组合应用替代方法评价5种化妆品中常用防腐剂的皮肤致敏性  

Integrated use of alternative methods for evaluating the skin sensitization potencies of five frequently used preservatives in cosmetics

作　　者：王瑞[1,2,3] 王欢 韩雨晴[1,2,3] 赵金枫 颜士玉 盘瑶 WANG Rui;WANG Huan;HAN Yu-qing;ZHAO Jin-feng;YAN Shi-yu;PAN Yao(Department of Cosmetics,College of Chemistry and Materials Engineering,Beijing Technology and Business University,Beijing 100048,China;Beijing Key Laboratory of Plant Research and Development,Beijing 100048,China;Institute of Cosmetic Regulatory Science,Beijing Technology and Business University,Beijing 100048,China)

机构地区：[1]北京工商大学化学与材料工程学院化妆品系,北京100048 [2]北京市植物资源研究开发重点实验室,北京100048 [3]北京工商大学化妆品监管科学研究院,北京100048

出　　处：《日用化学品科学》2023年第1期20-27,共8页Detergent & Cosmetics

基　　金：国家自然科学基金资助项目(81903361)。

摘　　要：采用基于不良反应结局路径(AOP)开发的体外致敏性检测方法对5种常用防腐剂进行皮肤致敏性评估。根据整合测试和评估方法(IATA)的3选2原则,使用直接多肽反应试验(DPRA)和人细胞系活化试验(h-CLAT)分别对化妆品中常用的防腐剂苯氧乙醇、4-羟基苯甲酸甲酯、4-羟基苯甲酸丙酯、咪唑烷基脲和DMDM乙内酰脲进行检测。其中,直接多肽反应试验和人细胞系活化试验参照OECD 442C/442E指南的内容进行。实验结果显示,苯氧乙醇、4-羟基苯甲酸甲酯在DPRA和h-CLAT中均为阴性;咪唑烷基脲和DMDM乙内酰脲在2个试验中均表现出阳性结果;而4-羟基苯甲酸丙酯在DPRA中为阴性,h-CLAT中为阳性。该研究结果表明,甲醛释放体类防腐剂咪唑烷基脲和DMDM乙内酰脲是皮肤致敏物,而苯氧乙醇和4-羟基苯甲酸甲酯不是皮肤致敏物,基于文献调研结合更多的实验数据判定4-羟基苯甲酸丙酯为非致敏物。DPRA和h-CLAT的组合测试弥补了单一方法检测的局限性,适用于化妆品原料皮肤致敏性的初筛。In vitro skin sensitization testing methods based on the adverse outcome pathway(AOP) were used to evaluate the skin sensitization potencies of 5 commonly used preservatives. According to the 2-out-of-3 principle of the integrated approaches to testing and assessment(IATA),the direct peptide reactivity assay(DPRA) and the human cell line activation test(h-CLAT) were used to detect the preservatives commonly used in cosmetics, including phenoxyethanol, methyl paraben, propyl paraben, imidazolidinyl urea and DMDM hydantoin. The DPRA and the h-CLAT were carried out according to the OECD 442C and 442E guidelines, respectively. The results show that, phenoxyethanol and methyl paraben are both negative in DPRA and h-CLAT, while imidazolidinyl urea and DMDM hydantoin are both positive in these two tests. Propyl paraben has negative result in DPRA but positive result in h-CLAT. Therefore, imidazolidinyl urea and DMDM hydantoin are sensitizers, while phenoxyethanol and methyl paraben are non-sensitizers. Taken animal and human data into consideration, it is predicted that propyl paraben should be a non-sensitizer. The combination of DPRA and h-CLAT can make up for the limitations of using a single method, and it is suitable for the preliminary screening of cosmetic raw materials according to skin sensitization.

关 键 词：皮肤致敏性 防腐剂 体外替代方法 直接多肽反应试验 人细胞系活化实验 不良反应结局路径 

分 类 号：TQ658[化学工程—精细化工]