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FP7 ERA-NET on
Nanosafety
Safe
Implementation of Innovative
Nanoscience
and Nanotechnology
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MNM
are released into the air and deposited on human airway epithelia by
several scenarios. Little is known about the aging processes of these
materials, above all under the potential influence of chemical
matrices. These aspects are necessary for assessing their potential
effects on living organisms as MNM are hardly exposed to human or the
environment without being altered by any chemical substances, either
coming from the products they are used in or by reactions in the
atmosphere. For addressing the open questions, an approach is being
designed to describe exemplarily the different fates of two
representative classes of MNM relevant for inhalation exposure:
1) soluble particles with a substance-specific toxicity using the example of Ag nanoparticles,
2) granular biodurable particles (GBP) using the example of CeO2 nanoparticles.
Both particle types will be investigated in a test system which
addresses the aerosol generation from liquid formulations under the
influence of chemi-cal substances. An experiment will be established
which will enable the release of MNM from liquid matrices into the
airborne state and which allows for a controlled variation of
parameters influencing the aerosol formation. The fate of MNM will then
be investigated after deposition on airway epithelia and abiotic
surfaces. The aging process in the aerosol may change the morphology,
density, size range and distribution of the particles. The aging
process is assumed to be affected by physicochemical properties of the
MNM, interaction with substances, and the releasing process parameters.
The
aging process of MNM during aerosol transport will be investigated
producing defined suspen-sions of different concentrations of nano-Ag
and -CeO2, using a range of active ingredients such as fluorocarbon
resins and silanes. The suspensions will be atomized into aerosol
states by standardized procedures. The presence of MNM and their size
distribution in the generated aerosol will be measured at different
time instants and measuring sites within the aerosol. At the same
positions, sampling grids, monolayer cultures of alveolar and bronchial
origin, 3D cell culture models, PCLS, as well as textile samples will
be used for collecting solid particles from the aerosols, which will
then be characterized i.a. by electron microscopy and Time of Flight -
Secondary Ion Mass Spectrometry (ToF-SIMS). The particle sampling will
be size selective by using a cascade impactor and a Nano- Differential
Mobility Analyser (DMA). Samples of the airway epithelium model will be
cultivated and analyzed for investigating cellular influences on
particle fate. For determining effects, in vitro tests will be
conducted addressing the epithelial barrier integrity, cytotoxicity and
inflammation. Furthermore, biokinetic studies on mice will be conducted
to determine their lung clearance and to evaluate the influence of
surface modifycations due to chemical surroundings of MNM on their
pulmonary toxicity. All data obtained will form the basis for a
standard model allowing the process from the state of formation of the
particle-laden droplets to the end of the drying process to be
described. The model will include the prediction of particle deposition
on lung tissue for real-life situations, using an approach developed
within the BMBF-project NanoGEM. To specify the nano-effect, all
experiments and investigations will addi-tionnally be conducted with
micro-sized particles. Five main steps will be established to close the
knowledge gap within the MNM fate:
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Production of formulation (WP PC): Generation of liquid formulations with different MNM |
2)
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Aerial Fate (WP E): Experimental analysis of MNM release from liquids under the influence of auxiliary substances |
3)
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Fate on lung tissue and abiotic surfaces (WP E): Analysis of MNM
reaching the airway epithelium and textiles as an example for abiotic
surfaces |
4)
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Effects of aerosolized MNM (WP T-A/B): In vitro toxicity and in vivo
tests covering respiratory cell types and endpoints including
cytotoxicity, pro-inflammatory cytokine expression, hemolytic capacity,
lung clearance over time, extrapulmonary retention and elimination
kinetics, and the analysis of intracellular dose |
5)
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Modelling (WP M): Development of an experimentally based model for predicting MNM fate during spraying and aerosol transport |
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All
steps are either attended by following strict protocols where available
(e.g. NanoGEM) or by establishing new protocols. In the latter case,
for the developing of the procedures, reference materials will be
utilized (e.g. well characterized MNM or isotope-based substances for
liquid formulations) where applicable. All experimental steps will be
validated before sampling to ensure reproducibility including process
controls to guarantee traceability of the individual steps.
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This project is part
of the SIINN ERA-NET and is funded under the ERA-NET scheme
of the Seventh Framework Programme of the European Commission,
Research
Directorate - General, Grant Agreement No. 265799
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