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

NanoSafetyCluster ‐ Compendium 2012
(via suitable program partners), promoting the concept of
infrastructure as a ‘learning’ organization. Thus, whilst the vision of
excellence and quality will be fixed, the means to achieve that end
will evolve responsively.
QNano is primarily an analytical infrastructure whose purpose is to
drive high quality research and testing practices. Physiochemical
and other analytical characterization in the biological and safety
contexts is quite different from analysis of nanomaterials for other
applications. Some of the important (relevant) physiochemical
characteristics are not yet fully understood. Even implementation
of known science is not always evident, but in a new industry
making its reputation, it is crucial. The fact that engineered
structures have access to biological machinery, combined with
their unique (for example high‐surface area) properties, means
that material quality and reproducibility are important, not just for
this program, but long term, in industry in general. Details such as
the tendency of nanomaterials to secrete difficult‐to‐remove
relatively immobile impurities into an organism, or to sequester
contaminants from the environment and transport them into living
organisms, for example, can have profound consequences for
predicting fate and behaviour in different cell types, tissues,
complex matrices, organisms, and all require detailed
characterisation to be interpreted correctly. Such aspects are
believed to underlie some early negative toxicity reports, leading
(in these specific cases) to unwarranted and widely publicised
fears. There is a critical need to separate issues of quality from the
durable questions of intrinsic nanomaterials safety. The potential
for these issues to have negative impact on trust in global trade
(where good practices are not universally accepted) are
incalculable.
By fostering a new quality‐based research and application
consensus that values both the durability, and reproducibility of
new findings, QNano will qualitatively affect the outcomes in this
domain. It cannot address all the challenges, but it will provide the
basis for those challenges faced, at what is certainly the most
pivotal period in the adoption of nanoscience and nanotechnology
in society.
The activities of QNano are summarised as follows:
Networking Activities:
� NA1 ‐ Management and coordination
� NA2 ‐ Nanomaterials Hub: an instrument for Quality
Assurance testing of nanomaterials via Round‐Robin
trials, and their provision to the wider User community.
� NA3 ‐ Training Hub covering all aspects of best practice in
nanomaterials for biological testing.
� NA4 ‐ Working Groups to drive future development and
sustainability of the infrastructure.
� Transnational Access:Provision of transnational access to
the nanomaterials processing, characterisation and
exposure assessment facilities of the 15 TA Participants
via a single application and evaluation process and 6‐
monthly calls for applications on the QNano website.
Joint Research Activities:
� JRA1 ‐ Development of strategies to eliminate and/or
reduce variability in nanomaterials batch‐to‐batch
reproducibility and to determine acceptable variability
levels for biological applications.
� JRA2 – Optimisation of traceability of nanoparticles by
development of reliable labelling (radioactive, stable
isotope and fluorescent).
� JRA 3 ‐ Development and validation of characterisation
tools for nanoparticles in situ in biological, environmental
or consumer milieu.
� JRA 4 – Development of optimal modes of presentation
of nanoparticles to cells, tissues, organisms and whole
animals for quantitative reproducibility.
� JRA 5 – Towards development of priority alternative in
vitro tests to replace animal testing.
4 Key Challenges being addressed by QNano
Irreproducibility in nanomaterials leads to irreproducible biological
impacts.
There remain genuine scientific challenges in making reproducible
nanomaterials using early manufacturing processes. This is not a
trivial issue, and it will take some years yet before it is resolved.
However, it must be noted in the current context. Thus, because of
the enormous surface‐to‐volume ratio presented by nanomaterials,
it is not uncommon for 1 millilitre of dispersed nanomaterials (1wt%,
70nm) to present over 8m 2 of surface area to the endogenous
machinery of biological organisms. The level of care taken by the
medical device industry to understand the role, and maintain the
quality and reproducibility of medical device implants, with much
smaller exposed surface areas, is barely conceivable in
nanomaterials preparation. Yet, this is the standard we have to
work towards and progress on urgently. Beneath several hundreds
of nanometers, the immune clearance system is less effective, and
nanomaterial surfaces may be in prolonged contact with biological
systems. Thus, irreproducibility in surface quality or properties
(more perhaps than variations in absolute surface area) inherent in
current, poorly controlled batch nanomaterials synthesis methods
can be amplified far beyond that expected based on their usual
applications, which is not necessarily all surface‐related. Not all
variations are expected to be biologically significant. Some known
factors include surface charge and crystallinity, but no systematic
studies of the biological impacts from batch‐to‐batch‐ variability
have been attempted, in part because of the large variations in the
methods themselves.
Paradoxically, even where such variations of surface quality do not
present a real hazard, they can lead to a troubling irreproducibility
in biological or toxicological assessments that in itself leads to
controversy and a general lack of confidence in the capacity to do
good science in this field. Attempts to suppress these effects (for
example, OECD, IANH, and other large national programs) have
been made, choosing one representative batch that is maintained
throughout the particular program, with the usual problems of
such approaches. With nanomaterials, however, the problems can
be more serious. Batch aging, especially in dispersion, is quite
serious, and for many materials requires disposal of a given batch
after three months, even if the storage conditions are optimal, an
organizational issue that is itself challenging, and fraught with
unforeseen difficulties. Additionally, chemical purity and surface
modifications can introduce further variability in biological
responses.
244 Compendium of Projects in the European NanoSafety Cluster