Here we describe the development of an Integrated Approach to Testing and Assessment (IATA) to support the grouping of different types (nanoforms; NFs) of High Aspect Ratio Nanomaterials (HARNs), based on their potential to cause mesothelioma. Hazards posed by the inhalation of HARNs are of particular concern as they exhibit physical characteristics similar to pathogenic asbestos fibres. The approach for grouping HARNs presented here is part of a framework to provide guidance and tools to group similar NFs and aims to reduce the need to assess toxicity on a case-by-case basis. The approach to grouping is hypothesis-driven, in which the hypothesis is based on scientific evidence linking critical physicochemical descriptors for NFs to defined fate/toxicokinetic and hazard outcomes. The HARN IATA prompts users to address relevant questions (at decision nodes; DNs) regarding the morphology, biopersistence and inflammatory potential of the HARNs under investigation to provide the necessary evidence to accept or reject the grouping hypothesis. Each DN in the IATA is addressed in a tiered manner, using data from simple in vitro or in silico methods in the lowest tier or from in vivo approaches in the highest tier. For these proposed methods we provide justification for the critical descriptors and thresholds that allow grouping decisions to be made. Application of the IATA allows the user to selectively identify HARNs which may pose a mesothelioma hazard, as demonstrated through a literature-based case study. By promoting the use of alternative, non-rodent approaches such as in silico modelling, in vitro and cell-free tests in the initial tiers, the IATA testing strategy streamlines information gathering at all stages of innovation through to regulatory risk assessment while reducing the ethical, time and economic burden of testing.

在这里，我们描述了一种综合测试和评估方法 (IATA) 的开发，以支持对不同类型（纳米形式；NF）的高纵横比纳米材料 (HARN) 进行分组，基于它们引起间皮瘤的可能性。吸入 HARN 造成的危害尤其令人担忧，因为它们表现出与致病石棉纤维相似的物理特性。这里介绍的对 HARN 进行分组的方法是框架的一部分，旨在为类似的 NF 分组提供指导和工具，旨在减少逐案评估毒性的需要。分组方法是假设驱动的，其中假设基于将 NF 的关键物理化学描述符与确定的命运/毒代动力学和危害结果联系起来的科学证据。HARN IATA 提示用户解决有关正在调查的 HARN 的形态、生物持久性和炎症潜力的相关问题（在决策节点；DN），以提供接受或拒绝分组假设的必要证据。IATA 中的每个 DN 都以分层方式寻址，使用来自简单最低层的体外或计算机模拟方法或最高层的体内方法。对于这些提议的方法，我们为允许做出分组决策的关键描述符和阈值提供了理由。正如基于文献的案例研究所证明的那样，IATA 的应用允许用户选择性地识别可能造成间皮瘤危害的 HARN。通过促进在初始层级中使用计算机建模、体外和无细胞测试等替代性非啮齿动物方法，IATA 测试策略简化了从创新到监管风险评估的所有阶段的信息收集，同时减少了道德，测试的时间和经济负担。