National Institute for Public Health and the Environment (RIVM), P.O. Box 1, NL-3720BA Bilthoven, The Netherlands.
Regul Toxicol Pharmacol. 2013 Jun;66(1):66-71. doi: 10.1016/j.yrtph.2013.02.006. Epub 2013 Feb 28.
The local lymph node assay (LLNA) is the preferred method for classification of sensitizers within REACH. To reduce the number of mice for the identification of sensitizers the reduced LLNA was proposed, which uses only the high dose group of the LLNA. To evaluate the performance of this method for classification, LLNA data from REACH registrations were used and classification based on all dose groups was compared to classification based on the high dose group. We confirmed previous examinations of the reduced LLNA showing that this method is less sensitive compared to the LLNA. The reduced LLNA misclassified 3.3% of the sensitizers identified in the LLNA and misclassification occurred in all potency classes and that there was no clear association with irritant properties. It is therefore not possible to predict beforehand which substances might be misclassified. Another limitation of the reduced LLNA is that skin sensitizing potency cannot be assessed. For these reasons, it is not recommended to use the reduced LLNA as a stand-alone assay for skin sensitization testing within REACH. In the future, the reduced LLNA might be of added value in a weight of evidence approach to confirm negative results obtained with non-animal approaches.
局部淋巴结检测（LLNA）是 REACH 中分类敏化剂的首选方法。为了减少鉴定敏化剂所需的小鼠数量，提出了简化的 LLNA，该方法仅使用 LLNA 的高剂量组。为了评估该方法用于分类的性能，使用了 REACH 注册中的 LLNA 数据，并将基于所有剂量组的分类与基于高剂量组的分类进行了比较。我们证实了先前对简化 LLNA 的检查结果，表明与 LLNA 相比，该方法的灵敏度较低。简化的 LLNA 将 3.3%的在 LLNA 中鉴定出的敏化剂分类错误，并且错误分类发生在所有效力类别中，而且与刺激性特征没有明显关联。因此，无法预先预测哪些物质可能会被错误分类。简化 LLNA 的另一个局限性是无法评估皮肤致敏效力。出于这些原因，不建议在 REACH 中单独使用简化 LLNA 进行皮肤致敏测试。将来，在使用非动物方法获得阴性结果的证据权重方法中，简化的 LLNA 可能会具有附加价值。
