Basketter D A, Roberts D W, Cronin M, Scholes E W
Unilever Environmental Safety Laboratory, Sharnbrook, Beds, UK.
Contact Dermatitis. 1992 Sep;27(3):137-42. doi: 10.1111/j.1600-0536.1992.tb05241.x.
The development of quantitative correlations between the physicochemical properties of a compound and its ability to act as a skin sensitizer is complicated by the number of variables associated with the current sensitization test data, combined with the absence of a truly objective end point. Recently, however, a novel approach to the assessment of skin sensitization potential, the local lymph node assay (LLNA), has been described, which determines the skin sensitization by measuring lymphocyte proliferation in lymph nodes draining the site of chemical exposure. The assay offers several advantages over traditional methods in the context of quantitative structure-activity relationship studies. In the present work, a range of bromoalkanes has been employed which demonstrate the robustness and reproducibility of the LLNA. Sensitizing activity increased with chain length up to a maximum at C15/C16, whereafter the response declined. The data were modelled against hydrophobicity, expressed as Clog P and (ClogP)2 to fit the biphasic nature of the results. The results demonstrate the utility of LLNA data for interpretation in the context of quantitative structure-activity relationships, the limited number of variables, inter-test reproducibility and quantitative end point, lending themselves to mathematical interpretations.
化合物的物理化学性质与其作为皮肤致敏剂的能力之间定量相关性的发展，因与当前致敏试验数据相关的变量数量众多，再加上缺乏真正客观的终点而变得复杂。然而，最近描述了一种评估皮肤致敏潜力的新方法——局部淋巴结试验（LLNA），它通过测量化学暴露部位引流淋巴结中的淋巴细胞增殖来确定皮肤致敏情况。在定量构效关系研究中，该试验相对于传统方法具有几个优点。在本研究中，使用了一系列溴代烷烃，以证明LLNA的稳健性和可重复性。致敏活性随链长增加，直至在C15/C16处达到最大值，此后反应下降。数据针对疏水性进行建模，以Clog P和(ClogP)2表示，以拟合结果的双相性质。结果证明了LLNA数据在定量构效关系背景下用于解释的效用，变量数量有限、试验间可重复性和定量终点使其适合进行数学解释。
