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Variation in dissolution behavior among different nanoforms and its implication for grouping approaches in inhalation toxicity
NanoImpact ( IF 4.9 ) Pub Date : 2021-07-12 , DOI: 10.1016/j.impact.2021.100341
Johannes G Keller 1 , Michael Persson 2 , Philipp Müller 1 , Lan Ma-Hock 1 , Kai Werle 1 , Josje Arts 2 , Robert Landsiedel 1 , Wendel Wohlleben 1
Affiliation  

Different nanoforms (NF) of the same substance each need to be registered under REACH, but similarities in physiological interaction -among them biodissolution- can justify read-across within a group of NFs, thereby reducing the need to perform animal studies. Here we focused on the endpoint of inhalation toxicity and explored how differences in physical parameters of 17 NFs of silica, and organic and inorganic pigments impact dissolution rates, half-times, and transformation under both pH 7.4 lung lining conditions and pH 4.5 lysosomal conditions. We benchmarked our observations against well-known TiO2, BaSO4 and ZnO nanomaterials, representing very slow, partial and quick dissolution respectively. By automated image evaluation, structural transformations were observed for dissolution rates in the order of 0.1 to 10 ng/cm2/h, but did not provide additional decision criteria on the similarity of NFs. Dissolution half-times spanned nearly five orders of magnitude, mostly dictated by the substance and simulant fluid, but modulated up to ten-fold by the subtle differences between NFs. Physiological time scales and benchmark materials help to frame the biologically relevant range, proposed as 1 h to 1 y. NFs of ZnO, Ag, SiO2, BaSO4 were in this range. We proposed numerical rules of pairwise similarity within a group, of which the worst case NF would be further assessed by in vivo inhalation studies. These rules divided the colloidal silica NFs into two separate candidate groups, one with Al-doping, one without. Shape or silane surface treatment were less important. The dissolution halftimes of many organic and inorganic pigment NFs were longer than the biologically relevant range, such that dissolution behavior is not an obstacle for their groupings.



中文翻译:

不同纳米形式溶解行为的差异及其对吸入毒性分组方法的意义

同一物质的不同纳米形式 (NF) 各自需要根据 REACH 进行注册,但生理相互作用的相似性 - 其中包括生物溶解 - 可以证明在一组 NF 中进行交叉读取,从而减少进行动物研究的需要。在这里,我们专注于吸入毒性的终点,并探讨了在 pH 7.4 肺内壁条件和 pH 4.5 溶酶体条件下,二氧化硅的 17 种 NF 以及有机和无机色素的物理参数差异如何影响溶解速率、半衰期和转化。我们将我们的观察结果与众所周知的 TiO 2、BaSO 4进行了比较和 ZnO 纳米材料,分别代表非常缓慢、部分和快速溶解。通过自动图像评估,在 0.1 至 10 ng/cm 2 /h的溶解速率下观察到结构转变,但未提供关于 NF 相似性的额外决策标准。溶出半衰期跨越近五个数量级,主要由物质和模拟流体决定,但由 NF 之间的细微差异调节高达十倍。生理时间尺度和基准材料有助于确定生物学相关范围,建议为 1 小时至 1 年。ZnO、Ag、SiO 2、BaSO 4的纳米纤维都在这个范围内。我们提出了一组内成对相似性的数值规则,其中最坏情况 NF 将通过体内吸入研究进一步评估。这些规则将胶体二氧化硅 NF 分为两个独立的候选组,一组掺杂 Al,一组不掺杂。形状或硅烷表面处理不太重要。许多有机和无机颜料 NF 的溶解半衰期长于生物学相关范围,因此溶解行为不会成为它们分组的障碍。

更新日期:2021-07-24
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