化妆品原料眼刺激性替代方法分层筛选模型的建立  

Establishment of layered screen model of eye irritation alternative methods for cosmetic ingredients

作　　者：李庆[1,2] 杨颖[2] 杨杏芬[2] 谢晓萍[2] 郭翔 薛金玉[4] 张文改[5] 

机构地区：[1]中山大学公共卫生学院,广东广州510080 [2]广东省疾病预防控制中心 [3]深圳市职业病防治院 [4]浙江省象山县疾病预防控制中心 [5]东莞市疾病预防控制中心

出　　处：《环境与健康杂志》2015年第2期116-121,共6页Journal of Environment and Health

摘　　要：目的建立化妆品原料眼刺激性的体外替代方法分层筛选模型。方法应用鸡胚绒毛膜尿囊膜试验(HET-CAM)、鸡胚绒毛膜尿囊膜-台盼蓝染色试验(CAM-TBS)、中性红摄取试验(NRU)、红细胞溶血试验(RBCH)、荧光素漏出试验(FLT)及离体兔眼试验(IRET)6种体外替代方法对30种化妆品原料的眼刺激性进行检测,将检测结果与Draize试验结果进行比对(指标为灵敏度、特异度和ROC曲线下面积),根据6种替代方法分别在区分有无刺激性、有无腐蚀性两个级别的效能设计、建立分层筛选模型,并对模型进行评价。结果 6种方法区分有无刺激性的效能为NRU>HET-CAM>IRET>CAM-TBS>RBCH,区分有无腐蚀性的效能为IRET>FLT>RBCH>NRU>HET-CAM>CAM-TBS。本研究建立并评价的4种模型中,以NRU(第一层)和FLT(第二层)组成的分层筛选模型具有最好的检测效能[Mc Nemar-Bowker检验,W=3.0(P=0.392),Gamma=0.85(P<0.001),Kappa=0.76(P<0.001),分级一致率为83.3%]。结论鉴于由NRU和FLT组成的分层筛选模型与Draize试验分级结果比较具有很高的相关性和分级一致性,检测效能明显优于单一替代方法,因此更适合检测化妆品原料的眼刺激性。Objective To establish the layered screen of eye irritation alternative methods for cosmetic ingredients. Methods Thirty cosmetic ingredients were tested with isolated rabbit eye test （IRET）, fluorescein leakage test （FLT）, red blood cell hemolysis （RBCH） test, neutral red uptake （NRU） assay, hen＇s egg test on the chorioallantoic membrane （HET-CAM） and ehorioallantoic membmne-try pan blue straining （CAM-TBS） methods.Based on the indices of sensitivity, specificity and ROC area under the curve,the predictive abilities of the alternative methods were compared with that of Draize test.Four screen models based on six alternative methods were designed and evaluated by the abilities of discriminating irritation and corrosion of cosmetic ingredients. Results The order of ability for discriminating irritation was NRU〉HET-CAM〉IRET〉CAM-TBS 〉 RBCH, and that for discriminating corrosion was IRET〉FLT〉RBCH〉NRU〉HET-CAM〉CAM-TBS.Among four screen models evaluated in this study, the layered screen model which combined NRU test （lst stage） with FLT test （2nd stage） appeared the most excellent predictive efficiency compared with Draize test [McNemar-Bowker test, W=3.0 （P=0.392）; Gamma=0.85（P〈0.001）, Kappa=0.76 （P〈0.001）, concordance rate：83.3%]. Conclusion The layered screen model （combined NRU test with FLT test） presents highly positive correlation and consistency with Draize test , the performance is better than any single alternative method.It is recommended that the layered screen model （combined NRU test with FLT test） is more suitable for eye irritation prediction of cosmetic ingredients.

关 键 词：眼刺激 替代方法 分层筛选 

分 类 号：R994.6[医药卫生—毒理学]