Chemicals Assessment and Research Center, Chemicals Evaluation and Research Institute, Saitama, Japan.
The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Japan.
J Appl Toxicol. 2018 Oct;38(10):1316-1322. doi: 10.1002/jat.3643. Epub 2018 May 23.
Photoallergic dermatitis, caused by pharmaceuticals and other consumer products, is a very important issue in human health. However, S10 guidelines of the International Conference on Harmonization do not recommend the existing prediction methods for photoallergy because of their low predictability in human cases. We applied local lymph node assay (LLNA), a reliable, quantitative skin sensitization prediction test, to develop a new photoallergy prediction method. This method involves a three-step approach: (1) ultraviolet (UV) absorption analysis; (2) determination of no observed adverse effect level for skin phototoxicity based on LLNA; and (3) photoallergy evaluation based on LLNA. Photoallergic potential of chemicals was evaluated by comparing lymph node cell proliferation among groups treated with chemicals with minimal effect levels of skin sensitization and skin phototoxicity under UV irradiation (UV+) or non-UV irradiation (UV-). A case showing significant difference (P < .05) in lymph node cell proliferation rates between UV- and UV+ groups was considered positive for photoallergic reaction. After testing 13 chemicals, seven human photoallergens tested positive and the other six, with no evidence of causing photoallergic dermatitis or UV absorption, tested negative. Among these chemicals, both doxycycline hydrochloride and minocycline hydrochloride were tetracycline antibiotics with different photoallergic properties, and the new method clearly distinguished between the photoallergic properties of these chemicals. These findings suggested high predictability of our method; therefore, it is promising and effective in predicting human photoallergens.
光变应性皮炎是由药物和其他消费品引起的，是人类健康中的一个非常重要的问题。然而，由于其在人类病例中的预测性低，国际协调会议的 S10 指南不推荐现有的光变应预测方法。我们应用局部淋巴结测定（LLNA），一种可靠的、定量的皮肤致敏预测试验，来开发新的光变应预测方法。该方法包括三步：（1）紫外线（UV）吸收分析；（2）基于 LLNA 确定皮肤光毒性的无观察不良效应水平；（3）基于 LLNA 进行光变应评价。通过比较在 UV 照射（UV+）或非 UV 照射（UV-）下用具有最小皮肤致敏和皮肤光毒性效应水平的化学品处理的淋巴结细胞增殖，评估化学品的光变应潜力。在 UV-和 UV+组之间淋巴结细胞增殖率存在显著差异（P<.05）的情况下，被认为对光变应反应呈阳性。在测试了 13 种化学品后，7 种人类光变应原呈阳性，而其他 6 种化学品没有引起光变应性皮炎或 UV 吸收的证据，测试结果为阴性。在这些化学品中，盐酸多西环素和盐酸米诺环素都是具有不同光变应性的四环素类抗生素，新方法清楚地区分了这些化学品的光变应性。这些发现表明我们的方法具有很高的预测性；因此，它在预测人类光变应原方面具有很高的应用前景。
