Kimmel, T., F. Guerriero, C. Seaman, S. Binks, A. Ader, and R. Sussman. Evaluating the Use of the Local Lymph Node Assay in the Prediction of Skin Sensitising Potential of Pharmaceuticals and Pharmaceutical Intermediates. ATLA. 1999. 27: 339.

The murine Local Lymph Node Assay (LLNA) was recently recommended by an interagency peer review panel for regulatory acceptance as a stand-alone alternative to guinea-pig skin sensitisation tests. The purpose of this collaborative study was to evaluate more extensively the performance of the LLNA, as a predictor of the skin sensitisation potential of pharmaceuticals and pharmaceutical intermediates. In the first phase of this study, over 60 compounds belonging to highly diverse chemical classes were tested using both the LLNA and guinea-pig test method (guinea-pig maximization test or modified Buehler method). Overall, the LLNA did not demonstrate strong agreement with either guinea-pig test, due to a high incidence of incidence of false negative results. In the second phase of the study, an attempt was made to identify key structural characteristics of these compounds by searching for the presence or absence of positive and negative structural alerts, as identified by a commercially-available SAR modeling program. The results of this collaborative study suggest that the LLNA might have limitations as a stand-alone alternative to guinea-pig test methods, particularly when used to predict the skin sensitizing potential of pharmaceuticals and pharmaceutical intermediates. Further investigation is recommended in order to evaluate this assay for use in the pharmaceutical industry.