Murphy Fiona A, Johnston Helinor J, Dekkers Susan, Bleeker Eric A J, Oomen Agnes G, Fernandes Teresa F, Rasmussen Kirsten, Jantunen Paula, Rauscher Hubert, Hunt Neil, di Cristo Luisana, Braakhuis Hedwig M, Haase Andrea, Hristozov Danail, Wohlleben Wendel, Sabella Stefania, Stone Vicki
Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh, UK.
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
ALTEX. 2023;40(1):125-140. doi: 10.14573/altex.2203241. Epub 2022 Jun 22.
Manufacturing and functionalizing materials at the nanoscale has led to the generation of a whole array of nanoforms (NFs) of substances varying in size, morphology, and surface characteristics. Due to financial, time, and ethical considerations, testing every unique NF for adverse effects is virtually impossible. Use of hypothesis-driven grouping and read-across approaches, as supported by the GRACIOUS Framework, represents a promising alternative to case-by-case testing that will make the risk assessment process more efficient. Through application of appropriate grouping hypotheses, the Framework facilitates the assessment of similarity between NFs, thereby supporting grouping and read-across of information, minimizing the need for new testing, and aligning with the 3R principles of replacement, reduction, and refinement of animals in toxicology studies. For each grouping hypothesis an integrated approach to testing and assessment (IATA) guides the user in data gathering and acquisition to test the hypothesis, following a structured format to facilitate efficient decision-making. Here we present the template used to generate the GRACIOUS grouping hypotheses encompassing information relevant to “Lifecycle, environmental release, and human exposure”, “What they are: physicochemical characteristics”, “Where they go: environmental fate, uptake, and toxicokinetics”, and “What they do: human and environmental toxicity”. A summary of the template-derived hypotheses focusing on human health is provided, along with an overview of the IATAs generated by the GRACIOUS project. We discuss the application and flexibility of the template, providing the opportunity to expand the application of grouping and read-across in a logical, evidence-based manner to a wider range of NFs and substances.
在纳米尺度上制造材料并使其功能化，已催生了一系列大小、形态和表面特性各异的纳米形式（NFs）物质。出于经济、时间和伦理方面的考虑，对每一种独特的NF进行不良反应测试几乎是不可能的。采用由GRACIOUS框架支持的假设驱动分组和类推方法，是一种有前景的替代逐个测试的方法，这将使风险评估过程更高效。通过应用适当的分组假设，该框架有助于评估NFs之间的相似性，从而支持信息的分组和类推，减少新测试的需求，并符合毒理学研究中动物替代、减少和优化的3R原则。对于每个分组假设，一种综合测试与评估方法（IATA）指导用户按照结构化格式收集和获取数据以测试该假设，从而促进高效决策。在此，我们展示用于生成GRACIOUS分组假设的模板，该模板涵盖与“生命周期、环境释放和人类暴露”、“它们是什么：物理化学特性”、“它们去向何处：环境归宿、吸收和毒代动力学”以及“它们会怎样：对人类和环境的毒性”相关的信息。我们提供了聚焦于人类健康的源自模板的假设总结，以及GRACIOUS项目生成的IATAs概述。我们讨论了该模板的应用和灵活性，为以合乎逻辑、基于证据的方式将分组和类推的应用扩展到更广泛的NFs和物质提供了契机。
