Some examples of known health effects of free metal ions that result in the formation of reactive oxygen species in metallo-chemical reactions are neurodegenerative disorders, such as Alzheimer’s disease, amyotrophic lateral sclerosis, prion disease, cataracts, mitochondrial disorders, and Parkinson’s disease (Thompson et al., 2001). In addition to these observations, Elder et al. (2006) have shown that manganese oxide NPs can enter the olfactory bulb below the forebrain subsequent to inhalational exposure of rats. The pathway of the NPs to the brain is, in this case, by means of the axons of the olfactory nerves in the nasal cavity (Oberdörster et al., 2004). It is reasonable to assume that the oxidative homeostasis in sensitive cells might be affected by the presence of even a small number of metal and metal oxide NPs, both as catalytic entities and as the source of metal ions (Limback et al., 2007). Nature has provided a variety of protective mechanisms against the uncontrolled uptake of metal ions and compounds. Nevertheless, high acute and/or continuous exposure to these potentially dangerous agents might lead to deposition and/or systematic uptake of critical amounts of NPs through either defects in the skin, the digestive tract or the lung and bronchial tissues. In fact, perhaps the most striking impacts of NPs have been identified in the lungs where titanium diodixe NPs have evoked inflammatory reactions (SCENIHR, 2007). In addition, carbonaceous NPs, notably carbon nanotubes, have been shown to induce pulmonary inflammation, granuloma formation, and even asbestosis like changes when introduced into the peritoneal cavity of mice (Poland et al., 2008).

Occupational production and handling of NPs involves a high risk of exposure to either repeated burst or long-term low-level exposures. Currently, producing and handling NPs does not require special regulation for protective equipment due to insufficient knowledge of exposure and NP hazard. Consumers may also be subject to acute high-level exposures during application of specific products and long-term exposure is evident during use of NP-based cosmetics and sun-creams. In concert with the increased implication of NPs in industry, the number of NP-based consumer products is expected to increase continuously over the next years to come.

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 and occupational hygiene.

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. 
2. Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) for the analysis of the uptake, distribution and release of NPs in vivo. 
3. Quantification and distribution studies at cellular level, by Ion Beam Microscopy (IBM), Electron Microscopy (EM) and Confocal Laser Scanning
4. Understanding the interaction of NPs with cellular and extra-cellular components
5. Determination of physiological effects of NPs in vitro.
6. Risk of exposure and toxicological effects of metal and metal oxide NPs.

The projected work in HINAMOX encompasses in this way a complete approach to understanding the safety and human health implications of NPs and nanotechnology based materials. This approach addresses aspects concerning hazard characterization, human exposure, occupational exposure, and the inflammatory and toxicological response to NPs. The HINAMOX project is particularly strong with respect to the monitoring of NPs in cells and their biodistribution in animal bodies, employing techniques such as IBM and PET/SPECT, which have been little used up to now for studying the fate of NPs in biological systems. In order to achieve this task, a complex and innovative work of engineering and labelling of NPs is proposed. Cellular and body distribution studies together with biodurability tests will enable us to understand the biological fate, transport and transformation of NPs within biological entities.

Aspects such as the behaviour, fate, bio-persistence, bio-kinetics, exposure and behaviour of NPs will be addressed by HINAMOX, providing significant knowledge beyond the state of the art.

The project has an international dimension consolidated by the presence of scientific institutions from Mexico and China.The Chinese and Mexican participation will help to develop common safety standards within these countries, which is of particular importance for Europe.

HINAMOX project fully adheres to the European Recommendation of 07/02/2008 on a code of Conduct for  Responsible Nanosciences and Nanotechnology Research. Furthermore, HINAMOX strongly identifies with the objectives of sustainability expressed by the Code of conduct that states that research activities in Nanotechnology and Nanosciences (N&N) must be safe, ethical and contribute to sustainable development. N&N research activities should not harm or create a biological, physical or moral threat to people, animals, plants or the environment at present or in the future. Therefore, HINAMOX will strive for the generation of a culture of responsibility and precaution to protect not only the researchers taking part in the project but also professionals, consumers, citizens and the environment that may get involved in the activities to be developed in the course of the research activities of HINAMOX.