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

NanoSafetyCluster – Compendium 2012
1 Summary
Project number: 228825
Project Duration: 1 October 2009 – 30 September 2012
Project Funding: EUR 2,297,337.26
HINAMOX is a 7th Framework project dedicated to the study of
metal and metal oxide nanoparticles (NPs) such as TiO2, ZnO,
Al2O3, CeO2, as potentially hazard to biological organisms
HINAMOX will accomplish an advanced work in the field of in vivo
and in vitro studies of NPs. The importance of this work lays on the
fact that will set the basis for proper dose relation quantifications
and distribution studies both at cellular and body level. This
represents indeed a milestone for the future definition of
nanosafety regulations, standards definitions and for the
assessment of the health effects of NPs on humans.
Research in HINAMOX focus on the correlation of materials
properties to their toxicological endpoints.
HINAMOX will provide knowledge on the biodistribution and
biological fate of metal oxide NPs. To achieve this goal procedures
for NP radiolabelling are being developed to allow for the
application of PET and SPECT techniques.
In parallel to the in vivo studies the work in HINAMOX will be
paramount in establishing quantitative data and practical
procedures to determine the concentration and distribution of NPs
at cellular level applying Ion Beam Microscopy, Confocal Raman
Microscopy and Transmission Electron Microscopy techniques.
The consortium generates new knowledge on the cytological and
pathological response to NPs, targeting innovative work of the
inflammatory response of the alveoli as a possible vehicle for the
introduction of NPs in the body. Detailed analysis of NP leaching
and dissolution for the assessment of NP biodurability and
residence times in tissue and lung-lining fluids will be developed.
All together, these studies will make an important contribution to
a deeper understanding of NP toxicology and will be fundamental
on defining regulations where dose effect relation are required
both at the cellular and body level.
2 Project Background
Among the immense variety of industrial and medically important
NP), the HINAMOX proposal will focus on metal and metal oxide
NPs as potentially dangerous to biological organisms. Metal oxide
and metal NPs are widely used in various industrial processes and
common products.
Metal oxide and metal NPs may be dangerous for humans because
of two reasons: their special catalytic activity coming from the
properties of their nanointerface may interfere with numerous
intracellular biochemical processes and the decomposition of NPs
and subsequent ion leakage could heavily interfere with the
intracellular free metal ion homeostasis, which is essential for cell
metabolism.
A very specific problem dealing with metal oxide NPs is the difficult
of localizing and quantifying them in cells and organs. Obtaining
dose effect relationships for these NPs is not simple, because of
the unknown amount of material present in affected cells.
Previous research and hypothesis suggest that the particle size,
shape, chemical composition and the chemistry of the capping
agent determine the catalytic properties and surface activity of
NPs as well as the materials where the NPs are incorporated. These
properties are important for the applications of the NPs and must
be studied in the context of their effects on human health. The
substantiated evaluation of the health risk, associated with the
exposure to metal oxide and metal NPs, requires a concerted
action. Our approach is a close collaboration in a highly
interdisciplinary consortium with expertise in synthetic chemistry,
production technology, particle physics and characterization,
biochemistry, toxicology, immunology and occupational hygiene.
3 What is HINAMOX
3.1 Project description
The integrated study of NP health effects in our project involves
the following steps:
1) Characterization of commercially available NPs, and the
fabrication and characterization of NPs with specific
properties and with either fluorescence or radioactive
labelling.
The company PlasmaChem, which is a member of our consortium,
provides us with metal oxide NPs. CeO2 and ZnO NPs have also
been purchased from Evonik, Germany. At least one example of
each of the metal oxide NPs with the most relevant applications or
potential, according to the Nanomaterial Roadmap 2015 of the 6th
Framework programme, is being considered for study. The
consortium is also working in the design of NPs endowed with
either fluorescence or radio labels. An important aspect of this
project is indeed the fabrication of NPs with proper labelling to
trace the fate of the NPs both in vitro and in vivo. This task implies
the development of proper routes of labelling both NP core and
capping agent. Also, it is important to learn to what extent the
labelling affects properties of the NPs such as aggregation, size,
charge, morphology and crystallinity, which can have a direct
impact on the interaction of the NPs with cells and organs and in
their toxicity.
Characterization of the structural properties of the commercial
NPs and those fabricated by the consortium is a key aspect in this
project. Surface and structural properties of NPs will be related to
their toxicological effect and a strong effort will be made in
understanding and relating to the characteristics of the materials
the differences in toxicity, uptake or distribution among NPs of the
same materials but from different sources.
36 Compendium of Projects in the European NanoSafety Cluster