Repeated long-term exposures of multi-walled carbon nanotubes to the 3D human lung model EpiAlveolar to predict the onset of fibrosis

Multi-walled carbon nanotubes (MWCNTs) with their extraordinary properties (e.g. stiffness, electrical conductivity, etc.) are among the most commonly used nanomaterials [1]. Human exposure to MWCNTs can occur throughout their life-cycle via inhalation [2,3], causing potential adverse effects, such as pulmonary fibrosis as was shown in animal experiments [4]. Therefore, there is a need to design human-relevant in vitro testing and exposure strategies to assess the biological effects of MWCNTs. The process that leads to pulmonary fibrosis can be organized into an adverse outcome pathway (AOP) framework. Starting with a molecular initiating event (MIE), AOPs (Fig. 2a) sequentially link the key events (KEs) that occur at different levels of biological organization, leading to an adverse outcome (AO) [5].

multi-walled carbon nanotubes (MWCNT), EpiAlveolar, pulmonary fibrosis, tumor necrosis factor-α(TNF-α), fibronectin, Vitrocell cloud exposure, particle deposition, repeat-low dose

Mitsui-7 MWCNT, transforming growth factor-β (TGF-b), bovine serum albumin (BSA, 0.1%)