Muller Julie, Huaux François, Moreau Nicolas, Misson Pierre, Heilier Jean-François, Delos Monique, Arras Mohammed, Fonseca Antonio, Nagy Janos B, Lison Dominique
Industrial Toxicology and Occupational Medicine Unit, Université Catholique de Louvain, Clos Chapelle-aux-Champs, 30.54; 1200 Brussels, Belgium.
Toxicol Appl Pharmacol. 2005 Sep 15;207(3):221-31. doi: 10.1016/j.taap.2005.01.008.
Carbon nanotubes focus the attention of many scientists because of their huge potential of industrial applications, but there is a paucity of information on the toxicological properties of this material. The aim of this experimental study was to characterize the biological reactivity of purified multi-wall carbon nanotubes in the rat lung and in vitro. Multi-wall carbon nanotubes (CNT) or ground CNT were administered intratracheally (0.5, 2 or 5 mg) to Sprague-Dawley rats and we estimated lung persistence, inflammation and fibrosis biochemically and histologically. CNT and ground CNT were still present in the lung after 60 days (80% and 40% of the lowest dose) and both induced inflammatory and fibrotic reactions. At 2 months, pulmonary lesions induced by CNT were characterized by the formation of collagen-rich granulomas protruding in the bronchial lumen, in association with alveolitis in the surrounding tissues. These lesions were caused by the accumulation of large CNT agglomerates in the airways. Ground CNT were better dispersed in the lung parenchyma and also induced inflammatory and fibrotic responses. Both CNT and ground CNT stimulated the production of TNF-alpha in the lung of treated animals. In vitro, ground CNT induced the overproduction of TNF-alpha by macrophages. These results suggest that carbon nanotubes are potentially toxic to humans and that strict industrial hygiene measures should to be taken to limit exposure during their manipulation.
碳纳米管因其巨大的工业应用潜力而吸引了众多科学家的关注，但关于这种材料的毒理学特性的信息却很少。本实验研究的目的是表征纯化的多壁碳纳米管在大鼠肺部和体外的生物反应性。将多壁碳纳米管（CNT）或研磨后的CNT经气管内给予Sprague-Dawley大鼠（0.5、2或5毫克），我们通过生化和组织学方法评估肺部的持久性、炎症和纤维化情况。60天后，肺中仍存在CNT和研磨后的CNT（最低剂量的80%和40%），两者均引发炎症和纤维化反应。2个月时，CNT诱导的肺部病变表现为支气管腔内突出形成富含胶原蛋白的肉芽肿，并伴有周围组织的肺泡炎。这些病变是由气道中大量CNT团聚物的积累引起的。研磨后的CNT在肺实质中分布更均匀，也引发炎症和纤维化反应。CNT和研磨后的CNT均刺激了处理动物肺部TNF-α的产生。在体外，研磨后的CNT诱导巨噬细胞过度产生TNF-α。这些结果表明碳纳米管对人类具有潜在毒性，应采取严格的工业卫生措施以限制在其操作过程中的接触。
