An increasing use of cobalt (Co)-based nanoparticles (NPs) in different applications and exposures at occupational settings triggers the need for toxicity assessment. Improved understanding regarding the physiochemical characteristics of Co metal NPs and different oxides in combination with assessment of toxicity and mechanisms may facilitate decisions for grouping during risk assessment. The aim of this study was to gain mechanistic insights in the correlation between NP reactivity and toxicity of three different Co-based NPs (Co, CoO, and Co₃O₄) by using various tools for characterization, traditional toxicity assays, as well as six reporter cell lines (ToxTracker) for rapid detection of signaling pathways of relevance for carcinogenicity. The results showed cellular uptake of all NPs in lung cells and induction of DNA strand breaks and oxidative damage (comet assay) by Co and CoO NPs. In-depth studies on the ROS generation showed high reactivity of Co, lower for CoO, and no reactivity of Co₃O₄ NPs. The reactivity depended on the corrosion and transformation/dissolution properties of the particles and the media highlighting the role of the surface oxide and metal speciation as also confirmed by in silico modeling. By using ToxTracker, Co NPs were shown to be highly cytotoxic and induced reporters related to oxidative stress (Nrf2 signaling) and DNA strand breaks. Similar effects were observed for CoO NPs but at higher concentrations, whereas the Co₃O₄ NPs were inactive at all concentrations tested. In conclusion, our study suggests that Co and CoO NPs, but not Co₃O₄, may be grouped together for risk assessment.

中文翻译：

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深入了解钴金属和氧化物纳米颗粒的反应性和（遗传）毒性的机理研究

钴（Co）基纳米颗粒（NPs）在不同应用中和在职业环境中暴露的日益增加的使用引发了对毒性评估的需求。结合对毒性和机理的评估，对钴金属纳米颗粒和不同氧化物的理化特性的进一步了解可能有助于在风险评估过程中进行分组决策。这项研究的目的是在NP反应性与三种不同的基于Co的NP（Co，CoO和Co ₃ O _4的毒性）之间的相关性方面获得机械方面的见解。），使用各种工具进行表征，传统的毒性试验以及六个报告细胞系（ToxTracker），用于快速检测与致癌性相关的信号通路。结果表明，Co和CoO NPs可以吸收肺细胞中所有NPs，并诱导DNA链断裂和氧化损伤（彗星试验）。对ROS产生的深入研究表明，Co的反应性较高，CoO的反应性较低，而Co ₃ O ₄ NP的反应性则较小。反应性取决于颗粒和介质的腐蚀和转化/溶解特性，这也突出了表面氧化物和金属形态的作用，这也得到了计算机技术的证实。造型。通过使用ToxTracker，Co NPs被证明具有高度的细胞毒性，并诱导了与氧化应激（Nrf2信号转导）和DNA链断裂有关的报告基因。对于CoO NPs观察到了类似的效果，但是在更高的浓度下，而Co ₃ O ₄ NPs在所有测试浓度下都没有活性。总之，我们的研究表明，可以将Co和CoO NP（而不是Co ₃ O _4）组合在一起进行风险评估。