National Research Centre for the Working Environment, Lersø Parkallé 105, Copenhagen, DK-2100, Denmark; Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, DK-1014, Denmark.
National Research Centre for the Working Environment, Lersø Parkallé 105, Copenhagen, DK-2100, Denmark.
Environ Toxicol Pharmacol. 2020 Jan;73:103266. doi: 10.1016/j.etap.2019.103266. Epub 2019 Oct 1.
The toxicological potential of halloysite nanotubes (HNTs) and variants after functional alterations to surface area are not clear. We assessed the toxicological response to HNTs (NaturalNano (NN)) before and after surface etching (NN-etched). Potential cytotoxicity of the two HNTs was screened in vitro in MutaTMMouse lung epithelial cells. Lung inflammation, acute phase response and genotoxicity were assessed 1, 3, and 28 days after a single intratracheal instillation of adult female C57BL/6 J BomTac mice. The doses were 6, 18 or 54 μg of HNTs, compared to vehicle controls and the Carbon black NP (Printex 90) of 162 μg/mouse. The cellular composition of bronchoalveolar lavage (BAL) fluid was determined as a measure of lung inflammation. The pulmonary and hepatic acute phase responses were assessed by Serumamyloida mRNA levels in lung and liver tissue by real-time quantitative PCR. Pulmonary and systemic genotoxicity were analyzed by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The etched HNT (NN-etched) had 4-5 times larger BET surface area than the unmodified HNT (NN). Instillation of NN-etched at the highest dose induced influx of neutrophils into the lungs at all time points and increased Saa3 mRNA levels in lung tissue on day 1 and 3 after exposure. No genotoxicity was observed at any time point. In conclusion, functionalization by etching increased BET surface area of the studied NN and enhanced pulmonary inflammatory toxicity in mice.
海泡石纳米管（HNTs）及其经表面积功能化修饰后的变体的毒理学潜能尚不清楚。我们评估了 HNTs（NaturalNano（NN））在表面蚀刻前后的毒理学反应（NN-etched）。在体外，使用 MutaTMMouse 肺上皮细胞筛选了两种 HNTs 的潜在细胞毒性。在单次气管内滴注成年雌性 C57BL/6 BomTac 小鼠后 1、3 和 28 天，评估了肺部炎症、急性期反应和遗传毒性。与载体对照组和 162μg/只的 Carbon black NP（Printex 90）相比，HNTs 的剂量分别为 6、18 或 54μg。通过支气管肺泡灌洗液（BAL）中细胞成分的变化来评估肺部炎症。通过实时定量 PCR 测定肺和肝组织中的血清淀粉样蛋白 mRNA 水平来评估肺部和肝脏的急性期反应。通过 BAL 细胞、肺和肝组织中的碱性彗星试验分析肺部和系统性遗传毒性。经蚀刻的 HNT（NN-etched）的 BET 表面积比未修饰的 HNT（NN）大 4-5 倍。在最高剂量下，NN-etched 的注入诱导了所有时间点肺部中性粒细胞的流入，并在暴露后第 1 和第 3 天增加了肺组织中的 Saa3 mRNA 水平。未在任何时间点观察到遗传毒性。总之，蚀刻的功能化增加了研究中 NN 的 BET 表面积，并增强了小鼠肺部的炎症毒性。
