A Research Strategy for Environmental, Health, and Safety Aspects of Engineered Nanomaterials (2012)

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1 Background OVERVIEW On January 21, 2000, President Clinton announced a new U.S. initiative to explore and exploit the science and technology of matter on the nanometer scale (often referred to as the nanoscale). In an address at the California Institute of Technology on science and technology, President Clinton asked his audience to imagine “materials with 10 times the strength of steel and only a fraction of the weight; shrinking all the information at the Library of Congress into a device the size of a sugar cube; detecting cancerous tumors that are only a few cells in size.” The speech laid the foundation for the National Nanotechnology Initiative (NNI) (The White House 2000). The NNI—“the government’s central locus for the coordination of federal agency investments in nanoscale research and devel- opment” (NRC 2009, p. 3)—has set the pace for national and international re- search and development in nanoscale science and engineering and has led the world in the development and use of knowledge at the nanoscale with the poten- tial to improve quality of life, stimulate economic growth, and address many of society’s most pressing challenges. With our understanding of the role that nanoscale science and engineering can play in the development of innovative materials, processes, and products has also come the knowledge that nanotechnology may lead to new mechanisms by which people and the environment may be harmed. In today’s complex, inter- connected, and resource-constrained world, it is important that products result- ing from novel and emerging technologies that have uncertain risks, such as nanotechnology, be developed responsibly; that all stakeholders have an active role in socially responsible development; and that potential risks are identified and avoided as early as possible during research, innovation, and commerciali- zation. This report maps out a research strategy that is intended to promote the responsible development of nanotechnology-enabled materials, processes, and products; and it offers an approach for helping to ensure that researchers, manu- facturers, regulators, and others have the necessary information on potential risks and how to prevent, avoid, or mitigate them. 18 

Environmental, Health, and Safety Aspects of Engineered Nanomaterials 19 OPPORTUNITIES AND CHALLENGES Increasing our understanding of how matter on the nanoscale behaves and interacts with humans and ecologic systems is socially and economically impor- tant. In a world where the needs of a growing population threaten to outstrip increasingly limited resources and many global challenges remain unresolved— from disease to hunger to renewable energy—nanotechnology, along with other fields of technologic innovation, can contribute to a sustainable future (Maynard 2010). Nanoscale science and technology are leading to new ideas and tools that can enhance existing technologies and create new ones, help to support new jobs, revitalize economies, and contribute to solutions to some of society’s most pressing problems. But investing in research and development is just one step toward ensuring socially responsible, relevant, and successful technologic inno- vation. Realizing the economic and societal benefits of nanotechnology also requires educating the workforce, lowering barriers to technology transfer, and engaging with diverse stakeholders. And success with nanotechnology will also depend on developing and implementing new approaches to risk prevention and risk management that avoid past mistakes, that address issues in the innovation process, and that develop materials responsibly without impeding innovation unduly. As nanotechnology research and development have led to new materials— nanomaterials—questions about the safety of these materials have prompted concerns that they are likely to be attended by new risks. Specifically, concerns have been raised that materials behaving in unconventional ways might lead to unanticipated risks to human health and the environment. Those concerns were underpinned and to an extent driven by research in the 1990s that showed that inhaled fine particles have the potential to cause more serious health effects than those estimated in studies of larger particles (for example, Oberdörster et al. 2007). The research signaled the beginning of a paradigm shift away from an understanding that risk stems from chemical composition alone to a recognition that physical form and chemical properties are both important for understanding, predicting, and preventing harm. The concerns were exacerbated by the increase in production of materials that behaved in unique ways because of their physical form on the nanoscale and by growing awareness that methods for detecting, characterizing, monitor- ing, or controlling these materials in the environment were not available and that the materials were in products or in environments in which human exposures could occur (for example, see Maynard et al. 2006). Consequently, there is un- certainty about the potential human health and environmental effects of products emerging from nanotechnology and recognition that the safe and successful de- velopment of nanotechnology depends on early, strategic action to address po- tential risks. In response to the concerns, there has been an increase in funding for re- search and in peer-reviewed publications addressing the environmental, health, and safety (EHS) effects of engineered nanomaterials (ENMs) (PCAST 2010). 

20 Background In FY 2005, the combined investment by U.S. federal agencies in research on and development of EHS implications of nanotechnology was $34.8 million (NSET 2006). In FY 2012, the President’s budget request proposes $123.5 mil- lion—more than a threefold increase (NSET 2010). Worldwide publications addressing the EHS effects of ENMs have increased similarly, with 791 papers published in 2009 compared with 179 publications in 2005 (PCAST 2010). In 2006, the NNI published the first U.S. interagency assessment of EHS research needs associated with ENMs, identifying 75 research needs in five broad categories (NEHI 2006). The needs were assigned priorities by the Nanotechnology Environmental Health Implications Working Group (NEHI 2007) and were incorporated into an interagency research strategy by NEHI in 2008 (NEHI 2008). Recently, NEHI published a draft update (NEHI 2010) of the interagency research strategy that responds to input from the President’s Council of Advisors on Science and Technology, a National Research Council review of the 2008 NEHI report (NRC 2009), and various stakeholder groups, including members of the public.1 Those documents and many similar and com- plementary assessments by government agencies, academic institutions, indus- try, and other stakeholders (see Table 1-1) have helped to direct where EHS re- search should be focused if ENMs are to be developed and used safely. Yet despite progress in the development of research needs and in the amount of re- search that is funded and conducted, developers, regulators, and consumers of nanotechnology-enabled products remain uncertain about the types and quantity of nanomaterials in commerce or in development, their possible applications, and the potential risks associated with them. It is the disconnect between risk research and its relevance to and use in informed decision-making that prompts the question, How can research best be guided and conducted to ensure that the products of nanotechnology are devel- oped as safely, responsibly, and beneficially as possible? That question is central to the charge to this committee. COMMERCIALIZATION OF ENGINEERED NANOMATERIALS The development and use of new materials cannot be separated from ques- tions of potential risk. Understanding and addressing the EHS implications of ENMs is intricately entwined with their development. Over the last few years, industries—ranging from electronics to energy, materials to medicine, and chemicals to clean technologies—have been using nanotechnology to develop breakthrough innovations for products. To respond to the many opportunities, a global network of large corporations, academic 1 A final version of the strategy was published in October 2011 (NEHI 2011). Because the committee’s report had already gone to peer review, NEHI 2011 was not reviewed by this committee. 

TABLE 1-1 Key Reports That Assess or Provide Information on Research Needs and Strategies for Addressing the Environmental, Health, and Safety Implications of Engineered Nanomaterialsa Year Report Source Relevance 2004 Nanoscience and Nanotechnologies: Opportunities and Uncertainties RS/RAE 2004 Identifies strategic-research gaps 2004 Technological Analysis: Industrial Application of Nanomaterials - Chances and Risks Luther 2004 Identifies strategic-research gaps 2004 Nanotechnology: Small Matter, Many Unknowns SwissRe 2004 Identifies strategic-research gaps 2005 Characterizing the Potential Risks Posed by Engineered Nanoparticles: A First UK DEFRA 2005 Identifies strategic-research gaps Government Research Report 2005 Communication from the Commission to the Council, the European Parliament and the EC 2005 Identifies strategic-research gaps Economic and Social Committee. Nanoscience and Nanotechnologies: An Action Plan for Europe 2005 - 2009. 2005 A Proposal to Increase Federal Funding of Nanotechnology Risk Research to at least Denison 2005 Identifies strategic-research gaps $100 Million Annually 2005 Joint NNI-ChI CBAN and SRC CWG5 Nanotechnology Research Needs Recommendations Vision 2020/SRC 2005 Identifies strategic-research gaps 2005 Small Sizes that Matter: Opportunities and Risks of Nanotechnologies Allianz/OECD 2005 Provides contextual information on strategic risk research 2006 Opinion on the Appropriateness of Existing Methodologies to Assess the Potential Risks SCENIHR 2006 Provides contextual information Associated with Engineered and Adventitious Products of Nanotechnologies on strategic risk research 2006 Nanotechnology: A Research Strategy for Addressing Risk Maynard 2006 Outlines a research strategy 2006 Safe handling of nanotechnology Maynard et al. 2006 Identifies strategic-research gaps 2006 Characterizing the Environmental, Health and Safety Implications of Nanotechnology: ICFI 2006 Provides contextual information Where Should the Federal Government Go From Here? on strategic risk research 2006 White paper on Nanotechnology Risk Governance Renn and Roco 2006 Provides contextual information on strategic risk research 2006 Environmental, Health and Safety Research Needs for Engineered Nanoscale Materials NEHI 2006 Identifies strategic-research gaps 2007 Opinion on the Appropriateness of the Risk Assessment Methodology in Accordance SCENIHR 2007 Identifies strategic-research gaps with the Technical Guidance Documents for New and Existing Substances for Assessing the Risks of Nanomaterials (Continued) 21 

22 TABLE 1-1 Continued Year Report Source Relevance 2007 Opinion on Safety of Nanomaterials in Cosmetic Products SCCP 2007 Provides contextual information on strategic risk research 2007 Nano Risk Framework EDF/DuPont 2007 Provides contextual information on strategic risk research 2007 Nanotechnology White Paper EPA 2007 Identifies strategic-research gaps 2007 Nanotechnology: A Report of the U.S. Food and Drug Administration Nanotechnology FDA 2007 Provides contextual information Task Force on strategic risk research 2007 Nanotechnology Recent Development, Risks and Opportunities Lloyds 2007 Provides contextual information on strategic risk research 2007 Prioritization of Environmental, Safety and Health Research Needs for Engineered NEHI 2007 Identifies strategic-research gaps Nanoscale Materials: An Interim Document for Public Comment 2007 Characterizing the Potential Risks Posed by Engineered Nanoparticles: A Second UK DEFRA 2007 Identifies strategic-research gaps Government Research Report. 2007 Meeting Report: Hazard Assessment for Nanoparticles—Report from an Interdisciplinary Balbus et al. 2007 Identifies strategic-research gaps Workshop 2008 Proceedings of the Workshop on Research Projects on the Safety of Nanomaterials: Höck 2008 Identifies strategic-research gaps Reviewing the Knowledge Gaps 2008 Small is Different: A Science Perspective on the Regulatory Challenges of the Nanoscale Council of Canadian Identifies strategic-research gaps Academies 2008 2008 Engineered Nanoscale Materials and Derivative Products: Regulatory Challenges Schierow 2008 Provides contextual information on strategic risk research 2008 Nanotechnology: Better Guidance is Needed to Ensure Accurate Reporting of Federal GAO 2008 Provides contextual information Research Focused on Environmental, Health and Safety Risks on strategic risk research 2008 Responsible Production and Use of Nanomaterials VCI 2008 Identifies strategic-research gaps 2008 Towards Predicting Nano-Biointeractions: An International Assessment of Nanotechnology ICON 2008 Identifies strategic-research gaps Environment, Health, and Safety Research Needs 2008 Strategic Plan for NIOSH Nanotechnology Research and Guidance: Filling the Knowledge NIOSH 2008 Outlines a research strategy Gaps. Draft Report 

2008 Strategy for Nanotechnology-Related Environmental, Health and Safety Research. NEHI 2008 Outlines a research strategy 2008 Novel Materials in the Environment: The Case of Nanotechnology RCEP 2008 Identifies strategic-research gaps 2009 Risk Assessment of Products of Nanotechnologies SCENIHR 2009 Identifies strategic-research gaps 2009 Scientific Opinion: The Potential Risks Arising from Nanoscience and Nanotechnologies EFSA 2009 Provides contextual information on Food and Feed Safety. on strategic risk research 2009 Workplace Exposure to Nanoparticles Kaluza et al. 2009 Provides contextual information on strategic risk research 2009 Nanomaterial Research Strategy EPA 2009 Outlines a research strategy 2009 Securing the Promise of Nanotechnologies: Towards Transatlantic Regulatory Cooperation Breggin et al. 2009 Provides contextual information on strategic risk research 2009 Review of the Federal Strategy for Nanotechnology-Related Environmental, Health, and NRC 2009 Identifies strategic-research gaps Safety Research 2009 EMERGNANO: A Review of Completed and Near Completed Environment, Health and Aitken et al. 2009 Identifies strategic-research gaps Safety Research on Nanomaterials and Nanotechnology 2009 FAO/WHO Expert Meeting on the Application of Nanotechnologies in the Food and FAO/WHO 2009 Provides contextual information Agriculture Sectors: Potential Food Safety Implications on strategic risk research 2010 ENRHES Engineered Nanoparticles: Review of Health and Environmental Safety Stone et al. 2010 Identifies strategic-research gaps 2010 Nanotechnology: Nanomaterials Are Widely Used in Commerce, but EPA Faces Challenges GAO 2010 Provides contextual information in Regulating Risk on strategic risk research 2010 Nanotechnologies and Food UKHL 2010 Identifies strategic-research gaps 2010 UK Nanotechnologies Strategy: Small Technologies, Great Opportunities HM Government 2010 Outlines a research strategy 2010 Report to the President and Congress on the Third Assessment of the National PCAST 2010 Provides contextual information Nanotechnology Initiative on strategic risk research 2010 Nanotechnology Research Directions for Societal Needs in 2020: Retrospective and Nel et al. 2010 Outlines a research strategy Outlook, Chapter 4 2010 National Nanotechnology Initiative NEHI 2010 Outlines a research strategy 2011 Environmental, Health, and Safety Strategyb a Reports are classified as either providing contextual information on strategic-risk research, identifying strategic-research gaps, or outlining a research strategy. With few exceptions (included for historical significance), these reports represent the assessments, opinions, and recommendations of panels of experts. b A final version of the strategy was published in October 2011 (NEHI 2011). 23 

24 Background laboratories, government-funded research centers, technology incubators, and startup companies has emerged to facilitate collaboration in technologic devel- opment. Those developers play unique roles in the three-stage nanotechnology value chain: production of ENMs, raw materials that make up the first stage of the value chain; primary products (also termed intermediate or nanointermediate products) that either contain ENMs or have been constructed from other materi- als to possess nanoscale features and that comprise the second stage; and secon- dary products, finished goods that incorporate ENMs or intermediate products— the third stage. In 2009, developers generated $1 billion from the sale of nanomaterials, which constitute the initial stage of the nanotechnology value chain (Lux Re- search in Wray 2010). In that year, the top 11 classes of nanomaterials (based on production volume) were ceramic nanoparticles, carbon nanotubes, nanoporous materials, graphene, metal nanoparticles, nanoscale encapsulation, fullerenes, dendrimers, nanostructured metals, nanowires, and quantum dots (Bradley 2010). Of these classes of nanomaterials, ceramic nanoparticles (50%), carbon nanotubes (20%), and nanoporous materials (20%) accounted for 90% of the total production volume (about 3,500 tons) (Bradley 2010). The market for products that rely on nanomaterials is expected to grow to $3 trillion by 2015 (Lux Research 2008a,b).2 Although the relative percentages (based on produc- tion volume) are not expected to change drastically through 2015, the more ex- otic materials, such as nanowires and quantum dots, are likely to experience the biggest jump in production because they are starting from a much lower baseline than older classes of materials, such as ceramic nanoparticles (Bradley 2010). The nanomaterials that make up the first stage of the value chain are used in the development of primary products or nanointermediates. In 2009, develop- ers generated $29 billion for this stage of the value chain (Lux Research in Wray 2010). The top 10 nanointermediate classes developed were coatings, compos- ites, catalysts, drug-delivery systems, energy storage, sensors, displays, memory, solar cells, and filters (Bradley 2010). For example, a variety of ceramic nanoparticles can be added to coating formulations to enhance function, includ- ing antiscratch, antifriction, and antimicrobial properties. Coatings, composites, and catalysts are the most prevalent of the nanointermediates. Nanointermediates are expected to generate about $480 billion in 2015 (Lux Research 2009a; Sibley 2009). Although the coatings, composites, and catalysts will make up a large share of the nanointermediate market in 2015 and beyond, they will be joined increasingly by intermediates in the health-care and life-sciences sectors, especially drug-delivery devices, and by intermediates in the electronics sector, that is, in logic chips and in memory applications. Both nanomaterials and nanointermediates feed into nanoenabled prod- ucts, the last stage of the value chain. In 2009, producers generated $224 billion from the sale of nanoenabled products (Lux Research in Wray 2010). The top 10 product classes developed were automotive products, buildings and construc- 2 This figure includes nanomaterials, intermediate products, and nanoenabled products. 

Environmental, Health, and Safety Aspects of Engineered Nanomaterials 25 tion, consumer electronics, personal care, marine, aerospace, sporting goods, food and agriculture, industrial equipment, and textiles (Bradley 2010). Of automotives, for example, ceramic nanoparticle-based coatings are added to engines to increase fuel economy, and carbon nanotubes are added to fuel lines to reduce the risk of fire. In the future, the overall value of nanoenabled products is projected to reach about $2 trillion by 2015 (Lux Research in Wray 2010; Hwang and Bradley 2010; Lux Research 2009b), with automotives, buildings and construction, and consumer electronics dominating this stage of the value chain. PRESENT STATE OF STRATEGIC NANOTECHNOLOGY ENVIRONMENTAL, HEALTH, AND SAFETY RESEARCH Despite extensive investment in nanotechnology and increasing commer- cialization over the last 10 years, uncertainties about the EHS effects of nanoma- terials and nanomaterial-based products remain. There continues to be a lack of clarity about the safety, regulatory, and governance challenges that need to be addressed if materials, processes, and products based on nanotechnology are to be developed responsibly. Research is slowly being translated and communi- cated between people who are generating new knowledge and those who hope to use it—regulators, businesses, and consumers. But in spite of the EHS research that is being conducted, there remains a lack of an overarching, priority-set, co- ordinated research strategy that encompasses stakeholders in the public and pri- vate sectors and that identifies critical questions, maps out a path to answers, and ensures accountability for providing decision-makers with timely informa- tion. Because nanotechnology is presenting new and unusual challenges, mov- ing from reactive to proactive research represents a substantial paradigm shift in how risk-related research is conducted. The specific EHS issues raised by ENMs remain difficult to address. Nevertheless, the NNI has succeeded in coordinating regulatory and research agencies in identifying cross-agency research needs and in beginning to address the needs. The NNI documents (NEHI 2006, 2007, 2008, and 2010) that set forth the federal government’s research strategy for addressing EHS implications of ENMs are a considerable achievement and help to identify further research that is needed. Those documents are complemented by agency-specific research strategies (described below). However, despite the progress that has been made toward developing an interagency research strategy, research on the potential EHS implications of ENMs still lacks context with respect to what is already known, what is occurring now, and what is likely to be important in the future. In the absence of a clear and implementable research strategy, research appears to be driven predominantly by assumptions of what is important and what is scientifically interesting rather than by a clear, rationale assessment of what is needed. 

26 Background The current need for an overarching research strategy has been responded to in part by National Nanotechnology Initiative 2011 Environmental, Health, and Safety Strategy (NEHI 2010). The closing chapter begins to develop a framework that will support coordination among federal agencies; including establishment of a set of principles to encourage agencies to work together pro- ductively and mechanisms that support the NEHI and the National Nanotech- nology Coordination Office (NNCO) in implementing the strategy. The principles in NEHI (2010) are designed to help to set priorities among nanomaterials; to establish systems for conducting reproducible, valid, and translatable research; to ensure that the resulting data are of high quality; to cou- ple research to different risk-assessment needs; and to support partnerships with stakeholders and engagement with the international community. The principles set the scene for ensuring that relevant and responsive research is conducted rather than dictating which agencies conduct what research. However, there re- mains the task of combining the emerging framework with a strategically re- sponsive research strategy that facilitates the generation and application of timely and relevant data and that extends beyond the borders of federal agencies to include engagement with stakeholders and the international community. HISTORY OF NANOTECHNOLOGY ENVIRONMENTAL, HEALTH, AND SAFETY RESEARCH ASSESSMENTS In the early 2000s, a number of reports from diverse sources began to question the safety of nanotechnology-enabled products and emerging ENMs. They ranged from the ETC Group’s call for a moratorium on nanotechnology research (ETC Group 2003) to Sun Microsystems founder Bill Joy’s influential article in Wired magazine questioning the dangers of emerging technologies (Joy 2000) to the reinsurance giant Swiss Re’s assessment of the uncertain im- pacts of nanotechnology (Swiss Re 2004). In 2004, those concerns were placed into context by the UK Royal Society and Royal Academy of Engineering (RS/RAE) (RS/RAE 2004). After an extensive consultation and assessment pe- riod led by a panel of experts, the RS/RAE published a highly influential report examining the opportunities and uncertainties of “nanoscience and nanotech- nologies.” Concluding that “the lack of evidence about the risks posed by manu- factured nanoparticles and nanotubes is resulting in considerable uncertainty” (RS/RAE 2004, p. 85), the report made recommendations for avoiding potential risks and developing a better understanding of them. Although the RS/RAE re- port’s recommendations were directed toward the UK government, they were used worldwide to ground discussions of the responsible development of nanotechnologies based on the state of knowledge about potential risks. A number of risk-research assessments followed. In the UK, a response to the RS/RAE report by the UK government began to map out strategic research needs and a plan of action to address them (DEFRA 2007), and the European Union (EU) incorporated nanotechnology EHS research and development into 

Environmental, Health, and Safety Aspects of Engineered Nanomaterials 27 its action plan (2005-2009) for developing nanoscience and nanotechnology. Those activities were complemented by the EU Scientific Committee on Emerg- ing and Newly Identified Health Risks (SCENIHR) publication of a comprehen- sive review of “engineered and adventitious products of nanotechnologies,” which is one of the most comprehensive reviews of the potential health risks associated with ENMs (SCENIHR 2006). In December 2004, the NNI published its first strategic plan, which in- cluded a specific commitment to address the potential EHS implications of nanotechnology (NSET 2004). Under the goal of supporting the responsible development of nanotechnology, the NNI committed to “as necessary, expand support for research into environmental and health implications of nanotechnol- ogy” (NSET 2004, p. 12). The strategic plan also stated (NSET 2004, p. 12) that NNI-funded research will (1) increase fundamental understanding of nanoscale material interactions at the molecular and cellular level through in vitro and in vivo experiments and models; (2) increase fundamental un- derstanding of nanoscale material interactions with the environment; (3) increase understanding of the fate, transport, and transformation of nano- scale materials in the environment and their life cycles; and (4) identify and characterize potential exposure, determine possible human health im- pact, and develop appropriate methods of controlling exposure when working with nanoscale materials. Federal activities were to be coordinated by NEHI, a group of representa- tives of research and oversight agencies that began meeting informally in 2003 and was formally established in 2004 (NSET 2004). In 2005, in a parallel development, the NNI established two Consultative Boards for Advancing Nanotechnology (CBAN), consisting of representatives of the chemical and semiconductor industries, to help to define research needs. Those boards assembled subgroups that drew on public- and private-sector ex- perts to address the potential EHS implications of nanotechnology and published joint research recommendations (Vision 2020/SRC 2005). Five key research needs were proposed by the joint groups: a testing strategy for assessing toxic- ity, best metrics for assessing particle toxicity, exposure-monitoring methods, risk-assessment methods, and communication and education concerning EHS and societal impacts (Ford 2005). In keeping with those key needs, specific research topics were developed. For example, more detailed recommendations for near-term research to address the toxicity of nanomaterials were offered in an associated document and re- flected discussions between government and industry representatives (NNI-ChI CBAN ESH Working Group 2007). In 2006, Maynard (a member of the present committee) wrote a report that evaluated nine sources of information on EHS research needs, including 

28 Background RS/RAE (2004) and CBAN (NNI-ChI CBAN ESH Working Group 2007), and outlined a possible federal research strategy (Maynard 2006). The report identi- fied 11 subjects on which further research was needed: human-health hazards, health outcomes, environmental impact, exposure, material characterization, exposure control, risk reduction, standards, safety, informatics, and effective approaches to research. Priorities were set among specific research needs asso- ciated with those subjects for generating new knowledge and supporting over- sight of emerging materials. In November 2006, “Safe Handling of Nanotechnology” was published (Maynard et al. 2006). The coauthors were experts in government, industry, and the nongovernment sector. It established five overarching research challenges to developing nanotechnology-based products safely and proposed a timeline for the international research community to address them. The five challenges were to develop “instruments to assess exposure to ENMs in air and water, within the next 3-10 years”; “validated methods to evaluate the toxicity of ENMs, within the next 5–15 years”; “models for predicting the potential impact of ENMs on the environment and human health, within the next 10 years”; “robust systems for evaluating the health and environmental impact of ENMs over their entire life, within the next five years”; and “strategic programmes that enable relevant risk-focused research, within the next 12 months.” In that same year, the 2006 NEHI report was published. It categorized the 75 nanotechnology-related EHS research needs in five broad categories: instru- mentation, metrology, and analytic methods; nanomaterials and human health; nanomaterials and the environment; health and environmental surveillance; and risk-management methods. The report was alluded to by Clayton Teague, direc- tor of NNCO, in testimony to the House Committee on Science and Technology on November 17, 2005, in which he noted that “a carefully designed research plan, along with shared Government and industry responsibility and collabora- tion should guide our efforts” (Teague 2005, p. 27). Following publication of NEHI (2006), a consultative document that presented 25 research priorities (five in each of the five research categories identified in the NEHI report) was pro- duced (NEHI 2007). In February 2008, the NNI strategy for nanotechnology-related EHS re- search was published (NEHI 2008). Building on the previous two reports (NEHI 2006, 2007), it expanded on the 25 research priorities identified in 2007 and indicated the changing emphasis that they should receive in the near, middle, and long terms in a research strategy. The document also developed a broad framework to guide strategic risk research and identified lead agencies for ad- dressing research needs. The strategy was developed predominantly by govern- ment-agency representatives but drew on feedback from public consultations and responses to earlier documents. The 2008 federal research strategy for nanotechnology-related EHS re- search (NEHI 2008) was reviewed by the National Research Council (NRC 2009), whose committee concluded (p. 10) that 

Environmental, Health, and Safety Aspects of Engineered Nanomaterials 29 The NNI’s 2008 Strategy for Nanotechnology-Related Environmental, Health, and Safety Research could be an effective tool for communicating the breadth of federally supported research associated with developing a more complete understanding of the environmental, health, and safety im- plications of nanotechnology. It is the result of considerable collaboration and coordination among 18 federal agencies and is likely to eliminate un- necessary duplication of their research efforts. However, the document does not describe a strategy for nano-risk research. It lacks input from a diverse stakeholder group, and it lacks essential elements, such as a vision and a clear set of objectives, a comprehensive assessment of the state of the science, a plan or road map that describes how research progress will be measured, and the estimated resources required to conduct such re- search. Central to the stated concerns of that committee was a lack of an assess- ment of the state of the science, including previous efforts to identify and ad- dress strategic research needs, a research-gap analysis that overstated the scope and extent of relevant federally funded research, and a lack of stakeholder input into the process. The federal strategic plan has recently been substantially up- dated, on the basis of input from a series of workshops, stakeholder consulta- tions, and reviews, including NRC (2009). In parallel with the NNI efforts (and in part coordinated with them), indi- vidual federal agencies developed their own internal research strategies. The National Institute for Occupational Safety and Health (NIOSH) first published a draft EHS research strategy in 2005 (NIOSH 2005), and the most recent itera- tion was released in 2010 (NIOSH 2010). The current NIOSH strategy addresses four strategic goals, developed in consultation with stakeholders: “determine if nanoparticles and nanomaterials pose risks for work-related injuries and ill- nesses” (p. 18); “conduct research to prevent work-related injuries and illnesses by applying nanotechnology products” (p. 24); “promote healthy workplaces through interventions, recommendations, and capacity building” (p.24); and “enhance global workplace safety and health through national and international collaborations on nanotechnology research and guidance” (p. 27). Each goal is accompanied by specific subgoals and performance measures. The Environmental Protection Agency (EPA) also developed a compre- hensive nanotechnology EHS research strategy (EPA 2009). Building on a white paper first published in draft form in 2005 (EPA 2005), the strategy—made final in 2009—focuses on four research themes: ”identifying sources, fate, transport, and exposure; understanding human health and ecological effects to inform risk assessments and test methods; developing risk assessment approaches; and pre- venting and mitigating risks” (EPA 2009, p. 1). Those themes are addressed in the context of a decision-making frame- work to aid in identifying important research questions and an environmental- assessment approach based on Davis and Thomas’s Comprehensive Environ- 

30 Background mental Assessment (Davis and Thomas 2006). For each theme, the strategy de- velops key scientific questions and outlines critical paths for the agency to fol- low to address them. Both the NIOSH and EPA strategies clarify their comple- mentary relationships with NEHI (2008). The agency-specific strategies have been complemented by a growing number of reviews and reports that identify nanotechnology EHS research needs, place nanotechnology EHS research within a broader context, and flesh out research strategies (see Table 1-1 for an illustrative list). In the UK, various organizations have addressed nanotechnology EHS issues in the wake of RS/RAE (2004), including the Royal Commission on Environmental Pollution (RCEP 2008) and the UK House of Lords (UKHL 2010). The UK government strategy for nanotechnology, published in 2010, places a high priority on under- standing and addressing the potential health and environmental implications of ENMs (HM Government 2010). In 2009, the Institute of Occupational Medicine published a comprehen- sive review of completed and nearly completed nanomaterial EHS research con- ducted worldwide (Aitken et al. 2009). Using a weight-of-evidence appraisal of over 260 research projects, the report assessed the current state of research and identified where information was lacking on the safety of ENMs. Seventy-one research gaps, covering all aspects of nanomaterial EHS effects, were identified. In 2007-2009, the International Council on Nanotechnology hosted a se- ries of three workshops to assess research needs related to EHS aspects of nanotechnology (ICON 2010a). The workshops brought together experts of various backgrounds, countries, and organizations to identify critical research needs in three categories: understanding principles that relate nanomaterial properties to defined risk factors, working toward predicting nano-bio interac- tions, and advancing the eco-responsible design and disposal of ENMs. The workshops led to 46 specific and ranked needs in research to ensure the safe development and use of ENMs (ICON 2008; 2010b). More recently, the World Technology Evaluation Center, in collaboration with the NNI, published a comprehensive review of efforts to address nanotech- nology EHS issues over the last 10 years with an eye toward the next 10 years (Nel et al. 2010). Written by leading researchers in the field, the report empha- sizes the need for integrative and predictive capabilities to address a growing number of increasingly sophisticated nanomaterials. The report also discusses the potential for sophisticated approaches to address potential health risks posed by nanomaterials by providing the means to avoid harm rather than reacting to it—approaches that underpin green chemistry and sustainable development. WHY ANOTHER STRATEGY IS NEEDED Over the last 7 years, there has been considerable international effort to identify research needs for the development and safe use of nanotechnology products. Perhaps more than in the case of any other emerging technology, the 

Environmental, Health, and Safety Aspects of Engineered Nanomaterials 31 possible consequences of new research and new developments have been ana- lyzed and reanalyzed in advance of widespread commercialization. However, despite growing awareness of the challenges of developing nanotechnology- enabled products and using them safely, the connection and integration between generating data and analyses on emergent risks and developing strategies to pre- vent and manage them remain. Connection and integration will be necessary if the goal of informed oversight over an increasing array of products that depend on ENMs is to be achieved. Despite increasing budgets for nanotechnology-EHS research and a growing number of publications, regulators, decision-makers, and consumers still lack the information needed to make informed public health and environmental policy and regulatory decisions. From reviewing the current state of research, and its relation to the needs of developers, regulators and users of ENMs, three particular points of “discon- nect” are apparent. First, little research progress has been made in some fields, such as the effects of ingested ENMs on human health and the development of relevant and useful material-characterization techniques. Second, there is rela- tively little research on the potential health and environmental effects of more sophisticated ENMs, including active nanomaterials (materials that may change their biologic behavior in response to their environment or a signal), that are expected to enter commerce over the next decade. Third, system-integrative ap- proaches that can address all forms of ENMs based on their properties and an understanding of the underlying biologic interactions that determine exposure and risk. Against that background, the identification of research needs in work- shops over the last several years has been slow to be reflected in active-research pursuits. Common themes that have been identified in workshops include the need for standardized ENMs and harmonized methods for in vitro to in vivo validation in hazard assessments. Also evident are a number of new and rapidly evolving research approaches, including an increasing emphasis on high- throughput screening and predictive modeling, that are considered essential for managing the complexity of ENMs.3 That is not to say that progress is not being made—it clearly is. Repeated analyses of the safety challenges presented by ENMs have been accompanied by increases in both the quantity and the quality of research addressing these chal- lenges. Assessing the impact of previous calls for targeted research is not straightforward—few (if any) authoritative studies have directly evaluated the response of funders, researchers, and practitioners to recommendations—but the evidence that does exist in the published literature suggests that progress has not been as strategically relevant as it could or should be. The documents listed in Table 1-1, suggest that expert communities have had a clear idea of what the key short-term questions are, but that there has been a failure to incorporate them 3 Maynard et al. (2006) challenged the research community to develop high- throughput screening methods and predictive models for ENMs. In 2010, high- throughput screening and predictive modeling were central themes in a forward-looking evaluation of nanomaterial EHS challenges by Nel et al. (2010). 

32 Background into integrated research strategies that lead to relevant and timely answers. The documents also indicate that the research community is involved in revisiting previously stated challenges rather than in demonstrating an awareness and ap- preciation of emerging challenges. For example, there is a repeated focus on simple nanomaterials, such as metal oxides, while researchers and developers are beginning to explore more complex and unconventional materials that are likely to require innovative means of understanding and addressing potential risks. Taken together, despite the substantial progress that has been made in re- cent years, there remains a need to develop an authoritative, integrative, and actionable research strategy that enables stakeholders in and outside the federal government to generate and apply new knowledge about the potential risks as- sociated with ENMs in a timely and responsive manner. In particular, progress over the past decade and the current state of research suggest that there is a broader need for a new conceptual framework within which strategic EHS R&D can be planned, implemented, and reviewed. SCOPE OF THIS REPORT In response to the study request from EPA, the National Research Council (NRC) established the Committee to Develop a Research Strategy for Environ- mental, Health, and Safety Aspects of Engineered Nanomaterials. The commit- tee was charged with developing and monitoring the implementation of an inte- grated research strategy to address the EHS aspects of ENMs. In response to the need for an authoritative, integrative, and actionable research strategy outlined above, this report will develop a conceptual framework for EHS-related re- search; establish a research plan with short- and long-term research priorities; and estimate resources necessary to implement this research plan. A subsequent report will evaluate research progress. The committee will consider current and emerging uses of ENMs and the scientific uncertainties related to physical and chemical properties, potential exposures, toxicity, toxicokinetics, and environ- mental fate of these materials. In its evaluation the committee will also consider existing research roadmaps and progress made in their implementation. A sec- ond report is to evaluate research progress and update the research priorities and resource estimates. The committee was not tasked with estimating the actual risk or benefits associated with EHS aspects of nanotechnology. In addition to developing a conceptual framework for EHS-related re- search, this first report considers seven specific questions:  What properties of ENMs need to be considered in assessing their po- tential exposures, toxicity, toxicokinetics, and environmental fate? What stan- dard testing materials are needed?  What methods and technologies are needed for detecting, measuring, analyzing, and monitoring ENMs? What gaps in analytic capability need to be addressed? 

Environmental, Health, and Safety Aspects of Engineered Nanomaterials 33  What studies of ENM exposure, toxicology, toxicokinetics, human health effects, and environmental fate are needed for assessing the risks that they pose?  What testing methods should be developed for assessing the potential toxicity, toxicokinetics, and environmental fate of ENMs?  What models should be developed for predicting the effects of ENMs on human health and the environment?  What are the research priorities for understanding life-cycle risks to humans and the environment from applications of nanotechnology?  What criteria should be used to evaluate research progress? ELEMENTS OF A NANOTECHNOLOGY ENVIRONMENTAL, HEALTH, AND SAFETY RESEARCH STRATEGY In addressing its charge, the committee considered the key elements of a successful research strategy, as articulated in the Review of the Federal Strategy for Nanotechnology-Related Environmental, Health, and Safety Research (NRC 2009) (see Box 1-1). The 2009 NRC committee defined those elements and used them to evaluate the federal strategy. The committee based its discussion on the proposition that a strategy will address a set of defined goals, that there will be a plan to achieve the goals, and that metrics for success will indicate when the goals have been achieved. Because of the value of articulating and discussing the elements of a research strategy, the present committee has chosen to adopt the elements and build on them. The elements of an effective research strategy were drawn from a histori- cal perspective about how others had shaped their approaches to risk research and had considered the need to address a mix of both “exploratory” and “tar- geted” research. The elements are discussed below in the context of the current effort. BOX 1-1 Elements of A Research Strategy  Vision or statement of purpose  Goals  Evaluation of the existing state of the science  Roadmap  Evaluation  Review  Resources  Mechanisms  Accountability Source: NRC 2009, p. 27. 

34 Background Vision or Statement of Purpose At the beginning of this chapter, the committee stated why a coherent risk- research strategy for nanomaterials is needed. Primary among the reasons is the rapid technologic advances that have resulted in the emergence of novel materi- als that have a potential for interaction with humans and ecosystems. There is considerable societal concern because of the potential, albeit unknown, risks. Scientific data and assessment are needed to determine the nature and extent of risks to the environment and health associated with a wide variety of existing and emerging nanomaterials. A strategy to address EHS issues would be a guide for scientists and decision-makers who need to set priorities for the use of lim- ited resources while addressing the key risk-related questions. Goals Goals for the EHS risk-research strategy, articulated at the end of this chapter, are intended to guide the responsible development of novel nanomateri- als and the management of existing nanomaterials and products to prevent and minimize their potential risks. The fulfillment of the goals will depend on the availability of resources and on the concerted efforts of government, academic, and industrial partnerships. Success in addressing these complex issues is possi- ble only through interdisciplinary problem-solving. Evaluation of the Existing State of the Science A key component in the development of the risk-research strategy is the evaluation of the existing state of the science. Numerous efforts to catalog and evaluate relevant data and models have been made, and many have been pub- lished (see Table 1-1). Although it is not the intent of the current effort to evalu- ate that information de novo or exhaustively, a summary of the existing state of the science is provided in Chapter 3. Roadmap Given the complexity of the issues—the variety of the materials and appli- cations of nanomaterial science not yet envisioned—it is critical that a roadmap (Chapters 5 and 6) be developed as a part of the current effort. The roadmap will need to address not only the path to short- and long-term research goals but the leveraging of available resources, institutions, and mechanisms both nationally and internationally. The roadmap will need to be flexible to incorporate new information and to be adjusted as knowledge and experience accumulate. It should also be responsive in the short term, providing approaches for environ- 

Environmental, Health, and Safety Aspects of Engineered Nanomaterials 35 mental and human health protection even as the knowledge base is growing and the strategy is evolving. Evaluation A key element of an effective strategy is evaluation, to be discussed in Chapter 6. Measuring progress in research is inherently difficult. As discussed in NRC (2008), research cannot be evaluated on the basis of “ultimate outcomes,” because outcomes often cannot be known or, in some cases, even expected. In- stead, the 2008 report concludes that research should be evaluated on the basis of its quality, relevance, and effectiveness in addressing current priorities and future needs. The present report attempts to develop reasonable milestones of success along a defined timeline, considering the advice and perspective of NRC (2008). Review Like the committee that wrote NRC (2009), the present committee recog- nizes the need for periodic review and adjustment of the strategy as knowledge and experience accumulate. Review is critical in realizing the committee’s vi- sion of success, and processes for review will be discussed. It will require in- volvement of a broad array of stakeholders to ensure that a comprehensive per- spective informs refinement of the strategy. Resources Resources to address the issues raised in the strategy will always be lim- ited, but it is incumbent on this committee to estimate the resources needed to make reasonable progress toward success. It is beyond the scope of this effort to propose how such resources will be obtained or leveraged, but the magnitude of the resources should be considered if the nature of the problem is to be ad- dressed. Mechanisms Optimal approaches and mechanisms for accomplishing exploratory and targeted research in the context of the strategy need to be discussed. As exam- ples, the balance between government and industry funding and ways to enable interdisciplinary funding of collaborative research that crosses traditional agency or administrative boundaries will be considered. Accountability Accountability needs to be an element of the strategy. Who will “take ownership” of the overarching strategy? Who will assume or assign responsibil- 

36 Background ity for individual aspects of the strategy? Who will be responsible for managing resources, ensuring review and stakeholder involvement, and developing the mechanisms discussed above? Those and other questions of accountability will be considered in Chapter 6. PRIOR APPROACHES TO SETTING RESEARCH AGENDAS ON OTHER TOPICS There are numerous examples of research agendas that have addressed major issues across a variety of domains. Spectacular successes of planned large-scale research and implementation strategies with defined objectives and end points are widely cited, including those of the Manhattan Project and the U.S. Human Genome Project. The Human Genome Project was implemented in 1991 with interrelated goals involving mapping of the human genome, the crea- tion of a complete sequence of human DNA and the DNA of other organisms, and development of capabilities and technologies (for example, through the Na- tional Human Genome Research Institute). In the plan for the initial 5 years (1991-1995), cost estimates were made for sequencing the human genome. At the 5-year mark, a new plan for the next 5 years was elaborated (Collins et al. 1998). Progress toward the initial goals was charted, including analysis of quan- tifiable outcomes, and new goals were proposed. The initial working draft of the genome was published in 2000, ahead of schedule (Pennisi 2000a,b). The pace reflected technologic advances and the competition between the National Hu- man Genome Research Institute and the Celera Corporation4. The project also benefited from a new paradigm of rapid and open data-sharing; sequence data were made available as they were generated. The research agenda set by the National Research Council's Committee on Research Priorities for Airborne Particulate Matter (referred to as the PM Com- mittee) is relevant to the charge of the present committee, although more nar- rowly defined in scope. The PM Committee was requested by Congress to ad- dress uncertainties in the scientific evidence related to airborne PM after the 1997 decision to establish a new National Ambient Air Quality Standard for fine PM. The uncertainties had been highlighted as the evidence on fine PM and health effects was reviewed. The PM Committee was charged with developing a multiyear research agenda, developing estimates of costs of implementing the strategy, monitoring progress, and evaluating the extent to which key uncertain- ties had been reduced. The PM Committee produced four reports related to its charge, the first in 1998 and the last in 2004 (NRC 1998, 1999, 2001, 2004). The development of a framework for characterizing the sources of uncer- tainty was central to the PM Committee's approach (Figure 1-1). That toxi- cologic framework helped in identifying the major uncertainties and the com- 4 Celera Corporation, a private company, worked in parallel with the government to sequence the human genome. 

Environmental, Health, and Safety Aspects of Engineered Nanomaterials 37 FIGURE 1-1 A general framework for integrating particulate-matter research. Source: NRC 1998, p. 35. plementary research topics. Several of the research topics were overarching, such as the development and testing of air-quality models, and analysis and measurement. The committee proposed a "portfolio" of research to be under- taken over a 13-year span and estimated costs on a year-by-year basis. In approaching its charge, the PM Committee elaborated on criteria for se- lecting its research topics, for characterizing progress on the agenda, and for evaluating the reduction of uncertainty. The committee selected three criteria for its initial list of research topics: scientific value, decision-making value, and feasibility and timing (NRC 1998). The first report (NRC 1998) provided defini- tions of the criteria and discussed their implementation. In its second and third reports (NRC 1999, 2001), the PM Committee added interaction, integration, and accessibility. With regard to the assessment of progress on the research agenda, the PM Committee screened existing approaches for useful models and took an evidence-based approach, involving surveying expenditures, research projects, and publications. For each topic, the final report covered the questions What has been learned? and What remains to be done? (NRC 2004). The PM Committee reports provided useful examples for the present committee as it addressed its charge with regard to ENMs. The adoption of a toxicologic framework and the designation of research topics around the frame- work provided a needed transparent structure. The PM Committee's listing of operational criteria ensured clarity in how the research agenda was developed and tracked. (The present committee uses those criteria for evaluating research progress in Chapter 6.) Finally, the evidence-based approach ensured objectivity in the assessment of progress. GOALS OF THIS STRATEGY Despite the progress made to date, it remains imperative that we generate timely and relevant knowledge that will underpin the responsible development of technologies based on manipulating matter at the nanoscale. Nanoscale sci- ence and engineering are leading to remarkable new discoveries that have the potential to address major societal challenges while providing for substantial 

38 Background economic growth. Those discoveries are enabling the emergence of new tech- nologies and the enhancement of existing technologies. Without strategic re- search on emergent risks associated with the new and enhanced technologies— and a clear understanding of how to prevent, manage, and avoid them—the fu- ture of safe and sustainable nanotechnology-based materials, products, and processes is uncertain. In today’s fast-paced and interconnected world, a worth- while economic and social return on government and industry investment in nanotechnology is unlikely to be fully realized without risk research, including research on translating knowledge into evidence-informed and socially respon- sible decision-making. Without the research, decision-makers will not have the tools and information that they need to develop safe and responsible technolo- gies, trust in business and government to ensure safety could erode, and there will continue to be an inability to identify materials that pose important risks and to confidently differentiate them from materials and products that pose little or no risk. There is a need to rethink and re-evaluate what is important from a human health and environmental perspective in addressing current and emerging ENMs and to establish a scientific foundation for risk-based decision-making. We need an EHS research strategy that is independent of any one stakeholder group, that reflects the interests of multiple types of stakeholders, that has as its primary aim protection of human and environmental health, that builds on past efforts and is flexible in anticipating and adjusting to emerging challenges, and that provides decision-makers and decision-influencers with timely, relevant, and accessible information. Ten years after the establishment of the NNI, the emphasis of nanotech- nology is shifting from research to commercialization. As it does, society cannot afford to remain entangled in confusion as the challenges and opportunities pre- sented by nanotechnology are addressed. Although they were invaluable in their own right, previous attempts to identify research needs and develop research strategies have not brought needed clarity to nanotechnology EHS research needs, nor provided a relevant and actionable research strategy. The strategy presented here marks the development of a forward-looking, multiple stake- holder perspective that protects human and environmental health while reaping the potential benefits of nanoscale science. In light of these needs, the goals of the research strategy are to generate scientific evidence that  Guides approaches to environmental and human health protection even as our knowledge of ENMs is expanding and the research strategy itself is evolving.  Makes it possible to identify and predict risks posed by nanomaterials with sufficient certainty to enable informed decisions on how the risks should be prevented, managed, or mitigated. 

Environmental, Health, and Safety Aspects of Engineered Nanomaterials 39  Makes it possible to identify and evaluate the relative merits of various risk-management options, including measures to reduce the inherent hazard or exposure potential of nanomaterials. Chapter 2 of this report presents a conceptual framework for considering the EHS risks associated with nanomaterials. Chapter 3 provides an overview of what is known about the EHS aspects of nanomaterials in the context of the con- ceptual framework and identifies knowledge gaps. Chapter 4 addresses cross- cutting tools needed to understand the relationship of ENM properties and their interactions with humans and the environment. Chapter 5 presents the commit- tee’s vision of the research agenda, including the recommended timing and costs of research activities. Chapter 6 describes implementation of the research strat- egy and how research progress will be evaluated. REFERENCES Aitken, R.J., S.M. Hankin, B. Ross, C.L. Tran, V. Stone, T.F. Fernandes, K. Donaldson, R. Duffin, Q. Chaudhry, T.A. Wilkins, S.A. Wilkins, L.S. Levy, S.A. Rocks, and A. Maynard. 2009. EMERGNANO: A Review of Completed and Near Completed Environment, Health and Safety Research on Nanomaterials and Nanotechnology. DEFRA (UK Department for Environment Food and Rural Affairs) Project CB0409. Report TM/09/01. Institute of Occupational Medicine, Edinburg, UK [online]. Available: http://www.safenano.org/Uploads/EMERGNANO_CB0409_ Full.pdf [accessed Nov. 10, 2010]. Allianz/OECD (Allianz Center for Technology and Organisation for Economic Co- operation and Development). 2005. Small Sizes That Matter: Opportunities and Risks of Nanotechnologies: Report in Co-operation with the OECD International Futures Programme, C. Lauterwasser, ed. Allianz AG, München, and OECD Inter- national Futures Programme, Paris [online]. Available: http://www.oecd.org/data oecd/32/1/44108334.pdf [accessed Sept. 7, 2011]. Balbus, J.M., A.D. Maynard, V.L. Colvin, V. Castranova, G.P. Daston, R.A. Denison, K.L. Dreher, P.L. Goering, A.M. Goldberg, K.M. Kulinowski, N.A. Monteiro- Riviere, G. Oberdörster, G.S. Omenn, K.E. Pinkerton, K.S. Ramos, K.M. Rest, J.B. Sass, E.K. Silbergeld, and B.A. Wong. 2007. Meeting report: Hazard assess- ment for nanoparticles-report from an interdisciplinary workshop. Environ. Health Perspect. 115(11):1654-1659. Bradley, J. 2010. Nanotech’s Evolving Environmental Health, and Safety Landscape. Presentation at Nanosafe 2010: International Conference on Safe Production and Use of Nanomaterials, Nov. 16-18, 2010, Minatec, France [online]. Available: http://www.nanosafe.org/home/liblocal/docs/Nanosafe%202010/2010_oral%20pre sentations/PL0a_Bradley.pdf [accessed Dec. 17, 2010]. Breggin, L., R. Falkner, N. Jaspers, J. Pendergrass, and R. Porter. 2009. Securing the Promise of Nanotechnologies: Towards Transatlantic Regulatory Cooperation. London: Chatham House [online]. Available: http://www.chathamhouse.org.uk/ files/14692_r0909_nanotechnologies.pdf [accessed Apr. 14, 2011]. 

40 Background Collins , F.S., A. Patrinos, E. Jordan, A. Chakravarti, R. Gesteland, L. Walters, and the members of the DOE and NIH planning groups. 1998. New goals for the U.S. Human Genome Project: 1998-2003. Science 282(5389): 682-689. Council of Canadian Academies. 2008. Small is Different: A Science Perspective on the Regulatory Challenges of the Nanoscale, Report of the Expert Panel of Nano- technology. Ottawa: Council of Canadian Academies [online]. Available: http:// www.scienceadvice.ca/uploads/eng/assessments%20and%20publications%20and% 20news%20releases/nano/(2008_07_10)_report_on_nanotechnology.pdf [accessed Apr. 13, 2011]. Davis, J.M., and V.M. Thomas. 2006. Systematic approach to evaluating trade-offs among fuel options: The lessons of MTBE. Ann. N.Y. Acad. Sci. 1076:498-515. DEFRA (Department for Environment, Food and Rural Affairs). 2005. Characterising the Potential Risks Posed by Engineered Nanoparticles: A First UK Government Re- search Report. Department for Environment, Food and Rural Affairs, Her Maj- esty’s Government, London [online]. Available: http://www.nanowerk.com/ nanotechnology/reports/reportpdf/report12.pdf [accessed Apr. 13, 2011]. DEFRA (Department for Environment, Food and Rural Affairs). 2007. Characterising the Potential Risks Posed by Engineered Nanoparticles: A Second UK Government Research Report. Department for Environment, Food and Rural Affairs, Her Maj- esty’s Government, London [online]. Available: http://archive.defra.gov.uk/envir onment/quality/nanotech/documents/nanoparticles-riskreport07.pdf [accessed Apr. 13, 2011]. Denison, R.A. 2005. A Proposal to Increase Federal Funding of Nanotechnology Risk Research to at Least $100 Million Annually. Environmental Defense Fund. April 2005 [online]. Available: http://www.edf.org/documents/4442_100milquestionl.pdf [accessed Apr. 13, 2011]. EC (European Commission). 2005. Communication from the Commission to the Council, the European Parliament and the Economic Social Committee: Nanosciences and Nanotechnologies: An Action Plan for Europe 2005-2009. European Commission, Brussels [online]. Available: http://ec.europa.eu/research/industrial_technologies/ pdf/nano_action_plan_en.pdf [accessed Nov. 9, 2010]. EDF/DuPont (Environmental Defense Fund and DuPont). 2007. Nano Risk Framework. Environmental Defense Fund, Washington, DC, and DuPont, Wilmington, DE. June 2007 [online]. Available: http://nanoriskframework.com/page.cfm?tagID=10 81 [accessed Mar. 17, 2010]. EFSA (European Food Safety Authority). 2009. Scientific Opinion: The Potential Risks Arising from Nanoscience and Nanotechnologies on Food and Feed Safety. EFSA J. 958:1-39 [online]. Available: http://www.efsa.europa.eu/fr/scdocs/doc/sc_op_ej 958_nano_en,0.pdf [accessed Apr. 14, 2011]. EPA (U.S. Environmental Protection Agency). 2005. Nanotechnology White Paper. Ex- ternal Review Draft. Nanotechnology Workgroup, Science Policy Council, U.S. Environmental Protection Agency, Washington, DC. December 2, 2005 [online]. Available: http://www.epa.gov/osa/pdfs/EPA_nanotechnology_white_paper_exter nal_review_draft_12-02-2005.pdf [accessed Nov. 10, 2010]. EPA (U.S. Environmental Protection Agency). 2007. Nanotechnology White Paper. EPA 100/B-07/001. Office of the Science Advisor, Science Policy Council, U.S. Envi- ronmental Protection Agency, Washington, DC. February 2007 [online]. Avail- able: http://www.epa.gov/osainter/pdfs/nanotech/epa-nanotechnology-whitepaper- 0207.pdf [accessed Apr. 13, 2011]. 

Environmental, Health, and Safety Aspects of Engineered Nanomaterials 41 EPA (U.S. Environmental Protection Agency). 2009. Nanomaterial Research Strategy. EPA 620/K-09/011. Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC. June 2009 [online]. Available: http://www.epa.gov/nano science/files/nanotech_research_strategy_final.pdf [accessed Nov. 10, 2010]. ETC Group (Action Group of Erosion, Technology and Concentration). 2003. Size Mat- ters! No Small Matter II: The Case for a Global Moratorium. Occasional Paper 7(1). ETC Group, Ottawa, Canada [online]. Available: http://www.etcgroup.org/ upload/publication/165/01/occ.paper_nanosafety.pdf [accessed Nov. 10, 2010]. FAO/WHO (Food and Agriculture Organization of the United Nation and World Health Organization) 2009. FAO/WHO Expert Meeting on the Application of Nanotech- nologies in the Food and Agriculture Sectors: Potential Food Safety Implications. Meeting Report. Food and Agriculture Organization of the United Nation, Rome, Italy, and World Health Organization, Geneva, Switzerland [online]. Available: http://www.fao.org/ag/agn/agns/files/FAO_WHO_Nano_Expert_Meeting_Report_ Final.pdf [accessed Apr. 14, 2011]. FDA (U.S. Food and Drug Administration). 2007. Nanotechnology. A Report of the U.S. Food and Drug Administration Nanotechnology Task Force. July 25, 2007. U.S. De- partment of Health and Human Services, Public Health Service, Food and Drug Ad- ministration, Rockville, MD [online]. Available: http://www.fda.gov/downloads/ ScienceResearch/SpecialTopics/Nanotechnology/ucm110856.pdf [accessed Apr. 13, 2011]. Ford, E. 2005. Recommendations for Nanotechnology ESH Research. Presentation at the American Institute of Chemical Engineers (AIChE) Annual Meeting, November 3, 2005, Cincinnati, OH [online]. Available: http://www.chemicalvision2020.org/ pdfs/nano_recs.pdf [accessed Nov. 10, 2010]. GAO (U.S. Government Accountability Office). 2008. Nanotechnology: Better Guidance is Needed to Ensure Accurate Reporting of Federal Research Focused on Envi- ronmental, Health and Safety Risks. GAO-08-402. Washington, DC: U.S. Gov- ernment Accountability Office [online]. Available: http://www.gao.gov/new.items/ d08402.pdf [accessed Apr. 14, 2011]. GAO (U.S. Government Accountability Office). 2010. Nanotechnology: Nanomaterials Are Widely Used in Commerce, but EPA Faces Challenges in Regulating Risk. GAO-10-549. Washington, DC: U.S. Government Accountability Office [online]. Available: http://www.gao.gov/new.items/d10549.pdf [accessed Apr. 14, 2011]. HM Government (Her Majesty’s Government). 2010. UK Nanotechnologies Strategy: Small Technologies, Great Opportunities. Her Majesty’s Government, London. March 2010 [online]. Available: http://www.bis.gov.uk/assets/BISPartners/GoScie nce/Docs/U/10-825-uk-nanotechnologies-strategy [accessed Apr. 14, 2011]. Höck, J. 2008. Proceedings of the Workshop on Research Projects on the Safety of Nanomaterials: Reviewing the Knowledge Gaps, 17-18 April 2008, Brussels. DG Research, European Commission [online]. Available: ftp://ftp.cordis.europa.eu/pu b/nanotechnology/docs/final_report.pdf [accessed Apr. 13, 2011]. Hwang, D., and J. Bradley. 2010. The Recession's Ripple Effect on Nanotech. Small Times, August 12, 2010 [online]. Available: http://www.electroiq.com/index/display/nano tech-article-display/5049629279/articles/small-times/nanotechmems/materials/gener al/2010/april/the-recession_s_ripple.html [accessed Apr. 13, 2011]. ICFI (ICF International). 2006. Characterizing the Environmental, Health and Safety Implications of Nanotechnology: Where Should the Federal Government Go From Here? ICF International, Fairfax, VA. 

42 Background ICON (International Council on Nanotechnology). 2008. Towards Predicting Nano- Biointeractions: An International Assessment of Nanotechnology Environment, Health and Safety Research Needs. No. 4. International Council on Nanotechnology, Rice University, Houston, TX. May 1, 2008 [online]. Available: http://cohesion.rice. edu/centersandinst/icon/emplibrary/icon_rna_report_full2.pdf [accessed Feb. 16, 2011]. ICON (International Council on Nanotechnology). 2010a. International Assessment of Research Needs for Nanotechnology Environmental, Health, and Safety. Interna- tional Council on Nanotechnology, Rice University, Houston, TX [online]. Avail- able: http://icon.rice.edu/projects.cfm?doc_id=12973 [accessed Nov. 22, 2010]. ICON (International Council on Nanotechnology). 2010b. Advancing the Eco- Responsible Design and Disposal of Engineered Nanomaterials: An International Workshop. No. 5. International Council on Nanotechnology, Rice University, Houston, TX. February 2010 [online]. Available: http://cohesion.rice.edu/center sandinst/icon/emplibrary/ICON_Eco-Responsible_Design_and_Disposal%20of_E ngineered_Nanomaterials_Full_Report.pdf [accessed Nov. 10, 2010]. Joy, B. 2000. Why the Future Doesn’t Need Us. Wired Magazine, August 4, 2000 [online]. Available: http://www.wired.com/wired/archive/8.04/joy.html?pg=1&top ic=&topic_set= [accessed Nov. 10, 2010]. Kaluza, S., J.K. Balderhaar, B. Orthen, B. Honnert, E. Jankowska, P. Pietrowski, M.G. Rosell, C. Tanarro, J. Tejedor, and A. Zugasti. 2009. Literature Review: Workplace Exposure to Nanoparticles, J. Kosk-Bienko, ed. European Agency for Safety and Health at Work [online]. Available: http://osha.europa.eu/en/publiccations/literature_ reviews/workplace_exposure_to_nanoparticles [accessed Apr. 14, 2011]. Lloyd’s. 2007. Nanotechnology Recent Developments, Risks and Opportunities. Lloyd’s Emerging Risks Team Report [online]. Available: http://www.lloyds.com/~/media/ c6f557f00581437ea4b9325293731275.ashx [accessed Sept. 7, 2011]. Luther, W., ed. 2004. Technological Analysis: Industrial Application of Nanomaterials- Chances and Risks. Future Technologies No. 54. Future Technologies Division of VDI Technologiezentrum GmbH, Düsseldorf. August 2004 [online]. Available: http://www.zukuenftigetechnologien.de/11.pdf [accessed Apr. 13, 2011]. Lux Research. 2008a. Nanomaterials State of the Market Q3 2008: Stealth Success, Broad Impact. Lux Research, July 1, 2008 [online]. Available: https://portal.lux researchinc.com/research/document_excerpt/3735 [accessed Dec. 17, 2010]. Lux Research. 2008b. Overhyped Technology Starts to Reach Potential: Nanotech to Im- pact $3.1 Trillion in Manufactured Goods in 2015. Press release: July 22, 2008 [online]. Available: http://www.luxresearchinc.com/press/RELEASE_Nano-SMR_7 _22_08.pdf [accessed Dec. 17, 2010]. Lux Research. 2009a. The Wizards of Nanointermediates: Assessing Catalysts, Coatings, and Composites on the Lux Innovation Grid. Lux Research, September 2, 2009 [online]. Available: https://portal.luxresearchinc.com/research/document_excerpt/ 5383 [accessed Dec. 17, 2010]. Lux Research. 2009b. The Recession’s Ripple Effect on Nanotech, State of the Market Research. Lux Research, June 9, 2009 [online]. Available: https://portal.luxresear chinc.com/research/document_excerpt/4995 [accessed Feb. 22, 2010]. Maynard, A.D. 2006. Nanotechnology: A Research Strategy for Addressing Risk. Project on Emerging Nanotechnologies PEN 3. Washington, DC: Woodrow Wilson Inter- national Center for Scholars. July 2006 [online]. Available: http://www.nanotech project.org/process/assets/files/2707/77_pen3_risk.pdf [accessed Nov. 10, 2010]. 

Environmental, Health, and Safety Aspects of Engineered Nanomaterials 43 Maynard, A.D., R.J. Aitken, T. Butz, V. Colvin, K. Donaldson, G. Oberdörster, M.A. Philbert, J. Ryan, A. Seaton, V. Stone, S.S. Tinkle, L. Tran, N.J. Walker, and D.B. Warheit. 2006. Safe handling of nanotechnology. Nature 444(7117):267-269. Maynard, A.D. 2010. Rethinking Nanotechnology—Responding to a Request for Infor- mation on the U.S. Nanotechnology Strategic Plan. 2020 Science, August 30, 2010 [online]. Available: http://2020science.org/2010/08/30/rethinking-nanotechnology- responding-to-a-request-for-information-on-the-us-nanotechnology-strategic-plan/ [accessed November 28, 2011]. NEHI (Nanotechnology Environmental Health Implications Working Group). 2006. En- vironmental, Health, and Safety Research Needs for Engineering Nanoscale Mate- rials. Nanotechnology Environmental Health Implications Working Group, Nano- scale Science, Engineering, and Technology Subcommittee, Committee on Technology, National Science and Technology Council. September 2006 [online]. Available: http://www.nano.gov/NNI_EHS_research_needs.pdf [accessed July 12. 2011]. NEHI (Nanotechnology Environmental Health Implications Working Group). 2007. Priori- tization of Environmental, Safety and Health Research Needs for Engineered Nano- scale Materials: An Interim Document for Public Comment. Nanotechnology Envi- ronmental Health Implications Working Group, Nanoscale Science, Engineering, and Technology Subcommittee, Committee on Technology, National Science and Tech- nology Council. August 2007 [online]. Available: http://nanotech.law.asu.edu/Docu- ments/2010/08/Prioritization_EHS_Research_Needs_Engineered_Nanoscale_Materi als_527_8119.pdf [accessed July 13, 2011]. NEHI (Nanotechnology Environmental Health Implications Working Group). 2008. Strategy for Nanotechnology-Related Environmental, Health, and Safety Research. National Nanotechnology Initiative. Nanotechnology Environmental Health Impli- cations Working Group, Subcommittee on Nanoscale Science, Engineering, and Technology, Committee on Technology, National Science and Technology Coun- cil. February 2008 [online]. Available: http://www.nano.gov/NNI_EHS_Resear ch_Strategy.pdf [accessed July 12. 2011]. NEHI (Nanotechnology Environmental Health Implications Working Group). 2010. Na- tional Nanotechnology Initiative 2011 Environmental, Health, and Safety Strategy - Draft for Public Comment, December 2010. Nanotechnology Environmental Health Implications Working Group, Subcommittee on Nanoscale Science, Engi- neering, and Technology, Committee on Technology, National Science and Tech- nology Council [online]. Available: http://ethics.iit.edu/NanoBank/Draft-2011- NNI-EHS-Research-Strategy.pdf [accessed July 12. 2011]. NEHI (Nanotechnology Environmental Health Implications Working Group). 2011. Na- tional Nanotechnology Initiative 2011 Environmental, Health, and Safety Strategy, October 2011. Nanotechnology Environmental Health Implications Working Group, Subcommittee on Nanoscale Science, Engineering, and Technology, Committee on Technology, National Science and Technology Council [online]. Available: http:// www.nano.gov/sites/default/files/pub_resource/nni_2011_ehs_research_strategy.pdf [accessed Nov. 23, 2011]. Nel, A., D. Grainger, P. Alvarez, S. Badesha, V. Castranova, M. Ferrari, H. Godwin, P. Grodzinski, J. Morris, N. Savage, N. Scott, and M. Wiesner. 2010. Nanotechnol- ogy environmental, health and safety issues. Pp. 107-156 in WTEC Panel Report on Nanotechnology Research Directions for Societal Needs in 2020: Retrospective and Outlook, M.C. Roco, C.A. Mirkin, and M.C. Hersam, eds. Springer [online]. 

44 Background Available: http://www.wtec.org/nano2/Nanotechnology_Research_Directions_to_ 2020/Nano_Resarch_Directions_to_2020.pdf [accessed Feb. 16, 2011]. NIOSH (National Institute for Occupational Safety and Health). 2005. Strategic Plan for NIOSH Nanotechnology Research, Filling the Knowledge Gaps, Draft [online]. Available: http://www.cdc.gov/niosh/topics/nanotech/strat_plan.html [accessed Aug. 1, 2011]. NIOSH (National Institute for Occupational Safety and Health). 2008. Strategic Plan for NIOSH Nanotechnology Research and Guidance: Filling the Knowledge Gaps. Draft Report. National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services. February 26, 2008 [online]. Available: http://www.cdc.gov/niosh/topics/nanotech/ pdfs/NIOSH_Nanotech_Strategic_Plan.pdf [accessed Apr. 14, 2011]. NIOSH (National Institute for Occupational Safety and Health). 2010. Strategic Plan for NIOSH Nanotechnology Research and Guidance: Filling the Knowledge Gaps. National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services [online]. Avail- able: http://www.cdc.gov/niosh/docs/2010-105/pdfs/2010-105.pdf [accessed Nov. 10, 2010]. NNI-ChI CBAN ESH Working Group (National Nanotechnology Initiative-Chemical Industry Consultative Board for Advancing Nanotechnology, Environmental Safety and Health Working Group). 2007. Recommended Topics for R&D Activi- ties: Toxicological Hazard Assessment of Nanomaterials. The Chemical Industry Vision2020 Technology Partnership (Vision 2020) [online]. Available: http:// www.chemicalvision2020.org/pdfs/cban_recommendedtopics.pdf [accessed Nov. 10, 2010]. NRC (National Research Council). 1998. Research Priorities for Airborne Particulate Matter. I. Immediate Priorities and Long-Range Research Portfolio. Washington, DC: National Academy Press. NRC (National Research Council). 1999. Research Priorities for Airborne Particulate Matter. II. Evaluating Research Progress and Updating the Portfolio. Washington, DC: National Academy Press. NRC (National Research Council). 2001. Research Priorities for Airborne Particulate Matter. III. Early Research Progress. Washington, DC: National Academy Press. NRC (National Research Council). 2004. Research Priorities for Airborne Particulate Matter. IV. Continuing Research Progress. Washington, DC: National Academies Press. NRC (National Research Council). 2008. Evaluating Research Efficiency in the U.S. Environmental Protection Agency. Washington, DC: National Academies Press. NRC (National Research Council). 2009. Review of the Federal Strategy for Nanotech- nology-Related Environmental, Health, and Safety Research. Washington, DC: National Academies Press. NSET (Nanoscale Science, Engineering, and Technology Subcommittee). 2004. The National Nanotechnology Initiative Strategic Plan. Subcommittee on Nanoscale Science, Engineering, and Technology, Committee on Technology, National Sci- ence and Technology Council. December 2004 [online]. Available: http://neutrons. ornl.gov/workshops/nni_05/nni_strategic_plan_0412.pdf [accessed July 12, 2011]. NSET (Nanoscale Science, Engineering, and Technology Subcommittee). 2006. The Na- tional Nanotechnology Initiative: Research and Development Leading to a Revolu- tion in Technology and Industry: Supplement to the President's FY 2007 Budget. Subcommittee on Nanoscale Science, Engineering, and Technology, National Sci- 

Environmental, Health, and Safety Aspects of Engineered Nanomaterials 45 ence and Technology Council. July 2006 [online]. Available: http://jcots.state.va.us/ 2007%20Content/Materials/2007%20NNI%20Budget.pdf [accessed July 12, 2011]. NSET (Nanoscale Science, Engineering, and Technology Subcommittee). 2010. The Na- tional Nanotechnology Initiative: Research and Development Leading to a Revolu- tion in Technology and Industry: Supplement to the President's FY 2011 Budget. Subcommittee on Nanoscale Science, Engineering, and Technology, National Sci- ence and Technology Council. February 2010 [online]. Available: https://engine eering.purdue.edu/nanotrees/files/NNI_2011_budget_supplement.pdf [accessed July 13, 2011]. Oberdörster, G., V. Stone, and K. Donaldson. 2007. Toxicology of nanoparticles: A his- torical perspective. Nanotoxicology. 1(1):2-25. PCAST (President’s Council of Advisors on Science and Technology). 2010. Report to the President and Congress on the Third Assessment of the National Nanotechnol- ogy Initiative. March 2010 [online]. Available: http://www.whitehouse.gov/sites/ default/files/microsites/ostp/pcast-nano-report.pdf [accessed Nov. 9, 2010]. Pennisi, E. 2000a. Chromosone 21 done. Phase two begun. Science. 288(5468):939. Pennisi, E. 2000b. And the gene number is…? Science. 288(5469):1146-1147. RCEP (Royal Commission on Environmental Pollution). 2008. Twenty-Seventh Report: Novel Materials in the Environment: The Case of Nanotechnology. Royal Commis- sion on Environmental Pollution. November 2008 [online]. Available: http://www. official-documents.gov.uk/document/cm74/7468/7468.pdf [accessed Nov. 10, 2010]. Renn, O., and M. Roco. 2006. White Paper on Nanotechnology Risk Governance. White Paper No. 2. International Risk Governance Council, Geneva [online]. Available: http://www.irgc.org/IMG/pdf/IRGC_white_paper_2_PDF_final_version-2.pdf [ac- cessed Apr. 13, 2011]. RS/RAE (The Royal Society and The Royal Academy of Engineering). 2004. Nano- science and Nanotechnologies: Opportunities and Uncertainties. London: The Royal Society. July 2004 [online]. Available: http://www.nanotec.org.uk/report/Na no%20report%202004%20fin.pdf [accessed Nov. 9, 2010]. SCCP (Scientific Committee on Consumer Products). 2007. Opinion on Safety of Nano- materials in Cosmetic Products. SCCP/1147/07. Scientific Committee on Con- sumer Products, Health and Consumer Protection Directorate, European Commis- sion. December 2007 [online]. Available: http://ec.europa.eu/health/ph_risk/com mittees/04_sccp/docs/sccp_o_123.pdf [accessed Apr. 13, 2011]. SCENIHR (Scientific Community on Emerging and Newly Identified Health Risks). 2006. Opinion on the Appropriateness of Existing Methodologies to Assess the Po- tential Risks Associated with Engineered and Adventitious Products of Nanotech- nologies. SCENIHR 002/05. Scientific Community on Emerging and Newly Iden- tified Health Risks, Health & Consumer Protection Directorate-General, European Commission. March 2006 [online]. Available: http://www.oecd.org/dataoecd/52/ 24/37999466.pdf [accessed Nov. 9, 2010]. SCENIHR (Scientific Community on Emerging and Newly Identified Health Risks). 2007. Opinion on the Appropriateness of the Risk Assessment Methodology in Accordance with the Technical Guidance Documents for New and Existing Substances for As- sessing the Risks of Nanomaterials. Scientific Community on Emerging and Newly Identified Health Risks, Health & Consumer Protection Directorate-General, Euro- pean Commission. June 2007 [online]. Available: http://ec.europa.eu/health/ph_risk/ committees/04_scenihr/docs/scenihr_o_010.pdf [accessed Apr. 13, 2011]. SCENIHR (Scientific Committee on Emerging and Newly Identified Health Risks). 2009. Risk Assessment of Products of Nanotechnologies. Scientific Committee on Emerg- 

46 Background ing and Newly Identified Health Risks, Health & Consumer Protection Directorate- General, European Commission. January 2009 [online]. Available: http://ec.europa. eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_023.pdf [accessed Apr. 14, 2011]. Schierow, L.J. 2008. Engineered Nanoscale Materials and Derivate Products: Regulatory Challenges. CRC Report for Congress RL34332. Congressional Research Service, Washington, DC. January 22, 2008 [online]. Available: http://www.fas.org/sgp/cr s/misc/RL34332.pdf [accessed Apr. 14, 2011]. Sibley, L. 2009. Cleantech Sector Offers Big Potential for Nanomaterials. Cleantech Group LLC, September 22, 2009 [online]. Available: http://www.cleantech.com/ news/5044/energy-applications-hold-big-potent [accessed Dec. 17, 2010]. Stone, V., S. Hankin, R.J. Aitken, K. Aschberger, A. Baun, F. Christensen, T. Fernandes, S.F. Hansen, N.B. Hartmann, G. Hutchison, H. Johnson, C. Micheletti, S. Peters, B. Ross, B. Sokull- Kluettgen, D. Stark, and L. Tran. 2010. Engineered Nanoparti- cles: Review of Health and Environmental Safety (ENRHES). Final Report. Edin- burgh Napier University (ENU), the Institute of Occupational Medicine(IOM), Ed- inburg, UK, the Technical University of Denmark (DTU), the Institute for Health and Consumer Protection of the European Commission’s Joint Research Centre (JRC), and Institute of Nanotechnology (IoN). European Commission [online]. Available: http://www.nanowerk.com/nanotechnology/reports/reportpdf/report133.p df [accessed Dec. 27, 2011]. Swiss Re (Swiss Reinsurance Company). 2004. Nanotechnology: Small Matter, Many Unknowns. Swiss Reinsurance Company, Zurich [online]. Available: http://www. nanowerk.com/nanotechnology/reports/reportpdf/report93.pdf [accessed Nov. 9, 2010]. Teague, E.C. 2005. Testimony on Environmental and Safety Impacts of Nanotechnology before Committee on Science and Technology, 109th Cong., November 17, 2005 [online]. Available: http://ftp.resource.org/gpo.gov/hearings/109h/24464.pdf [ac- cessed March 1, 2011]. The White House. 2000. President Clinton’s Address to Caltech on Science and Technol- ogy, California Institute of Technology, Pasadena, CA. January 21, 2000 [online]. Available: http://www.dtrends.com/Nanotech/nano_clinton.html [accessed Feb. 16, 2011]. UKHL (United Kingdom House of Lords). 2010. Nanotechnologies and Food. HL Paper 22-1. United Kingdom House of Lords, Science and Technology Committee. Lon- don: The Stationery Office. January 2010 [online]. Available: http://www.pub lications.parliament.uk/pa/ld200910/ldselect/ldsctech/22/22i.pdf [accessed Nov. 10, 2010]. VCI (Verband der Chemischen Industrie e.V. German Chemical Industry Association). 2008. Responsible Production and Use of Nanomaterials. German Chemical Indus- try Association. March 11, 2008 [online]. Available: http://www.vci.de/tem- plate_downloads/tmp_VCIInternet/122306Nano_Responsible_Production.pdf?Do kNr=122306&p=101 [accessed Apr. 14, 2011]. Vision 2020/SRC (Chemical Industry Vision 2020 Technology Partnership and Semi- conductor Research Corporation). 2005. Joint NNI-ChI CBAN and SRC CWG5 Nanotechnology Research Needs Recommendations [online]. Available: http://www.chemicalvision2020.org/pdfs/chem-semi%20ESH%20recommendatio ns.pdf [accessed Nov. 10, 2010]. 

Environmental, Health, and Safety Aspects of Engineered Nanomaterials 47 Wray, P. 2010. Nano Products Taking a Hit During the Current Recession CTT, March 12, 2010 [online]. Available: http://ceramics.org/ceramictechtoday/2010/03/12/nan o-products-taking-a-hit-in-hard-times/ [accessed Nov. 23, 2011].