Incorporation of engineered nanomaterials (ENMs) into toners used in laser printers has led to countless quality and performance improvements. However, the release of ENMs during printing (consumer use) has raised concerns about their potential adverse health effects. The aim of this study was to use "real world" printer-emitted particles (PEPs), rather than raw toner powder, and assess the pulmonary responses following exposure by intratracheal instillation. Nine-week old male Balb/c mice were exposed to various doses of PEPs (0.5, 2.5 and 5 mg/kg body weight) by intratracheal instillation. These exposure doses are comparable to real world human inhalation exposures ranging from 13.7 to 141.9 h of printing. Toxicological parameters reflecting distinct mechanisms of action were evaluated, including lung membrane integrity, inflammation and regulation of DNA methylation patterns. Results from this in vivo toxicological analysis showed that while intratracheal instillation of PEPs caused no changes in the lung membrane integrity, there was a pulmonary immune response, indicated by an elevation in neutrophil and macrophage percentage over the vehicle control and low dose PEPs groups. Additionally, exposure to PEPs upregulated expression of the Ccl5 (Rantes), Nos1 and Ucp2 genes in the murine lung tissue and modified components of the DNA methylation machinery (Dnmt3a) and expression of transposable element (TE) LINE-1 compared to the control group. These genes are involved in both the repair process from oxidative damage and the initiation of immune responses to foreign pathogens. The results are in agreement with findings from previous in vitro cellular studies and suggest that PEPs may cause immune responses in addition to modifications in gene expression in the murine lung at doses that can be comparable to real world exposure scenarios, thereby raising concerns of deleterious health effects.

中文翻译：

---

气管内灌注激光打印机发射的工程纳米粒子对小鼠模型的影响：消费者使用过程中释放的纳米材料毒理学意义的案例研究

将工程纳米材料 (ENM) 纳入激光打印机使用的碳粉中，已导致无数的质量和性能改进。然而，在印刷（消费者使用）过程中释放的 ENM 引起了人们对其潜在不利健康影响的担忧。这项研究的目的是使用“真实世界”的打印机发射颗粒 (PEP)，而不是原始碳粉，并评估气管内滴注暴露后的肺部反应。九周大的雄性 Balb/c 小鼠通过气管内滴注暴露于不同剂量的 PEP（0.5、2.5 和 5 毫克/千克体重）。这些暴露剂量与真实世界的人类吸入暴露量相当，范围从 13.7 到 141.9 小时的印刷。评估了反映不同作用机制的毒理学参数，包括肺膜完整性、DNA 甲基化模式的炎症和调节。体内毒理学分析的结果表明，虽然气管内滴注 PEP 不会导致肺膜完整性发生变化，但存在肺免疫反应，表现为中性粒细胞和巨噬细胞百分比高于载体对照组和低剂量 PEP 组。此外，与对照组相比，暴露于 PEP 上调了小鼠肺组织中 Ccl5 (Rantes)、Nos1 和 Ucp2 基因的表达以及 DNA 甲基化机制 (Dnmt3a) 的修饰成分和转座因子 (TE) LINE-1 的表达. 这些基因参与氧化损伤的修复过程和对外来病原体的免疫反应的启动。