Accelerated Innovation in Nanomanufacturing. Research Strategies for addressing Ethical, Environmental, Health, safety and responsibilitiesCEFIC Stakeholder Dialogue:Enabling responsible innovations of nanotechnologies Professor Terry WilkinsYorkshire Forward Professor of Nanomanufacturing InnovationCEO, Nanomanufacturing Institute, University of Leeds, UKBrussels, 24 June 2008

Topics

Why E, H & S considerations are importantStrategies for addressing E, H &SLatest position on Carbon NanotubesEthics debate and public engagementConcluding remarks

Nanoparticles & HealthN a n o p a r t i c l e sLungNoseProfessor K Donaldson, U Edinburgh

Research funding in EuropeSubstantial interdisciplinary research is needed Member States have responded to the challenge Eg:UK46 Projects (6 Env)CH24 Projects (2 Env)DK12 Projects(1 Env) EC has developed a visionary strategic approach:(Helped by Expert Advisory Group and Programme Committee)Largest source of funds for collaborative researchSought to develop and stimulate international collaborations

EU Investment in Nano E, H & S Research Millions

Chart5

2.419

29.484

20

Sheet1

FP5FP6FP7 Year-1

2.41929.48420

No of projects310?

E03?

H & S310?

2.6

2.79

0.74

3.3

2.4

0.799

6.999

0.45

1.306

8.1

Sheet1

0

0

0

Sheet2

Sheet3

A Strategy for Nanotoxicity for Research?Interdisciplinary science research skills are needed for toxicology studies of new nanomaterials: Materials Characterisation (size, shape & chemical properties) Data mining & QSAR Cell Membrane penetration DNA damage (free radical & oxidative damage) Intra-cell interactions (Inc Mutagenicity) Whole organ effects Whole organism effects Clinical studies Environmental impact E, H & S Monitoring tools (Sensors & High-throughput systems)

Leeds research strategy

Leeds QSAR Nanotoxicity Research CapabilityIntegrated Data Mining Tool BoxResults Presentation Graphs Tables ASCII filesDiscovery Validation Statistical significance Results for training and test setsData Mining ToolboxRegressionPCA and ICAART2 networksKohonen networksK-nearest neighboursFuzzy c-meansDecision trees and rulesFeedforward neural networks (FFNN)Summary statisticsVisualisationMixture QSAR models Data import Excel ASCII Files Database XMLData Pre-processing Scaling Missing values Outlier identification Feature extractionDescriptor calculationProfessor Xue Wang, IPSE, Leeds

Lipid Bilayer SensorsNanoparticle passing through lipid bilayer changes electrical properties detected at electrodesDr Andrew Nelson, SOMS, Leeds

Examples of Comet Assay Results

MinimalMildModerateSevereStrategyAssess DNA damage in:Lung epithelial cellsSkin epithelial cellsGut CaCo2 cells Study SizeShapeStructure(Bio)chemistryProfessor Alastair Hay, LIGHT, Leeds

supFpSP189+mutantDamaged DNA is replicated in human cells and mutants are screened for in E.colisupF Mutation Assay(Secondary screen for germ cell mutation risk).Human cellsProfessor Alastair Hay, LIGHT, Leeds

New approaches for occupational exposure monitoringLeeds was the first trial site for UK government Health and Safety Executives new equipment for monitoring nanoparticles in the atmosphere..biggest contribution to nanoparticles in our laboratories atmosphere was from traffic exhausts from road outside!!!!!

The Challenge of Standardisation

Can pragmatic approaches of the past help us?Rosalyn Yalows invention of radioimunnoassay stimulatedan explosion of new clinical assays for diseases based on impure, degraded and poorly characterised proteins.Yet we made useful diagnoses and later through good normative research we iterated to:

Pure and fully characterised reference materialsProper standardsInternational consensus on clinical rangesImproved our diagnoses and patient management

Recent Nature Nanotechnology LetterProfessor K Donaldson, U Edinburgh

The Asbestos Pathogenicity Paradigm

Asbestos is harmful because the fibres it releases into the air are:- thin, long, do not dissolve in the lungsProfessor K Donaldson, U Edinburgh

NT MorphologyLong StraightLong TangledShort TangledShortMechanism for the Harmfulness of Long Straight Fibres

Quantitative Structure activity relationships (QSAR) control particle toxicityThe onus is on toxicologists to determine them and put them to use in models to predict toxicity without recourse to animal experimentationThe fibre QSAR is mature and predicts that any fibre longer than about 15microns, that is thin (less than 3-5 microns) and biopersistent (does not dissolve so the dose builds up) will be pathogenicAll fibres so far studied have conformed to this paradigm asbestos, glass fibres, ceramic fibres, para-aramid fibres, MWCNTs etcOur study confirmed the length-dependent pathogenicity of MWCNT , using a direct mesothelial exposure model. Further research is needed to determine if inhaled long MWCNT can reach the pleural mesothelium , and what the levels of long MWCNT in workplaces are.Conclusions of Poland et als StudyProfessor K Donaldson, U Edinburgh

Ethics & Nanotechnology?PlatoResearch by Rob Naylor IDEA Applied Ethics Centre, Leeds

Ethics, E, H & S for NanotechnologySolving Platos problem?Plato

Conclusions .But the world moves on. There has been a healthy debate on the societal issues since 2000 and both EU industry and the regulators (REACH) are preparing: We now need to get on with the science and deliver new knowledge The science is complex and needs interdisciplinary research Planned FP7 EU/US Joint Calls key for success China (CAS) and India are keen to join in Global collaboration makes sense Work with industry to inform regulation (REACH & EPA) Involve citizens every step of the wayEurope has a distinguished track record, led by industry, in innovation of Safety, Health and Environment standards & procedures (E.g. HAZOP, COSHH etc).Learn from the best practice of the past to earn our License to Operate in the future

Stop Press INTERIM ADVICE on Wastes containing unbound Carbon Nanotubes - 19 May 2008The hazard classification of CNTs should be similar to asbestosUnbound CNT waste should be rendered safe by exposure to 850 deg C for at least 2 seconds US NNI Reauthorisation BillPrioritize nanoscale characterization and metrology research as the basis for understanding and addressing any risks or dangers associated with nanoparticles and nanomaterials.FDA does not have separate category yet for nano materials (Inc. CNTs) but is keeping the situation under review