Advanced Materials Research, Dept. of Material Physics and Analytics and Dept. of Experimental Toxicology and Ecology, BASF SE, Ludwigshafen, Germany.
Athena Research Center, Athens, Greece.
NanoImpact. 2022 Apr;26:100390. doi: 10.1016/j.impact.2022.100390. Epub 2022 Feb 7.
Grouping of substances is a method used to streamline hazard and risk assessment. Assessment of similarity provides the scientific evidence needed for formation of groups. This work reports on justification of grouping of nanoforms (NFs) via similarity of their surface reactivity. Four reactivity assays were used for concentration dependent detection of reactive oxygen species (ROS) generated by NFs: abiotic assays FRAS, EPR and DCFH2-DA, as well as the in vitro assay of NRF2/ARE responsive luciferase reporter activation in the HEK293 cell line. Representative materials (CuO, MnO, BaSO, CeO and ZnO) and three case studies of each several NFs of iron oxides, Diketopyrrolopyrroles (DPP)-based organic pigments and silicas were assessed. A novel similarity assessment algorithm was applied to quantify similarities between pairs of NFs, in a four-step workflow on concentration-response curves, individual concentration and response ranges, and finally the representative materials. We found this algorithm to be applicable to all abiotic and in vitro assays that were tested. Justification of grouping must include the increased potency of smaller particles via the scaling of effects with specific surface, and hence quantitative similarity analysis was performed on concentration-response in mass-metrics. CuO and BaSO were the most and least reactive representative materials respectively, and all assays found BaSO/CuO not similar, as confirmed by their different NOAECs of in vivo studies. However, similarity outcomes from different reactivity assays were not always in agreement, highlighting the need to generate data by one assay for the representative materials and the candidate group of NFs. Despite low similarity scores in vitro some pairs of case study NFs can be accepted as sufficiently similar because the in vivo NOAECs are similar, highlighting the conservative assessment by the abiotic assays.
物质分组是一种用于简化危害和风险评估的方法。评估相似性为形成分组提供了形成分组所需的科学依据。这项工作报告了通过纳米形式（NFs）的表面反应性相似性对 NF 进行分组的理由。使用了四种反应性测定法来检测 NF 产生的活性氧物种（ROS）的浓度依赖性：非生物测定 FRAS、EPR 和 DCFH2-DA，以及在 HEK293 细胞系中检测 NRF2/ARE 反应性荧光素酶报告基因激活的体外测定法。评估了代表性材料（CuO、MnO、BaSO、CeO 和 ZnO）和三种铁氧化物、二酮吡咯并吡咯（DPP）基有机颜料和硅的每个案例研究的几个 NF。应用一种新的相似性评估算法，通过在浓度-反应曲线、单个浓度和响应范围以及最终的代表性材料的四个步骤工作流程中，对 NF 对之间的相似性进行量化。我们发现该算法适用于所有经过测试的非生物和体外测定法。分组的理由必须包括通过特定表面积的效应缩放来提高较小颗粒的效力，因此在质量度量的浓度-反应中进行了定量相似性分析。CuO 和 BaSO 分别是最具反应性和反应性最低的代表性材料，所有测定法都发现 BaSO/CuO 不相似，这与体内研究的不同 NOAEC 一致。然而，不同反应性测定法的相似性结果并不总是一致的，这突出表明需要通过一种测定法为代表性材料和候选 NF 组生成数据。尽管体外相似性得分较低，但由于体内 NOAEC 相似，一些案例研究 NF 对可以被认为具有足够的相似性，这突出了非生物测定法的保守评估。
