Timing, hosts and locations of (grouped) events of NanoImpactNet

NanoSafetyCluster - Compendium 2012
6. The active monitoring of relevant literature and the
providing of an information point for interested scientists
and industry partners
7. Participation in and organization of comparative studies
including ring studies.
The core function of the Center, however, is to develop and
implement standardized in vitro and in vivo tests for the
determination of the toxicity of nanostructured materials. This is
an absolute necessary basis for the systematic investigation of
toxicological effects as well as for toxicological mechanisms.
Hence, the EURO-NanoTox was conceived as a vehicle that will
bring all these aspects together. Through the application of
standardized methods in a quality assured environment, expensive
failures in product development and/or potential hazards occurring
upon product release can be avoided.
The toxicological profile of a given nanostructured material is
determined by multiple parameters, including, but are not limited
to: size, payload, composition and geometrical structure. Thus, it is
essential to develop, in each case, an individual toxicological
strategy tailored to each unique nanostructured material. The
strategy should reflect current literature-based knowledge and
enable an approach that is both cost-effective and well structured
(see figure 1).
Figure 1: Risk assessment and development of a strategy for the
determination of a nanotoxicological profile.
EURO-NanoTox prepares such testing strategies, accompanied by
an overview of the relevant published information. The risk
assessment and the development of a strategy for the
determination of the nanotoxicological profile should constitute
the first step in the toxicological testing of each novel
nanostructured material.
Additionally, when gaps in the portfolio of available methods
become visible, they will be filled by the development of new
methods within the context of national or international research
projects.
Starting with the formulation of testing strategies for
nanostructured materials and with the preparation of a review to
evaluate the state of the art literature, nanostructured materials
are characterized in different (biological) media according to their
size, size distribution, surface, agglomeration and zeta-potential.
These are significant factors influencing the standardization of a
method. Standardized protocols addressing nanoparticle-specific
interferences by the inclusion of additional controls are used for
these assays.
The systematic in-vitro toxicology is based on cytotoxicology and
hemotoxicology concerning the effect of the port of entry into the
human body (pulmonary, dermal, nasal, buccal, oral, and
endothelial) and the effect onto specific organs (liver, kidneys,
spleen). Additionally, a 3D liver model can be used for testing
metabolic activity, cell viability, cell toxicity, biochemical
assessment of ROS generation (oxidative stress), CYP450 activity
(xenobiotic metabolism), stress and genotoxic as well as
inflammatory responses. Genotoxic effects are identified by the
assessment of changes in the structure of chromosomes and DNA.
Evaluations of the in-vivo effect of nanoparticles include blood
count and clinical chemistry (serum parameters for liver damage,
kidney function, inflammation, and immune response),
histopathology and immunohistochemistry, all of which address
specific questions (proliferation, inflammation, oxidative stress
etc.).
An improved understanding of tissue specific toxicology of
nanoparticles is critically dependent on the development of
procedures that are able to sample the tissue microenvironment in
a manner that enables continuous sampling, i.e. without taking
biopsies. Open Flow Microperfusion [OFM] enables such an
approach to be realized in a highly effective and elegant manner
given that it: (i) is a minimal invasive procedure, (ii) allows
continuous sampling and (iii) enables the full spectrum of analytes
to be harvested from the surrounding milieu, i.e. ranging from
small molecules to nanoparticles (micro dialysis in contrast
employs a catheter containing a semi-permeable membrane).
The latter features allow a broad spectrum for analysis of all
potential nanoparticles and substances (electrolytes, small
molecules, peptides or proteins) to be performed. All these
expertises are collected in the “Assessment of Toxicological
Effects by in-vitro and in-vivo Assays and open flow
microperfusion”-folder available on the EURO-NanoTox Homepage
(www.EURO-NanoTox.at).
4 Organisation of EURO-NanoTox
The pooling of the scientific expertise of all partners involved and
the formation of a link with the structured network of BioNanoNet
Forschungsgesellschaft mbH has facilitated the creation of a broad
base for a toxicology Center. The embedding of this know-how in
international research and development landscape in collaboration
with regulatory bodies and authorities will lead to the extension
and further development of EURO-NanoTox as an international
hub. EURO-NanoTox is also eager to pursue strategic
collaborations with other European nanotoxicology centers which
will lead to the establishment of a European nanotoxicology
network.
30 Compendium of Projects in the European NanoSafety Cluster