Assessing skin sensitization hazard in mice and men using non-animal test methods
Assessing skin sensitization hazard in mice and men using non-animal test methods
复制标题
DOI：
10.1016/j.yrtph.2014.12.008
复制
发表时间：
2015-03-01
影响因子：
3.4
通讯作者：
Sakaguchi, Hitoshi
中科院分区：
文献类型：
--
作者：
Urbisch, Daniel;Mehling, Annette;Sakaguchi, Hitoshi
致敏是过敏性接触性皮炎发生的先决条件，是危害和风险评估的关键参数。所涉及的途径最近已在OECD皮肤致敏不良结局途径（AOP）中正式描述。单一的非动物试验方法不足以完全解决这一AOP，在许多情况下，需要使用一系列试验。现在已经充分开发和验证了一些方法。为了便于监管和科学界接受这些方法，已汇编了单一检测方法（DPRA、KeratinoSens（TM）、LuSens、h-CLAT、（m）MUSST）以及213种物质的简单“3选2 "ITS的结果，并与动物和人体数据进行了定性比较。该数据集还用于通过可能的蛋白质结合机制来定义不同的机制域。一般而言，与局部淋巴结试验（LLNA）数据相比，非动物试验方法显示出良好的预测性，与人体数据相比，预测性甚至更好。当与人类或LLNA数据相比时，“3选2”预测模型分别实现了90%或79%的准确度，从而甚至略微超过LLNA的准确度。(C)2014作者爱思唯尔公司出版这是一篇在CC BY许可证下的开放获取文章
Sensitization, the prerequisite event in the development of allergic contact dermatitis, is a key parameter in both hazard and risk assessments. The pathways involved have recently been formally described in the OECD adverse outcome pathway (AOP) for skin sensitization. One single non-animal test method will not be sufficient to fully address this AOP and in many cases the use of a battery of tests will be necessary. A number of methods are now fully developed and validated. In order to facilitate acceptance of these methods by both the regulatory and scientific communities, results of the single test methods (DPRA, KeratinoSens (TM), LuSens, h-CLAT, (m)MUSST) as well for a the simple '2 out of 3' ITS for 213 substances have been compiled and qualitatively compared to both animal and human data. The dataset was also used to define different mechanistic domains by probable protein-binding mechanisms. In general, the non-animal test methods exhibited good predictivities when compared to local lymph node assay (LLNA) data and even better predictivities when compared to human data. The '2 out of 3' prediction model achieved accuracies of 90% or 79% when compared to human or LLNA data, respectively and thereby even slightly exceeded that of the LLNA. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license