化妆品纳米原料的国际监管及最新研究进展

目的：近年来随着纳米技术的不断发展,在世界范围内,纳米原料在化妆品中的应用日益增多, 其安全性和监管问题也备受关注,急需研究相应的管理制度和技术支撑体系。方法：在系统研究国际化妆品监管合作组织(ICCR)对化妆品纳米原料技术性文件工作基础之上,进一步跟踪消费者安全科学委员会(SCCS)等的最新研究进展以及相关法规动态,对化妆品纳米原料定义、实际使用情况、关键参数及其测量、安全性评价方法、监管要求等进行总结比对,结合我国监管现状进行分析。结果与结论：与传统原料相比,纳米原料具有一定的特殊性和需关注重点。建议借鉴ICCR、SCCS等的研究成果,收集我国化妆品纳米原料实际使用情况、开展方法学研究、建立安全性评价体系,建立健全我国化妆品纳米原料管理和技术体系。     

纳米技术在化妆品中的应用现状及监管建议

目的阐述纳米技术在化妆品中的应用现状及监管建议。方法介绍纳米技术原理,纳米技术在化妆品中的主要应用领域,纳米化妆品的作用,化妆品中几种常用纳米成分,纳米材料的安全性问题,主要发达国家(地区)对纳米材料应用于化妆品的监管情况,并对我国纳米原料及纳米化妆品的监管进行探讨。结果与结论纳米技术逐渐成熟已成为化妆品领域发展的一个战略平台,利用纳米技术可减小化妆品中功效成分的粒子粒径,使各种纳米级化妆品功效成分颗粒能顺利渗透到皮肤,并通过其产生的表面效应和尺寸效应最大限度地发挥护肤、疗肤效果。     

化妆品原料安全监管模式探讨

目的 本文通过分析化妆品行业原料管理的现状、原料监管中存在的问题,旨在探索化妆品原料监管的新模式.方法 通过查阅文献,深入生产企业调研,结合对化妆品企业监管的经验形成此篇文章.结果 提出了两种化妆品原料监管的模式即加强化妆品生产企业原料监管,对存在安全风险的物质建立化妆品原料要求以及建立新的原料标准体系.结论 化妆品原料对产品的安全性具有重要影响,相关部门应从源头做好监管,建立健全原料监管制度,探索科学监管的新模式.     

我国化妆品安全监测体系的现状及相关对策

目的:为进一步加强我国化妆品安全监测提供参考,为探索适合我国国情的化妆品安全监测体系提供思路。方法:从化妆品的生产、流通、上市等环节介绍我国化妆品安全监测体系现状,分析存在的问题,同时借鉴国外发达国家的化妆品管理方法以及我国药品监管的经验,提出相应对策。结果与结论:我国化妆品安全监测体系目前多局限于化妆品成品的生产和经营环节,尚未涵盖化妆品储运、使用全过程;化妆品原料的监管也只局限于对生产企业的原料管理,对化妆品包材和美容领域尚缺乏有效的监管手段。存在的问题主要是法律法规滞后、缺乏统一标准、质量管理滞后、不良反应监测体系不健全等。建议相关部门尽快健全化妆品监管法律法规,加强对化妆品研究、生产、流通、使用全程的监管,完善化妆品标准体系与技术监测机制、监测网络与应急机制。     

5种纳米原料的透皮吸收及安全评估研究进展

为了解纳米原料作用于皮肤时的暴露情况和总体风险,探讨透皮吸收研究在纳米原料安全评估中的应用,对三联苯基三嗪、氧化锌、炭黑、二氧化钛、亚甲基双-苯并三唑基四甲基丁基酚5种已收录于欧盟化妆品法规的纳米原料的透皮吸收试验研究以及相关安全评估工作进行总结。结果显示皮肤对于这5种纳米原料具有较好的屏障作用,未来在进行纳米原料透皮吸收研究以及纳米化妆品、经皮给药纳米药物的安全性评价时,应充分考虑皮肤屏障作用的影响,结合纳米原料的质量规格关键参数进行逐案分析。     

我国药品和医疗器械关联审评审批制度对化妆品原料管理和产品安全评价的启示

目的：研究我国药品、医疗器械关联审评审批相关制度,为化妆品原料管理和产品安全评价提供参考。方法：对近年来国家药品监督管理部门发布的药品、医疗器械关联审评审批政策进行梳理总结,对相关监管要求和技术管理手段进行分析,并与化妆品监管要求和管理现状进行对比。结果与结论：在考虑行业差异和监管差异的基础之上,可参考借鉴我国药品和医疗器械关联审评审批相关制度和配套措施,优化我国化妆品审评审批流程、划清安全责任界限、加强原料信息管理、借助信息化支撑手段,探索“化妆品原料安全信息库”的科学应用,提高化妆品原料管理和产品安全评价的整体效率。     

纳米氧化锌安全性评价及化妆品法规管理现状

目的：了解国内外纳米氧化锌安全性评价及化妆品法规管理现状,为我国对纳米原料与纳米化妆品监管提供参考。方法：通过文献研究,总结目前国内外纳米氧化锌的毒理学研究进展及世界主要国家及地区对纳米氧化锌的化妆品法规管理现状。结果：透皮吸收试验发现防晒霜中的纳米氧化锌主要聚集在人体皮肤角质层和毛囊皮脂腺开口处,微量锌可经皮肤吸收进入血液,但不能确定是以氧化锌还是锌离子的形式吸收。体外彗星试验结果显示纳米氧化锌引起人表皮细胞、人鼻粘膜细胞DNA损伤。亚急性经口毒性试验发现纳米氧化锌通过氧化应激介导小鼠肝脏细胞DNA损伤和凋亡。纳米氧化锌对小鼠具有生殖发育毒性。急性吸入毒性试验显示纳米氧化锌导致大鼠肺脏、肝脏组织损伤。亚慢性毒性试验显示纳米氧化锌高剂量组（536.8 mg·kg^-1）SD大鼠出现贫血及轻度到中度胰腺炎,纳米氧化锌的未观察到有害作用水平（NOAEL）为268.4 mg·kg^-1。欧盟、美国、中国台湾已出台了一系列化妆品纳米材料的法规或文件,指导化妆品行业开展纳米材料的安全性评价。结论：化妆品中纳米氧化锌对人体具有潜在安全风险,我国应尽快制定化妆品中纳米原料的相关管理政策。     

植物源化妆品原料安全性问题及监管建议

针对目前已广泛使用的植物源化妆品原料,如防腐剂、香精香料、美白剂,总结并列出其安全性问题,分析和归纳出含这些原料的产品在监管方面的特点,提出可将方法标准、管理清单、技术规范等技术监管工具作为化妆品监管科学研究中解决植物源化妆品原料安全问题的对策。     

皮肤类器官与皮肤芯片在药品及化妆品原料毒性测试中的应用进展

随着药品及化妆品新原料和新剂型的不断出现,亟需能够满足当代药品及化妆品新原料测试需求的新模型新方法。介绍了药品及化妆品原料毒性测试中的体外皮肤模型发展现状,列举了皮肤类器官和皮肤芯片在药品、化妆品原料毒性测试中的应用实例,并结合我国法规和监管现状对类器官与器官芯片模型的验证及标准化提出了建议,最后对皮肤类器官和皮肤芯片作为原料毒性测试工具可能在监管决策中发挥的作用进行了展望,以期为此类新型复杂体外模型的研发和应用提供建议。     

我国化妆品原料安全管理对策研究

目的：了解我国化妆品原料安全管理中面临的挑战并提出相关的管理建议,为我国化妆品原料的科学监管提供参考。方法：通过对我国已发布的化妆品原料安全相关管理法规进行调查研究,分析我国在化妆品新原料、美白原料和植物类原料管理方面所面临的问题和挑战,提出对我国化妆品原料管理改革的建议。结果：我国对化妆品原料的管理主要实行目录管理,制订了禁限用组分、准用组分（包括防腐剂、防晒剂、着色剂、染发剂）目录和《已使用化妆品原料名称目录》;并在化妆品新原料管理、原料的溯源和标识管理等方面均制订了相关管理法规。我国将对化妆品新原料管理模式进行调整;并需制订美白原料和植物类原料管理法规及技术指导文件。结论：我国急需调整和完善化妆品新原料、美白原料和植物类原料的管理体系建设。     

A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: Eye irritation

The need for alternative approaches to replace the in vivo rabbit Draize eye test for evaluation of eye irritation of cosmetic ingredients has been recognised by the cosmetics industry for many years. Extensive research has lead to the development of several assays, some of which have undergone formal validation. Even though, to date, no single in vitro assay has been validated as a full replacement for the rabbit Draize eye test, organotypic assays are accepted for specific and limited regulatory purposes. Although not formally validated, several other in vitro models have been used for over a decade by the cosmetics industry as valuable tools in a weight of evidence approach for the safety assessment of ingredients and finished products. In light of the deadlines established in the EU Cosmetics Directive for cessation of animal testing for cosmetic ingredients, a COLIPA scientific meeting was held in Brussels on 30th January, 2008 to review the use of alternative approaches and to set up a decision-tree approach for their integration into tiered testing strategies for hazard and safety assessment of cosmetic ingredients and their use in products. Furthermore, recommendations are given on how remaining data gaps and research needs can be addressed.     

拓展性同情使用临床试验用药制度的相关问题研究

目的 研究国外部分国家拓展性同情使用临床试验用药制度及申请批准情况,为我国拓展性临床试验用药制度设计提供参考.方法 通过查阅美国、欧盟药品监管机构发布的法规政策、技术指南、年度报告及相关文献,深入分析欧美拓展性临床试验用药的相关概念、类别、申请要求、风险获益评估等内容.结果和结论 拓展性同情使用临床试验用药是在不能通过...     

The science and politics of medicines control.

Drug development and regulation are often presented as purely matters of technical science. In this paper it is argued that, in principle, toxicology, clinical pharmacology and pharmacovigilance in drug testing and regulation are necessarily a combination of science and politics. This has important implications for how one attempts to make progress in drug regulation, such as in interpreting technical evidence and in the setting of regulatory standards with which evidence should be evaluated. In practice, drug testing and regulation are shown to be hybrids of science and politics. Moreover, drawing on existing empirical evidence, it is suggested that this mixture currently, and for some time, has had the wrong ingredients for optimal drug safety and public health outcomes. For example, too often the balance of the scientific doubts about drug safety are weighed to the interests of manufacturers rather than to those of patients and public health, while some scientific standards with which drug safety is to be interpreted are being reshaped in ways that give insufficient priority to the protection of public health. Finally, it is proposed that: drug regulation should include comparative efficacy testing; regulatory agencies should conduct some key tests, charging the costs to industry and without duplication; and the regulatory system should be less secretive and more accountable to public scrutiny. Greater efforts should be made to eliminate experts' conflicts of interest within the regulatory process.     

新药临床试验期间药物警戒和风险控制研究六:完善新药临床试验期间药物警戒和风险控制监管体系的建议

目的：为完善我国新药临床试验期间药物警戒和风险控制监管体系提供参考。方法：基于本课题组组织开展的“新药临床试验期间药物警戒和风险控制研究”课题研究，在本栏目相关论文对欧美等国家药物警戒监管体系的深入研究，对国内外药物警戒法规和指导原则等的对比分析，以及结合对问卷调查结果进行综合分析的基础上，提出完善我国新药临床试验期间药物警戒和风险控制监管体系的研究建议。结果与结论：从监管体系和关键要素两个方面，提出了完善我国新药临床试验期间药物警戒和风险控制监管体系的建议，包括完善监管机构人员培训、政策法规宣贯、引进专业人才、共享监管信息，以及强化临床试验期间临床试验方案、研究者手册、知情同意、非预期严重不良反应和研发期间安全性更新报告、研发期间安全性更新报告审核和反馈、不良反应事件报告、风险控制计划等药物警戒关键要素管理等。     

European regulation affecting nanomaterials - review of limitations and future recommendations

After learning about the potential risks associated with various specific nanomaterials, concerns have been raised about adequacy of existing regulation in Europe and what should be done to address any potential regulatory gaps related to nanomaterials. Understanding the limitations of the current regulation in regard to nanomaterials is a starting point in a democratic and transparent process towards adapting existing laws and facilitating an informed discussion about which kind of regulatory options best address the identified limitations. In the following we will introduce key pieces of European legislation affecting nanomaterials, analyze their limitations, and provide a number of recommendations on how these can be overcome. We find that, although nanomaterials are in principle covered by the scope of many of the existing legislative frameworks, it is often unclear, if current regulations are actually applicable when it comes to specific nanomaterials and their diverse applications. Main limitations seem to be: that requirements to do safety evaluations are triggered by production volumes by tonnage not tailored to the nanoscale, the profound lack of (eco)toxicological data, and that thresholds values and occupational exposure limits cannot be established with existing methodologies.     

Nanotechnology in cosmetics

Nanomaterials are being used in cosmetic products for various effects. However, their use also raises potential safety concerns. Some of these concerns can be addressed by determining the type of nanomaterials used, as well as stability, potential for skin absorption, route of exposure, and how they are formulated in cosmetic products. There has been considerable effort internationally to harmonize approaches in order to address definitional issues and safety concerns related to the use of nanomaterials in cosmetic products.     

A perspective on the safety of cosmetic products: a position paper of the American Council on Science and Health

Over the years, some activist groups have targeted cosmetics as possible human health threats, claiming that cosmetic ingredients are not adequately tested for safety and may pose risks to consumers. The groups allege that industry practices related to safety testing are flawed, that there is little government oversight, and that cosmetics contain cancer-causing chemicals and other toxicants. A critical review of the scientific data related to these claims indicates the following: (1) Industry has the primary responsibility to ensure that all ingredients, preservatives, and coformulants used in products are safe for their intended uses. (2) The U.S. Food and Drug Administration (FDA) has regulatory oversight of the cosmetic industry. Its authority includes the banning or restriction of ingredients for safety reasons. (3) The Cosmetic Ingredient Review (CIR), an independent, scientific review board, critically evaluates chemical ingredients used in cosmetics and publishes the results of its findings in the peer-reviewed literature. (4) Health-related allegations about cosmetic ingredients are generally based on the results of high-dose laboratory testing in animals and have little relevance for humans. As true now as when Paracelsus said it in the 16th century, "It is the dose that makes the poison." (5) The health-related allegations involving specific chemicals (e.g., phthalates, parabens, and 1,3-butadiene) fail to consider important scientific studies and recent regulatory conclusions about these chemicals, which have found that they are not hazardous. (6) Animal and human physiology differ in crucial ways, further invalidating simplistic attempts to extrapolate rodent testing to human health risks. The cosmetic industry should be encouraged to publish more of its toxicity studies and safety evaluations, which would aid in dispelling the uncertainty that some consumers have about cosmetic safety.     

Safety evaluation of cosmetics in the EU. Reality and challenges for the toxicologist

Council Directive 76/768/EEC, its seven amendments and 30 adaptations to technical progress form the basis of the cosmetic EU legislation today. There are actually four key principles for safety in the cosmetic legislation. (i) The full responsibility for the safety of cosmetics for human health is placed on the manufacturer, first importer in the EU or marketer. (ii) The safety evaluation of finished products is based on safety of individual ingredients, more specifically on their chemical structure, toxicological profile and their level of exposure. (iii) A compilation of information on each cosmetic product (dossier) must be kept readily available for inspection by the competent authorities of the Member State concerned. This information source, usually called a technical information file (TIF) or product information file/requirements (PIF(R)), contains, as the most important part, the safety assessment of the product undersigned by a competent safety assessor. (iv) The use of validated replacement alternative methods instead of animal testing forms the 4th key principle for safety of cosmetic products on the EU market. The 7th amendment imposes strict deadlines for the abolition of animal in vivo studies on cosmetic ingredients. These legal requirements induce a number of important challenges for the cosmetic industry and more specifically for the toxicologist involved as safety assessor.