Safety assessment of graphene‐based materials (GBMs) including graphene oxide (GO) is essential for their safe use across many sectors of society. In particular, the link between specific material properties and biological effects needs to be further elucidated. Here, the effects of lateral dimensions of GO sheets in acute and chronic pulmonary responses after single intranasal instillation in mice are compared. Micrometer‐sized GO induces stronger pulmonary inflammation than nanometer‐sized GO, despite reduced translocation to the lungs. Genome‐wide RNA sequencing also reveals distinct size‐dependent effects of GO, in agreement with the histopathological results. Although large GO, but not the smallest GO, triggers the formation of granulomas that persists for up to 90 days, no pulmonary fibrosis is observed. These latter results can be partly explained by Raman imaging, which evidences the progressive biotransformation of GO into less graphitic structures. The findings demonstrate that lateral dimensions play a fundamental role in the pulmonary response to GO, and suggest that airborne exposure to micrometer‐sized GO should be avoided in the production plant or applications, where aerosolized dispersions are likely to occur. These results are important toward the implementation of a safer‐by‐design approach for GBM products and applications, for the benefit of workers and end‐users.

中文翻译：

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氧化石墨烯薄板对小鼠的大小相关性肺部影响：通过设计安全。

包括氧化石墨烯（GO）在内的石墨烯基材料（GBM）的安全评估对于其在社会许多部门的安全使用至关重要。特别是，还需要进一步阐明特定材料特性与生物学效应之间的联系。在这里，比较了GO片的横向尺寸对小鼠单次鼻内滴注后在急性和慢性肺反应中的作用。尽管减少了向肺的移位，但微米级的GO诱导的肺部炎症比纳米级的GO更强。全基因组RNA测序还揭示了GO独特的大小依赖性效应，与组织病理学结果一致。尽管大的GO（但不是最小的GO）触发肉芽肿的形成，这种肉芽肿持续长达90天，但未观察到肺纤维化。后者的这些结果可以通过拉曼成像得到部分解释，这证明了GO逐渐生物转化为较少的石墨结构。研究结果表明，横向尺寸在肺部对GO的反应中起着根本性的作用，并建议在可能发生气雾弥散的生产工厂或应用中，应避免空气中暴露于微米级的GO。这些结果对于为GBM产品和应用程序实施更安全的设计方法非常重要，以使工作人员和最终用户受益。并建议在可能发生气溶胶分散的生产工厂或应用中，避免在空气中暴露于微米级的GO。这些结果对于为GBM产品和应用程序实施更安全的设计方法非常重要，以使工作人员和最终用户受益。并建议在可能发生气溶胶分散的生产工厂或应用中，避免在空气中暴露于微米级的GO。这些结果对于为GBM产品和应用程序实施一种更安全的设计方法非常重要，从而使工作人员和最终用户受益。