| 117 | 0 | 78 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 本研究以斑马鱼胚胎发育毒性分析为基础，旨在初步建立并验证一种可用于评估化妆品毒性的安全性评价方法。方法 采用受精后2 d的斑马鱼胚胎，暴露于人用药品技术要求国际协调理事会(ICH)收录的23种致畸剂(阳性对照化合物)和10种非致畸剂(阴性对照化合物),通过观测斑马鱼致死情况以及发育毒性表型，计算25%致死浓度(LC25)和未观察到有害效应最大剂量(NOAEL),以建立评价模型并验证方法学可靠性。进一步，将国家化妆品法规禁止添加的典型发育毒性成分以常规添加量混入已确认安全的化妆品中，利用建立的斑马鱼模型评估其发育毒性，以确认方法的可靠性。结果 该方法对23种致畸剂的预测准确率为78%,对10种非致畸剂的预测准确率为60%。在将7种阳性样品以常规添加量混入已确认安全的化妆品中后，成功检测出其中6个样品存在发育毒性风险，预测准确率达到86%。结论 基于斑马鱼胚胎发育毒性的测试方法在化妆品安全性评价中具有应用潜力，可为开发化妆品安全评估的替代检测方法提供重要参考。
Abstract：Objective This study focuses on analyzing developmental toxicity to zebrafish embryos, with the goal of establishing and preliminarily validating a scientific evaluation method for assessing the safety of cosmetics. Methods To test the reliability of this method, the embryos of zebrafish at 2 days post-fertilization were used to verify the effects of 23 teratogens(positive controls) and 10 non-teratogens(negative controls) listed by ICH on zebrafish embryonic developmental toxicity. The 25% lethal concentration(LC25) and the no observed adverse effect level(NOAEL) of these compounds were calculated by evaluating the malformation and mortality of zebrafish embryos. To further verify the reliability of this method, several typical ingredients that are prohibited by national regulations from being added to cosmetics were incorporated at conventional concentrations into confirmed safe cosmetics and subjected to zebrafish embryonic developmental toxicity testing. Results This testing method achieved a prediction accuracy of 78% for the 23 teratogens and 60% for the 10 non-teratogens. After mixing 7 positive samples into cosmetics at conventional concentrations, developmental toxicity risks were successfully detected in 6 samples, achieving a prediction accuracy of 86%. Conclusion Testing method based on zebrafish embryo developmental toxicity demonstrate potential applicability in cosmetic safety evaluation and could provide valuable references for developing alternative testing method in cosmetic safety assessment.
[1] 本刊讯.我国已成为世界上第二大化妆品消费市场[J].口腔护理用品工业，2021,31(1):59.
[2] 《化妆品监督管理条例》编写组.化妆品监督管理条例[M].北京：中国民主法制出版社，2020:39.
[3] 国家药品监督管理局.家药监局关于发布《化妆品安全评估技术导则(2021 年版)》的公告(2021 年第51号)[EB /OL].(2021-04-08) [2021-07-05].https:/ /www.nmpa.gov.cn /xxgk /ggtg /qtggtg /20210409160436155.html.
[4] 刘颖.国内化妆品安全性评价体系现况及分析[J].广东化工，2021,48(12):103-104.
[5] 张伟，邬国庆，秦美蓉，等.化妆品安全风险评估工作机制探讨[J].食品与药品，2024,26(1):57-62.
[6] 张殿义.中国动物保护伦理与化妆品使用安全的增量博弈[J].中国化妆品，2020,28(2):86-91.
[7] Chen JB,Gao HW,Zhang YL,et al.Developmental toxicity of diclofenac and elucidation of gene regulation in zebrafish (Danio rerio)[J].Sci Rep,2014,4:4841.
[8] Nishimura Y,Inoue A,Sasagawa S,et al.Using zebrafish in systems toxicology for developmental toxicity testing[J].Congenit Anom (Kyoto),2016,56 (1):18-27.
[9] Song YS,Dai MZ,Zhu CX,et al.Validation,optimization,and application of the zebrafish developmental toxicity assay for pharmaceuticals under the ICH S5(R3) guideline[J].Front Cell Dev Biol,2021,9:721130.
[10] 孙昭.胚胎发育的分期及发育表[J].四川解剖学杂志，1999,17(1):61-64.
[11] Kimmel CB,Ballard WW,Kimmel SR,et al.Stages of embryonic development of the zebrafish[J].Dev Dyn,1995,203(3):253-310.
[12] Ball JS,Stedman DB,Hillegass JM,et al.Fishing for teratogens:a consortium effort for a harmonized zebrafish developmental toxicology assay[J].Toxicol Sci,2014,139(1):210-219.
[13] 杨杏芬，吴永宁，贾旭东，等.食品安全风险评估[M].北京：化学工业出版社，2017:336.
[14] 徐飞飞，赵晓晗，周濛，等.毒性测试替代方法及其在化妆品安全风险评估中应用进展[J].中国药理学与毒理学杂志，2024,38 (10):723-733.
[15] Chahardehi AM,Arsad H,Lim V.Zebrafish as a successful animal model for screening toxicity of medicinal plants[J].Plants (Basel),2020,9 (10):1345-1345.
[16] Hong T,Park J,An G,et al.Evaluation of organ developmental toxicity of environmental toxicants using zebrafish embryos[J].Mol Cells,2024,47 (12):100144.
[17] Bauer B,Mally A,Liedtke D.Zebrafish embryos and larvae as alternative animal models for toxicity testing[J].Int J Mol Sci,2021,22 (24):13417.
[18] Jiang LL,Li K,Yan DL,et al.Toxicity assessment of 4 Azo Dyes in zebrafish embryos[J].Int J Toxicol,2020,39 (2):115-123.
[19] Str?hle U,Scholz S,Geisler R,et al.Zebrafish embryos as an alternative to animal experiments--a commentary on the definition of the onset of protected life stages in animal welfare regulations[J].Reprod Toxicol,2012,33 (2):128-132.
[20] Belanger SE,Balon EK,Rawlings JM.Saltatory ontogeny of fishes and sensitive early life stages for ecotoxicology tests[J].Aquat Toxicol,2010,97 (2):88-95.
[21] Zhu JJ,Xu YQ,He JH,et al.Human cardiotoxic drugs delivered by soaking and microinjection induce cardiovascular toxicity in zebrafish[J].J Appl Toxicol,2014,34 (2):139-148.
[22] Brannen KC,Panzica-Kelly JM,Danberry TL,et al.Development of a zebrafish embryo teratogenicity assay and quantitative prediction model[J].Birth Defects Res B Dev Reprod Toxicol,2010,89 (1):66-77.
基本信息:
DOI：10.16421/j.cnki.1002-3127.2025.06.005
中图分类号:TQ658
引用信息:
[1]刘中旺,彭逸,周示玉,等.基于斑马鱼胚胎发育毒性评价化妆品毒性的初步研究[J].毒理学杂志,2025,39(06):419-425.DOI:10.16421/j.cnki.1002-3127.2025.06.005.