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

NanoSafetyCluster - Compendium 2012
importance of Third Countries such as China, Russia and
Japan. The inclusion of the prestigious Academies of Sciences
from China, Russia (for Toxicology) and the Japanese National
Institute of Materials Science (for ENM synthesis,
characterisation and Toxicology) as well as our existing US
partners through current FP7 projects goes beyond the
scientific excellence and will enable MARINA to reflect a true
global effort in addressing this important issue and to
promote our strategy for risk management of ENM globally.
• we will interconnect all MARINA activites with other relevant
ongoing activities such as the forthcoming EC European
Technology Platform(s), Nanofutures, Infrastructure and
cluster activities of FP7 projects, the ERAnet, the OECD WPMN
sponsorship programme as well as National Research
programmes, such as NanoCare2 and NanoNature.
Although the database that supports risk assessment and
management continues to expand, the general approaches have
not changed significantly. Risk assessment and management must
be based on the best available science, which is continually
progressing. These changes appearing in the nature and the
interpretation of data prompt the MARINA approach: Specifically:
1. The likelihood of increasing restrictions and public acceptance of
the use of animals for testing purposes in the EU drive MARINA to
go for integrated test systems (ITS) targeting modules of hazard
endpoints, fate and exposure, and monitoring.
2. The availability of data from new/rapidly advancing
methodologies is fully acknowledged in MARINA - systems biology
and early marker detection are used for integrated assessment
schemes (IAS) for occupational and environmental exposure
assessment and monitoring schemes.
3. Advances in mode of action research and in the understanding
of effects/disease mechanistic processes in MARINA lead to
addressing hazard more specifically and develop interconnecting
module systems (IMS) for risk assessment and risk management as
methodology for supporting decision making.
In summary, MARINA stands for integrated testing, integrated
assessment and modular interconnection of knowledge and
information for science-based risk management methods. The
approach is to translate scientific advancements and methodology
in contribution to shifting from toxicological studies of specific
individual nanomaterials towards a more systematic health and
environmental safety assessment and management that handle
the overall risks for types or classes of ENM based on their
intrinsic, e.g. physico-chemical properties.
4 Progress beyond the state-of-the-art
In the following sections, the scientific state-of-the-art is
summarised and the many aspects of MARINA which go beyond
the state-of-the-art to achieve the objectives listed above will be
clearly described.
4.1 The state-of-the-art
Currently, the EC has funded many projects through their 6 th and
7 th Framework programmes. These projects generally cover the
state-of-the-art landscape of health and safety issues related to
ENM:
(a) for Materials, characterising the physico-chemical properties of
ENM in bulk materials is generally accepted as essential to all
toxicology studies. The detection and characterisation of ENM in
biological matrices is being investigated in FP7 NANOLYSE. To date
there is no attempt in harmonising and standardizing
characterisation methods, although this has been widely debated..
Furthermore, the lack of reference materials to be used, means
that there is difficulty in extrapolating the results between studies.
Also, almost no study has characterized the ENM that are actually
released into the envrionment. The new FP7 NANOHOUSE is going
to do this but only for ENM released from paints.
(b) for Toxicology, it is well known that exposure to particles is
likely to lead to adverse effects. Following exposure, some ENM
have been shown to translocate beyond the portal of entry organ 5
, the extent of translocation is dependent on the ability of ENM to
cross biological barriers (blood-brain, blood-air, placental, and so
on) which is a function of ENM size, surface properties, (e.g.
surface charge 6 ) or the formation of the protein or lipid corona 7 on
the ENM surface. Inhaled ENM could be translocated to the brain
via the olfactory bulb 8 . These ENM can also reach the terminal
bronchial region and for high-aspect ratio ENM, they are likely to
be further translocated to the pleura 9 . A small ENM fraction can
reach the blood system where they can travel to secondary
organs 5 like the heart, liver, kideny and beyond. The biodistribution
of internalised ENM follows a different pattern
depending on the route of exposure: inhalation, ingestion or
dermal 10 . For dermal exposure, there is some evidence that ENM
can penetrate beyond the stratum corneum 11 . For oral exposure,
TiO2 ENM have been shown to induce DNA damage and genetic
instability in mice 12 . The paradigm for the adverse response is
currently oxidative stress leading to inflammation 13 . Chronic
inflammation could lead further to fibrosis, DNA damage and
cancer 14 . ENM can also be genotoxic by direct by a totally new
mechanism 15 . ENM driven oxidative stress also plays an important
role in the immune response and apoptosis 16 . Cardio-vascular
effects have been demonstrated in susceptible animal models
exposed to ENM 17 although it is not clear whether these are caused
by systemic inflammation or direct ENM interaction with cardiovascular
plaques causing plaque disruption. The ability of some
ENM to cause a pro-thrombotic effect like platelet aggregation
should also be noted 18 . Data on the adverse responses are
generated from many FP projects. For example, the protein corona
issue is being investigated in the FP6 NANOINTERACT project, the
central nervous response is investigated in FP7 NEURONANO, the
pulmonary and cardiovascular effects were investigated in FP6
NANOSH, PARTICLE_RISK and more recently in FP7 ENPRA,
NANOTEST. Other target organ effects are also studied in ENPRA
and NANOTEST and immunotoxicity is the research topic for FP7
NANOMMUNE. Taken together, a coherent toxicity profile of ENM
begins to emerge. However, there are still many short-comings to
be addressed. These include the proper validation of the test
protocols developed in these FP projects, and the comparison of
in vitro and in vivo results to reduce animal testing as part of the
3R strategy for toxicology testing.
(c) for Eco-Toxicology, relatively little is known about the
68 Compendium of Projects in the European NanoSafety Cluster