Brunnleitenweg 41, A-5061 Elsbethen, Salzburg, Austria.
Ann Transl Med. 2014 May;2(5):46. doi: 10.3978/j.issn.2305-5839.2014.04.12.
Theoretical knowledge of carbon nanotube clearance in the human respiratory tract represents an essential contribution to the risk assessment of artificial airborne nanomaterials. Thus, single phases of nanotube clearance were simulated with the help of a theoretical model.
In this study, clearance of single-walled carbon nanotubes (SWCNT) and multi-walled carbon nanotubes (MWCNT) was simulated by using a validated mathematical approach that includes all clearance mechanisms known hitherto. Fast mucociliary clearance is approximated by a steady-state steady-flow mucus model, whereas slow clearance mechanisms are modeled by definition of related clearance half-times.
Clearance may be subdivided into three phases, including fast bronchial clearance (mucociliary escalator), slow bronchial clearance (particle uptake by airway macrophages, transcytosis), and alveolar clearance (phagocytosis by alveolar macrophages, endocytosis by alveolar epithelium). According to the clearance model used in this study, mucociliary clearance is completed within the first 24 h after exposure, whereas slow bronchial clearance is characterized by a half-time of 5 d. Alveolar clearance is marked by half-times >100 d. As a result of their different deposition patterns, SWCNT and MWCNT show some discrepancies with regard to their clearance insofar as long SWCNT reside significantly longer in the lungs than MWCNT. This circumstance is among other expressed by higher 24-h, 10-d, and 100-d retentions computed for SWCNT compared to MWCNT.
Due to their partly high residence times in distal lung regions, carbon nanotubes may bear the potential to act as triggers of inflammatory reactions or fibrotic modifications of the lung structure. Further they may also induce malignant transformations of lung cells, resulting in the development of lung tumours.
对人类呼吸道中碳纳米管清除的理论知识代表了对人工空气传播纳米材料风险评估的重要贡献。因此,借助理论模型模拟了纳米管清除的各个单一阶段。
在这项研究中,使用一种经过验证的数学方法模拟了单壁碳纳米管(SWCNT)和多壁碳纳米管(MWCNT)的清除,该方法包括迄今为止已知的所有清除机制。快速黏液纤毛清除通过稳态稳定流黏液模型进行近似,而缓慢的清除机制则通过定义相关的清除半衰期来建模。
清除可分为三个阶段,包括快速支气管清除(黏液纤毛扶梯)、缓慢支气管清除(气道巨噬细胞摄取颗粒、转胞吞作用)和肺泡清除(肺泡巨噬细胞吞噬、肺泡上皮细胞内吞)。根据本研究中使用的清除模型,黏液纤毛清除在暴露后的头 24 小时内完成,而缓慢的支气管清除则以半衰期为 5 天为特征。肺泡清除的半衰期大于 100 天。由于它们不同的沉积模式,SWCNT 和 MWCNT 在清除方面存在一些差异,因为长 SWCNT 在肺部中的停留时间明显长于 MWCNT。这种情况在其他方面表现为,与 MWCNT 相比,SWCNT 的 24 小时、10 天和 100 天保留率更高。
由于碳纳米管在远端肺部区域的部分停留时间较长,它们可能有潜力作为引发肺部炎症反应或纤维化改变的触发因素。此外,它们还可能诱导肺细胞恶性转化,导致肺癌的发展。