NACIVTNano Aerosol Chamber In-Vitro Toxicity

Risk of inhaled nanoparticles in health and disease by in vitro technology
NRP64, Project 406440-131267

 

Inhalation of engineered nanoparticles handled as powders, dispersions or sprays in industrial processes and in consumer products pose a potential and largely unknown risk for incidental exposure. Thereby individuals with chronic lung diseases, as well as children and the elderly are expected to be more vulnerable to adverse effects by inhaled engineered nanoparticles than adult healthy subjects.

Introduction

It is the aim of this project to investigate health impacts of widely used engineered nanoparticles upon inhalation by comparing healthy and susceptible, i.e., diseased, lungs using in vitro technology.

We will focus on healthy adults and adult patients with the most prevalent chronic respiratory diseases, i.e. chronic obstructive pulmonary disease COPD (smokers) and allergic asthma (house dust mites).
placeholder Schematic of inner lung surface in disease
Schematic of inner lung surface in disease

 

Analysis of nanoparticle toxicity will be performed on state-of-the-art cell cultures of primary lung surface macrophages and fully differentiated air-liquid interface airway epithelia. These cells are the immediate targets of inhaled particles and known to play a major role in lung disease. In addition to primary cells, commercially available fully differentiated human lung epithelial cells and macrophages will be included for possible future acceptance by the European Centre for the Validation of Alternative Methods (ECVAM) and OECD in order to be used in regulatory (toxicity) testing.

 

Cells will be exposed in a new, broadly applicable aerosol deposition chamber for efficient and quantitative deposition of nanoparticles out of a continuous air-stream, thus reflecting the in vivo situation. The chamber will be transportable and mobile to be used at any particle source of interest and there is no limitation with respect to the kind of nanoparticles or fibers used.

 

Schematic of aerosol deposition chamber
Schematic of aerosol deposition chamber

 

The toxicity of currently available commercial engineered nanoparticles, which have a high risk to be inhaled will be tested, i.e. titanium dioxide, carbon black and silver as well as a consumer product containing engineered nanoparticles i.e., a deodorant spray. Dose-response curves will be established comparatively for all the above-mentioned nanoparticles in cells from healthy and diseased donors to evaluate the health risks by inhaled engineered nanoparticles and the influence of nanoparticle aggregation will be assessed.

 

 

Interaction of particles with the organism: Routes of entry, barriers

The organism is delimited by barriers from the environment, but also allows "cross-border traffic."

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Test System Aerosol Deposition Chamber

The research team uses a novel, portable and realistic test system with cell cultures which replicate the inner lung surface. The versatile system can be used for particles from various particle sources and for a variety of cell cultures and it makes realistic in vitro toxicity testing possible.

 


Aerosol chamber test system: Circumferential view.

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Analysis: Impaired lung homeostasis

The research team analyses the effects of inhaled nanoparticles on healthy and diseased lung tissue.

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Publications

The results of the research team can be found in selected publications.