School of Engineering, Newcastle University, Newcastle Upon Tyne, United Kingdom; Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
Toxicol In Vitro. 2019 Mar;55:108-115. doi: 10.1016/j.tiv.2018.12.007. Epub 2018 Dec 17.
Parabens, esters of parahydroxybenzoic acid, are widely used in cosmetic, food and pharmaceutical industries mainly for their antibacterial and fungicidal properties. Methyl paraben has shown very low toxicity in a wide range of in vitro and animal tests. However, butyl paraben and derivatives, such as isobutyl parabens, are classified as allergens and have been shown to induce toxic effects. In the present study the effects of exposure to methyl or butyl paraben (5-1000 μM) on cytotoxicity, oxidative stress, mitochondrial dysfunction and genotoxicity were measured in a hepatocarcinoma cell line (HepG2) and human dermal fibroblasts neonatal (HDFn). Butyl paraben caused a concentration dependent decrease (above 400 μM) in cell viability for both cell lines. Toxicity of butyl paraben observed appeared to be mediated via ATP depletion as seen from luminescence assays. Depletion of glutathione was also observed for higher concentrations of butyl paraben, which may indicate the involvement of oxidative stress. Methyl paraben, however, did not show any significant decrease in cell viability, reduction in ATP or glutathione levels in HepG2 and HDFn cell lines at the concentrations tested. In vitro studies based on human cell lines can provide information in the early stages of multitier paraben toxicity studies and can be combined with in vivo and ex vivo studies to build more comprehensive, scientifically sound strategies for paraben safety testing. The results obtained in this study could supplement existing in vivo toxicity data for defining more robust limits for human exposure.
对羟基苯甲酸酯是对羟基苯甲酸的酯类，广泛应用于化妆品、食品和制药行业，主要因其具有抗菌和杀菌特性。在各种体外和动物试验中，已证明甲基对羟基苯甲酸酯具有非常低的毒性。然而，丁基对羟基苯甲酸酯及其衍生物（如异丁基对羟基苯甲酸酯）被归类为过敏原，并已被证明会引起毒性作用。在本研究中，在肝癌细胞系（HepG2）和人真皮成纤维细胞新生儿（HDFn）中测量了暴露于甲基或丁基对羟基苯甲酸酯（5-1000 μM）对细胞毒性、氧化应激、线粒体功能障碍和遗传毒性的影响。丁基对羟基苯甲酸酯对两种细胞系的细胞活力均表现出浓度依赖性下降（高于 400 μM）。从发光测定中可以看出，观察到的丁基对羟基苯甲酸酯的毒性似乎是通过 ATP 耗竭介导的。较高浓度的丁基对羟基苯甲酸酯也观察到谷胱甘肽耗竭，这可能表明氧化应激的参与。然而，在 HepG2 和 HDFn 细胞系中，在测试浓度下，甲基对羟基苯甲酸酯并未显示出任何明显的细胞活力下降、ATP 或谷胱甘肽水平降低。基于人细胞系的体外研究可以为多阶段对羟基苯甲酸酯毒性研究的早期阶段提供信息，并可以与体内和体外研究相结合，构建更全面、科学合理的对羟基苯甲酸酯安全性测试策略。本研究获得的结果可以补充现有的体内毒性数据，以确定更严格的人类暴露限制。
