ToxSci Advance Access originally published online on October 20, 2008
Toxicological Sciences 2009 107(1):78-84; doi:10.1093/toxsci/kfn212
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Published by Oxford University Press 2008.
Physical-Chemical and Solvent Considerations in Evaluating the Influence of Carbon Chain Length on the Skin Sensitization Activity of 1-Bromoalkanes
Allergy and Clinical Immunology Branch, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505
1 To whom correspondence should be addressed at Allergy and Clinical Immunology Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, MS 4020, Morgantown, WV 26505. Fax: (304) 285-5720. E-mail: pds3{at}cdc.gov
Received August 13, 2008; accepted September 25, 2008
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Abstract |
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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.
Key Words: bromoalkane; structure-activity relationship; murine local lymph node assay; contact allergen.
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.