Department of Toxicology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.
Mutagenesis. 2014 Mar;29(2):115-21. doi: 10.1093/mutage/get068. Epub 2014 Jan 16.
To evaluate the mutagenicity/genotoxicity of cosmetic ingredients at the regulatory level, usually a battery of three in vitro tests is applied. This battery, designed to be very sensitive, produces a high number of positive results, imposing the need for in vivo follow-up testing to clear the substance under study. In Europe, the use of experimental animals has become impossible for cosmetic ingredients due to the implementation of animal testing and marketing bans. Consequently, the possibility to 'de-risk' substances with positive in vitro results disappear and potentially safe cosmetic substances will be lost for the EU market unless currently used in vitro assays can be adapted or new non-animal mutagenicity/genotoxicity studies become available. Described strategies to improve the specificity of existing in vitro assays include optimisation of the used cell type and cytotoxicity assay and lowering of the applied top concentration. A reduction of the number of tests in the battery from three to two also has been suggested. In this study, the performance of the 'standard' in vitro mutagenicity/genotoxicity testing battery is analysed for a number of cosmetic ingredients. We composed a database with toxicological information on 249 cosmetic ingredients, mainly present on the Annexes of the European cosmetic legislation. Results revealed that the in vitro mutagenicity/genotoxicity tests showed a low specificity for the cosmetic ingredients concerned, comparable to the specificity published for chemicals. Non-confirmed or 'misleading' positive results amounted up to 93% for the in vitro test batteries. The cell type and top concentrations did not have a major impact on the specificity. With respect to cytotoxicity determinations, different end points were used, potentially leading to different testing concentrations, suggesting the need for a consensus in this matter. Overall, the results of this retrospective analysis point to an urgent need of better regulatory strategies to assess the potential mutagenicity/genotoxicity of cosmetic ingredients.
为了在监管层面评估化妆品成分的致突变性/遗传毒性，通常会应用一组三项体外测试。该测试组合旨在具有高度敏感性，会产生大量阳性结果，从而需要进行体内后续测试以明确受试物质。在欧洲，由于实施了动物测试和销售禁令，化妆品成分已不可能使用实验动物。因此，如果不能对具有阳性体外结果的物质进行“降低风险”处理，那么潜在安全的化妆品物质将无法进入欧盟市场，除非目前使用的体外检测方法能够得到改进，或者能够开展新的非动物致突变性/遗传毒性研究。提高现有体外检测方法特异性的策略包括优化所用细胞类型和细胞毒性检测，以及降低应用的最高浓度。还建议将测试组合中的测试数量从三项减少到两项。在这项研究中，对一些化妆品成分的“标准”体外致突变性/遗传毒性测试组合的性能进行了分析。我们构建了一个数据库，其中包含 249 种化妆品成分的毒理学信息，这些成分主要存在于欧洲化妆品法规的附件中。结果表明，体外致突变性/遗传毒性测试对所涉及的化妆品成分的特异性较低，与公布的化学物质特异性相当。非确认或“误导性”的阳性结果在体外测试组合中达到 93%。细胞类型和最高浓度对特异性没有重大影响。关于细胞毒性测定，使用了不同的终点，可能导致不同的测试浓度，这表明需要在这方面达成共识。总体而言，这项回顾性分析的结果表明，迫切需要制定更好的监管策略，以评估化妆品成分的潜在致突变性/遗传毒性。
