The value of the local lymph node assay in quantitative structure-activity investigations.

Abstract

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.