  Paul D. Siegel, Allergy and Clinical Immunology Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, MS 4020, Morgantown, WV 26505
• Email:
  pds3@cdc.gov
• Federal Fiscal Year:
  2009
• Peer Reviewed:
  True
• Source Full Name:
  Toxicological Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e70ba6518220c14d4433b07134ccf6f79b76b59e536fa99a2911dcbd10a733694c11881f7a95cae8517fdb597c7742b55b89c1830ebef487074f0f92e9190a02
• Download URL:
  https://stacks.cdc.gov/view/cdc/186906/cdc_186906_DS1.pdf
• File Type:
  [PDF - 192.90 KB ]