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 development” (NRC 2009, p. 3)—has set the pace for national and international research and development in nanoscale science and engineering and has led the world in the development and use of knowledge at the nanoscale with the potential 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, interconnected, and resource-constrained world, it is important that products resulting 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 commercialization. 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, manufacturers, regulators, and others have the necessary information on potential risks and how to prevent, avoid, or mitigate them.

OPPORTUNITIES AND CHALLENGES

Increasing our understanding of how matter on the nanoscale behaves and interacts with humans and ecologic systems is socially and economically important. 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 innovation. 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, monitoring, 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 uncertainty about the potential human health and environmental effects of products emerging from nanotechnology and recognition that the safe and successful development of nanotechnology depends on early, strategic action to address potential risks.

In response to the concerns, there has been an increase in funding for research and in peer-reviewed publications addressing the environmental, health, and safety (EHS) effects of engineered nanomaterials (ENMs) (PCAST 2010). 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 million—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 complementary assessments by government agencies, academic institutions, industry, and other stakeholders (see Table 1-1) have helped to direct where EHS research 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 research 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.

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 Nanomaterials.

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 developed 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 questions 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 laboratories, government-funded research centers, technology incubators, and startup companies has emerged to facilitate collaboration in technologic development. 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 materials to possess nanoscale features and that comprise the second stage; and secondary 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 Research 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 production volume) are not expected to change drastically through 2015, the more exotic 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, developers generated $29 billion for this stage of the value chain (Lux Research in Wray 2010). The top 10 nanointermediate classes developed were coatings, composites, 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, including 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 products, 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 construction, 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 commercialization over the last 10 years, uncertainties about the EHS effects of nanomaterials 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 communicated 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, coordinated research strategy that encompasses stakeholders in the public and private sectors and that identifies critical questions, maps out a path to answers, and ensures accountability for providing decision-makers with timely information.

Because nanotechnology is presenting new and unusual challenges, moving 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.

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 productively and mechanisms that support the NEHI and the National Nanotechnology 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 couple 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 remains the task of combining the emerging framework with a strategically responsive 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 impacts 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 period led by a panel of experts, the RS/RAE published a highly influential report examining the opportunities and uncertainties of “nanoscience and nanotechnologies.” Concluding that “the lack of evidence about the risks posed by manufactured 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 report'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 its action plan (2005–2009) for developing nanoscience and nanotechnology. Those activities were complemented by the EU Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) publication of a comprehensive 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 included 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 nanotechnology” (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 understanding of nanoscale material interactions with the environment; (3) increase understanding of the fate, transport, and transformation of nanoscale materials in the environment and their life cycles; and (4) identify and characterize potential exposure, determine possible human health impact, and develop appropriate methods of controlling exposure when working with nanoscale materials.

Federal activities were to be coordinated by NEHI, a group of representatives 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 experts 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 toxicity, 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 reflected 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 RS/RAE (2004) and CBAN (NNI-ChI CBAN ESH Working Group 2007), and outlined a possible federal research strategy (Maynard 2006). The report identified 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 associated with those subjects for generating new knowledge and supporting oversight 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: instrumentation, 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, director 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 collaboration 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 produced (NEHI 2007).

In February 2008, the NNI strategy for nanotechnology-related EHS research 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 addressing research needs. The strategy was developed predominantly by government-agency representatives but drew on feedback from public consultations and responses to earlier documents.

The 2008 federal research strategy for nanotechnology-related EHS research (NEHI 2008) was reviewed by the National Research Council (NRC 2009), whose committee concluded (p. 10) that

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 implications of nanotechnology. It is the result of considerable collaboration and coordination among 18 federal agencies and is likely to eliminate unnecessary 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 research.

Central to the stated concerns of that committee was a lack of an assessment of the state of the science, including previous efforts to identify and address 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 updated, on the basis of input from a series of workshops, stakeholder consultations, and reviews, including NRC (2009).

In parallel with the NNI efforts (and in part coordinated with them), individual 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 iteration 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 illnesses” (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 comprehensive 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 preventing and mitigating risks” (EPA 2009, p. 1).

Those themes are addressed in the context of a decision-making framework to aid in identifying important research questions and an environmental-assessment approach based on Davis and Thomas's Comprehensive Environmental Assessment (Davis and Thomas 2006). For each theme, the strategy develops key scientific questions and outlines critical paths for the agency to follow to address them. Both the NIOSH and EPA strategies clarify their complementary 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 understanding and addressing the potential health and environmental implications of ENMs (HM Government 2010).

In 2009, the Institute of Occupational Medicine published a comprehensive review of completed and nearly completed nanomaterial EHS research conducted 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 series 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 interactions, 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 nanotechnology 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 emphasizes 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 possible consequences of new research and new developments have been analyzed 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 prevent 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 “disconnect” 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 relatively 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 approaches 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 workshops 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 challenges. 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 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 appreciation 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 recent 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 associated 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 Environmental, Health, and Safety Aspects of Engineered Nanomaterials. The committee was charged with developing and monitoring the implementation of an integrated 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 research; 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 environmental fate of these materials. In its evaluation the committee will also consider existing research roadmaps and progress made in their implementation. A second 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 research, this first report considers seven specific questions:

• What properties of ENMs need to be considered in assessing their potential exposures, toxicity, toxicokinetics, and environmental fate? What standard 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?
• 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.

BOX 1-1

Elements of A Research Strategy. Vision or statement of purpose Goals

The elements of an effective research strategy were drawn from a historical perspective about how others had shaped their approaches to risk research and had considered the need to address a mix of both “exploratory” and “targeted” research. The elements are discussed below in the context of the current effort.

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 creation of a complete sequence of human DNA and the DNA of other organisms, and development of capabilities and technologies (for example, through the National 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 quantifiable 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 Human Genome Research Institute and the Celera Corporation.⁴ 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 Committee) is relevant to the charge of the present committee, although more narrowly defined in scope. The PM Committee was requested by Congress to address 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 uncertainties 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 uncertainty was central to the PM Committee's approach (Figure 1-1). That toxicologic framework helped in identifying the major uncertainties and the complementary 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 undertaken over a 13-year span and estimated costs on a year-by-year basis.

FIGURE 1-1

A general framework for integrating particulate-matter research.

In approaching its charge, the PM Committee elaborated on criteria for selecting 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 definitions 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 framework 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 science and engineering are leading to remarkable new discoveries that have the potential to address major societal challenges while providing for substantial economic growth. Those discoveries are enabling the emergence of new technologies and the enhancement of existing technologies. Without strategic research on emergent risks associated with the new and enhanced technologies—and a clear understanding of how to prevent, manage, and avoid them—the future of safe and sustainable nanotechnology-based materials, products, and processes is uncertain. In today's fast-paced and interconnected world, a worthwhile 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 responsible decision-making. Without the research, decision-makers will not have the tools and information that they need to develop safe and responsible technologies, 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 nanotechnology is shifting from research to commercialization. As it does, society cannot afford to remain entangled in confusion as the challenges and opportunities presented 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 stakeholder 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.
• 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 conceptual 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 committee's vision of the research agenda, including the recommended timing and costs of research activities. Chapter 6 describes implementation of the research strategy and how research progress will be evaluated.

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Footnotes

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.

2

This figure includes nanomaterials, intermediate products, and nanoenabled products.

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).

4

Celera Corporation, a private company, worked in parallel with the government to sequence the human genome.