Nanotechnology and human health: Scientific evidence and risk governance Report of the WHO expert meeting 10–11 December 2012, Bonn, Germany Nanotechnology and human health: Scientific evidence and risk governance Report of the WHO expert meeting 10–11 December 2012, Bonn, Germany ABSTRACT Nanotechnology, the science and application of objects smaller that 100 nanometres, is evolving rapidly in many fields. Besides the countless beneficial applications, including in health and medicine, concerns exist on adverse health consequences of unintended human exposure to nanomaterials. In the 2010 Parma Declaration on Environment and Health, ministers of health and of environment of the 53 Member States of the WHO Regional Office for Europe listed the health implications of nanotechnology and nanoparticles among the key environment and health challenges. The WHO Regional Office for Europe undertook a critical assessment of the current state of knowledge and the key evidence on the possible health implications of nanomaterials, with a view to identify options for risk assessment and policy formulation, and convened an expert meeting to address the issue. Current evidence is not conclusive. As complexity and uncertainty are large, risk assessment is challenging, and formulation of evidence-based policies and regulations elusive. Innovative models and frameworks for risk assessment and risk governance are being developed and applied to organize the available evidence on biological and health effects of nanomaterials in ways to inform policy. Keywords NANOPARTICLES — NANOTECHNOLOGY — PHARMACEUTICALS AND BIOLOGICALS — RISK MANAGEMENT — TOXICOLOGY Address requests about publications of the WHO Regional Office for Europe to: Publications WHO Regional Office for Europe UN City, Marmorvej 51 DK-2100 Copenhagen Ø, Denmark Alternatively, complete an online request form for documentation, health information, or for permission to quote or translate, on the Regional Office web site (http://www.euro.who.int/pubrequest). Citation advice: Nanotechnology and human health: Scientific evidence and risk governance. Report of the WHO expert meeting 10–11 December 2012, Bonn, Germany. Copenhagen, WHO Regional Office for Europe, 2013. © World Health Organization 2013 All rights reserved. The Regional Office for Europe of the World Health Organization welcomes requests for permission to reproduce or translate its publications, in part or in full. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. The views expressed by authors, editors, or expert groups do not necessarily represent the decisions or the stated policy of the World Health Organization. Copy-editing: Elias Owen Design: Marta Pasqualato Cover photo: nano tube visualization © DeMango / iStockphoto V Content Abbreviations VII Acknowledgements VIII 1. Introduction 1 1.1. Global nanomaterial uses and trends 1 2. Exposure assessment 2 2.1. Assessing direct and secondary exposures 2 2.2. Determination of exposure metrics 3 2.3. Exposure in children and other vulnerable subgroups 3 2.4. Exposure assessment and toxicological data generation 3 3. Nanotoxicology 4 3.1. General toxicological methods 4 3.2. Possible adverse health effects 4 3.3. Vulnerable subgroups 5 4. Risk assessment 5 4.1. Assessing risks of nanomaterials one by one 5 4.2. Options for evolution of risk assessment 6 4.3. Life-cycle perspective of nanoproducts 7 4.4. Detection, tracking and monitoring 7 5. Regulation and risk governance 7 5.1. Regulatory initiatives under way 7 5.2. Risk governance 8 5.3. Risk communication 10 5.4. Multistakeholder dialogue 10 5.5. Transboundary environmental, health and safety issues 10 VI Nanotechnology and human health: Scientific evidence and risk governance 6. Conclusion 11 References 11 Annex 1 15 NANO SUPPORT – Assessment of nanomaterials in REACH registration dossiers 17 Control/risk banding nano tools 18 European Chemicals Agency activities on nanomaterials 21 REACH implementation projects on nanomaterials: Outcomes and implementation 23 Nanomaterials in EU regulation 29 Pulmonary effects of exposure to nanoparticles 30 The IRGC Risk Governance Framework: Applications in food and cosmetics 33 Annex 2 35 Scope and Purpose 37 Programme 38 List of participants 40 Annex 3 43 Background Document 45 VII Abbreviations μg microgram μm micrometre ANSES French Agency for Food, Environmental and Occupational Health and Safety CB Control Banding CLP Classification, Labelling and Packaging of chemicals CNT carbon nanotube CoRAP Community Rolling Action Plan EC European Commission ECHA European Chemicals Agency EINECS European Chemical Substances Information System EU European Union GAARN Group Assessing Already Registered Nanomaterials GMO genetically modified organism IOM Institute of Occupational Medicine IRGC International Risk Governance Council ITS Integrated Testing Strategies IUCLID International Uniform Chemical Information Database MWCNT multiwalled carbon nanotube NIOSH National Institute for Occupational Safety and Health nm nanometre OC operational conditions OECD Organisation for Economic Co-operation and Development OEL occupational exposure limit REACH Registration, Evaluation, Authorisation and Restriction of Chemicals REL recommended exposure level RIP-oN REACH Implementation Project on Nanomaterials SAA serum amyloid A SDS safety data sheets SWCNTs single-walled carbon nanotubes TWA time-weighted average WHO World Health Organization WPMN OECD Working Party on Manufactured Nanomaterials VIII Nanotechnology and human health: Scientific evidence and risk governance Acknowledgements Preparatory work was based on results from the EU co-funded PAVEL Project (Grant Agreement 2006WHO01). The German Ministry of Environment, Natural Conservation and Nuclear Safety financially supported the meeting and the preparation of the report. The meeting was chaired by Professor Michael Depledge, University of Exeter Medical School, and the rapporteur was Dr Steffen F. Hansen, Technical University of Denmark. The report was edited by Steffen F. Hansen, Charles V. Howard, Marco Martuzzi and Michael Depledge. Participants in the expert meeting reviewed the text and provided comments. Report of the WHO expert meeting 10–11 December 2012, Bonn, Germany Meeting report 1 1. Introduction Nanomaterials and products based on nanotechnological applications are being commercialized and used at an increasing pace. In the Parma Declaration on Environment and Health,1 the health implications of nanotechnology and nanoparticles are listed among the key environment and health challenges that ministers are committed to act on. Along with a call for increased research on the use of nanoparticles in products and nanomaterials, the ministers pledged to develop and use improved health risk and benefit assessment methods. Research into the environmental, health and safety aspects of nanomaterials is extensive and growing rapidly. The World Health Organization (WHO) Regional Office for Europe has been reviewing recent and current research, with a view to clarifying the connections between nanotechnology and health. Findings from this exercise suggest that a rigorous risk assessment is not feasible and that a pragmatic model of “risk governance” seems desirable. In order to explore how the Regional Office can contribute to progressing risk governance of nanotechnologies, a two-day workshop was held in December 2012. Participants with a wide range of expertise were invited to present their work, with the purpose of providing input to WHO. A background document on nanotechnology and health (not representing a comprehensive or systematic overview of the issue) was used as the basis for this meeting and is included in this report. Abstracts of the presentations made by participants are included in the annex. The workshop’s discussion focused on four key areas (i) exposure assessment of nanomaterials, (ii) nanotoxicology, (iii) risk assessment, and (iv) regulation and risk governance. 1.1. Global nanomaterial uses and trends Nanomaterials are making their way into all aspects of our lives; these materials are being increasingly used in pharmaceutical and medical applications, cosmetics and personal products, energy storage and efficiency, water treatment and air filtration, environmental remediation, chemical and biological sensors, military defence and explosives (Chaudhry, 2012), and in countless consumer