Abstract

New registration requirements for nanomaterials under REACH consider the possibility to form ‘sets of similar nanoforms’ for a joined human health and environmental hazard, exposure and risk assessment. We developed a tool to create and justify sets of similar nanoforms and to ensure that each of the nanoforms is sufficiently similar to all other nanoforms. The decision logic is following the ECHA guidance in a transparent and evidence-based manner. For each two nanoforms the properties under consideration are compared and corresponding thresholds for maximal differences are proposed. In tier1, similarity is assessed based on intrinsic properties that mostly correspond to those required for nanoform identification under REACH: composition, impurities/additives, size, crystallinity, shape and surface treatment. Moreover, potential differences in the agglomeration/aggregation state resulting from different production processes are considered. If nanoforms were not sufficiently similar based on tier1 criteria, additional data from functional assays are required in tier2. In rare cases, additional short-term in vivo rodent data could be required in a third tier. Data required by tier 2 are triggered by the intrinsic properties in the first tier that did not match the similarity criteria. Most often this will be data on dissolution and surface reactivity followed by in vitro toxicity, dispersion stability, dustiness. Out of several nanoforms given by the user, the tool concludes which nanoforms could be justified to be in the same set and which nanoforms are outside. It defines the boundaries of sets of similar nanoforms and generates a justification for the REACH registration.

抽象的

根据REACH对纳米材料的新注册要求考虑了形成“相似纳米形式组”的可能性，以共同对人类健康和环境危害，暴露和风险进行评估。我们开发了一种工具来创建和证明一组相似的纳米形式，并确保每个纳米形式与所有其他纳米形式足够相似。决策逻辑以透明且基于证据的方式遵循ECHA指南。对于每两种纳米形式，都比较了所考虑的性质，并提出了最大差异的相应阈值。在第1层中，相似性是根据与REACH中纳米级鉴定所要求的内在特性基本相对应的：组成，杂质/添加剂，尺寸，结晶度，形状和表面处理。而且，考虑了由于不同生产工艺而导致的团聚/聚集状态的潜在差异。如果根据第1层标准，纳米形式的相似性不够，则在第2层中需要功能测定的其他数据。在极少数情况下，还会有短期的在第三层可能需要体内啮齿动物数据。第2层所需的数据由第一层中与相似性标准不匹配的固有属性触发。最常见的是有关溶解度和表面反应性的数据，然后是体外毒性，分散稳定性和粉尘。在用户给出的几种纳米形式中，该工具得出结论：可以证明哪些纳米形式在同一集合中是合理的，哪些纳米形式在外部。它定义了相似纳米形式的集合的边界，并为REACH注册产生了理由。