近年来,化妆品接触性皮炎、化妆品痤疮等化妆品皮肤病发病率呈明显上升趋势,日益严峻的化妆品的安全问题引起了社会的广泛关注。因此,国家陆续出台了一系列法律法规进一步规范化妆品的安全性问题,企业也必须对化妆品原料及成品进行充分的安全性评价和风险物质评估。皮肤致敏性检测是化妆品安全评价的毒理学终点之一。由于欧盟已全面禁止化妆品成分动物实验和禁止销售经过动物实验的化妆品原料及成品,因此,传统的动物实验尽管能满足皮肤致敏性测试要求,但不符合3R原则,所以替代实验逐渐取代动物实验成为化妆品安全性评价的重要工具。目前,通过OECD认证的单一致敏替代实验主要包括直接肽链反应检测实验、KeratinoSensTM实验、人细胞系活化实验等等。但单一的致敏替代实验通常不足以准确判断化合物的致敏性。因此,常将不同的单一实验结果根据AOP通路组合成整合策略,综合判定化合物的皮肤致敏性,从而提高预测准确性。目前,现有的整合策略主要由巴斯夫、欧莱雅、资生堂等几大日化企业自主开发,包括3选2原则、stacking- meta模型、ANN-EC3模型等。由于中国对动物替代实验方法引入较晚,国内日化企业及机构尚未开发自有的整合模型,但我们正在努力开发新型的皮肤致敏替代技术,例如在基因实时表达报告细胞构建、新QSAR计算机系统开发及THP-1/KC共培养系统构建等方向均已取得了较好成果。文章就日化相关企业目前使用的皮肤致敏测试的整合策略方法进行概括与阐述,并总结了中国自主开发的皮肤致敏替代方法的发展现状。
In recent years, the incidence of cosmetic skin diseases such as cosmetic contact dermatitis and cosmetic acne has been increasing significantly, and the increasingly severe safety issues of cosmetics have aroused widespread concern in the society. Therefore, the state has promulgated a series of laws and regulations to further regulate the safety of cosmetics, and the enterprises must also carry out sufficient safety evaluation and risk substance evaluation on cosmetics raw materials and finished products. Skin sensitization is one of the toxicological end points of cosmetic safety evaluation. Although traditional animal experiments can meet the requirements of skin sensitization testing, they do not comply with the 3R principle. The European Union has imposed a total ban on animal testing of cosmetic ingredients and on the sale of cosmetic ingredients and finished products tested on animals. Therefore, alternative methods have gradually replaced animal experiments as an important tool for cosmetic safety evaluation. At present, the alternative methods that have certified by OECD mainly include direct peptide reaction test, KeratinoSensTM test, human cell line activation test and so on. However, a single substitution test is usually insufficient to accurately determine the skin sensitization of a compound. Therefore, different single experimental results are often combined according to the AOP pathway into an integrated strategy to comprehensively determine the skin sensitization of compounds, so as to improve the prediction accuracy. At present, the existing integrated strategies are mainly developed by BASF, L ’Oreal, Shiseido and other industries, including the ‘2 out of 3’ principle, stacking Meta model, ANN-EC3 model, etc. Due to the late introduction of animal alternative methods in China, domestic cosmetic companies and institutions have not yet developed their own integrated models, but we are working hard to develop new skin sensitization alternative technologies, such as the construction of real-time gene expression reporter cells, the development of new QSAR computer system and the construction of THP-1/KC co-culture system. Good results have been achieved in these new technologies. This paper summarizes and expounds the integrated strategies and methods of skin sensitization test currently used by daily chemical related enterprises, and summarizes the development status of self-developed skin sensitization alternative methods in China.
