Abstract

Extensive production and use of nanomaterials (NMs), such as titanium dioxide (TiO2), raises concern regarding their potential adverse effects to humans. While considerable efforts have been made to assess the safety of TiO2 NMs using in vitro and in vivo studies, results obtained to date are unreliable, possibly due to the dynamic agglomeration behavior of TiO2 NMs. Moreover, agglomerates are of prime importance in occupational exposure scenarios, but their toxicological relevance remains poorly understood. Therefore, the aim of this study was to investigate the potential pulmonary effects induced by TiO2 agglomerates of different sizes at the air–liquid interface (ALI), which is more realistic in terms of inhalation exposure, and compare it to results previously obtained under submerged conditions. A nano-TiO2 (17 nm) and a non-nano TiO2 (117 nm) was selected for this study. Stable stock dispersions of small agglomerates and their respective larger counterparts of each TiO2 particles were prepared, and human bronchial epithelial (HBE) cells were exposed to different doses of aerosolized TiO2 agglomerates at the ALI. At the end of 4h exposure, cytotoxicity, glutathione depletion, and DNA damage were evaluated. Our results indicate that dose deposition and the toxic potential in HBE cells are influenced by agglomeration and exposure via the ALI induces different cellular responses than in submerged systems. We conclude that the agglomeration state is crucial in the assessment of pulmonary effects of NMs.

Highlights

  • Nanotechnology is ubiquitous, brings novel advancements in all aspects of human life on a daily basis, and has a wide variety of applications, such as in consumer goods, electronics, communication, environmental treatments and remediations, agriculture, nanomedicine, water purification, textiles, aerospace industry, and efficient energy sources, among many others

  • The results indicated that, only the small agglomerates of 5 nm sized TiO2 NMs caused a significant increase in cytotoxic effects while the small agglomerates of all TiO2 NMs, irrespective of primary particle size, induced a significant increase in oxidative damage compared to larger agglomerates, which showed no significant effects for these endpoints

  • We investigated the influence of agglomeration on the deposition and cytotoxic potency of TiO2 NMs at the air–liquid interface (ALI)

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Summary

Introduction

Nanotechnology is ubiquitous, brings novel advancements in all aspects of human life on a daily basis, and has a wide variety of applications, such as in consumer goods, electronics, communication, environmental treatments and remediations, agriculture, nanomedicine, water purification, textiles, aerospace industry, and efficient energy sources, among many others. Nanomaterials (NMs) are generally defined as a material with at least one dimension in the nanoscale (1–100 nm) range [2]. While NMs are abundant in nature and produced by various sources, such as forest fires and volcanic eruptions, they are intentionally manufactured by nanotechnologies on a global scale for industrial and commercial purposes. Nanomaterials 2021, 11, 3226 that “natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50% or more of the particles in the number size distribution, one or more external dimensions is in the size range. Among the manufactured NMs, titanium dioxide (TiO2 ) is one of the widely used

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