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Mitigation of risk and control of exposure in nanotechnology based inks and pigments - NANOMICEX -

Final Report Summary - NANOMICEX (Mitigation of risk and control of exposure in nanotechnology based inks and pigments - NANOMICEX -)

Executive Summary:
Nanotechnology is one of the fastest growing and most promising technologies in our society, promoting the development of a new generation of smart and innovative products and processes that have created tremendous growth potential for a large number of industry sectors.

In the particular case of the pigment, ink and paint industry, the use of engineered nanoparticles (ENPs), has a great potential for new applications, leading to products with new or enhanced properties, and opening new market opportunities. Consequently, many promising applications emerge nowadays, based on the use of ENPs such as Fe3O4, TiO2 or ZnO, silver (Ag) and quantum dots (QDs), which confer a wide range of properties to the final products, covering the most requested properties in pigment, inks and paints applications for the nearest future.

Along with the benefits, there is an on-going debate about their potential effects on human health or the environment. In the occupational context, it has been demonstrated that workers have the potential to be exposed to uniquely ENPs with novel sizes, shapes, and chemical properties, at levels far exceeding ambient concentrations.

In view of this context, as stated in the document of work, the main goal of the project to reduce the potential risk upon worker´s exposure to engineered nanoparticles (ENPs) through the design, development and implementation of cost effective risk management strategies, considering validated surface modifications to reduce the toxicological profile of targe ENPs, and the selection of proven personal protective equipment (PPE) and engineering controls to reduce and/or mitigate the exposure to airborne nanoparticles in the workplace.

The scientific activities conducted were focussed on the characterization of the specific physicochemical properties and hazard profile of relevant ENPs to the pigment, ink and paint industry, the selection of adequate surface modification methodologies to reduce the potential hazardous properties of ENPs of special concern, the evaluation of the likelihood and extent of human exposure to these ENPs in a lifecycle perspective, and the evaluation of the effectiveness of risk and waste management strategies when dealing with submicron sized particles.

The toxicological studies revealed a major toxicological concern associated with ZnO NPs, Ag NPs and CdSe-ZnS QDs. Proper surface modifiers and modification strategies to reduce the toxicity of these ENPs were investigated and applied at industrial level, concluding that the ZnO NPs and QDs can be modified with BSA and glucose, respectively. For the Ag NPs, the synthesis procedure can be modified to obtain larger AgNPs, which behave less cytotoxic.
The exposure measurement conducted revealed that the activities involving the handling of powdered materials are the most likely to result in the release of respirable-sized materials into the occupational settings. For its part, the evaluation of common prevention measures revealed that the use of FPP3 filtered half mask respirators, laboratory gloves and non-woven protective suits provide medium to high levels of protection against nanomaterials depending of the specific operative conditions and mode of use.

A set of 4 cases studies were conducted to demonstrate the applicability of the surface modifiers and risk management measures defined within the project. These activities included a complete cost analysis of the proposed solutions. BSA modified ZnO-NPs and in-situ PEG coating modification of QDs were found to be the only safe by design approaches directly applicable at industrial scale.

A number of dissemination activities were completed. The accessible via the internet site Classical print media have been produced to be freely circulated for project information and promotion at relevant events. The results of the project were disseminated in workshops, trade shows, technical fairs, congresses and other events.

All partners have cooperated actively to perform the work accordingly, professionally and with the highest possible scientific standards.

Project Context and Objectives:
a) Background Information

The pigment and ink industry all over the world is being driven by innovation, which allows manufacturers to develop new and innovative products for hundreds of industrial applications and billions of people who use them every day. The pigment industry has always been striving to improve application technology properties and the market demands properties such as dispersibility, color strength, light and weather fastness, migration resistance, color shade or hiding power.

These properties depend on the chemical composition of inks and pigments and on the size and morphology of their particles. Therefore, nanotechnology and in particular, the use of nanoparticles have a great potential for new applications, leading to products with new or enhanced properties such as thermal stability, water repellence, scratch resistance, durability and antimicrobial properties. Consequently, many promising applications emerge nowadays, based on the use of nanoparticles such as FexOy, TiO2, ZnO, quantum dots or mixed-metal oxides at the nanoscale, which confer a wide range of properties to the final products, covering the current societal needs and market developments.

Along with the benefits, there are also concerns related to the possible health hazards and risks deriving from the unusual characteristics of nanoparticles such as small size, high aspect ratio, shape, surface reactivity, solubility or airborne properties. Furthermore, while research on developing new nanotechnology based products has prolific for more than a decade, research aiming to improve our understanding of the health and environmental impacts arising from all stages of the production, use and disposal of nanoparticles is far less advanced. However, due to the extraordinary possibilities derived by the application of nanotechnologies in different industrial sectors, the use of engineered nanoparticles is steadily increasing and the number of workers dealing with nanoparticles is dependently on the rise.

On the other hand, significant regulatory concerns from the European Commission have arisen about unforeseen risks likely to arise from the products of nanotechnology. At the moment, the most important piece of legislation in the area of health and safety at work is the Framework Directive 89/391/EEC "on the introduction of measures to encourage improvements in the safety and health of workers", which fully applies to the risks associated with nanoparticles. This Directive places a number of obligations on employers to take measures necessary for the safety and health protection of workers, considering also the risk mitigation as a recommendation when it is not possible to eliminate the risks.

At the same time, the REACH regulation, which is the main legal instrument to ensure the safety use of chemicals in the European market, establishes the need to ensure the safety of substances, such as those included into mixtures (e.g. inks). Even if there is no specific regulation to nanomaterials, REACH regulation applies to all substances and mixtures supplied in the European Union, regardless to their size, shape or physical state. Nonetheless, in the absence of specific regulations, the precautionary principle should be first applied.

b) Project Concept

The concept of NANOMICEX stems from the need to ensure the safety of workers dealing with the production or handling of engineered nanoparticles employed in the pigment/ink industry, as well as the need to provide the workers appropriate strategies to control the exposure to engineered nanoparticles, together with integrated and cost effective scenarios

The manufacture of nanotechnology based inks and pigments will bring new opportunities to the European Ink/Pigment industry in general, nonetheless, the safety issues related to workers have to be faced. First, the risks derived from the use of nanoparticles ought to be managed to ensure a safe working environment through identification of the hazard, knowledge of the potential adverse effects, measurement and control of the exposure. On the other hand, as a key issue within the project, industrial users involved in the manufacture of nanotechnology based ink/pigments must check and ensure the applicability of the proposed solutions, providing the European Industry with easy to implement and affordable measures to mitigate the hazard and control the exposure to nanoparticles, guaranteeing the safety of workers dealing with nanoparticles.

In order to address these major concerns and considering the project concept, the main objective of NANOMICEX project is to reduce the potential risk upon worker’s exposure to engineered nanoparticles through the modification of nanoparticles properties with effective surface modifiers and the characterization of practical and cost effective risk management strategies in the particular operative conditions of the inks and pigments industry.
Related to the nanoparticles considered, our proposal is focused on those nanoparticles employed in large scale by ink and pigment industries, covering an extensive range of high-tech applications and added value properties (semiconductor, insulator, luminescent, catalytic, refractive and magnetic properties). Such criteria are satisfied by several metal oxide nanoparticles (ZnO, TiO2, Al2O3 and Fe3O4), Ag metal nanoparticles, CdSe Quantum Dots and the mixed metal oxide Cobalt Aluminate spinel, therefore, these nanometer-sized particles will be studied within NANOMICEX proposal.

On the basis of this concept, the following activities were conducted within the project:
a. Design and application of surface modifiers to obtain less hazardous ENPs at source, while maintaining their desired properties at industrial scale;
b. Toxicological and ecotoxicological evaluation of nanoparticle impacts, selecting methods that are reproducible, simple, non-expensive and reliable;
c. Characterization of critical exposure scenarios on the basis of the information requirements laid down on REACH regulation, including a complete exposure and risk characterization;
d. Assessment of the effectiveness of conventional personnel protective equipment (PPE), ventilation, filtration and other control systems against ENPs;
e. Validation and implementation of proven risk management strategies in cases studies.

In detail, NANOMICEX focused on the design of functional groups to modify the properties of the engineered nanoparticles employed in the pigment and ink industry in terms of toxicological profile, cell interaction and surface reactivity, but without causing significant changes in the nanoparticles properties, reproducible applications in real conditions and using modification techniques that are easy to implement by non-expert personal. In this sense, the surface modifications of metal oxide nanoparticles, AgNPs, CdSe quantum dots (QDs) and mixed-metal oxides (CoAl2O4) NPs are aimed for their inclusion into inks and pigment formulations, reduce their hazardous properties and adverse effects on living systems, without compromising their further application in their current industrial pigment/ink formulations.

Regarding the potential hazards posed by nanoparticles, NANOMICEX focused of the evaluation of the cytotoxicity (in vitro approach), sub-lethal toxicity and dermal effects, considering the relevance of such aspects in relation with the occupational exposure to nanoparticles. This work allows the determination of the toxic responses in the worker place, and also allow a comparison of the effects of modified and unmodified particles. In addition, the work developed provides the stakeholders with scientific and consensuated data to conduct regulatory actions.

In terms of environmental impacts, NANOMICEX provides new knowledge in relation to the environmental fate and behaviour of nanoparticles. A comprehensive ecotoxicological study based on selected OECD test models was conducted, including the assessment of acute toxicity, sub-lethal ecotoxicity and bioaccumulation.

In terms of exposure assessment, the research activities within NANOMICEX focused on the development if real exposure scenarios in order to assess the exposure in the real operative conditions of workers dealing with engineered nanoparticles. In relation to the protection strategies, during the NANOMICEX project several protective measures were assessed, evaluating the effectiveness of the existing technical and management exposure control strategies, providing the ink and pigment industry with proper recommendations to control the exposure to engineered nanoparticles and therefore to minimize the risk.

The project conducted a life cycle assessment combined with risk assessment, studying the health and the environmental impacts of NP-based inks and pigments at all the stages of their life cycle. In addition, concerning the disposal of nanomaterial-based products, NANOMICEX promotes novel strategies for the management of the waste produced along the life cycle of inks and pigments containing nanoadditives.

Finally, as key action within the project, the surface modification strategies and risk management measures selected were testes in representative case studies. Several surface modification procedures, as well as specific implementation plans were developed to support the reproducibility of the safe by design approaches developed, ensuring the transference of the results to the industry.

c) Specific objectives

The overall objective of the project is to develop an integrated strategy to ensure the safety of workers dealing with nanoparticles, with specific focus on developing standard techniques to obtain less hazardous and more stable NPs, assess the workers exposure and provide cost effective methodologies to protect workers and the environment from the release of nanoparticles during all stages of the nanotechnology based-nks and pigments production, use and disposal.

In detail, the objectives included in the Grant Agreement and agreed between partners can be split as follow:

• To conduct a full characterization of the ENPs selected in terms of size, shape, mass, surface area, chemical composition, physical and optical properties;
• To design biocompatible surface modifiers to reduce the potential hazardous properties of the ENPs of special concern;
• To design surface modification methodologies and protocols applicable at industrial scale in terms of functionality and cost;
• To determine the hazards posed by the ENP panel to human health and the environment, including the selection of key representative cell types on the basis of the potential exposure routes, and organisms with ecologically relevant sensitivity to toxicants and ecological importance.
• To characterize the exposure to nanoparticles (exposure scenarios) in real operative conditions in the context of REACH regulation;
• To assess the potential impact and evaluate the risk posed by ENPs on workers at the different life cycle stages at the workplace;
• To assess the effectiveness of existing risk management strategies against ENPs;
• To define and validate cost effective risk management measures according to the industrial settings of the ink/pigment industry;
• To characterize suitable waste management/treatment measures;
• To validate the results taking into account the product functionality;
• To implement the safety procedures and risk management strategies to industrial partners and SMEs;
• To disseminate the research results for a large community of SMEs and potential stakeholders;

The objectives listed above were agreed between partners, being all of them achievable and realistic.

Project Results:
The main outcome of the project is a list of cost-effective strategies based on proven surface modifiers and effective Risk Management Measures to reduce the environmental, health and safety impacts of the ENPs used in large scale by the printing ink, paint and pigment industry.

At a glance, the results of the project can be summarized as follows:

- A compendium of proven surface modifiers based on bio-ligands such as carbohydrates and polymeric structures to obtain less toxic ENPs;
- A complete description of the physicochemical, toxicological and ecotoxicological properties of the most common ENPs employed by the printing ink, paint and pigment industry.
- A complete description of the current exposure scenarios during the synthesis, mass production, and use at industrial sites of ENPs, taken into consideration the specific processes, operations and production steps related with the use of the selected ENPs to produce nano-pigments, and inks or paints formulated with nano-additives.
- New knowledge on the airborne behaviour of the target ENPs, including new data on their aggregation/agglomeration patterns and deposition factors under the specific operative conditions of use presented in the reference sectors of the project.
- New knowledge on the effectiveness of common personal protective equipment (PPEs), ventilation and filtration systems against ENPs
- A complete description of the procedures and risk management measures that shall be implemented to control and mitigate the exposure to ENPs at industrial scale.
- New information on the environmental impact of the target ENPs on a life cycle basis, including the characterization of the risk ratios to workers and the release rates to air, surface fresh and marine water, waste water and soil for each relevant stage on the life cycle.
- A structured compendium of scientific reports and documents to support the training of end users and stakeholders in the use and implementation of the cost-effective strategies developed within the project.
- Participation in relevant workshops and conferences to disseminate the project actions at National and European level.

In order to achieve the objetives listed above, the work plan was divided into 9 workpackages, which can be grouped into 4 specific activities, including scientific and technological activities, demonstration, management, and dissemination. These activities were organized in the following workpackages:

• WP 1. Characterization of engineered nanoparticles
• WP 2. Development and selection of functional modified nanoparticles
• WP 3. Hazard assessment
• WP 4. Exposure Assessment
• WP 5. Risk Management and Control Measures
• WP 6. Nano SLCRA: Adaptive Streamlined Life Cycle / Risk Assessment of nanoparticle-based inks and pigment
• WP 7. Industrial Case Studies
• WP 8. Project Coordination and Management
• WP 9. Project Dissemination, training and networking

The activities conducted within the project has been focused on the design, development and validation of scientifically validated strategies to reduce and control the potential environmental, health and safety (EHS) risks related with production and downstream use of ENPs in the pigment, ink and paint industry. The overall work conducted since the beginning of the project can be summarized as follows:

1. Selection of target ENPs on the basis of market data and industrial feasibility (WP 1)

2. Preparation of industrial samples of selected ENPs by Industrial partners (WP1);

3. Characterization of the chemical and physical properties of the selected ENPs, including pristine and modified particles, through, for example, imaging, structural, and spectroscopic techniques such as TEM, SEM, DLS, UV-Vis, FT-IR, Raman, etc. (WP 1);

4. Exploration of the surface chemistry alteration strategies for Al2O3, TiO2, Fe2O3, CoAl2O4 and ZnO NPs. A variety of ligands with biological origin such as carbohydrates and oligonucleotides has been tested (WP 2);

5. Cytotoxicity screening for all pristine NPs, including the preparation of a complete literature review of biological effects of the nanoparticles involved in the project (WP 2-WP3);

6. Selection of ENPs of special concerns on the basis of available information on the literature and cytotoxicity screening test (WP2 – WP3)

7. Design and experimental validation of surface chemistry alteration strategies for ZnO NPs, Ag NPs and CdSe-ZnS QDs (WP 2);

8. Assessment of the toxicity, ecotoxicity and environmental fate of pristine and surface modified ENPs. A holistic approach was conducted to perform this assessment, including the use of available data on the potential adverse effects and mode-of-action of the selected ENPs, as well as data obtained from in vitro and in vivo experiments (WP3);

9. Quantification of the exposure to ENPs used state-of-the-art measurement devices and exposure assessment methodologies during the most relevant exposure scenarios defined and identified during the production and use of ENPs in the pigment, ink and paint industry (WP4);

10. Experimental evaluation of the effectiveness of respiratory protective equipment (RPE), protective clothing, chemical resistant gloves, and local exhaustive ventilation systems against ENPs (WP5);

11. Definition of the specifications that shall be considered when selecting adequate and cost-effective personal protective equipment (PPE) and engineering controls against nanoparticles and/or nanostructured materials (WP5);

12. Evaluation of the impact and risk posed by the use of ENPs on worker and the environment. The evaluation was conducted using a combined Risk Assessment (RA) - Life Cycle Assessment (LCA) approach, including the characterization of the risks on workers and the environment by means of modelling approaches and LCA tools respectively (WP6);

13. Validation of the functionality and cost-effectiveness of the surface modification strategies and risk management measures defined within the project by indsutrial partners. Special attention was considered to the applicability of the strategies proposed at industrial level, and the compatibility of the surface modification protocols with ink and paint formations (WP7);

14. Development and implementation of the plan for the dissemination and use of the foreground - PDUF (WP8-WP9)

15. Monitoring of the project actions and consortium management (WP8);

16. Development of the project web site and dissemination materials, including the project brochure, newsletters and scientific publications (WP9);

17. Participation in international events related to the research topic of the project, mainly workshops and conferences (WP9).

A detailed explanation of the activities conducted within each WP and the most relevant scientific and technical results achieved is provided in the following paragraphs:

WP1. Characterization of Engineered Nanoparticles

Summary of progress towards objectives and details for each task - WP1

The mail goal of this WP is the investigation and the description of the most relevant physicochemical properties of the specific types of metal oxide nanoparticles (MOx-NPs), silver-NPs, quantum dots, mixed metal oxides, as well other interesting NPs, which have a broader applicability in the pigment, ink and paint industry.

The objectives of WP1 have been fully achieved. They included: a) the identification and selection of various metal oxide, Ag, CdSe QDs and CoAl2O4 ENPs, most widely employed by the printing ink, paint and pigment industry; b) the complete characterization of the ENPs before and after surface modification following the endpoints listed on the guidance manual for the testing of manufactured nanomaterials published by the OECD in relation to the physical-chemical properties and material characterization.

In summary, the tasks and activities conducted can be divided as follows:

a. Identification and selection of the most relevant ENPs: to this end, a set of specific activities were conducted, including the review of international market reports, the collation of the opinions from SME Associations and SME partners and the compilation of data from International publications including scientific peer reviewed journals.

b. The complete characterization of the ENPs selected before and after surface functionalization following the endpoints listed by the OECD in terms of size, shape, mass, surface area, chemical composition, physical and optical properties by means of specific and standardized techniques.

c. Quantitative characterization of the concentration of target particles in tested organisms to support dose-response analysis

Significant Scientific and Technical Results - WP1

-Target ENPs: The panel of ENPs studied within the project was defined during the first months of the project. The decision was taken on the basis of the interest showed by the industrial partners included in the project, as well as in view of the potential application of the ENPs to enhance the properties of pigments and ink/paint formulations.On the basis of the information retrieved, the consortium considered the following ENPs: ZnO, TiO2, Al2O3 and Fe3O4, Ag-NPs, CdSe quantum dots (QDs) and the mixed metal oxide cobalt aluminate spinel.

-Characterization: The results showed that most of the samples were highly polydispersed with broad range in size and shape. Furthermore, according to the XRD data, all samples were crystalline whereas TEM study showed that nanocrystals were mainly present as aggregates. FT-IR spectroscopy and elemental analysis studies indicated that the aggregates were formed mainly due to the lack of organic stabilizers.

-Surface modifications: The results clearly showed the success of the surface modifications performed within WP2, however, further studies are needed to understand the stability of the selected modifiers in biological media, including both cell lines or/and model organism, where a large number of biological processes can occur, being able to modify the surface properties of the ENPs.

The modification of metal oxide NPs with biocompatible polymers with and without the presence of silica shell was found to be successful according to the FTIR analysis.The XRD characterization showed that the crystallinity of the particles was not influenced by the modification processes for most of the samples. The modification of QDs with silane and glucose coating was found successful.

-Characterization in tested organisms: ICP-MS analysis conducted showed the presence of metal ions (Ag, Cd) inside tested species, incluiding Daphnia magna and Lumbriculus variegatus. Some discrepancies were found out mainly between the nominal and determined concentration of the metal ions, especially Zn2+. This issue was widely discussed with partners involved in the project, mainly WP2 and WP3, in order to conduct a realistic interpretation of the results of the toxicological and ecotoxicological studies.

WP2. Development and Selection of Functional Modified Nanoparticles

Summary of progress towards objectives and details for each task

The proposed work was focused on the design, development and validation of surface modification strategies to obtain less toxic ENPs. Proper surface modifiers were determined by taking into consideration of their nontoxicity, stability, biocompatibility, compatibility in ink formulation, cost and availability. Several surface modifiers and modification strategies were investigated for each type of NMs since each ENP has a different surface chemistry and availability for surface modification. The activities have been conducted following the task and deadlines scheduled in the document of work. In detail, the following activities have been conducted:

- Design of surface modifiers: The selection of the potential surface modifiers was conducted considering relevant data retrieved from the literature and the information retrieved form the surface chemistry analysis conducted (TEM, FTIR, Raman, Fluorescence Spectroscopy and DLS).

- Surface modifications: the surface modifications were pursued based on the specifications and limitations defined by the industrial partners. In this sense, the specific surface properties of the target ENPs were clearly defined to avoid significant variations on the properties of the nano-pigments and ink/paint formulations developed using the surface modified particles designed in the previous task. Metal oxides were coated with a silica layer that also allows for further modifications with a biocompatible molecule or polymer. Two main approaches were conducted in this case.In the first approach, a direct attachment of small biomolecules to the NP surface through –OH groups available has been pursued. In the second approach, a complete coating of the NP surface was performed.

Silver NPs were modified by adsorption chemisorption of a molecular structure possessing a thiol moiety. It is also possible to coat the AgNP with a thin layer of a polymer for higher stability, such as PVP. On the other hand, for Quantum Dots (QDs) and Ag NPs, adsorption and chemisorption of thiol-group containing ligands and polymeric structures through Ag NP-S- and QD-S- bonds have been pursued using the well-defined procedures reported in the literature. Alternatively, QDs can be completely coated with a layer of silica before further modification to prevent the release of toxic ions (such as Cd2+, Se2-, S2- and so on) through the defect on the surface of the QDs.

- Characterization of synthesized/prepared NPs: This task was focused on the physico-chemical characterization of the unmodified and modified ENPs selected within the project in order to evaluate the success of the surface modification conducted.The specific analytical techniques selected to perform the studies were the following: FT-IR Analysis, Thermogravimetric Analysis (TGA), Dynamic Light Scattering and UV/ Vis Spectroscopy Analysis, TEM Analysis, and Fluorescence Spectroscopy.

- Testing the functionality of the new NP-ink complex structures: This activity focused on the evaluation of the applicability of the surface modified ENPs developed within the project in ink and paint formulations. Ink-nanoparticle complexes were tested on laboratory samples to evaluate their performance in real life applications, considering specially their stability in ink and pigment formulations.

Significant Scientific and Technical Results - WP2

Several surface modification strategies have been explored in order to reduce the possible toxic effects of the NPs. Three types of NPs were finally selected for modification based on their initial toxicity assessments, which are ZnO NPs, QDs and AgNPs.

Several stabilizing agents and modifiers were investigated in a first stage, including biodegradable polymers, carbohydrates, proteins, peptides, oligonucleotides and silica. The modifications were performed separately for each of the NPs selected due to the observed differences in the surface properties of each particle.

The two major difficulties encountered during the surface modifications are the unavailability of the NM surface for chemistry and the agglomeration status. The synthesis or preparation method of NPs has critical importance since it defines their surface chemical properties.

The proposed surface modifications are the followings:

a) Proposed Surface Modification for ZnO NPs: The toxicity of ZnO NP is the major problem that limits application areas. To overcome this limitation, a surface modification based on the attachment of Bovine serum albumin (BSA) onto silica coated ZnO NPs was selected on the basis of the cytotoxicity studies conducted.

b) Proposed Surface Modification for QDs: the toxicity of the QDs was reduced by coating them with a silica layer and modifying the silica layer further with glucose.

c) Proposed Surface Modification for Silver NPs: in the scope of this project, various modifiers were evaluated via direct attachment of ligands such as lactose, starch, folic acid (FA) and oligonucleotide (oligo) onto AgNPs, however, all attempts to reduce the toxicity did not change the toxic behavior of this NP.A thorough study of the cytotoxicity of the Ag NPs modified with several molecules was completed. The analysis of the results indicated that the major source of the toxicity could be originating from the very small AgNPs (a few nm)

In view of the results, it can be stated that the modification of the target ENPs with biodegradable polymers and proteins can be used to reduce the toxicity of ZnO NOs and QDs. The toxicity of AgNPs depends on their size, dissolution rate and the reducing agent used for the production or stabilizer used, therefore, the modifications with starch, lactose, oligonucleotide and folic acid do not decrease the cytotoxicity of the AgNPs tested, and being advised to increase the size of the Ag NPs performing better control of the synthesis process.

WP3. Hazard Assessment

Summary of progress towards objectives and details for each task-WP3

The activities conducted within WP3 have been focussed on the potential hazards posed by the nanoparticle panel to human health and the environment, comparing any effect of the same NPs treated with the selected surface modifiers. The following activities were conducted under the scope of WP3:

- Literature review of the biological effects, mode-of-action, fate and behaviour of the selected NPs
- Toxicological assessment, including:
1. Evaluation of the cytotox effects of unmodified and modified NPs
2. Evaluation of sub-lethal effects of unmodified and modified NPs
3. In vivo sub-lethal experiments of NPs of special concern
4. Literature review of the dermal effects of the target NPs

- Ecotoxicological assessment, including:
1.Evaluation of the acute effects on relevant environmental compartments by means of screening tests with the model organisms Daphnia magna,
2.Lumbriculus variegatus and Pseudokirchneriella subcapitata.
3.Evaluation of sub-lethal effects of unmodified and modified NPs
4 Development of uptake/depuration experiments of NPs of special concern

- Characterization of the physiochemical properties of the NPs in biological and environmental media
- Statistical analysis of the information generated on the physicochemical, toxicological and ecotoxicological properties

Significant Scientific and Technical Results - WP3

The main conclusion from the studies completed were:

a) Effects on Human health

• The literature review suggests that the most hazardous NPs in mammalian and environmental systems are ZnO, CdSe QDs and Ag.
• Based on cytotoxicity studies (J774 cells), we can rank the toxicities of the particles as follows based on LC50 estimations, ZnO>QDots>Ag>Ag (H) =TiO2>Co=Fe>Al
• Sub-lethal test demonstrated that the most active particles are both Ag particle types, Qdots and Zn.
• There is evidence to suggest that penetration of NPs through skin is minimal, and that the stratum corneum is an effective barrier.

b) Effects on ecosystems

• On the basis of the data obtained with the most sensitive organism (D. magna), we established the following toxicity ranking: Ag > ZnO > CdSe QDs > Fe2O3 = Al2O3 = CoAl2O4 = TiO2
• No relevant sub-lethal effects were detected for either unmodified or modified ZnO particles

In detail, the following results were achieved:

a) Human Health

1. Cytotoxicity testing of unmodified particles: only pristine ZnO and Qdots were significantly cytotoxic to J774, A549 and C3a cells. Based on LC50 estimations, we can rank the toxicities of the particles as follows: Zn>QDots>Ag>Ag(H)=TiO2>Co=Fe>Al.

2. Cytotoxicity testing of modified particles: ZnO and Qdots were significantly cytotoxic to J774, A549 and C3a cells. The surface modifications (BSA and Si-glucose) significantly reduced the cytotoxic potential of unmodified particles accoriding with the results observed.

3. Sublethal effects of unmodified particles: overall, from all the endpoints studied, It is clear that the most active particles were Ag particle, Qdots and ZnO. Following the results of teh citotoxicity assays, Ag ,Qdots and ZnO NPs produced significant damage to A549 cell DNA.

4. Sublethal effects of modified particles: surface modification of ZnO had a positive effect on the cellular impacts of these particles. Over several endpoints, the modified form of this particle type was less reactive than it’s unmodified form. In contrast, modified QDots did not produce such effects in all endpoints measured.

5. In vivo effects of unmodified and surface modified particles: Ag (hydrophilic), ZnO and QDots, and BSA Modified ZnO were tested by means of selected in vivo methods, including: inflammation, lung damage, superoxide production by bronchoalveolar cells (production of reactive oxygen species), and GSH concentration in the liver (distal effects to the site of exposure).

We ranked the particles in terms of their in vivo inflammogenicity as follows: Ag>ZnO>Qdots>Ag(ions)=Co=Zn(ions). ZnO instillation suggest damage to the lung epithelial/endothelial barrier. No difference in the GSH (total or reduced) in the liver of particle instilled animals, suggesting a lack of distal effects such as oxidative stress in the liver. Ag and ZnO particles significantly (p<0.001) reduced the superoxide anion production in non-stimulated BAL cells, potentially due to cytotoxicity to these cells.

BSA surface modification of the ZnO particles reduced the ability of the ZnO particles to induce lung inflammation. There was no difference in the GSH (total or reduced) content in the liver of BSA modified ZnO particle instilled animals compared with instillation of unmodified ZnO particles.

6. Potential dermal penetration and sensitization: There is evidence to suggest that penetration of NPs through skin is minimal, and that the stratum corneum is an effective barrier.However conversely it has been demonstrated that NPs can penetrate intact and damaged skin. It is evident that the physico-chemical properties of NPs, the integrity of skin and the experimental design (e.g. model used, NP concentrations tested) may be responsible for the lack of agreement between studies, and thus it is recommended that more research is undertaken in this area.

b) Environmental Hazard

1. Acute ecotoxicity of each particle type prior to surface modifications: on the basis of the data obtained with the most sensitive organism (D. magna), we established the following toxicity ranking: Ag > ZnO > CdSe QDs > Fe2O3 = Al2O3 = CoAl2O4 = TiO2.

2. Acute ecotoxicity of each particle type following surface modifications: ZnO-Si-BSA and CdSe-ZnS-Si-Glucose NPs were selected from the particle panel due to their high toxicity. Overall, the acute ecotoxicity was reduced by the surface modifier. Overall, the resuslt showed a decrease in the ecotoxicological profile of the modified particles. In the case of ZnO NPs, further studies are needed to evaluate the concentration of ZnO NPs after the dispersion of the modified ZnO-Si-BSA in the testing media.

3. Sub-lethal toxicity of the unmodified nanoparticles to the test species: the work focused on the three most toxic materials (Ag, ZnO and hydrophobic CdSe QDs). The 21 d chronic reproduction test in D. magna revealed no adverse effect of either Ag and ZnO at sub-lethal concentrations. Body reversal effects only observed for Ag and CdSe particles. Results suggest that hydrophobic QDs induced oxidative stress in L. variegatus, while no effects were observed in D. magna.

4. Sub-lethal toxicity to the test species of specific particles following surface modifications: two modified particles (ZnO-Si-BSA and CdSe-ZnS-Si-Glucose) were tested. The modified quantum dots reduced effects on body reversal compared to the unmodified hydrophobic CdSe cores. Results suggest that modified QDs did not affect oxidative stress activity in L. variegatus, as opposed to the hydrophobic QD cores, which increased oxidative stress activity.

WP4. Exposure Assessment

Summary of progress towards objectives and details for each task - WP4

The activities conducted focused on the identification and quantification of the potential exposure to the target NPs during their synthesis, production of intermediate NPs, formulation of products (directly from ENPs or from intermediates) and industrial/professional use. Domestic use such as application of commercial paints in private homes and waste disposal is not within the scope of the NANOMICEX project. The exposure assessment is conducted through the study of peer-reviewed literature; information from the industrial partners in NANOMICEX and characterisation of airborne nanoparticles (NP) during site visits.

The work in WP4 is split into two different tasks.Task 4.1 aims to identify exposure situations, based on study of the literature as well as through collection of information from industrial partners using questionnaires and during scoping visits. Task 4.2 aims to collect further information and carry out detailed measurement surveys to characterise the release and potential for exposure over the key life cycle stages identified in Task 4.1.

The purpose of the scoping visit was to obtain a preliminary set of data on the levels of release and exposure. The analysis of the data contributed to determining appropriate monitoring approaches to characterize the levels of the release during the second tier studies.

Tier 1 studies were performed with the support of the industrial partners of the NanoMICEX consortium. A suit of instruments were used to monitor the nanoparticles released in indoor facilities, including a particle counters (CPC – TSI Model 3007 and the Aerasense Nanotracer - Philips Electronics), an Optical Particle Sizer (OPS – TSI Model 3330), which provides data on particle size distributions, and the DustTrack (DT II - TSI Model 8532), which provides measures in terms of mass per volume (in units of mg/m3 for 5 dust size fractions).

Tier 2 assessments within task 4.2 consisted in a more detailed analysis of the properties of the particles released. The instrument suite defined previously was complemented with an Aerodynamic Particle Sizer (APS) for assessing micro-scale particle number concentrations and size distributions, a Fast Mobility Particle Sizer (FMPS) for assessing particle number concentrations and size distributions in the nanoscale range. These second tier measurements involved monitoring particle concentration and size distributions prior to (background) and during ENPs manufacture and use at specific work area locations.

Several filter-based air samples (37-mm open-faced cassettes) were collected during the measures conducted in order to characterize the size, shape and composition of the ENPs released. These air samples were collected as close as possible to the suspected emission source to increase the probability of detecting any release (near field). In addition, far field air samples were also collected.The filters collected were further analysed by Scanning Electron Microscopy (SEM) and/or Energy Dispersive X-ray Spectroscopy (EDXS) to obtain relevant morphological and compositional data.

Significant Scientific and Technical Results - WP4

We identified eight tasks (contributing exposure scenarios) as having particular potential to release nanoparticles into the work place environment. These tasks were selected based on the current scale of production or after ‘extrapolation’ of this to an industrial scale. These tasks are (1) dry synthesis via a pyrolysis reaction; (2-3) harvesting/isolating synthesised or functionalised ENM; (4) drying an ENM paste to a powder; (5) milling an ENM powder; (6) charging a process with an ENM powder; (7) packaging an ENM powder and (8) maintenance work on production plant and on ventilation systems.

The exposure scenarios monitored on the full measurement survey were selected on the basis of the likelihood of release and exposure, including: the dry synthesis of ENPs; preparation of an intermediate product, and formulation of a prototype nano-paint. These exposure scenarios include activities such as the pyrolysis reaction; harvesting/isolating synthesised or functionalised ENM and charging a process with powdered ENM. In addition to the measurement survey, the activites within the project also investigated release of ENMs from printing inks during ink jet printing.

The results from the measurement campaigns showed that there was little evidence of release from engineered nanomaterials during the various activities. Possible exceptions to these were the dry synthesis in a pilot plant and the mixing powders into a paint.

The following bullet points summarize the results for the NPs studied:

- Production of CoAl2O4: results suggest that the particle number concentration, in particular with a mode of 250 nm diameter, was increased during the pyrolysis stage.

- Synthesis of nano-TiO2: elevated particle concentrations were observed during the pyrolysis at around 90 and 250 nm compared to background, but interestingly particle concentrations at 15 nm were increased only towards the end of the pyrolysis process and during furnace shut down.It is not clear from the results or the information provided by the company why particle concentrations were elevated. It is possible that the increase is due to combustion of fuel in the furnace, rather than the release of any ENMs.

- Measurements during the mixing of nano-enabled paints, showed that particle concentrations at 250nm were increased compared to background and that there were some episodes of elevated particle number concentrations around 30 nm, although it was not clear whether this was associated with handling of nano powders (ZnO, TiO2). However, there are strong suggestions that the elevated levels could be due to other materials being handled (eg CaCO3) within site.

WP5. Risk Management and Control Measures

Summary of progress towards objectives and details for each task - WP5

The objectives of this WP is to evaluate the protective effectiveness of various personal protective equipment and engineered controls against nanoparticles, as well as design a cost effective integrated strategy to mitigate the risks posed by nanoparticles based on the combination of safety procedures, personal protective equipment and engineering controls. The experimental approach applied within this task can be split as follows:

- Effectiveness testing: This task focusses on the evaluation on the effectiveness of RMMs to prevent or minimize exposure in the workplace. Within this task common operative conditions are reproduced under controlled conditions to simulate the levels of exposure in the workplace.

- Design and selection of proper RMMs: This task focusses on the selection on proven integrated strategies based on the outcomes of the previous tasks, and the definition of those specifications able to increase the performance of the RMMs tested.

- Development of safe exposure scenarios: The last task focusses on the selection of adequate RMMs considering the exposure scenarios across the life cycle of the target NPs and products

Significant Scientific and Technical Results - WP5

a) RMM performance

The main results achieved by means of the experimental approaches described below described below:

- Average penetration levels for the three different masks were between 15 and 2%. The results showed that Disposable and Half Mask Respirators provided medium performance levels of filtration efficiency against nanoparticles. Total inward leakage (TIL) ratios determined in relevant studies suggest that face seal leakage, and not filter penetration, is a key parameters to be considered when working with nanoparticles.

- The penetration factors for hand and body protection were very low, meaning that gloves, suits and coats are effective against the tested ENPs. It shall be noticed that the nanoparticles levels reached during the tests were very high, which may induce the textile “filter” to clog, meaning that the effectiveness of the textiles can increase in dusty environments, limiting the number of ENPs able to cross the fabrics or the polymeric fibres.

- The analysis of the results suggest that the control of exposure via inhalation is a key priority for ENPs. The tested ENPs were able to cross the respirators tested and reach the tracheobronchial area of the Sheffield head, where the real time measurement devices where located.

- High densitypolyethylene protection suits for dusty environments showed penetration levels > 15 % at 4 cm/s.

b) Design of Risk Controls

• Respiratory Protective Equipment

In view of the experimental results, and considering data from relevant guidelines and scientific publications, the following recommendations can be defined:

1.Use of RPE equipped with highly charged microfibers. Much of the PPE manufacturers have available in their product catalogue half mask and full-face respirators incorporing electrostatically charged fibers (electret media).

2. A key parameter to ensure the effectiveness of respiratory protective equipment is the face seal. It is highly recommended to use RPE offering innovation in face seal, ranging from new silicone based materials to inflatable seals. Moreover, the use of a double flange facepiece for full-facepiece respirators is thought to be both more comfortable and to fit better, because it didn’t slip and because the second flange offered a backup seal in case of leakage through the first flange

3. Strap attachment and design can play an important role in the effectiveness of respirators. Five adjustable straps on a full face mask appear to be the minimum number to ensure a seal. It is recommended to avoid a strap across the ears. In this sense, the strap must pass either above or below, with further adjustment generally required because a strap will remain anchored on the back of the worker’s head only at certain points.

4.The incorporation of an adhesive sealing material in the face seal has also been reported to increase the fitting factor and reduce the total inward leakage.

It shall be noticed that a wide range of material properties are important to good design, including mechanical, chemical and physical properties, comfort, ability to withstand degradation, thermal conductivity, transparency, compatibility with other parts of the respirator, cost and speech transmission.

• Chemically resistant gloves

In view of the current start of the art, the following recommendations can be defined:

- A much higher efficiency against nanoparticle penetration is expected form nitrile, vinyl, latex and neoprene commercial gloves. These materials are thus recommended when working with nanoparticles.

- The mechanical deformations suffered by gloves in service as well as the presence of a microclimate inside the gloves may also affect the penetration of the nanoparticles. To cope with this situation, the thickness of glove material and the requirement for textured or non-slip surfaces to improve grip must be considered.

- Attention must be paid to the adequate mechanical stability of gloves and to damage to the glove material in order to prevent skin contact. The overlap of the gloves with other protective clothing and the correct way in which they are put on and removed are more important for the avoidance of possible skin contact than the permeation properties of the material.

- Wear latex or nitrile gloves when handling nanoparticle powders and nanoparticles in water suspension (glove changes should be performed frequently).
- Great care must be taken when selecting protective gloves for handling nanoparticles in solutions. The use of butyl rubber gloves in highly recommended, providing excellent chemical resistance to a wide range of chemicals, including colloidal dispersions of nanoparticles.

• Dermal Protective Equipment

In view of the current start of the art, the following recommendations can be defined:

- Particulate protection clothes are mostly made from non-woven fabrics. Porous fabrics are used for particulate protection and coated/laminated fabrics are used for liquid and gas protection. Microporous non-wovens fabrics exhibit high barrier performance.

- Tyvek type suit (High densitypolyethylene protection suits) offers excellent barrier protection for sub-micron particles, with up to 99% holdout of < 0.5 micron particles.

- Avoid the use of protective clothing made with cotton fabrics. Woven protective clothing materials offer poorer protection than membrane materials. Additional protection against chemicals may be necessary under certain circumstances.

- Breathability of material is another important factor to be considered. To achieve an effective protection, protective clothing materials that can provide a combination of high barrier performance and thermal comfort is essential.

• Engineering controls

The use of HEPA filter effectively remove nanoparticles. Hence, any LEV system should be at least HEPA filtered (filter class H14), and wherever reasonably practicable vent to a safe place outside.The use of LEV systems are higly recommended when working with nanoparticels. The data retrieved from the literature, and studies conducted within task 5.1 revealed that:

- Dilution ventilation can be used for non-hazardous exposures, but isn’t acceptable for nanoparticles
- LEV systems are a primary method for controlling occupational exposures to NPs. The most relevant and most often used LEV types for nanoparticles are enclosing and capturing hood.
- Ductless HEPA-filtered safety cabinets and recirculating HEPA-filtered microbiological safety cabinets can be used with small quantities of NPs (<1 gram)

Improvements based on the use of a flange, a rim or disc-shaped collar at the sides around the hood of LEV, has been shown to increase velocities in front of hoods up to 55%. Moreover, it is recommended the use of hoods with an opening with an aspect ratio of width/length > 0.2

WP6. NanoSLCRA: Adaptive Streamlined Life Cycle / Risk Assessment of nanoparticle-based inks and pigment

Summary of progress towards objectives and details for each task - WP6

The objective of this WP is to assess the potential environmental life cycle impact as well as to evaluate the risks posed by the target ENPs on workers in all relevant exposure scenarios identified at the different life cycle stages at the work place: production (i.e. Synthesis and Functionalization), use (i.e. Manufacture of Intermediates and ink/paint formulation) and disposal. The activities related this WP were focused on the development of the following activities:

- Analysis and evaluation of information on the physico-chemical properties and toxicity data of the nanoparticle selected within the project. Process parameters and risk management measures were also analyzed and evaluated in order to be integrated in the risk assessment analysis.

- Risk Characterization: exposure levels were compared to reference dose descriptors (DNEL and PNEC) in order to estimate the risk characterisation ratios (RCRs) and decide whether risks were adequately controlled for workers and environment. These studies have been carried out in all relevant exposure scenarios at the different life cycle stages.

- Life Cycle Impact Assessment: a streamlined Life Cycle Assessment (LCA) was carried out considering a cradle-to-gate approach, including raw materials production, synthesis, functionalization, intermediates (blending) stages and formulation. The impact assessment was completed using reliable data from the industrial partners.

- Definition of nano-specific Waste Management Strategies: the last activity within WP6 was focussed on the identification and description of new treatment alternatives to adapt conventional production processes to the presence of nanoparticles. To this end, current limitations of the different waste management alternatives (water treatment, incineration and landfilling) to the treatment of the nanowaste fractions were assessed in a first stage. Secondly, the study focussed on the analysis of the novel solutions and processes with the potential to improve the treatment of the nanowaste generated in the ink and pigment industry

Significant Scientific and Technical Results - WP6

The main results achieved can be split as follows:

a) Environmental Risk Assessment

• Environmental hazard assessment: the data on the ecotoxicological profiled of the target ENPs was analysed to estimate PNECs values for the freshwater compartment.The estimated PNECs were 1550, 1550 and 1.7 ng L-1 for pristine ZnO, QD and Siver NPs, respectively. Surface modification showed a lower toxicity to aquatic organisms with derived PNECs of 10.900 and 338.200 for modified QD and modified ZnO NP, respectively.

• Environmental Risk characterization: a multi-media high-level probabilistic Material Flow analysis (pMFA) based on Monte Carlo method developed by ITENE was applied to estimate the predicted environmental concentration (PEC) of the target NPs. For nano-ZnO and QDs, both, the predicted exposure and effect concentrations were only partially overlapping, with expected exposure concentrations lower than the effect concentrations, while for nano-Ag, the predicted exposure and the PNEC were both in the ng/L range. The analysis of the results concluded that risk is mainly expected from nano-Ag and nano-ZnO. In surface water risk is mainly expected for algae and invertebrates with potential issues of long term effects on populations. There are not enough data to discuss the long-term toxicity of realistic concentrations of ENP in the environment.

b) Occupational Risk Assessment

• Occupational hazard assessment: the risk assessment was focused on Ag (hydrophilic&hydrophobic), ZnO and QDs. The DNELs values used were based on information retrived from experimental data and peer reviewed publications. The DNELs estimated according to the data obtained from the literature for AgNP, ZnO and quantum dots were calculated to be between 0.002 and 2 μg/m3 while those for silver and quantum dots were below 1 μg/m3. When the DNELs were estimated according to the in vivo data provided in WP3, the same DNEL value (0.041-0.138 µg/m3) was found for all the unmodified particles.

• Exposure assessment: exposure by ingestion and dermal exposure was not considered on the basis of the data retrieved from WP4 and WP5, thus, only inhalation exposure was considered. The exposure assessemt conducted was based on the comparision of the measured levels of exposure with the DNELs values calcualted as described previously. When there was no measured data, modeling approaches were used in order to lead to the most appropriate assessment along the relevant life cycle stages.

According to the risk characterization ratios (RCR > 1) calculated, ten tasks were identified with the highest potential risk:

- Synthesis via a pyrolisis reaction
- Harvesting/isolation synthesized and functionalized ENM
- Drying an ENM paste to a powder
- Milling an ENM powder
- Charging a process with a powdered ENM
- Packaging ENM powder
- Cleaning of plant and premises
- Maintenance work on ventilation systems and pyrolysis unit
- Printing commercially conductive Ag ink
- Prototype paint formulation TiO2&ZnO powders

The implementation of the Risk Management Measures defined with the project reduced the risk characterization ratios to values below 1, which means that risk are adequately controlled. This is due to the lees toxic profile of the modifies NPs. In the case of the silver, for which it was impossible a suitable modification for reducing its hazard profile, was possible to reduce the risk when applied the proposed RMMs but still over one. Therefor further work in needed for obtaining a modification able to reduce its toxicity and thus its DNEL value.

c) Environmental Impact Assessment

The results of the LCA impact assessment showed that:

• The synthesis stage, compared to the formulation and functionalization stages, is the most contributing for all the impact categories analysed: Global Warming Potential, CumulativeEnergy Demand, Acidification, Abiotic Depletion, Photochemical Ozone Formation, Ozone depletion, Marine Eutrophication and Freshwater Eutrophication.

• In the case of the inputs, the raw materials are the main contributors for the impact categories of Global Warming Potential, Cumulative Energy Demand, Acidification, Abiotic Depletion, Photochemical Ozone Formation, Ozone depletion and Freshwater Eutrophication.

• In the case of the impact category of Marine Eutrophication, the ancillary materials are the most contributing input followed by the raw materials and the energy inputs.

• In terms of the impact categories of Human Toxicity (cancer), Human Toxicity (non cancer) and Ecotoxicity, the most contributing stage is the synthesis and the most contributing inputs are the raw materials followed by the ancillary materials and then the energy inputs

d) Waste management strategies

The nanowaste fractions potentially generated in each were identified as well as the processes to treat them and the limitations associated. New strategies to improve the treatment of these waste fractions have been identified and described with a view to guarantee the adequate management of nanowaste in the ink and pigment industry.

The nanowaste fractions generated in each of the processes studied within the project are listed below:

1. Production of paint with additivated varnish (TiO2, ZnO). Nanowaste fractions are: paint residue stored in intermediate bulk containers (IBC), paper packaging, plastic packaging with traces of raw materials, materials dust/powder emitted to the air, personal protective equipment (PPE), cans of paint with manufacturing defects, paint residue hardened, sepiolite contaminated, lids and containers not used due to manufacturing defects, treatment sludge and solvent distillation dust.

2. Production of ZnO nanopowders (ZnO). Nanowaste fractions are: used carbon filters, PPE, waste water, sludge, waste solvents with inks, ink residues, contaminated sepiolite and contaminated packaging.

3. ZnO functionalization (ZnO). Nanowaste fractions are: used PPE, used laboratory equipment and filters from glove chamber, waste water, no valid contaminated packaging and air emissions.

4. Digital printing (Ag). Nanowaste fractions are: ink empty containers, air emissions, ink residues, screen printing plates, stencils and proof prints, waste water, waste solvents with inks and solvent empty containers.

5. Quantum dots synthesis, functionalization and formulation (CdSe). Nanowaste fractions are: used PPE, used laboratory equipment, waste water, waste solvents
with inks, solvent empty containers, air emissions, ink residues, sepiolite contaminated, no valid contaminated packaging and air emissions.

In relation with the applicability of waste treatment strategies, traditional waste management processes (water treatment, incineration and landfilling) present limitations to treat these residues.Water treatment does not achieve high efficiencies in the elimination of nanoparticles. Moreover, this process present problems to the treatment of sludge.

Incineration presents lower filtering ratios. Moreover, problems arise related to the treatment of ashes and the formation of toxic pollutants. Finally, landfilling of nanowaste can produce interferences in methanogenesis. Moreover, the treatment of leachates also generates some concerns.

Despite the current lack of nano-specific treatments, several novel techniques, adapted to nanowaste fractions, are currently being developed. These techniques can be divided in three groups: liquid treatment (activated sludge, anaerobic digestion, electrocoagulation/ electrofiltration/ microfiltration/ ultrafiltration), air treatment (scrubber, electrostatic precipitation), and solid treatment (fast crystal growth, phytoremediation).

The implementation of these techniques should be taken into account in order to treat the nanowaste fractions generated by the pigment, ink and paint industry, as well as in others nanobased production processes. The efficiency of each process for each nanowaste should be taken into account.

WP7. Industrial case studies

Summary of progress towards objectives and details for each task - WP7

The tasks conducted within this WP focused on the performance of a complete technical and economic viability study of the selected unmodified and modified NPs, considering specific requirement such as functionality and process parameters such as temperature profiles, production times, process cost and scale-up viability.

These activities were complemented by a set of case studies, where the companies involved in the project studied the applicability of the modified NPs and selected RMMs. The case studies selected were:

1. Scaling up of Surface Modified ZnO (ZnO-BSA)
2. Surface mondification + water based formulation for paint applications (TiO2 and ZnO water based mixtures)
3. Silica coated QDs to be used in ink jet applications
4. New paints based on TiO2-ZnO dispersions
5. Formulation of Ag-NPs based inks

Significant Scientific and Technical Results - WP7

The main results achieved can be split as follows:

a) Cost Effective Analysis

ZnO coating procedures increase process cost between 34 and 57 %. Besides technical validation that has shown ZnO-BSA to improve risk mitigation, market acceptance has to be considered for the ZnO coated.

In case of application on ceramics tiles, the calculated increase in price is too high at this moment. Further research on cost effective raw materials for coating is required. The simple stabilization of the particles in water increases the price of particles on a much lower basis. Of course this does not change anything on the chemistry of the particles, and does not bring any benefit on a safe-by-design approach. But on a business perspective, could be just a first acceptable step through a safer material, at least from a workers perspective.

In-situ PEG coating modification of QDs were found to be the only one with the excellent performance in the printing application. The derived value of the costs-per-filling (per one cartridge) of just 57 cents is acceptable for the market.This strategy was was not only delivering perfect printing results, but also was found to be acceptable from the cost-effectiveness point of view.

Finally, RMM and PPEs resulted to be in line with standard cost, at least for laboratory activity

b) Application of safe by design approaches

- ZnO Modifications

Validatiion of ink jet applications: after the validation studies, It was observed that the use of modified NPs required adjustment of voltages to get a satisfactory jetting behavior. Afterwards right printing behavior was observed. Moreover, inks were kept one week in the printer, carrying out test prints. During that time the nozzle were observed in terms of clogging and wetting. No failure were observed neither for standard nor ink based on modified nanoparticles.

UV protection: The ZnO- BSA NPs were testes in paint formulations. Unfortunately, tested paints loose their UV filtering behavior, being a uniform filter over the UV + visible spectrum. A future step to investigate after the end of the project is to apply this modification to a different kind of ZnO nanoparticle, with a smaller diameter. Smaller nanoparticles are, indeed, more effective from a UV filtering perspective and, eventually, can maintain their UV properties, being less problematic from a toxicological point of view.

- QD Modifications

The modified QDs prepared in up-scaled procedures were used to prepare an ink for the new generation Canon Pixma iP7250 printer on the base of the Ink formulation kindly provided by Octopus GmbH (Germany). Several pages were printed using ink formulation based on the particles prepared by the in situ anchoring of PEG-thiol to the growing ZnS shell, and a correct printing behavior was observed.

- Implementation of Risk Management Measures

A set of reliable and proven strategies that can be applied by at industrial scale to adequately control the exposure and avoid the release of nanoparticles to the workplace and the environment were defined and evaluated in terms of implementation costs. On the basis the outcomes from the project, as well as the information retrieved from published guidelines on the safe handling and use of nanomaterial, the following strategies were recommended to the companies:

1. Avoid manipulating nanomaterials in a free particle state (i.e. dry nanopowders).
2. Use of good laboratory/good workplace practices, including adequate information and training for workers, use of adequate containers to storage ENMs as free dry particles or dispersed in a solution.
3. Apply and design adequate administrative controls, including proper labeling and storage, implementation of cleaning and maintenance procedures, and limitation of the duration of the tasks and/or process involving the use of ENMs.
4. Use of properly designed local exhaust ventilation (LEV) systems for conducting processes that cannot fit in a common partial enclosures suitable for handling particulate materials such as fume cupboards, containment cabinets or microbiological safety cabinets (MSCs).
5. Use of Personal protective equipment (PPE) when engineering and/or administrative controls are not feasible or effective in reducing exposures to acceptable levels. PPE to be use restricted to the specification defined with deliverable 5.3.

The respiratory protective equipment (RPE) (FFP3 class) tested within NanomICEX reduce the respiratory exposure to the NMs, with approximated cost of 7€/unit, and the safety googles reduces the contact of the NM with the ocular mucous, and an accidental transfer of the NM by touch the eyes with the contaminated glove with a 10€/unit approximated cost.

On the other hand, the RMMs tested in the project shows than single-use nitrile and latex safety gloves can eliminate the contact with the NMs, but the effectiveness of the gloves decrease with the time, then the gloves must be replaced because aren’t adequate for work all the day. The single-use gloves cost less than 20 cents/unit.

The use of LEV systems were also recommended in all the case studies. The cost of a capturing hood range from € 5,000 to €30,000 and increases depending on the flow rate, filtering, size, materials and other factors. Moreover, the capturing hood needs an extraction system connected to a ventilation system, which implies new added costs.

In terms of process safety, due to some EHS concerns, appropriate occupational health and safety mechanisms should be in place in order to prevent exposure. According with the results of the project, the use of adequate risk management measures (RMMs) reduces the level of exposure in the workplace, ensuring a low level of respirable and inhalable fractions of particulate matter without a representative increase of the cost.

Finally,several dissemination activities were conducted to present the project activities to the target audience, including regulatory bodies, industry and academia. Dissemination activities were performed through various instruments and media, including press releases, newsletters, brochures, conferences and workshops and Academic-level papers published in renowned scientific journals.

The most relevant dissemination events where the activities of the project and main results were presented are listed below:

• Safety issues and regulatory challenges of nanomaterials.Join Workshop. May 2012. San Sebastian (Spain)
• Safe Implementation of Nanotechnologies: Common Challenges. May 2012. Grenoble (France)
• Health and Environmental Impact of nano-enabled Products along the Life Cycle. Join Workshop. May 2013. Barcelona (Spain)
• Nanotechnology and the Coatings Industry. October 203. Nottingham (Uk)
• 10th Nanoscience and Nanotechnology Conference (Nano TR-10). June 2014. Istambul (Turkey)
• Industrial Technologies 2014, held from 9-11 April 2014 in Athens (Greece)
• 7th International Nanotoxicology Congress (NanoTox 2014), held from 23-26 April 2014 in Antalya (Turkey)
• Aerosol Technology 2014, held from 16-18 June 2014 in Karlsruhe (Germany)
• Nanosafe 2014, held from 18-20 November 2014 in Grenoble (France)

Overall Conclusions

The project activities have been conducted on the basis of the tasks described in the document of work. Relevant activities have been conducted since the beginning of the project, especially those related with the selection of surface modifiers able to reduce the toxicity of the pristine NPs.

The results of the project show how the toxicity can be reduced, however the properties of the ENPs can be also modified, being necessary validation studies in coordination with the industrial partners to avoid changes in the properties and functions of the ink and paint formulations.

Similarly, it was demonstrated that the use of proper designed risk management measures (RMM) allows the reduction of the levels of exposure in the workplace, being of special interest the selection of adequate measures to reduce the exposure via the inhalatory route.

The combination of both surface modification and properly designed risk controls reduced the risk characterization ratios, promoting a safe working environment and reducing the impact of the NPs in the human health and the environment.

The results of the project will be further disseminated and published in relevant events, being expected a strong impact in the promotion of the safety use of nanoparticles and nanoproducts in the workplace.

Potential Impact:
1. Analysis of the Impact of the project

a) Overall considerations

Regarding the impact of the project, it should be noted that the NanoMICEX project tries to overcome the current barriers to use ENPs at industrial level, improving the current knowledge on the potential exposure across the nanoparticles life cycle and defining proven measures to control and manage the risks.

In terms of Worker`s safety, the research activities within the NanoMICEX project provide quantitative information on the levels of exposure, appropriate measures to control the exposure to engineered nanoparticles and therefore to minimize the risk, as well as easy to use procedures to mitigate the risk at source by means of safe by design approaches.

Aditionally, in terms of environmental safety, the implementation of new and tested risk management measures will improve the effectiveness of the spill control system and the minimization of nanoparticles released to the environment during the manufacturing process.

Finally, in socio-economic terms, the safety improvement of the production process and the development of safe and eco-friendly nano-enabled products will improve the business opportunities of the EU industry, as well as open new business opportunities to SMEs involved in the use of ENPs. New nanostructures-based products will offer good opportunities due to their enhanced environmental acceptability and superior performance traits.

Similarly, a further acquisition of knowledge on hazard profile, exposure potential and on protection measures will promote the sustainable growth of the printing ink, paint and pigment industry, being able to generate new jobs that directly or indirectly will support the further development of the local and regional economies.

Moreover, improved worker and consumer safety have obvious economic benefits for the EU with respect to healthcare provision.

A more detailed analysis of the impact on EU policies and the environment is detailed below:

b) Impact on the Industry

The project have a strong impact on the industry to the extent that promotes the use of nanoparticles to develop new added value products in the pigment and ink industry. The possibilities for application of nanosized particles in these sectors are rapidly increasing on the basis of the current societal needs and market trends. Nevertheless, there are number of issues that warrant concern about the mass commercialization of nanopigments and nano-formulated inks and paints, considering mainly technical and safety concerns.

The industrial sector targeted by the project represents a large number of SME and large companies, being driven by innovation, which allows manufacturers to develop new and innovative products for hundreds of industrial applications and billions of people who use them every day. Recent reports from representative European Associations such as the European council of producers and importers of paints, printing inks and artists’ coloursor (CEPE) or the European Printing Inks Association EuPIA show the importance of the pigment and ink industry for the European economy.In terms of market share, the global market for pigments is forecast to reach 9.9 million tons and 26.53 US billion dollars by the year 2017, driven by the growth in key end-use industries. Additionally, demand in the market would stem from stringent and increasingly rigorous quality, performance and environmental standards. Increasing consumer preference for environment-friendly products, which in turn would drive the consumption of higher performance pigments such as nanopigments, is expected. Similarly, the ink industry represents a large market that will generate 2.2 US billion dollars in 2015.

Printing ink sales in Europe amounted to about 1 million tons with a value of around €3 billion in 2012. In relation to the European ink and pigment industry structure, there are more than forty large enterprises, including market leaders as DuPont, BASF, Clariant, Degussa or Merk, which are allocating more than a 10 percent of its R&D budget to nanotechnology, with roughly 23.000 staff and sales of 8.1 billion Euros. Zno NPs will be directly applicable in paint formulations, especially by Monto Paints, a Spanish paints manufacturer. Regarding the market, only in Spain the paint industry reached sales of €1.280 millon Euros, with roughly 10.300 staff and 427 companies.

In view of such data, both applications paints and inks represent more than 30.000 staff than can benefit from the reduction of the toxicity of the nanoparticles. In addition, the sales values show a high impact in the population, end –user of paints and inks

Ink and Paint and industries are seeking for more and more performing products, mainly for world wide market applications (automotive and construction field, for example), able to solve typical problems for surface finishing (corrosion and scratch). At the moment, much of the research and development work in the pigment and ink industry is concentrated on the development of innovative products, considering new properties that improve the final application, while at the same time ensuring the safety at all stages of products manufacturing, use and disposal. Overall market value will benefit from important consumer preferences toward safe and environmentally friendly products, which will support consumption of high-performance inks and pigments.

The activities of the project are aligned with the current barriers that limit the use of nanoparticles at industrial levels, including safety issues, scaling up and applicability. Similarly, the results of teh project are directly exploitable by the industry, including new reliable data on the physical and chemical, toxicological and ecotoxicological properties of relevant nanoparticles, new approaches to reduce the toxicity at source, as well as a set of adequate measures to reduce the exposure to nanoparticles in occupational settings.

The main impacts to be noted are described below:

1. Access to reliable information on the properties of relevant nanoparticles: the data have been obtained with high sensitive instrumentation, providing a great level of detail and information concerning size distribution, surface area, shape, surface chemistry, as well as relevant information on key (eco)toxicological endpoints for risk assessment. The information on the physicochemical and (eco)toxicological properties of the target NPs generated within the project comply the information requirements to be provided upon registration of nanomaterials according with regulation (EC) 1907/2006 REACH. Moreover, the data can be used under the framework of REGULATION (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

2. Surface modifiers"safe by design approaches": the surface modifiers designed within the project are highly innovative to the extent that they were developed to reduce the toxicity of both pristine nanoparticles and nano-formulation. Moreover, these modifiers were performed to be used to achieve a functional product on the market and at the same time reduce the toxicity and exposure potential (= no risk). Placing on the market products designed to be safe is great competitive advantage. For one side, these products are not toxic, therefore, can be used for consumer applications. On the other hand, the surface modifiers have been validated within the project, therefore, can be used to formulate products without incompatibilities.

The surface modifiers can be applied in different markets, including the market of the target nanoparticles, as well as the specific markets of the industrial applications addressed in the project.

3. Scaling up of surface modifications: there are no protocols in the market intended to reduce toxicity. As in the previous result, the capacity of a company to place on the market products designed to be safe is a great competitive advantage. For one side, these products are not toxic, therefore, can be used for consumer applications. On the other side are product oriented, thus, can be used to formulate products without incompatibilities.

The scaling up of the protocols will enable to produce new and safer nanomaterials. The market share is directly related with the markets where the industrial members of the consortium are currently present, including nano-pigments (Torrecid), Ag / QDs based formulations (Plasmachem), paints (Montó) and nano-additives in plastic/inks applications.

4. New specifications to improve the efficacy of respiratory protective equipment and filtration systems against NPs: one of the most relevant results of the project is the introduction of several improvements in the design of half mask respirators and filtration systems with the goal of increase the capacity of these devices to retain the NPs.There are not tailored designed products in the market for NMs, therefore, the design of new respirators can be considered innovative.

In 2007, the EU Personal Protective Equipment market was estimated to be approximately €5.9 billion (at end-user prices) compared with a global market of €19.2 billion. The EU holds approximately 30 percent of the global market. The market trend in this area is the need of protect workers from any potential risk related to the exposure to hazardous chemicals. The designs and specifications defined and described in the project are intended to ensure a high degree of protection against emerging risk (nanotechnology), supporting the market acceptance.

Moreover, the improvement in the safety of the production process and the development of safe and eco-friendly nanopigments, and nano-enabled products will improve the business opportunities of the European pigment, ink and paint industry, promoting the opening of new business lines based on the use of nanoparticle and/or the commercialization of nano-enabled products.

The project promotes the investment in new nanostructured products, being expected to dominate the market and remain widely employed in large-volume markets. In addition, the project provides valuable information to limit the cost related with the use of nanoparticles and the production of nanotechnology based products. Furthermore, improved worker and consumer safety have obvious economic benefits for the EU with respect to healthcare provision.

On the other hand, the improvement in the safety of the production process and the fulfilment of a key European regulation such as the regulation on Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) will improve the business opportunities of those SMEs affected by REACH provisions, with special emphasis in those that handle or manufacture substances at the nanometre scale, as is the case of nanocomposites manufacturers. In fact, The EC recognizes that compliance with Health & Safety directives will play a key role in promoting economic growth and employment in the EU but also realizes that the costs of compliance for SMEs are high, then, the definition of effective protection and prevention measures will minimize the costs to control the risks during the production process, supporting at the same time the economic growth of the SME and their competitiveness.

It shall be noticed that the cost of REACH implementation could reach up to €3.2 billion to the chemicals industry and €2.8–3.6 billion to downstream users. In this sense, NanoSafePack will support the European industry to reduce cost derived from the investment on low-efficiency engineering techniques, and saving money due to the reduction in the insurance premium.

Moreover, improved worker and consumer safety have obvious economic benefits for the EU with respect to healthcare provision. In this sense, several studies describe business benefits in terms of savings related to occupational health due to the proven efficiency of the control measures for protecting workers from the risks related to chemical agents.

c) Social impact

Beyond the toxicity risks to human health and the environment which are associated with first generation nanomaterials, nanotechnology has broader societal implications and poses broader social challenges. In this sense, NanoMICEX tries to meet social objectives in term of nanotechnology application, principally in terms of safety and health related to the use and commercialization of nanotechnology based products.

The contribution of the project to the safety of the workers and nanocomposites placed on the market will improve the approbation of this kind of products into the society as well as a better image of the new technologies, ensuring the commercialization in the near future. The expected benefits in terms of product quality, safety and environmental respect, will be key issues to accept the changes towards the new nanostructured products, which will be better accepted by the consumers.

Simultaneously, the participation of enterprises in the project implementation and the direct application by the members of the SME associations will help in the dissemination of the project results, providing the industrial stakeholders and the general public with appropriate knowledge to successfully control the risks posed by the use of nanomaterials, as well as with new information to perform a complete risk assessment on the basis of REACH regulation.

d) Impact on EU policies

The project explored legal and policy issues, as well as scientific and technical issues, that might arise in the application of the regulatory process related to the use of NMs at the workplace. At this stage, the project results provide a better understanding of the risk to the human health and the environment of ENPs, supporting regulatory bodies with scientific data to establish new legal requirements to the use of NMs in the pigment, inks and paint industry in particular and other nanotechnology fields in general.

The project is aligned with the considerations expressed by the European Parliament resolution of 24 April 2009 on regulatory aspects of NMs, which explains that the use of NMs should respond to the real needs of citizens and that their benefits should be realized in a safe and responsible manner,considering the potential EHS problems.

Research activities are ongoing under the Research Framework Programmes and the Joint Research Centre, as well as in EU Member States and internationally within the OECD Working Party on MNMsand the International Organization for Standardisation. According to the Europe 2020 strategy, one of the strategic goals will be ensuring the safe development and application of nanotechnologies by advancing scientific knowledge of the potential impact of nanotechnologies on health or on the environment, and providing tools for risk assessment and management along the entire life cycle.

In this sense, the future needs may include identifying and demonstrating the effectiveness of containment technologies for safe handling of NPs through the life cycle, investigating the effectiveness of different work practices for human and environmental exposure mitigation, and strengthening current research on the toxicological and ecotoxicological profile of nanofillers already applied at industrial level.

The project is in line with the research areas underpinning risk assessments and management in which new knowledge is more needed, bringing value to the European development of risk management knowledge by the identification of proven measures and controls to reduce exposure to NMs during its entire life cycle.

The project have also a strong impact onthe International Standardization since it works on the development of methods for testing RMM against NMs by evaluating the adequacy of the published harmonized Standards from ISO, CEN, BSI and ASTM, and adapting them to the specific NM properties. In addition, the development of the project has generated new reliable information to be implemented in the current European legislation, considering different stages of the NMs life cycle.

e) Impact on environmental protection

In relation to the environmental impact, the project will promote the development of environmentally benign nanoprodcuts. The implementation of efficient procedures to control the exposure and the choice of more efficient techniques will improve the environmental safety, minimizing the release to the environment of nanoparticles with potential ecotoxic effects. In fact, the implementation of new and tested risk management measures improves the effectiveness of the spill control system and the minimization of the release of nanofillers to the environment during the manufacturing process.

Simultaneously, the selection of effcientie risk management measures ensure a high level of protection to the environment, and provides new knowledge to the development of new Best Available Techniques (BATs) to prevent pollution, considering both the manufacturing plants of engineered nanoparticles and the industrial settings where the nanoparticles, to be included into the polymeric matrix, are processed.

Beside the above, the outcomes from the release has provided a better understanding of the fate of the nanoparticles in their service life, generating nee reliable data on the potential release of nanoparticles during the their use and disposal.

Finally, the application of a life cycle assessment approach has been essential for the improvement of the current knowledge about resource and energy consumption, emissions and their impact, providing a useful insight about bare NPs, nanopigments, inks and paints, as well as a proxy for the toxicological and ecotoxicological impact due to the emissions.

In summary, the implementation of the recommendations, procedures and technologies developed within the project, the industry will be able to comply with the current regulation in terms of environmental protection, product and worker safety, manufacturing innovative and sustainable composites materials without endanger the human health and the environment and becoming cost competitive with the present and growing threat posed by the Far East.

2. Dissemiantion activities and foreground generated

a) Dissemination

The dissemination activities were performed through various instruments and media. These have been carefully selected for facilitating collaboration among involved parties. The first activity completed was the design and selection of the project logo. The project web site was published last may 2012, being accessible via the internet site

Regarding the main dissemination materials, classical print media (brochure and poster) have been produced to be freely circulated for project information and promotion at workshops, trade shows, technical fairs, congresses and other events. The electronic version of these materials is downloadable from the website. Several press releases were published by the consortium members with the aim of communicate the goal and scope of the project.

Finally, the project results and contents have been disseminated in several international conferences.

In detail, the dissemination activities conducted have been the following:

i) Presence at trade shows and conferences across Europe, including;

• 2nd QNano Integrating Conference
• Clinam 2014
• Euronanoforum 2013
• Health and Environmental Impact of nano-enabled Products along the Life Cycle
• Nanosafe 2014
• Nanotechnology and the Coatings Industry
• Nanotoxicology 2014
• NanoTR9
• NanoTR10
• Pittcon 2013
• Safe Implementation of Nanotechnologies: Common Challenges
• Safety Issues and Regulatory Challenges of Nanomaterials
• SETAC Europe 2013
• SETAC Europe 2014
• SETAC North America 2013
• IOHA 2015
• NanoSpain 2015
• ImagineNano 2015
• SUN-SNO-GUIDENANO Sustainable Nanotechnology Conference 2015
• Pittcon 2015

ii) Trainning webinars

Three training webinars were held in February and March 2015. The webinars were advertised through the newsletter and through the standardisation committees CEN/TC352 and ISO/TC229. Registrants to the webinar series were from the academia, the standardisation community and from industry.

- The NanoMICEX Webinar on Surface Modification was held on 27 February 2015. The results of were presented by Mustafa Culha from Yeditepe University. 15 people registered to this webinar.

- The NanoMICEX Webinar on Personal Protective Equipment was held on 24 March 2015. Results were presented by Carlos Fito from ITENE. 12 people registered to this webinar.

- The NanoMICEX Webinar on Exposure Assessment was held on 27 March 2015, Sally Spankie and Andrew Apsley from IOM presented the results of WP4. 15 people registered to this webinar.

iii) Workshops

On 11 March 2015, a joint workshop was organised to highlight the results achieved in the two long-term FP7 projects MARINA and nanoMICEX with a view to pooling their results in the SUN project. This event was held in coordination with VenetoNanotech and was organised just before the NanoSafetyCluster’s ‘4th EU-US workshop’.

On 15 April 2015, a join workshop was organized in cooperation with the FP7 projects Sanowork and Scaffold. This event was was organised during the second “International Congress on Safety of Engineered Nanoparticles and Nanotechnologies” held by the Finnish Institute of Occupational Health in Helsinki.

iv) Scientific papers

The findings of the project have been published as scientific papers. Partners have written and submitted their work in this format to scientific peer reviewed journals. The list of articles published are listed below:

1. Influence of surface properties of zinc oxide nanoparticles on their cytotoxicity.Mine Altunbek, Aslı Baysal, Mustafa Culha. 2014. Colloids and Surfaces B: Biointerfaces.

2. Effect of 10 different TiO2 and ZrO2 (nano)materials on the soil invertebrate Enchytraeus crypticus. Susana IL Gomes, Gianvito Caputo, Nicola Pinna, Janeck J Scott-Fordsmand, Mónica JB Amorim. 2014. Journal of Nanoparticle Research

3.Safety by Design Approach to Reduce the Cytotoxicity of Silver Nanoparticles. Seda Keleştemur, Mine Altunbek, Manolya Hatipoğlu, Mustafa Culha. 2014. Journal of Nanoparticle Research

4. Protein Coating Reduces The Cytotoxicity of ZnO Nanoparticles Seda Keleştemur, Mine Altunbek, Gianvito Caputo, Nicola Pinna, Mustafa Culha. 2014. In press

5. Nanoparticle Release in Indoor Workplaces: Emission Sources, Release Determinants, and Release Categories Based on Workplace Measurements. Fito-López, Carlos, Domat-Rodriguez, Maida, Van Tongeren, M2, Sally Spankie. 2015. In press

v) Networking

The networking activities conducted within the project mainly related with the establishment of direct contacts with projects working in areas related to some of the NanoMICEX fields of work. To this end, two main strategies are in place:

a) Participation of the EU NanoSafety cluster, being one of the 5 relevant projects working in the safe use of NMs by industry. The participation of the project coordinator in this forum is especially important for establishing synergies with other projects and in the avoidance of the duplicity of efforts, as well as in characterizing the possibilities of cooperation with other project in order to share information.

b) Cooperation with EU-US Communities of Research (CoRs), a recently created platform for scientists working in NanoSafety to develop a shared repertoire of resources and to enhance their professional relationships. As the previous case, the participation of the project coordinator in this forum is especially relevant to improve the quality of the work conducted, avoid duplicity of efforts and support the dissemination at international level.

Apart from the above, the project coordinator is aware of the activities conducted under the framework of relevant projects in the field of work of the project, especially NanoREG, GuideNano, MARINA and SUN, two projects where relevant activities on risk assessment and management are being conducted.

Relevant Contacts:

Coordinator: Carlos Fito López
Packaging,Transport and logistics research center
Albert Einstein, 1 CP.46.980 Paterna (Valencia) – Spain

Dissemination Leader: Guillaume Flament
Nanotechnology Industries Association
101 Avenue Louise. 1050 Brussels (Belgium)