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Nanomaterial categorization by surface reactivity: A case study comparing 35 materials with four different test methods
NanoImpact ( IF 4.9 ) Pub Date : 2020-07-01 , DOI: 10.1016/j.impact.2020.100234
Aileen Bahl , Bryan Hellack , Martin Wiemann , Anna Giusti , Kai Werle , Andrea Haase , Wendel Wohlleben

Abstract Nanomaterials (NMs) can be manufactured in plenty of variants differing in their physicochemical properties. Functional assays can be highly useful to cope with the enormous variability by supporting prioritization and categorization. Oxidative potential (OP) seems to be in particular important in this context and different assays are available. However, their reliability and predictivity are not well-characterized. This study compares four different test methods for measuring NM OP. Reactive oxygen species (ROS) generation was measured on a set of 35 different materials, all extensively characterized with respect to physicochemical properties and most of them with respect to toxicity. Different acellular assays were applied, namely electron spin resonance (ESR) spectroscopy using CPH spin probe and DMPO spin trap, and the ferric reduction ability of serum (FRAS) assay. In addition, protein carbonylation as a marker for oxidative protein damage was analyzed in NRK-52E cells. All assays were assessed individually for their predictivity compared to established toxicological endpoints. We also aimed to identify the optimal assay combination using multivariate logistic regression and other statistical measures. BET surface area-based doses were more suitable to relate surface reactivity to toxicity. In addition, normalization to the deposited dose was advantageous for cellular assays as it improved the predictivity for in vitro as well as in vivo toxicity. The carbonylation assay, potentially in combination with ESR (DMPO spin trap) or FRAS assay, led to the best predictive performance. In summary, we propose a testing strategy for NM OP and demonstrated the applicability in an extended case study on 35 materials. This work is an important contribution towards reliable grouping and testing strategies for NMs.

中文翻译:

按表面反应性对纳米材料进行分类:比较 35 种材料与四种不同测试方法的案例研究

摘要 纳米材料 (NMs) 可以制造成多种不同的物理化学特性。通过支持优先排序和分类,功能分析对于应对巨大的可变性非常有用。在这种情况下,氧化电位 (OP) 似乎特别重要,并且可以使用不同的检测方法。然而,它们的可靠性和预测性并没有得到很好的表征。本研究比较了测量 NM OP 的四种不同测试方法。在一组 35 种不同的材料上测量了活性氧 (ROS) 的生成,所有材料都具有广泛的物理化学特性特征,其中大部分具有毒性。应用了不同的脱细胞分析,即使用 CPH 自旋探针和 DMPO 自旋陷阱的电子自旋共振 (ESR) 光谱,血清铁还原能力(FRAS)测定。此外,在 NRK-52E 细胞中分析了蛋白质羰基化作为氧化蛋白质损伤的标志物。与已建立的毒理学终点相比,所有测定均单独评估其预测性。我们还旨在使用多变量逻辑回归和其他统计措施来确定最佳检测组合。基于 BET 表面积的剂量更适合将表面反应性与毒性联系起来。此外,对沉积剂量的标准化有利于细胞分析,因为它提高了体外和体内毒性的预测性。羰基化分析可能与 ESR(DMPO 自旋阱)或 FRAS 分析相结合,产生最佳的预测性能。总之,我们提出了 NM OP 的测试策略,并在对 35 种材料的扩展案例研究中证明了适用性。这项工作是对 NM 的可靠分组和测试策略的重要贡献。
更新日期:2020-07-01
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