A practical approach to assess inhalation toxicity of metal oxide nanoparticles in vitro

Abstract

Exposure of humans to metal oxide nanoparticles (NPs) occurs mainly via air, and inhaled metal oxide NPs may generate inflammation. The aim of this study was to investigate the proinflammatory potential of six metal oxide NPs (CeO , Mn O , CuO, ZnO, Co O and WO ; 27-108 μg ml ) using human primary 3-dimensional airway epithelium (MucilAir™) and dendritic cell (DC) models. Metal oxide NPs were mainly aggregated/agglomerated in the cell media, as determined by dynamic light scattering, scanning electron microscopy and differential centrifugal sedimentation. WO and ZnO were highly soluble, both with and without respiratory mucus. Proinflammatory signalling by the epithelium was evaluated after a 24 hour exposure by increased interleukin-6 and -8 and monocyte chemoattractant protein 1 cytokine release, which occurred only for CuO. Moreover, maturation of immature human DCs, which play a key role in the lung immune system, were evaluated by expression of surface markers HLA-DR, CD80, CD83 and CD86 after a 48 hour exposure. Only Mn O consistently upregulated DC maturation markers. Furthermore, by addition of medium from metal oxide NP-exposed 3-dimensional airway cultures to metal oxide NP-exposed DC cultures, the interplay between lung epithelium and DCs was studied. Such an interplay was again only observed for Mn O and in one of five DC donors. Our results show that, even when using dosages that represent very high in vivo exposure levels, up to 27 hours of constant human airway exposure, metal oxide NPs cause minimal proinflammatory effects and that epithelial cells not necessarily interfere with DC maturation upon metal oxide NP exposure. The present approach exemplifies a relevant translation towards human safety assessment.

Toxicological Assessment of ITER-Like Tungsten Nanoparticles Using an In Vitro 3D Human Airway Epithelium Model

“…This might result in a less effective mucous protection in A549 cells whose cellular viability was, consequently, impaired. This assumption has already been made in another study on the MucilAir TM model [26].…”

“…In contrast, no toxicity was observed on the MucilAir™ model exposed 24 h to WO 3 nanoparticles. Upon exposure to doses corresponding to a high level of exposure in vivo, neither viability (lactic dehydrogenase assay), nor the release of pro-inflammatory cytokines (IL-6, IL-8 and MCP1) were affected [26].…”

Short-term and Long-term Exposure of the MucilAir™ Model to Polycyclic Aromatic Hydrocarbons

“…To the best of our knowledge, fewer than 20 peer-reviewed articles have been published on studies involving the MucilAir model, and less than half of these address the effects of air pollutants. [22][23][24][25] Furthermore, none of these studies (including those based on other ALI cell models [26][27][28] ) have focused on the effects of long-term exposure (i.e. lasting several weeks).…”

Smart fertilizers: What should we mean and where should we go?

“…An example is a study conducted by Lin and Xing (2007), where five nanofertilizers tested on six different crops resulted in opposite effects among crops. Nanofertilizers could negatively impact human health due to their size that, as reviewed by Kalia et al (2019) and Surendhiran et al (2020), enables them to enter the human body through inhalation (Geiser et al, 2017), ingestion through contaminated drinking water and agricultural produce that have accumulated nanomaterials or dermal absorption (Crosera et al, 2009) causing toxicity (Bahadar et al, 2016; Accepted paper Dankers et al, 2018).…”