Siegel Paul D, Fedorowicz Adam, Butterworth Leon, Law Brandon, Anderson Stacey E, Snyder James, Beezhold Don
Allergy and Clinical Immunology Branch, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.
Toxicol Sci. 2009 Jan;107(1):78-84. doi: 10.1093/toxsci/kfn212. Epub 2008 Oct 20.
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.
小鼠局部淋巴结试验（LLNA）是一种国际认可的用于鉴定接触性过敏原的试验。LLNA也已用于研究中，以评估接触性过敏原的效力以及化学结构与致敏活性的关系。1-溴代烷烃一直以这样的方式使用，因为它们代表了一个化学系列，通常具有相同的化学反应性，但在烷烃碳链长度依赖性脂溶性方面有所不同。先前的报告指出，随着碳链长度增加，LLNA反应呈双相性，在1-溴十六烷（以丙酮-橄榄油[AOO]载体；4:1递送）的16碳链（C16）处达到峰值。在本研究中，证实了这种双相LLNA反应，并使用建模工具和进一步的实验室研究探索了1-溴代烷烃的化学物理因素，以帮助理解这一发现。评估了挥发性以及载体对1-溴代烷烃致敏作用的影响。选用1-溴代烷烃在LLNA中使用极性质子载体四氢呋喃-丁醇（THF-BuOH；1:1）进行测试，以比较与非极性（非质子）载体AOO的1-溴代烷烃-LLNA反应。使用THF-BuOH载体观察到1-溴代烷烃的LLNA反应增强，但仍观察到1-溴十六烷（C16）的活性最高。较短的1-溴代烷烃在应用时会发生挥发性损失，在室温下，1-溴己烷（C6）表面在5分钟内约有75%的挥发性损失。得出的结论是，除了脂溶性外，包括载体、溶剂化作用和在皮肤表面的滞留等多种因素都有助于1-溴代烷烃在LLNA中的表观效力。
