4.6 Article

The influence of exposure approaches to in vitro lung epithelial barrier models to assess engineered nanomaterial hazard

Journal

NANOTOXICOLOGY
Volume 16, Issue 1, Pages 114-134

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/17435390.2022.2051627

Keywords

In vitro; epithelial cells; co-culture; lung; nanoparticles

Funding

  1. PATROLS project, European Union's Horizon 2020 Research and Innovation Programme [760813]

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Exposure to engineered nanomaterials can pose health risks, and this study aimed to determine the level of hazard using in vitro lung cell cultures. The results showed that DQ(12) caused pro-inflammatory responses, while TiO2 and BaSO4 did not. These findings highlight the importance of considering the appropriateness of positive controls, cell culture model, exposure time, and type when determining the response to specific ENMs.
Exposure to engineered nanomaterials (ENM) poses a potential health risk to humans through long-term, repetitive low-dose exposures. Currently, this is not commonplace within in vitro lung cell cultures. Therefore, the purpose of this study was to consider the optimal exposure approach toward determining the stability, sensitivity and validity of using in vitro lung cell mono- and co-cultures to determine ENM hazard. A range of exposure scenarios were conducted with DQ(12) (previously established as a positive particle control) (historic and re-activated), TiO2 (JRC NM-105) and BaSO4 (JRC NM-220) on both monocultures of A549 cells as well as co-cultures of A549 cells and differentiated THP-1 cells. Cell cultures were exposed to either a single, or a repeated exposure over 24, 48- or 72-hours at in vivo extrapolated concentrations of 0-5.2 mu g/cm(2), 0-6 mu g/cm(2) and 0-1 mu g/cm(2). The focus of this study was the pro-inflammatory, cytotoxic and genotoxic response elicited by these ENMs. Exposure to DQ(12) caused pro-inflammatory responses after 48 hours repeat exposures, as well as increases in micronucleus frequency. Neither TiO2 nor BaSO4 elicited a pro-inflammatory response at this time point. However, there was induction of IL-6 after 24 hours TiO2 exposure. In conclusion, it is important to consider the appropriateness of the positive control implemented, the cell culture model, the time of exposure as well as the type of exposure (bolus or fractionated) before establishing if an in vitro model is appropriate to determine the level of response to the specific ENM of interest.

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