Toxicidad de los Nanomateriales para la salud. Introducción. Ejemplos. Situación actual y próximos pasos. Proyectos NANoREG y NanoReg 2.

Transcription

1 Toxicidad de los Nanomateriales para la salud. Introducción. Ejemplos. Situación actual y próximos pasos. Proyectos NANoREG y NanoReg 2. Blanca Suarez Merino DPhil 1

2 Nano products VS Some Australians Prefer Skin Cancer to Sunscreens with Nanoparticles By Dexter Johnson Posted 10 Feb :09 GMT EU votes for labels on nano, cloned and GM food Ecologist 5th May, 2010 Regulation needs to keep pace with innovation! UK and other member states expected to fight proposals to bring in compulsory labelling for consumers on novel foods MEPs have voted almost unanimously in 2

3 A natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50 % or more of the particles in the number size distribution, one or more external dimensions is in the size range 1 nm nm. Types of MNM Natural Side product from human activities Volcanic emissions Fumes Nano-capsules Engineered NM (ENMs) Forest fire Tobacco smoke Metals and oxides Viruses Hybrid Quantum dots 3

4 1.- Nanomateriales inorgánicos no metálicos. 2.- Metales y aleaciones metálicas 3.- Nanomateriales con base de carbono. 4.- Nanopolímeros y dendrímeros. 5.- Quantum dots. 6.- Nanoarcillas. 7.- Otros nanomateriales AA CALIBRI 18 BLANCO. NEGRITA. MAYUS 4

5 Properites Gold Gold NM Melting temperature (ºC) ~ 1000 Colour Yellow ~ 830 (5 nm) ~ 350 (2 nm) Blue (~70-90 nm) Red (~ < 30 nm) Magnetic properties Diamagneticc Ferromagnetic Reactivity Inert Catalytic properties NM properties compared to standard material 5

6 Energy Food, Cosmetics Coatings NM provide novel properties providing a real market advantage IT Applications Construction Military Materials PoC Medicine 6

7 What is toxicology? All things are poison, and nothing is without poison; only the dose permits something not to be poisonous. "The dose makes the poison." Paracelsus Conventional toxicology is being challenged!!!! Nanotoxicology = Study of the toxicity of nanomaterials 7

8 What we know Oomen et al

9 Dissolution as a toxicity mechanism! 9

10 Shape and biopersistance Boyles et al 2014 Rounded materials are easier to be phagocytised than fibers 10

11 Dh (nm) BACKGROUND Agglomeration state F12 Ø BEGM Ø [TiO2] (ug/ml) 11

12 BEAS2 Inhalation and dermal route are the most relevant for NM safety assessment Diam (nm) Diam (um) A549 State Nasal area Bronchial area Alveolar area 1 0,001 Dispersed 80% 20% 0% 5 0,005 Dispersed 45% 37% 20% 10 0,01 Dispersed 20% 25% 45% 20 0,02 Dispersed 15% 15% 50% 100 0,1 Aggregates 10% 8% 20% Aggregates 40% 2% 15% Aggregates 75% 0% 0% 12

13 Metabolism soluble NP Blood Biopersistence Excretion Cleared by ciliated cells and swollen insoluble NP Accummulated at the alveolar region Phagocytosis Interaction with other cells from the immune system 13

14 Downfalls of current publications unrealistic doses, lack of validated protocols, lack of harmonization No data correlation (when experiments are based on mass) Unrealistic experimental doses (need for in vitro in vivo extrapolation) GENOTOXICITY??? 14

15 REGULATION REACH CLP Biocides Pesticides Cosmetics EFSA FCM Novel Food EMA Medical Devices Occupatio nal Technical dossiers Guidance documents Multi-Criteria Decision based Analysis Technological developments Socio-economic analysis NANoREG PROSAFE NanoReg2 National Initiaves NanoGem Serenade EHSAdvance NanoSafety Cluster 15

16 REGULATION European Comunity Regulation on Chemicals (REACH) Is the European Community Regulation on chemicals and their safe use (EC 1907/2006). It deals with the Registration,Evaluation, Authorisation and Restriction of Chemical substances. The law entered into force on 1 June a. Improve the protection of human health and the environment b. Enhance innovation and competitiveness of the EU chemicals industry c. Transparency d. Avoid unnecessary animal experimentation Toxicity studies with nanoparticles according to the REACH regulations have not been validated for nanoparticles. These are being looked at by European authorities so nanoparticles could be evaluated for safety as any ordinary chemical product. Major problem is adapting dosage. 16

17 Background information RIPoN reports REACH Implementation Project on Nanomaterials (RIPoN), which it intended to provide advice on key aspects of the implementation of REACH with regard to nanomaterials. They are REACH annexes. RIPoN 1: Substance identification RIPoN 2: Information requirements RIPoN 3: Chemical Safety Assessment 17

18 EXAMPLE: CARBON NANOTUBES Dimensions 0.5-2µm x 1-2 nm Intrinsic toxicity (phys-chem) Toxicology evaluation Size? Length? Catalyst? Pristine nanomaterials Functionalized nanomaterials? System dependent toxicity Cost in US: > $ 249M years Charge Protein corona Stability Cellular interactio Identify characteristics and Tests to predict toxicity Safe by design 18

19 Two main problems!!! Too many possibilities for safety assessment Grouping Lower risk assessment costs- SAFE BY DESIGN Graphik: A. Worth, JRC 19

20 Nanotechnology Time for decision-making Shape Biodegradability Surface modification Inflammation Biodisponibility Cause Effects Oxidative stress Purification Formulation Disease Which characteristics provoke which biological responses? 20

21 NANoREG is common and regulatory relevant 1. Regulatory relevant scientific questions formulated in collaboration with regulators and regulatory agencies (under consideration of non-european aspects and developments) [WP1] 2. Coordinated scientific research targeted to answer the regulatory relevant questions [WP2 WP5] 3. Acknowledgement of and in-built degree-of-freedom for nanotechnology innovation [WP6] 21

22 NANoREG Strategy and Complexity Level 1 DoW as a leading document Harmonize SOPs Suite of NM Exchange of test data Copenhagen Meeting Sub-sampled JRC Level 2 Results to political process (NC, Industry, NGOs) Prosafe Level 3 Global context, exchange and cooperation 22

23 Development and implementation of grouping and safe by design approaches within regulatory frameworks Work plan Inputs from on-going Research & regulatory oriented projects Outputs to regulatory and standardization activities To be implemented in industry 23

24 NanoReg2 24

25 Nanoreg2 Development and implementation of grouping and safe by design approaches within regulatory frameworks Safe innovation approach 25

26 The Nanoreg2 Approach 1. Definition of Grouping strategies to accelerate MNM safety assessment 2. Definition of a set of MNM to validate grouping strategies 3. Implementation of RA framework on all 3 pillars 4. SbD Approaches Presentation of Nanoreg2 Grouping criteria at OECD meeting on 14 th April 26

27 GRACIAS ESKERRIK ASKO THANK YOU Blanca Suarez Merino Parque Tecnológico, Ed Zamudio (Spain) T.: F.: