Institute of Toxicology, University of Mainz, Mainz, Germany.
Arch Toxicol. 2012 Jul;86(7):985-94. doi: 10.1007/s00204-012-0838-y. Epub 2012 Mar 29.
This review is based on the lecture presented at the April 2010 nanomaterials safety assessment Postsatellite to the 2009 EUROTOX Meeting and summarizes genotoxicity investigations on nanomaterials published in the open scientific literature (up to 2008). Special attention is paid to the relationship between particle size and positive versus negative outcome, as well as the dependence of the outcome on the test used. Salient conclusions and outstanding recommendations emerging from the information summarized in this review are as follows: recognize that nanomaterials are not all the same; therefore know and document what nanomaterial has been tested and in what form; take nanomaterials specific properties into account; in order to make your results comparable with those of others and on other nanomaterials: use or at least include in your studies standardized methods; use in vivo studies to put in vitro results into perspective; take uptake and distribution of the nanomaterial into account; and in order to become able to make extrapolations to risk for human: learn about the mechanism of nanomaterials genotoxic effects. Past experience with standard non-nanosubstances already had shown that mechanisms of genotoxic effects can be complex and their elucidation can be demanding, while there often is an immediate need to assess the genotoxic hazard. Thus, a practical and pragmatic approach to genotoxicity investigations of novel nanomaterials is the use of a battery of standard genotoxicity testing methods covering a wide range of mechanisms. Application of these standard methods to nanomaterials demands, however, adaptations, and the interpretation of results from the genotoxicity testing of nanomaterials needs additional considerations exceeding those used for standard size materials.
这篇综述是基于在 2010 年 4 月的 EUROTOX 会议的 Postsatellite 上所做的关于纳米材料安全评估的演讲,以及对发表在开放的科学文献中的纳米材料的遗传毒性研究(截至 2008 年)进行了总结。特别关注了颗粒尺寸与阳性和阴性结果之间的关系,以及测试方法对结果的依赖性。从本综述中总结的信息中得出了以下重要结论和突出建议:认识到纳米材料并非完全相同;因此,要了解并记录所测试的纳米材料及其形式;考虑纳米材料的特殊性质;为了使你的结果与他人和其他纳米材料的结果具有可比性:使用或至少包括标准化方法;使用体内研究将体外结果置于适当的背景下;考虑纳米材料的摄取和分布;为了能够将风险外推到人类:了解纳米材料遗传毒性作用的机制。过去对标准非纳米物质的经验已经表明,遗传毒性作用的机制可能很复杂,阐明这些机制可能具有挑战性,而通常需要立即评估遗传毒性危害。因此,对新型纳米材料进行遗传毒性研究的实用和务实方法是使用涵盖广泛机制的一系列标准遗传毒性测试方法。然而,将这些标准方法应用于纳米材料需要进行适应性调整,并且需要对纳米材料的遗传毒性测试结果进行额外的考虑,这些考虑超出了对标准尺寸材料的考虑。