Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
Inhal Toxicol. 2011 Nov;23(13):814-28. doi: 10.3109/08958378.2011.614968. Epub 2011 Oct 17.
The present study was conducted to assess the pulmonary and systemic responses in rats after intratracheal instillation of highly pure, well-dispersed, and well-characterized SWCNTs. Exposure to SWCNTs up to 2 mg/kg did not produce mortality, changes in clinical signs, or body weights during the observation period. Dose-dependent changes were observed in the lung weight, BALF inflammatory cells, and biochemical parameters such as LDH value, protein content, IL-1β and IL-6 activity, and histopathology. In the 0.04 mg/kg SWCNT-exposed group, almost no changes were observed during the observation period. In the 0.2 mg/kg SWCNT-exposed group, pulmonary inflammatory responses were observed after instillation. In the 1 mg/kg and 2 mg/kg SWCNT-exposed group, acute lung inflammation and subsequent granuloma accompanied by increased lung weights were observed. Furthermore, the histopathological findings in the lungs of rats exposed to SWCNTs showed inflammatory responses related with the vital reaction to the foreign substance that was instilled intratracheally, and there were no fibrosis, atypical lesion, or tumor-related findings even at the highest dose (2 mg/kg) of SWCNT-exposed groups up to 6 months after instillation. For all groups, histopathological changes due to the instillation exposure of SWCNTs were observed only in the lungs and lung-associated lymph nodes and not in the other tissues examined (i.e. the liver, kidney, spleen, and cerebrum).
本研究旨在评估经气管内滴注高度纯净、分散良好且特性明确的单壁碳纳米管后大鼠的肺部和全身反应。在观察期间,暴露于高达 2mg/kg 的 SWCNTs 不会导致死亡率、临床症状变化或体重变化。在肺重、BALF 炎性细胞以及生化参数(如 LDH 值、蛋白含量、IL-1β和 IL-6 活性)和组织病理学方面观察到剂量依赖性变化。在 0.04mg/kg SWCNT 暴露组中,在观察期间几乎没有观察到变化。在 0.2mg/kg SWCNT 暴露组中,在滴注后观察到肺部炎症反应。在 1mg/kg 和 2mg/kg SWCNT 暴露组中,观察到急性肺炎症和随后的肉芽肿,伴有肺重增加。此外,暴露于 SWCNTs 的大鼠肺部的组织病理学发现显示与经气管内滴注的异物有关的炎症反应,即使在 SWCNT 暴露的最高剂量(2mg/kg)下,也没有纤维化、非典型病变或肿瘤相关发现,直至滴注后 6 个月。对于所有组,SWCNTs 滴注暴露引起的组织病理学变化仅在肺部和肺相关淋巴结中观察到,而在检查的其他组织(即肝脏、肾脏、脾脏和大脑)中未观察到。