Inhalation of multi-walled carbon nanotubes (MWCNTs) poses a potential risk to human health. In order to safeguard workers and consumers, the toxic properties of MWCNTs need to be identified. Functionalization has been shown to either decrease or increase MWCNT-related pulmonary injury, depending on the type of modification. We, therefore, investigated both acute and chronic pulmonary toxicity of a library of MWCNTs derived from a common pristine parent compound (NC7000). MWCNTs were thermally or chemically purified and subsequently surface functionalized by carboxylation or amination. To evaluate pulmonary toxicity, male C57BL6 mice were dosed via oropharyngeal aspiration with either 1.6 or 4 mg/kg of each MWCNT type. Mitsui-7 MWCNT was used as a positive control. Necropsy was performed at days 3 and 60 post-exposure to collect bronchoalveolar lavage fluid (BALF) and lungs. At day 3 all MWCNTs increased the number of neutrophils in BALF. Chemical purification had a greater effect on pro-inflammatory cytokines (IL-1β, IL-6, CXCL1) in BALF, while thermal purification had a greater effect on pro-fibrotic cytokines (CCL2, OPN, TGF-β1). At day 60, thermally purified, carboxylated MWCNTs had the strongest effect on lymphocyte numbers in BALF. Thermally purified MWCNTs caused the greatest increase in LDH and total protein in BALF. Furthermore, the thermally purified and carboxyl- or amine-functionalized MWCNTs caused the greatest number of granulomatous lesions in the lungs. The physicochemical characteristics mainly associated with increased toxicity of the thermally purified derivatives were decreased surface defects and decreased amorphous content as indicated by Raman spectroscopy. These data demonstrate that the purification method is an important determinant of lung toxicity induced by carboxyl- and amine-functionalized MWCNTs.

中文翻译：

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羧化或胺化的多壁碳纳米管对小鼠的肺毒性通过先前的纯化方法确定

吸入多壁碳纳米管（MWCNT）对人体健康构成潜在风险。为了保护工人和消费者，需要确定多壁碳纳米管的毒性。已显示功能化可减少或增加与MWCNT相关的肺损伤，具体取决于修饰的类型。因此，我们研究了源自普通原始母体化合物（NC7000）的MWCNTs库的急性和慢性肺毒性。MWCNT经过热或化学纯化，然后通过羧化或胺化进行表面官能化。为了评估肺毒性，通过口咽抽吸对雄性C57BL6小鼠给药1.6或4 mg / kg的每种MWCNT类型。将Mitsui-7 MWCNT用作阳性对照。暴露后第3天和第60天进行尸检，以收集支气管肺泡灌洗液（BALF）和肺。在第3天，所有MWCNTs增加了BALF中的中性粒细胞数量。化学纯化对BALF中促炎细胞因子（IL-1β，IL-6，CXCL1）的影响更大，而热纯化对促纤维化细胞因子（CCL2，OPN，TGF-β1）的影响更大。在第60天，热纯化的羧化MWCNT对BALF中的淋巴细胞数量影响最大。热纯化的多壁碳纳米管引起了BALF中LDH和总蛋白的最大增加。此外，热纯化和羧基或胺官能化的MWCNT引起了肺部最大数量的肉芽肿性病变。如拉曼光谱法所示，主要与热纯化衍生物的毒性增加有关的理化特性是表面缺陷减少和无定形含量减少。这些数据表明纯化方法是由羧基和胺官能化的MWCNT诱导的肺毒性的重要决定因素。