QSAR Lab Ltd., Trzy Lipy 3, 80-172 Gdansk, Poland.
University of Gdansk, Faculty of Chemistry, Wita Stwosza 63, 80-308 Gdansk, Poland.
Nanoscale. 2022 May 16;14(18):6735-6742. doi: 10.1039/d2nr00664b.
There is growing interest in developing novel strategies to support assessment of human health risks due to chemicals. Regulatory and decision-making agencies have recommended that non-animal-based alternatives should be applied whenever possible instead of experimentation on living animals. These alternative methods are beneficial because they are ethical, inexpensive, and rapid. Herein, we review recent activities aimed at developing to extrapolation (IVIVE) models as a part of the Next Generation Risk Assessment (NGRA) of nanomaterials. In this context, we show the adverse outcome pathway (AOP)-based methodology for the identification of mechanistically relevant events serving as biomarkers for the targeted selection of assays. Considered events need to be biologically plausible, regulatory relevant, and crucial for the examination of occurrence of adverse outcomes. The promising advantages of using high-throughout-based omics data are highlighted. Furthermore, the application of 3D models and nano genome atlases to study nanoparticle toxicity is briefly summarized. Additionally, the challenges related to the extrapolation of doses into -relevant responses are presented. We also discuss the limitations of models applied thus far to study the fate of chemicals in the human body, which exist due to the lack of available knowledge regarding transformations of nanomaterials occurring in biological systems.
人们越来越关注开发新策略，以支持评估化学品对人类健康的风险。监管和决策机构建议，只要有可能，就应采用基于非动物的替代方法，而不是在活体动物上进行实验。这些替代方法是有益的，因为它们具有伦理、经济和快速的特点。在此，我们综述了近期旨在开发从测试到推断（IVIVE）模型的活动，作为纳米材料下一代风险评估（NGRA）的一部分。在这种情况下，我们展示了基于不良结局途径（AOP）的方法学，用于识别作为目标选择测试的生物标志物的机制相关事件。所考虑的事件需要在生物学上是合理的、监管相关的，并且对于检查不良结局的发生至关重要。突出强调了使用高通量组学数据的有前途的优势。此外，简要总结了使用 3D 模型和纳米基因组图谱来研究纳米颗粒毒性的应用。此外，还提出了将剂量外推到相关反应中所面临的挑战。我们还讨论了迄今为止应用于研究化学物质在人体中命运的模型的局限性，这些局限性是由于缺乏有关生物系统中纳米材料转化的可用知识所致。
