Non-targeted screening and toxicity study of safety risk substances in facial skincare products:Molecular networking and computational toxicology strategy  

作　　者：Dong Guo Yaxiong Liu Jingwen Liang Yayang Huang Yangjie Li Jihui Fang Sheng Yin 

机构地区：[1]School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China [2]NMPA Key Laboratory for Safety Risk Assessment of Cosmetics,Guangdong Institute for Drug Control,Guangzhou 510006,China

出　　处：《Journal of Dermatologic Science and Cosmetic Technology》2024年第4期26-37,共12页皮肤科学与化妆品技术期刊(英文)

基　　金：supported by the Scientific and technological innovation project of Guangdong Provincial Drug Administration(ZA20230069,2024ZDZ04);the Science and Technology Plan Project of Guangdong Provincial(2023A1111120025).

摘　　要：Background:Risk substances in cosmetics have long been associated with adverse reactions.However,as risk substances become more concealed and diversified,conventional targeted analysis methods are no longer sufficient to meet regulatory requirements.Objective:To construct a rapid and effective non-targeted screening method for the identification of risk substances,and to provide a high-throughput method for toxicity assessment.Methods:Molecular networking was utilized for the non-targeted screening of risk substances in facial skincare products,and the toxicity of these risk substances was evaluated through molecular docking and quantitative structure-activity relationship(QSAR)models.Results:Through molecular networking,we identified seven known prohibited ingredients,six of which were confirmed using standard substances.In addition,17 potential risk substances were discovered within molecular clusters containing prohibited ingredients,including antibiotics,antihistamines,and phthalates,etc.Notably,chloramphenicol base and N-desmethyl chlorpheniramine exhibited stronger binding affinity to keratin 5/14 than chloramphenicol and chlorpheniramine through molecular docking,respectively.Additionally,toxicity prediction results indicated that the carcinogenicity of antibiotics presented gender differences in mice and rats,and two chlorpheniramine derivatives also showed carcinogenicity in mice.Moreover,of the 24 compounds,11 showed skin sensitization,while 14 caused skin irritation.Furthermore,half of these compounds demonstrated potential developmental toxicity,and only 4-nitrobenzenethiol was found to be mutagenic.Conclusion:In this study,we developed a visualization strategy for non-targeted screening of risk substances and a high-throughput method for initial toxicity assessment of risk substances.

关 键 词：Risk substances Non-targeted screening Molecular networking technology Computational toxicology 

分 类 号：R114[医药卫生—卫生毒理学]