NanoMaterials & Responsible Development

NanoMaterials & ResponsibleDevelopment How to conciliateResearch, Innovation and Safety E. Gaffet NanoMaterialsResearch Group Eric.Gaffet@utbm.fr EuropeanAcademy of Sciences Member President of ScientificCommittee « NanoSciences & Nanotechnologies » / ANR Member High Council for Public Health (France) Member SCENIHR –Nanodefinitions (Europe) President of OECD / WPMN - Physico – Chem. NanoCharact. Comm. Practice President of Expert Groups for ANSES (France) (2006, 2008’s Expertise Report) French Representative for RIP – oN1 (REACH) ICSU - CODATA Workshop - Description of Nanomaterials Paris - 23-24 February 2012

to address the following topics: • Does your organization have any standards or guidelines (formal or informal) for nanomaterials description, either under development or already developed? If so, what are they and what aspects of nanomaterials are addressed? • What aspects of the description of nanomaterials are most important from your perspective? • Why? • From your perspective, which properties are most important for characterizing a nanomaterial? Or stated differently, which properties must be reported to characterize a nanomaterial for applications or use within your discipline? • Why? Eric.Gaffet@utbm.fr NanoMatériaux & Développement Responsable Concilier Recherche, Innovation, Sécurité Sanitaire

RiskPrevention in CNRS Labs (Internal Note) 28 Feb 2007 Risk Prevention for Unit working with nanomaterials CNRS Dpts Chemistry, Physic, Engineering And Secretariat Général

Several nm < At least one dimension < Several 100 nm Free or not Embedded or not Working (polishing,…) Emission parameter Massive materials < Suspensions in liquid < Dry free nanoparticules

to address the following topics: • Does your organization have any standards or guidelines (formal or informal) for nanomaterials description, either under development or already developed? If so, what are they and what aspects of nanomaterials are addressed? • What aspects of the description of nanomaterials are most important from your perspective? • Why? • From your perspective, which properties are most important for characterizing a nanomaterial? Or stated differently, which properties must be reported to characterize a nanomaterial for applications or use within your discipline? • Why? Eric.Gaffet@utbm.fr NanoMatériaux & Développement Responsable Concilier Recherche, Innovation, Sécurité Sanitaire

TiO2 nClay ZnO TiO2 Yet on the Market nClay • 1.317 NanoProduits (Woodrow Wilson Institute – updated in March 2011) • 9,509 products (Cosmetic (Environmental Working Group – 2006) • 526Produits Nano- Argent (http://www.ec21.com/ec-market/nano_silver.html) • 2.707 NanoParticules / 169 Suppliers (w3.nanowerk.com – updated Sept. 2011) • 150 Milliards $ en 2007 (Emballages alimentaires 4 Milliards $ en 2008) Ag nTC nClay nClay nClay TiO2 TiO2 nTC Ag nTC Eric.Gaffet@utbm.fr

Examples of nano-silver products available online or within Australia (FOE - Sept. 2011) Soap, Baby bottle, Baby toothbrush, Ladies Cycling Jersey, Cleaning cloth, Socks, Shoes, Sports jacket Food storage container, Food storage container, Bed mattress, Refrigerator, Vacuum cleaner, Epilator , Hair brush, Hair straightener, Pool cleaner, Paints and surface coatings, Industrial disinfectant for Hong Kong trains and subway, Agricultural fungicide, Aquaculture disinfectant Nano Silver NanoProducts Inventory FOE– Australian Market (Sept 2011) « One » Chemical (Silver) nanoparticle : Various uses and various lifecycle exposures http://nano.foe.org.au/sites/default/files/Nano-silver%20-%20Policy%20failure%20puts%20public%20health%20at%20risk%203.77MB.pdf Eric.Gaffet@utbm.fr

Laponite (Rockwood Company) 0.92 nm One Particle : Multiple uses on market 25 nm Eric.Gaffet@utbm.fr http://www.laponite.com

Applications de la Laponite (source : Rockwood) One Particle : Multiple uses on market Surface Coatings House Products HealthCare Papers Films Polymers Building Agriculture General Industry Eric.Gaffet@utbm.fr http://www.laponite.com

to address the following topics: • 1. Does your organization have any standards or guidelines (formal or informal) for nanomaterials description, either under development or already developed? If so, what are they and what aspects of nanomaterials are addressed? • 2. What aspects of the description of nanomaterials are most important from your perspective? Why? • From your perspective, which properties are most important for characterizing a nanomaterial? Or stated differently, which properties must be reported to characterize a nanomaterial for applications or use within your discipline? • Why? Eric.Gaffet@utbm.fr NanoMatériaux & Développement Responsable Concilier Recherche, Innovation, Sécurité Sanitaire

Unstabilised Knowledge !! Nano Toxicity ≠ Micro Toxicity Specific Toxicity of THE nanoparticle (protocole also !) Trojan Horse « Key – Lock (clé – Serrure) » Source : Future TechonologiesDivison of VDI TechnologiezentrumGmbH

Medical surveillance, exposureregistries, and epidemiologic research for workers exposed to nanomaterials There is a growing and coalescing level of evidence that exposure to some nanomaterials can cause adverse effects on health. The increasing evidence comes from various sources, for example, animal and human studies of ultrafine aerosols, air pollution, and manmade mineral fibers, as well as from an increasing number of animal studies with engineered nanoparticles providing mechanistic information and demonstrating end effects. This evidence has been reviewed by numerous organizations that have concluded that there is enough preliminary information to treat engineered nanoparticles “as if” they are hazardous (ASCC 2006-IRSST 2006-AFSSET 2006-DOE 2007-BSI 2007-AFSSET 2008,-HCSP 2009-NIOSH 2009) Clearly, prudent controls should be implemented and more research is needed but at present, there also is sufficient evidence and concern to consider whether there is need for occupational health surveillance of nanomaterials workers and whether formation of exposure registries and conduct of epidemiologic research is appropriate To treat engineered nanoparticles“as if” they are hazardous Risk Control = Exposition Control Nano : à considérercommepotentiellement (!!) Dangereux «Case by Case» Study Etude au «cas par cas» Douglas B. Trout, Paul A. Schulte (NIOSH – CDCP) Toxicology (2008), doi:10.1016/j.tox.2009.12.006

http://nanotrust.ac.at/nano08/slides_kearns.pdf

Nanomaterial Information/Identification (9) • Nanomaterial name (from list) • CAS Number • Structural formula/molecular structure • Composition of nanomaterial being tested (including degree of purity, known impurities or additives) • Basic morphology • Description of surface chemistry (e.g., coating or modification) • Major commercial uses • Known catalytic activity • Method of production (e.g., precipitation, gas phase) Endpoints (OCDE) 1/2 ENV/JM/MONO(2008)13/REV (Jul 2008) Physical-Chemical Properties and Material Characterization (16+) • Agglomeration/aggregation • Water solubility • Crystalline phase • Dustiness • Crystallite size • Representative TEM picture(s) • Particle size distribution • Specific surface area • Zeta potential (surface charge) • Surface chemistry (where appropriate) • Photocatalytic activity • Pour density • Porosity • Octanol-water partition coefficient, where relevant • Redox potential • Radical formation potential • Other relevant information (where available) http://www.olis.oecd.org/olis/2008doc.nsf/LinkTo/NT000034C6/$FILE/JT03248749.PDF

Environmental Fate (15+) • Dispersion stability in water • Biotic degradability • Ready biodegradability • Simulation testing on ultimate degradation in surface water • Soil simulation testing • Sediment simulation testing • Sewage treatment simulation testing • Identification of degradation product(s) • Further testing of degradation product(s) as required • Abiotic degradability and fate • Hydrolysis, for surface modified nanomaterials • Adsorption- desorption • Adsorption to soil or sediment • Bioaccumulation potential • Other relevant information (when available) Endpoints (OCDE) 2/2 ENV/JM/MONO(2008)13/REV (Jul 2008) Environmental Toxicology (5+) • Effects on pelagic species (short term/long term) • Effects on sediment species (short term/long term) • Effects on soil species (short term/long term) • Effects on terrestrial species • Effects on microorganisms • Other relevant information (when available) Mammalian Toxicology (8+) • Pharmacokinetics (ADME) • Acute toxicity • Repeated dose toxicity If available: • Chronic toxicity • Reproductive toxicity • Developmental toxicity • Genetic toxicity • Experience with human exposure • Other relevant test data Material Safety (3) Where available: • Flammability • Explosivity • Incompatibility http://www.olis.oecd.org/olis/2008doc.nsf/LinkTo/NT000034C6/$FILE/JT03248749.PDF

8 Parameters (ISO) i) Agglomeration State/Aggregation ii) Composition iii) Particle Size/Distribution iv) Shape (includinglength to diameter ratio for nanfibers and naotubes) v) Solubility /Dispersibility vi) Surface Area vii) Surface Chemistry viii) Surface Charge Density ISO / Nanotechnologies — Guidance on physico-chemical characterization for the detailed identification of manufactured nanomaterials subjected to toxicological testing - ISO/PDTR 13014 Source : Future TechonologiesDivison of VDI TechnologiezentrumGmbH

NO APPROVED UNIVERSAL CHARACTERIZATION METHODS Club NanoMétrologie (LNE – C’ Nano) W de Jong (2010)

8 Parameters (ISO) i) Agglomeration State/Aggregation ii) Composition iii) Particle Size/Distribution iv) Shape (includinglength to diameter ratio for nanofibers and naotubes) v) Solubility /Dispersibility vi) Surface Area vii) Surface Chemistry viii) Surface Charge Density Eric.Gaffet@utbm.fr NanoMatériaux & Développement Responsable Concilier Recherche, Innovation, Sécurité Sanitaire

Size Distribution Nanometer Scale Dimension nanométrique Ø = 10 nanomètre 1016 particules (10 Quadrillions ou 10 Millions de Milliards) Distribution de taille ? i) En nombre de particules Ou ii) Répartition en masse Quel Seuil ?? (0.1% , 10% ?) Eric.Gaffet@utbm.fr http://www.spiegel.de/international/germany/bild-656482-25501.htmlt

Agglomerate size Aerosol distribution duringlifecycle ? O. Witschger, JF Fabries – HST ND 2227, 199 - 05

NanoparticleStability(Aggregate Size – Fct (pH)) Les propriétés de surface et la composition de l’eau conditionnent la coagulation Détermination de la taille d’agrégats de ZnO par DLS (Dynamic Light Scattering, Malvern NanoZS) en fonction du pH (suspension à 10 mg/l de ZnO). Malgré la sous-saturation des solutions vis-à-vis de la Zincite, des particules sont présentes dans la solution. Leur taille décroît avec l’augmentation du pH entre 7 et 9, c’est-à-dire en s’éloignant du pHZPC (diminution des forces répulsives avec l’éloignement du pHZPC). Les tailles plus faibles sont observées à pH inférieur à 7, probablement liées à la plus grande solubilité de ZnO à ce pH. http://www.rmnt.org/com/J3N2008/posters/ANR%2007-NANO-035.pdf

NanoparticleStability(Aggregate Size & Zeta Potential - Fct (pH)) Les propriétés de surface et la composition de l’eau conditionnent la coagulation Evolution de la taille et du potentiel zêta des nanoparticules de cérium CeO2, de taille différente (suspension à 20 mg/l de CeO2). A pH acide, les nanoparticules sont présentes sous forme d’agrégats de petite taille constitués de quelques particules, pour des potentiels zêta très positifs. La taille moyenne croît soudainement à pH = 6,8 = pH ZPC (détermination par titrage), au moment ou le potentiel zêta est nul. La taille des nanoparticules est au-dessus de la limite de détection (supérieure à 1 μm de pH 7 à pH 10) pour des potentiel zêta décroissants et négatifs. http://www.rmnt.org/com/J3N2008/posters/ANR%2007-NANO-035.pdf

NanoparticleStability(Aggregate Size & Zeta Potential - Fct (pH))Les propriétés de surface et la composition de l’eau conditionnent la coagulation Détermination du point de charge nulle des nanoparticules de titane TiO2, (taille élémentaire 32 nm). Le comportement est similaire à celui des nanoparticules de cérium. La taille des nanoparticules augmente très légèrement jusqu’au passage du potentiel zêta à 0, à pH proche de 6,4. A pH alcalin, la taille des agrégats décroît avec un potentiel zêta très négatif. AquaNano http://www.rmnt.org/com/J3N2008/posters/ANR%2007-NANO-035.pdf

Researchers Pinpoint Neural Nanoblockers in Carbon Nanotubes (1/2) A team of Brown University scientists has pinpointed why carbon nanotubes tend to block a critical signaling pathway in neurons. It’s not the tubes, the team finds, but the metal catalysts used to form the tubes. The discovery means carbon nanotubes without metal catalysts may be useful in treating human neurological disorders. Results appear in Biomaterials. PROVIDENCE, R.I. [Brown University] — Carbon nanotubes hold many exciting possibilities, some of them in the realm of the human nervous system. Recent research has shown that carbon nanotubes may help regrow nerve tissue or ferry drugs used to repair damaged neurons associated with disorders such as epilepsy, Parkinson’s disease and perhaps even paralysis. Yet some studies have shown that carbon nanotubes appear to interfere with a critical signaling transaction in neurons, throwing doubt on the tubes’ value in treating neurological disorders. No one knew why the tubes were causing a problem. Now a team of Brown University researchers has found that it’s not the tubes that are to blame. Writing in the journal Biomaterials, the scientists report that the metal catalysts used to form the tubes are the culprits, and that minute amounts of one metal — yttrium — could impede neuronal activity. The findings mean that carbon nanotubes without metal catalysts may be able to treat human neurological disorders, although other possible biological effects still need to be studied. Lorin Jakubek “It’s a problem we can fix.” “We can purify the nanotubes by removing the metals,” said Lorin Jakubek, a Ph.D. candidate in biomedical engineering and lead author of the paper, “so, it's a problem we can fix.” Yttrium in trace amounts — less than 1 microgram per milliliter of water — may disrupt normal calcium signaling in neurons and other electrically active cells, Neural Nanoblocker Metal catalysts — nickel and particularly yttrium — used to create carbon nanotubes can block a key signalling pathway in neurons. Experiments show the metal particles tend to plug cellular pores normally reserved for calcium ions http://news.brown.edu/pressreleases/2009/08/nanoblockers

8 Parameters (ISO) i) Agglomeration State/Aggregation ii) Composition iii) Particle Size/Distribution iv) Shape (includinglength to diameter ratio for nanofibers and nanotubes) v) Solubility /Dispersibility vi) Surface Area vii) Surface Chemistry viii) Surface Charge Density Eric.Gaffet@utbm.fr NanoMatériaux & Développement Responsable Concilier Recherche, Innovation, Sécurité Sanitaire

Shape dependance on Synthesis Processes (and life cycle) K. Yu,Tet al. Materials Letters 59 (2005) 1866– 1870 Eric.Gaffet@utbm.fr F.Z. Wang et al. / Materials Letters 59 (2005) 560–563

Researchers Find Controls to Gold Nanocatalysis ▲ Au ▼ ▲ Au ▼ Yellow – Gold Green – Mg Red – O Blue - Mo ▲ ↑MgO ▼ ▲ MgO ↓ ▼ ▲ Mo ▼ ▲ Mo ▼ A cluster of 20 gold atoms on a thick magnesium-oxide bed shows charge accumulation (pink), but little charge depletion (light blue) so the cluster retains its shape. A cluster of 20 gold atoms on a thin magnesium-oxide bed shows a good amount of charge accumulation (pink) and depletion (light blue). The attraction causes the cluster to collapse. Shape Physico ChemicalStability DuringProductlifecycle ? In this study, Landman and company simulated the behavior of gold nanoclusters containing eight, sixteen and twenty atoms when placed on catalytic beds of magnesium oxide with a molybdenum substrate supporting the magnesium oxide film. Quantum mechanical calculations showed that when the magnesium oxide film was greater than 5 layers or 1 nm in thickness, the gold cluster kept its three-dimensional structure. However, when the film was less than 1nm, the cluster changed its structure and lied flat on the magnesia bed –wetting and adhering to it. July 21, 2006 issue of the journal Physical Review Letters.

NanoparticleStability(Solubility - Fct (pH)) Les propriétés de surface et la composition de l’eau conditionnent la coagulation Solubilité des nanoparticules Dans la gamme de pH communément rencontrée dans les eaux souterraines, les nanoparticules de ZnO sont très solubles. La solubilité des nanoparticules de CeO2 est plus faible et dépend des conditions redox. Exemples de solubilité de Nanoparticules dans les eaux souterraines Composition chimique d’eaux d’aquifère - de socle en présence de pyrite (faibles pH et pe); - karstique correspondant à une ré-émergence de la Loire (conditions pH and redox plus élevées ) À l’équilibre avec des nanoparticules de ZnO et CeO2 http://www.rmnt.org/com/J3N2008/posters/ANR%2007-NANO-035.pdf

Hydration and Dispersion of C60 in Aqueous Systems: The Nature of Water-Fullerene Interactions Surface Chemistry / Zeta Potential Hydrophobic → Hydrophilic character after exposure to water The nature of fullerene-water interactions and the role that they play in the fate of C60 in aqueous systems is poorly understood. This work provides spectroscopic evidence for the surface hydroxylation of the initially hydrophobic C60 molecule when immersed in water. This mechanism appears to be the basis for stabilizing the hydrophilic nC60 aggregates in suspension. It is remarkable that such a chemical transformation and dispersion are achieved under mild conditions that are readily produced in an aquatic environment. This acquired affinity for water is likely to play asubsequent role in the reactivity, mobility, and bioavailability of fullerenes in aqueous media Fourier transformed infrared spectroscopy (FTIR) and 1H solid state nuclear magnetic resonance (NMR) Jerome Labille,Armand Masion,Fabio Ziarelli, Jerome Rose,Jonathan Brant,Frederic Villieras, Manuel Pelletier, Daniel Borschneck,Mark R. Wiesner, and Jean-Yves Bottero – Langmuir Letter - DOI: 10.1021/la9022807

+ Crystallographic Structure Evolution 8 Parameters (ISO) i) Agglomeration State/Aggregation ii) Composition iii) Particle Size/Distribution iv) Shape (includinglength to diameter ratio for nanofibers and naotubes) v) Solubility /Dispersibility vi) Surface Area vii) Surface Chemistry viii) Surface Charge Density Eric.Gaffet@utbm.fr NanoMatériaux & Développement Responsable Concilier Recherche, Innovation, Sécurité Sanitaire

An Environmentally Sensitive Phase of Titania Nanocrystals The calculated phase map indicates that the equilibrium boundary between anatase and rutilenanocrystals is surface charge chemistry dependent (fct Acidity), which relates to both their formation and postsynthesisenvironments. Anatase Figure 2. The (D,T) phase map of titania, based on first principles calculations and melting enthalpies form experiment: (a) the solid-solid phase transition lines for nanocrystals with OH2- and OH-terminated surfaces and the coexistence region where the relative stability depends on the type of adsorbed groups, and (b) the low temperature and size regime with the size range of experimental observations at 180 °C and 0,2 MHCl marked (anatase in blue, and rutile in red). Identification of individual anatase and rutile nanocrystals are base on their periodicities of lattice fringes in HRTEM images. The diameter refers to the anatase phase. Co-Existence Rutile PH Acide (high HCl concentration) : pure rutilenanocrystals(ex. : Estomac) PH intermédiaire (low HCl concentration), both rutile & anatasenanocrystals(ex. : Colon) PH basique (low acidity and pure watersolutions) : anatasenanocrystal Structure Physico ChemicalStability DuringHuman Body lifecycle ? Co-Existence Rutile Anatase A.S. Barnard, H. Xu -ACS Nano, 2(11) (2008) 2237 - 2242

8 Parameters (ISO) i) Agglomeration State/Aggregation ii) Composition iii) Particle Size/Distribution iv) Shape (includinglength to diameter ratio for nanofibers and naotubes) v) Solubility /Dispersibility vi) Surface Area vii) Surface Chemistry viii) Surface Charge Density Proteins Corona !! Eric.Gaffet@utbm.fr NanoMatériaux & Développement Responsable Concilier Recherche, Innovation, Sécurité Sanitaire

Protein-nanoparticle interactions: What does the cell see? I. Lynch, A. Salvati & K. A. Dawson - Nature Nanotechnology 4, 546 - 547 (2009) http://www.nature.com/nnano/journal/v4/n9/fig_tab/nnano.2009.248_F1.html

Nanoparticle proteomics: Characterizing protein-nanoparticle interactions in biofluids (Nanowerk News) New insights about how the human body interacts with nanoparticles at the protein level December 2011 issue 23 of Proteomics ("Quantitative proteomics analysis of adsorbed plasma proteins classifies nanoparticles with different surface properties and size"). Protein profile analysis, as shown in the heat map above, reveals that different nanoparticle sizes (50 nm, 100 nm) and surface chemistries (amine, carboxylate) may have different accumulation, fate, and health effects. They incubated the nanoparticles with human blood plasma, allowing plasma proteins to adsorb to their surface, and then digested the proteins while they were still attached to the nanoparticles. These digested proteins were identified and quantified using EMSL's LTQ Orbitrap mass spectrometers and LC-MS based proteomics. Remarkably, the team identified 88 nanoparticle-adsorbed plasma proteins in different conditions. Their data showed that the proteins coated the nanoparticles in fewer than five minutes, suggesting the protein-nanoparticle interaction is immediate. Furthermore, different nanoparticle sizes and surface chemistries resulted in different adsorbed protein profiles, indicating that different kinds of nanoparticles may have different accumulation, fate, and health effects. 9 Janvier 2012 http://www.nanowerk.com/news/newsid=23904.php

Nanobiotechnology: Nanoparticle Coronas Take Shape Source:Nature NanotechnologyAuthor:Marco P. Monopoli, Francesca Baldelli Bombelli and Kenneth A. Dawson Researchers at the Centre for BioNano Interactions, University College Dublin, Ireland, write in the journal Nature Nanotechnology that understanding the impact of nanomaterials on human health will require more knowledge about the protein corona that surrounds nanoparticles in biological environments. Nanoparticles have been shown to seek to lower their surface free energy by creating a surrounding "corona" made of proteins, lipids and other biomolecules.This long-lived protein corona could, under suitable circumstances, influence the internal workings of any cells they come into contact with. The authors write: "The composition and size of the nanoparticle influences how it interacts with the biomolecules, leading to different types of corona, composed of relatively few proteins compared with the numbers in the biological environment. Moreover, it has been suggested that the corona is sufficiently long-lived to be the most important interface in interactions between cells and many (perhaps most) nanoparticles." Ongoing research shows that the biological identity of the particle is a consequence of the corona, and this conclusion is beginning to feed into the safety assessment literature. They conclude: "Within the narrower scientific community active in this arena, it may be time to frankly assess what tools we would have available to classify nanomaterials if the corona proves to be as important as these results suggest. Hopeful signs seem to be emerging in terms of predictive science, but researchers in the field face big challenges: in essence, the core of our present knowledge about the corona is compositional and macrostructural, rather than microscopic. If broader developments continue in this direction, scientists will need to learn a lot more about the microscopic details of the corona." The article can be viewed online at the link below. http://www.nature.com/nnano/journal/v6/n1/full/nnano.2011.267.html Dec. 2010

8 Parameters (ISO) i) Agglomeration State/Aggregation ii) Composition iii) Particle Size/Distribution iv) Shape (includinglength to diameter ratio for nanofibers and naotubes) v) Solubility /Dispersibility vi) Surface Area vii) Surface Chemistry viii) Surface Charge Density « Cocktail » Effect Eric.Gaffet@utbm.fr NanoMatériaux & Développement Responsable Concilier Recherche, Innovation, Sécurité Sanitaire

n_Anontoxic, n_Bnontoxic but n_A + n_Btoxic ! Cocktail Effect The research teams of Professor IlpoVattulainen (Department of Physics, Tampere University of Technology, Finland) and academy researcher EmppuSalonen (Department of Applied Physics, Helsinki University of Technology, Finland) have together with Professor Pu-Chun Ke's (Clemson University, SC, USA) team researched how carbon-based nanoparticles interact with cells. The results provided strong biophysical evidence that nanoparticles may alter cell structure and pose health risks. It emerged from the research that certain cell cultures are not affected when exposed to fullerenes, i.e. nano-sized molecules that consist of spherical, ellipsoid, or cylindrical arrangement of carbon atoms. Cells are also not affected when exposed to gallic acid, an organic acid that is found in almost all plants and, for instance, in tea. However, when fullerenes and gallic acid are present in the cell culture at the same time, they interact to form structures that bind to the cell surface and cause cell death. E. Salonen, S. Lin, M. L. Reid, M. Allegood, X. Wang, A. M. Rao, I. Vattulainen, P.-C. Ke. Real-time translocation of fullerene reveals cell contraction. Small, 4, 1986-1992 (2008 Commentaire de Science Daily http://www.sciencedaily.com/releases/2008/11/081113100710.htm The research demonstrates how difficult it is to map out the health effects of nanoparticles. Even if a certain nanoparticle does not appear toxic, the interaction between this nanoparticle and other compounds in the human body may cause serious problems to cell functions. Since the number of possible combinations of nanoparticles and various biomolecules is immense, it is practically impossible to research them systematically

Nanocoated Film as a Bacteria KillerSource:Nanowerk - Author:n/a Researchers at the Institute for Chemical and Bioengineering of ETH Zurich, Switzerland, have developed a plastics film made with silver and calcium phosphate nanoparticlesthat is lethal to bacteria and self-disinfecting. The combination of these two substances results in a product that is 1000 times more lethal to Escherichia coli than conventional silicon-based silver preparations. The silver, which kills the bacteria, is only released when the bacteria consume the calcium substrate and cause it to disintegrate. The silver is thus used in a targeted manner, and in a controlled amount, saving costs and incurring less stress on the human body. The film, which is already being manufactured, can be used by hospitals in areas that are hotspots for germ transmission, such as door handles, beds, and sanitary equipment. The film is not effective indefinitely and must be replaced periodically. The article can be viewed online at the link below. Cocktail Effect Efficiency : x 1000 http://www.nanowerk.com/news/newsid=8997.php

Conclusion and Perspectives ► Physico ChemicalParameters are not intrinsic They are dependant of the lifecycle (continuousevolution / major steps ?) ► EachNanoProduct has itsown consumer dependantlifecycle (unique and specific) ► Reactivity (Tox – Eco Tox): fct (Environment -Cocktail Effect) Large Variation (up to 1.000 x efficiency) ► To develop ●Metrology and Physico ChemicalCharacterization (in real life conditions and full lifecycle) ● Protein corona and Cocktail effect to characterise Eric.Gaffet@utbm.fr NanoMatériaux & Développement Responsable Concilier Recherche, Innovation, Sécurité Sanitaire

Tin Whisker (Peter Bush, SUNY at Buffalo) Questions Discussion Eric.Gaffet@utbm.fr NanoMatériaux & Développement Responsable Concilier Recherche, Innovation, Sécurité Sanitaire Thank you for your Attention E. Gaffet

NanoMaterials & Responsible Development