A Matter of Size: Triennial Review of the National Nanotechnology Initiative (2006)

Although the concept of responsible development of technology is frequently mentioned in government reports, industry publications, and the popular press, it is seldom defined. In the committee’s view, responsible development of nanotechnology can be characterized as the balancing of efforts to maximize the technology’s positive contributions and minimize its negative consequences. Thus, responsible development involves an examination both of applications and of potential implications. It implies a commitment to develop and use technology to help meet the most pressing human and societal needs, while making every reasonable effort to anticipate and mitigate adverse implications or unintended consequences.

The societal dimensions program component area of the National Nanotechnology Initiative (NNI) is defined as encompassing three subtopics: (1) research to characterize environmental, health, and safety (EHS) impacts of the development of nanotechnology and assessment of associated risks; (2) education-related activities such as development of materials for schools, undergraduate programs, technical training, and public outreach; and (3) research directed at identifying and quantifying the broad implications of nanotechnology for society, including social, economic, workforce, educational, ethical, and legal implications.^1,2 The committee’s analysis of responsible development focused on current EHS research. Its efforts included looking at EHS-related activities and studies relevant to nanotechnology and examining some of the recently published work on toxicological and environmental effects of nanoengineered materials. In addition, the committee

took note of efforts to address concerns about worker health and safety, including regulatory and standards-setting activities, as well as the importance of communicating about and involving the public in discussions of ethical and social issues in the responsible development and use of nanotechnology.

Nanomaterials have unusual and useful properties. But their unique attributes make nanomaterials a double-edged sword: they can be tailored to yield special benefits but also can have unknown and possibly negative impacts, such as unexpected toxicological and environmental effects. The environmental, health, and safety implications of nanotechnology are of significant concern to and a topic of serious discussion by government agencies and commissions, nongovernmental organizations (NGOs), the research community, industry, insurers, the media, and the public. A host of meetings and published reports have addressed EHS issues relating to nanotechnology, some of which are discussed below. EHS research published to date has provided some data indicating the potential for risks to laboratory animals exposed to nanomaterials and has shown that much more work is needed to assess the potential risks involved. Since much of what is learned as a result of EHS research will have a direct impact on R&D and manufacturing personnel who are initially exposed to nanomaterials, occupational health and safety risks, specifically in a workplace setting, must be considered.

The federal government has committed resources to address such societal dimensions of nanotechnology as responsible nanomanufacturing and human health and safety. In 2004, memos from the Office of Management and Budget (OMB) and the Office of Science and Technology Policy (OSTP) to federal agency heads reiterated this focus, noting that “agencies should support research on the various societal implications of the nascent technology” by placing “a high priority on research on human health and environmental issues … [and] cross-agency approaches.”³

According to the March 2005 supplement to the President’s FY 2006 Budget,⁴ $38.5 million was planned under the NNI for investment toward EHS R&D for FY 2006. In its role as the National Nanotechnology Advisory Panel, the President’s Council of Advisors on Science and Technology (PCAST) defined nanotechnology-related EHS R&D as “efforts whose primary purpose is to understand and address potential risks to health and to the environment posed by this technology. Potential risks encompass those resulting from human, animal, or environmental exposure

to nanoproducts—here defined as engineered nanoscale materials, nanostructured materials, or nanotechnology-based devices, and their byproducts.”⁵

An ongoing EHS R&D activity involves the use of the National Toxicology Program (NTP) by the National Institutes of Health (NIH) to investigate the potential toxicology of nanomaterials and to initiate inhalation exposure studies for engineered nanomaterials such as carbon nanotubes and quantum dots. Another effort, at the Environmental Protection Agency’s (EPA’s) Office of Research and Development (ORD), includes the Science to Achieve Results (STAR) program. On March 16, 2006, 14 grants totaling $5 million were awarded to universities through the STAR program, in partnership with NSF and NIOSH,⁶ for the investigation of potential health and environmental effects of manufactured nanomaterials. In addition, to date, EPA has funded 65 research grants for more than $22 million to study applications of nanotechnology to protect the environment.⁷ Examples of results from STAR programs include the development of low-cost, rapid, and simplified methods of removing toxic contaminants from surface water; development of more sensitive sensors for measuring pollutants; green manufacturing of nanomaterials; and development of more efficient, selective catalysts. Other projects in ORD laboratories include research on nanostructured photocatalysts as green alternatives for oxygenation of hydrocarbons; studies of nanomaterials for use as adsorbents, membranes, and catalysts to control air pollution and emissions; and research on the effects of ultrafine particulate matter that could help inform research on manufactured nanomaterials.⁸

In other federal agency efforts, the National Cancer Institute (NCI), in collaboration with the National Institute of Standards and Technology (NIST) and the U.S. Food and Drug Administration (FDA), established the Nanotechnology Characterization Laboratory in 2005 to perform preclinical efficacy and toxicity testing of nanoparticles. In addition, the FDA has a grants program in support of orphan products research and development, but it does not conduct research in support of particular product applications.⁹ Currently, the FDA’s National Center for Toxicological Research is collaborating with the NIH, National Institute of Environmental Health Sciences (NIEHS), and NTP in evaluating size dependence on translocation of quantum dots in vivo and the phototoxicity of nano-sized titanium dioxide and zinc oxide.^10,11

In its May 2005 report, PCAST acknowledged that current knowledge and data to assess the actual risks posed by nanotechnology products are incomplete. Furthermore, PCAST said that since exposure to nanomaterials is most likely to occur during the manufacturing process, research on potential hazards associated with workplace exposure must be given the highest priority. Also in 2005, the Nanoscale Science, Engineering, and Technology (NSET) Subcommittee formed the Nanotechnology Environmental and Health Implications (NEHI) Working

Group, which now involves over half of the federal agencies participating in the NNI. (See Chapter 1 for a description of all NNI’s working groups.) The FDA is co-chair of the NEHI Working Group to develop new test methods and procedures to identify and prioritize risk analysis research.¹²

The NEHI Working Group provides an infrastructure for coordination within and between agencies, focusing on EHS research and programs relating to nanotechnology. Specifically, the NEHI Working Group aims to:^13,14

• Provide for exchange of information among agencies that support nanotechnology research and those responsible for regulation and guidelines related to nanoproducts (defined as indicated above), to enable better communication of information on EHS issues relating to nanotechnology;

• Facilitate the identification, prioritization, and implementation of research and other activities required for responsible research and development, utilization, and oversight of nanotechnology, including research methods for life cycle analysis, and support the development of tools and methods to identify and prioritize risk analysis research;

• Promote communication of information related to research on environmental and health implications of nanotechnology to other government agencies and non-government parties, and support the development of nanotechnology standards, including nomenclature and terminology, by consensus-based standards organizations; and

• Assist in the development of information and strategies for safe handling and use of nanoproducts by researchers, workers, and consumers.

In June 2005, the EPA held its first public meeting about a voluntary proposed pilot program that would allow companies to submit information on the nanomaterials they are producing, how much is being produced, and possible worker exposure. On November 17, 2005, the House Committee on Science held a hearing titled “Environmental and Safety Impacts of Nanotechnology: What Research Is Needed?” to examine current concerns about environmental and safety impacts of nanotechnology and to assess the status and adequacy of related research programs and plans. NGOs have also been increasingly involved in addressing EHS issues. For instance, in 2005 the U.S. NGO Environmental Defense released a paper calling for the federal government to invest $100 million per year (about 10 percent of the NNI budget) in research on the potential environmental and health risks of nanotechnology for a period of at least 7 years.¹⁵ In August 2005, the International Council on Nanotechnology (ICON), based at Rice University and affiliated with the Center for Biological and Environmental Nanotechnology, launched a database

compiling publications relating to nanotechnology-associated environmental and health risks.¹⁶

The Woodrow Wilson International Center for Scholars and the Pew Charitable Trusts launched the Project on Emerging Nanotechnologies and, in November 2005, unveiled a database compiling global government-funded research on EHS issues relating to nanotechnology.¹⁷ A 2006 report by Davies of the Woodrow Wilson Center argues that better and more aggressive oversight and new resources are needed to manage the potentially adverse effects of nanotechnology and promote its continued development.¹⁸ In addition, in early 2006 the center launched a publicly available, online, and searchable inventory of nanotechnology-based consumer products.¹⁹

In October 2005, the International Life Sciences Institute (ILSI) released “Principles for Characterizing the Potential Human Health Effects from Exposure to Nanomaterials: Elements of a Screening Strategy,” a paper by top toxicological experts that gives researchers the elements of a framework for assessing potential health effects from exposure to engineered nanomaterials.²⁰ It is noteworthy that the paper presents only elements of a screening strategy rather than a detailed testing protocol because of the lack of research data currently available. The paper focuses specifically on the need for thorough characterization of the properties of nanomaterials used in screening studies in order to obtain meaningful and useful results.

An update of a June 2004 report by Nanoforum, a networking activity funded by the European Union’s Fifth Framework Programme, concluded that information and data are insufficient to accurately assess the risks of nanotechnology.²¹ It pointed out in addition that many unanswered questions revolve around both the definition of nanotechnology and the framework of toxicity studies, and it encouraged continuing toxicology research. Swiss Re, a global reinsurer in the field of risk and capital management, published Nanotechnology: Small Matter, Many Unknowns, a report that addresses the risks and implications of nanotechnology, including EHS effects.²²

Nanoscience and Nanotechnologies: Opportunities and Uncertainties, a report released in 2004 by the Royal Society and Royal Academy of Engineering in the United Kingdom, identified a need for more research to assess the potential risks relating to nanotechnology and recommended that the UK government establish an interdisciplinary program for research on the toxicological effects of nanotechnology.²³ The UK government’s initial response²⁴ acknowledged the need for more research but did not lay out any plans for accomplishing it. However, on December 2, 2005, the UK government published a report that addressed the current state of knowledge on the potential risks of nanoparticles and identified areas in need of

more research.²⁵ In another effort the UK Royal Society and the Science Council of Japan published a report based on a workshop they organized on EHS issues relating to nanotechnology.²⁶

In summary, various activities in the United States and abroad reflect steps taken toward addressing EHS issues, but it is clear to the committee that there is still much work to be done. Ultimately, the studies and reports noted above suggest that there is a need for continued risk assessment and the establishment of regulations as appropriate, but more importantly, they also point out that for now there is very little information and data on, or analysis of, EHS impacts related to nanotechnology.

The activities and studies mentioned above highlight some of the EHS issues relating to nanotechnology, but the body of published research addressing the toxicological and environmental effects of engineered nanomaterials is still relatively small.²⁷ As was pointed out by a workshop participant, two attributes of engineered nanomaterials are particularly important in relation to EHS issues—nanomaterials can enter the body, and their nanostructure can lead to specific biological activity. Such materials can include nanoparticles in the environment that can be inhaled or absorbed through the skin—such as aerosols, powders, suspensions, and slurries—as well as materials in the workplace that degrade during grinding, cutting, machining, or other occupational use.²⁸ What follows are some of the committee’s observations on aspects of nanotechnology-related EHS research currently being reported.

A search in PubMed of the literature up to 2005 showed publications on the toxicological effects of two classes of particles—that is, chemically defined ultrafine particles (incidental, or naturally occurring) such as carbon black and silica, and intentionally engineered nanomaterials such as fullerenes and carbon nanotubes. The number of publications relating to incidental ultrafine particles exceeds the number relating to engineered nanomaterials by about 100 to 1.²⁹ Because of the discrepancy in the amount of toxicological data on each of the two types of particles and the unique differences in the particles’ properties, data on incidental particles cannot easily be extrapolated and applied to engineered nanomaterials.³⁰ Now research to address the EHS impacts of engineered nanomaterials must thus be conducted.

In the small amount of research that has been done, there is evidence of adverse effects of engineered nanomaterials on laboratory animals.^31–33 For example, in two separate, high-impact studies, Lam et al.³⁴ and Warheit et al.³⁵ investigated the pulmonary toxicity effects of single-wall carbon nanotubes (SWNTs), intratracheally

instilled, on mice and rats. Each concluded independently that these engineered nanomaterials showed unique toxic properties different from those of incidental particles such as carbon black, suggesting that it was the toxicity of these engineered nanomaterials, and not just the size, that presented potential EHS risks. In the study conducted by Lam et al., three different carbon nanotubes were used: raw nanotubes, purified HiPco^TM nanotubes, both provided by the Center for Nanoscale Science and Technology of Rice University, and CarboLex, Inc.’s nickel-containing electric-arc nanotubes. In the work of Warheit et al., SWNT soot was generated via a laser ablation process and obtained from DuPont Central Research.

According to Warheit, health risk is a product of immediate hazards presented by, as well as the effects of longer-term exposure to, nanomaterials, and many different variables are involved in assessing toxicological effects.³⁶ For example, variables such as surface coatings of particles can yield different results from study to study, particularly with respect to toxicological effects.³⁷ Other variables that can affect toxicity include the surface charge and surface area of particles, differences in pulmonary response from species to species, the potential for particle aggregation and disaggregation, and whether the particles are fumed or precipitated. In particular, the absorption, distribution, metabolism, and excretion characteristics and toxicity of quantum dots have been shown to be highly dependent on both inherent physicochemical properties and environmental conditions.³⁸

Developing a better understanding of the toxicity of nanomaterials also involves evaluating the effects of routes of exposure (inhalation, oral, dermal), the dose and magnitude of exposure, and the extent of biological response (local versus systemic).³⁹ For example, Semmler et al. and Elder et al.^40,41 found systemic effects that spread beyond the lungs of rats exposed to ultrafine particles by inhalation. In FY 2005, in collaboration with the EPA and NSF, NIOSH funded extramural research through a $7 million competitive grant to principal investigators conducting studies in the areas of fate and transport, and exposure to and toxicity of nanoparticles and nanotubes.⁴²

In carrying out EHS R&D, it is critical to know exactly what is being characterized and to track apparent cause and effect relationships precisely and specifically Nanoscale particles and nanotechnologies differ and do not all fit under one giant umbrella with respect to predictions of their effects.⁴³ Classifying nanoscale particles and identifying relevant characteristics and properties are important steps in avoiding generalizations about all matter at the nanoscale. Information on the composition and structure of nanomaterials, purity levels, and well-defined controls and baselines must be known to identify potential risks.

An indication of the number of variables and degree of complexity involved is apparent in the above-mentioned study conducted by Lam et al. on the effects of inhaled SWNTs on mice: For example, the three types of carbon nanotubes used

were each made by different methods and contained different types or amounts of residual metals. In addition, both negative and positive controls were used with the carbon black (Printex 90^®), from Degussa Corporation, and the quartz (Min-U-Sil-5^®), from US Silica, respectively.⁴⁴ Each of these materials has its own Material Safety Data Sheet outlining its specifications. The study by Warheit et al. cited above used SWNTs that were 1.4 nm in diameter and greater than 1 micron in length⁴⁵ and that existed not as individual units but as 30-nm-diameter agglomerates. The composition of the soot was 30 to 40 percent amorphous carbon, 5 percent each of nickel and cobalt, and the remainder SWNT agglomerates. Quartz particles in the form of crystalline silica (Min-U-Sil-5), from Pittsburgh Glass and Sand Corporation, and carbonyl iron particles, from GAF Corporation, were used as positive and negative controls, respectively.⁴⁶

The number and types of variables in these two studies alone suggest the type and amount of work needed to ensure reproducibility of the results of these experiments, in particular, in regard to the nanomaterials used and the resulting specific EHS impact posited. That is, the experimental methodology should inspire confidence in the results, data, and conclusions.

The ability to carry out comprehensive EHS R&D requires that techniques and instrumentation for characterization and measurement be developed that will enable determination of the exact composition of a nanomaterial in a substance or product, as well as the physicochemical properties of specific nanomaterials. Chemical and physical data developed previously on chemically identical materials cannot be extrapolated to materials at the nanoscale, in part because bulk properties of materials significantly differ from the surface properties that are dominant at the nanoscale. Gathering relevant data specific to nanomaterials is essential to developing a relevant risk assessment process.

Most of the studies done to date have been conducted on laboratory rats, rabbits, and pigs, in which observed responses may differ from those in humans. Limited data are available on which to base predictions of real risks to humans; results of experimentation using animal models must be reproduced and extended in additional studies. Some preliminary studies have been performed in vivo in humans, including, for example, investigation of the effects of inhaled nanoparticles and ultrafine particles.⁴⁷

In addition, work by Oberdörster et al., for example, suggests elements of a strategy for screening the toxicity of engineered nanomaterials that involves in vitro and in vivo assays of physicochemical characteristics.⁴⁸ In addition, the NCI Nanotechnology Characterization Laboratory also provides an assay cascade for characterizing nanoparticles’ physical attributes, their in vitro biological properties, and their in vivo compatibility using animal models.⁴⁹

The laboratory or manufacturing environments are the settings where the initial contact between people—for example, researchers, technicians, and manufacturers—and nanomaterials occurs. Therefore, assessing risk as a basis for developing risk-management and risk-communication processes for the workplace is a critically important priority in the early stages of EHS R&D. As mentioned above, due to the potentially toxic properties of engineered nanomaterials, nanotechnology poses new challenges to conventional approaches to addressing occupational health and safety risk.

Proactive risk assessment and management of any technology require extensive strategic research⁵⁰ that could include such critical issues as assessing how toxicity differs as a function of type of nanomaterial, exposure route, dose, and biological effects and activity.⁵¹ Understanding these issues requires the development of metrics for gauging exposure, methods and techniques for measurement and monitoring, and instrumentation.^52,53 In addition, the development of screening strategies and a framework involving elements such as those proposed in the work by Oberdörster et al. on toxicity screening for engineered nanomaterials can help in developing and evaluating the effectiveness of worker protection and workplace control strategies. Particular industries and working groups, such as the NNI-Chemical Industry CBAN group, could use such frameworks and help tailor them to specific sectors.

The National Institute for Occupational Safety and Health (NIOSH) has been providing national and world leadership in the responsible development and prevention of work-related illness and injury associated with nanotechnology.⁵⁴ In 2004, NIOSH established the NIOSH Nanotechnology Research Center (NTRC) to coordinate nanotechnology research across the institute. The NTRC’s mission is “to provide national and world leadership for research into the application of nanoparticles and nanomaterials in occupational safety and health and the implications of nanoparticles and nanomaterials for work-related injury and illness.”⁵⁵ Along with NTRC, which in FY 2005 funded five projects, other intramural nanotechnology research programs at NIOSH include the Nanotechnology Safety and Health Research Program under the National Occupational Research Agenda (NORA), which funded six projects, and the small NORA program, which funded one project. Under NORA, research has focused on characterization of the physical and chemical properties of nanoaerosols, their effects on health, and whether they present work-related health risks. In addition, other NIOSH divisions have funded intramural nanotechnology research relating to occupational safety and health.⁵⁶

In 2005, NIOSH published a strategic plan for NIOSH nanotechnology research whose goals included preventing work-related injuries and illnesses caused by

nanoparticles and nanomaterials; conducting research to prevent such injuries and illnesses caused by nanotechnology products; promoting healthy workplaces through intervention, recommendations, and capacity building; and enhancing global workplace safety through national and international collaborations.⁵⁷ To further encourage research on effects of nanotechnology on occupational safety and health, NIOSH published “Approaches to Safe Nanotechnology” to raise awareness of potential risks in handling nanomaterials and nanoparticles.⁵⁸ In that document, NIOSH requested data and information from stakeholders on the development of occupational safety and health guidelines and will be able to use that information to develop recommendations based on the best available science for working safely with nanomaterials. As new research developments occur, NIOSH will then update these recommendations and guidelines.

NIOSH has also established for public use and comment the Web-based Nanoparticle Information Library (NIL) (available at www2a.cdc.gov/niosh-nil/), which provides information on the physical and chemical characteristics of nanomaterials, as well as their health and safety implications, to occupational health professionals, industrial users, worker groups, and researchers. The library contains images of nanoparticles, as well as information on the origin and synthesis of different kinds of nanoparticles, known applications and industries, and health and safety notes, including links to material safety data sheets.

Outside the United States, NIOSH and the UK Health and Safety Executive sponsored the First International Symposium on Nanotechnology and Occupational Health in October 2004.⁵⁹ The second international symposium was held in October 2005. In addition, NIOSH sponsored an international symposium, “Nano-Toxicology: Biomedical Aspects,” in January 2006.

Notwithstanding the need for further EHS R&D as discussed above, there has been increasing initial consideration at U.S. agencies regarding regulation of the development of nanotechnology. In addition, the European Commission has also enacted new regulations. This section discusses some of these developments.

Under current TSCA guidelines, EPA must assess whether commercialization of nanomaterials might present a risk or potential risk to the environment and human health owing to the materials’ unique physical dimensions and properties. A particularly daunting challenge is deciding whether a nanomaterial is a new chemical substance under the TSCA Chemicals Substance Inventory. TSCA defines a

chemical substance as “any organic or inorganic substance of a particular molecular identity, including any combination of such substance occurring in whole or in part as a result of a chemical reaction or occurring in nature and any element or uncombined radical.”⁶¹ A new chemical substance is “any chemical substance which is not included in the chemicals substance list compiled and published under section 2607(b) of the TSCA Chemicals Substance Inventory.”⁶² Two nanomaterials that have the same chemical composition can have different chemical properties due to size differences, thus making it difficult to ascertain whether or not certain nanomaterials are new chemical substances. In addition, too little research has been conducted on environmental health and safety issues to assess whether certain nanomaterials are a risk or a potential risk to the environment or human health. Therefore it is not clear whether the TSCA in its existing form can address these challenges in nanotechnology.⁶³

On June 23, 2005, in an attempt to address these issues, EPA conducted a public meeting on nanomaterials to discuss a proposed voluntary pilot program to collect information on nanomaterials that are manufactured, imported, processed, or used by companies.^64,65

On October 29, 2003, the European Commission (EC) proposed a new EU regulatory framework for chemicals, COM (2003) 644. Under the new system called REACH (Registration, Evaluation and Authorisation of Chemicals), businesses that manufacture or import more than 1 ton of a chemical substance per year would be required to register it in a central database. The aims of the proposed regulations are to improve the protection of human health and the environment while maintaining the competitiveness and enhancing the innovative capability of the EU chemicals industry. REACH is designed to give greater responsibility to industry to manage the risks from chemicals and to provide safety information on the substances. This information would be passed down the chain of production.⁶⁶

REACH shifts the burden of proof to industry to ascertain the risk of a material before it is introduced to the EU market.^67,68 The 2004 EC communication Towards a European Strategy for Nanotechnology called for risk assessment to be integrated into “every step of the life cycle of nanotechnology-based products.”⁶⁹ In July 2005, the EC reinforced this idea in its action plan by stating that risk assessment should start at “the point of conception and including R&D, manufacturing, distribution, use and disposal or recycling” (Box 4-1). The action plan goes on to say that risk management procedures should be “elaborated before e.g. commencing with the mass production of engineered nanomaterials.”⁷⁰ This statement suggests that

manufacturing and distribution of nanomaterials could be significantly delayed unless a company is able to demonstrate that a nanomaterial is safe.

At the time of this writing, the EC’s REACH proposal is expected to be adopted by the end of 2006. Concerns have been expressed by EU member states, industry, and the U.S. government about the high regulatory costs and burdens that would be associated with the implementation of REACH, with estimates of 2.3 billion over an 11-year initial period and €50 billion over a 30-year period in direct costs to industry.⁷¹

The U.S. Food and Drug Administration (FDA) anticipates that many of the nanotechnology-enabled products that it would regulate will be “combination

products,” that is, drug-device, drug-biologic, device-biologic, or drug-device-biologic—products made of constituents that are physically or chemically combined, co-packaged in a kit, or separate cross-labeled products.^72,73 The Office of Combination Products was established in 2002 to develop policies and processes to clarify the regulation of combination products.^74,75 If a product meets the definition of a combination product, then that product will be assigned to a lead center within FDA. This assignment to a lead center would be based on the “primary mode of action” of the combination product. The May 7, 2004, Federal Register included a proposal for a rule that would define the primary mode of action as “the single mode of action of a combination product that provides the most important therapeutic action of the combination product.”⁷⁶ In addition, the proposed rule described an algorithm that the FDA would follow to determine the center assignment.

The FDA regulates products only as a result of claims made by the product sponsor; that is, if a manufacturing company makes no claims with respect to a role for nanotechnology in the manufacture or performance of the product, the FDA may be unaware that nanotechnology is being used.^77,78 In addition, the FDA has only limited authority over potentially high-risk products, such as cosmetics.^79,80 Since little research has been done to assess the health risks of these products, many nanoproducts are not regulated. The FDA regards its existing pharmacotoxicity tests as adequate for evaluating most nanoproducts, but as new materials or new conformations of existing materials are developed that are identified as having the potential to pose new toxicological risks, new tests will be required.⁸¹

Existing Consumer Product Safety Commission (CPSC) regulations and guidelines are being used to assess the potential safety and health risks of nanomaterials that are incorporated into consumer products. Under the Consumer Product Safety Act (CPSA), the CPSC can develop a standard to reduce or eliminate an unreasonable risk of injury associated with a consumer product.⁸² Under the Federal Hazardous Substances Act (FHSA),⁸³ the CPSC can ban by regulation a hazardous substance if it deems the product to be so hazardous that the cautionary labeling is inadequate to protect the public. The FHSA defines as hazardous a substance that is “toxic, corrosive, flammable or combustible, an irritant, a strong sensitizer, or that generates pressure through decomposition, heat, or other means.”⁸⁴ In addition, a substance may also be “hazardous” if the product “may cause substantial personal injury or substantial illness during or as a proximate result of any customary or reasonable foreseeable handling or use, including reasonable foreseeable ingestion by children.”⁸⁵ Under both the CPSA and FHSA, pre-market

registration or approval is not required, placing the burden of responsibility on manufacturers to ensure that their products are labeled as required by the FHSA.

In its 2006 Performance Budget Request to Congress, the CPSC identified nanotechnology as one of the emerging hazards in consumer products.⁸⁶ The CPSC has indicated that it will review and update existing chronic hazard guidelines to address the incorporation of nanomaterials and nanotechnology into consumer products. However, the assessment of health risks relating to nanotechnology is incomplete and inconclusive. Once these risks become well characterized and as proof of any hazards emerges, other regulations and guidelines, such as the Flammable Fabrics Act and the Poison Prevention Packaging Act, may also apply to consumer products in which nanotechnology is used.⁸⁷ The CPSC is also a participant in the NEHI Working Group to promote data sharing and best available practices for regulations of nanomaterials.

In general, standards, guidelines, and best practices can create a framework for advancing the development of emerging technologies, while, at the same time, addressing and mitigating potential risks. As research in nanotechnologies progresses, information on health and safety and societal implications is being generated and examined, and potentially valuable data sets are being established. Government, industry, universities, and national laboratories all have a role in establishing standards for manufacturing, guidelines for safety and health, and protocols for the conduct of research—these are not the responsibility of any one single entity. Many of these stakeholders are engaging in the discussions and activities needed to provide the data, information, and ideas on which guidelines, standards, and practices can be based. These stakeholders include groups within professional organizations such as the American National Standards Institute (ANSI); government agencies such as NIST, NIOSH, NIEHS, NTP, and EPA; and a host of universities and industries, as well as NGOs and insurers.

The development of standards applicable to nanotechnology, including terminology and materials characterization and measurement, has been an increasing focus of professional groups in which activities have just begun. In 2004, ANSI formed the Nanotechnology Standards Panel (ANSI-NSP) composed of representatives from the national laboratories, federal agencies, academia, and industry. A draft charter was drawn up for the panel, whose mission was “to serve as the cross-sector coordinating body and provide the framework within which stakeholders can work cooperatively to promote, accelerate, and coordinate the timely development of useful voluntary consensus standards to meet identified needs related to

nanotechnology, including: nomenclature and terminology, research, development, and commercialization.”⁸⁸

The Steering Committee of the ANSI-NSP has evaluated a proposal from the British Standards Institute (BSI) to the International Organization for Standardization (ISO) and recommended modifications based on public review comments. ANSI submitted its official position on the BSI proposal to ISO in April 2005. The recently created ANSI-accredited U.S. Technical Advisory Group to ISO TC 229 Nanotechnologies held its inaugural meeting at the National Institute of Standards and Technology in July 2005. More than 45 representatives from academia, government, industry, NGOs, and standards-developing organizations attended the plenary to formulate U.S. positions in preparation for the first ISO TC 229 meeting in November 2005 in the United Kingdom.⁸⁹ The American Society for Testing and Materials (ASTM) International has established the Committee E56 on Nanotechnology to create standards for nanotechnology. The committee encompasses over 100 organizations and individuals from 12 countries, including China, the United Kingdom, and Japan. The scope of the committee is twofold: to develop standards and guidance for nanotechnology and nanomaterials, and to coordinate with existing ASTM committees and standards related to nanotechnology. Subgroups have been formed to author documentation on terminology and nomenclature, metrology, and EHS issues.⁹⁰

In anticipation of the impact that nanotechnology will have on the electronics industry, the Institute of Electrical and Electronics Engineers (IEEE) has partnered with other standards development organizations to develop certificates of compliance and standard operating procedures for high-volume manufacturing, to ensure reliable output, to protect workers, and to address environmental concerns. IEEE has developed consensus-based standards on how to electronically characterize carbon nanotubes. Because characterizing nanomaterials requires cross-disciplinary expertise, IEEE has worked with Semiconductor Materials and Equipment International and ASTM International to propose standards for the types and characteristics of nanoparticles, and nomenclature and terminology for nanotechnology.⁹¹

Although they were not a central issue for its deliberations, the committee recognized that addressing ethical and societal concerns pertaining to the emergence of nanotechnology will be an important part of responsible development. Currently, ethical considerations specific to nanotechnology have not come into focus, yet the concerns were articulated by experts in bioethics and engineering

ethics and others^92–94 at the workshops held during this study (see Appendix D for examples). Although near-term and tangible ethical concerns related to use of nanotechnology have yet to be determined, it is not too early now to think about how to inform, communicate with, and engage the public to ensure broad consideration of what responsible development of nanotechnology might entail from a societal perspective.

One approach to addressing societal concerns involves application of the precautionary principle—the concept that action can be taken by responsible parties (such as government and industry) to prevent harm to human health or the environment even before certainty of harm has been established scientifically. At the 1975 Asilomar conference, for example, molecular biologists and geneticists developed a set of voluntary safety guidelines for the conduct of research on recombinant DNA⁹⁵ even as interest was growing in the potential for beneficial uses of recombinant DNA technology. The debate over and resultant approaches to addressing concerns about genetic modification of food items such as corn or soy are also worth examining^96–98 as efforts are made to integrate societal concerns into decision making about nanotechnology. A 2003 paper from the European Institute of Health and Medical Sciences, “Nanotechnology and Survival—Ethics and Organisational Accountability,” suggests two components as important aspects of such efforts.⁹⁹ The first involves risk management based on an assessment of the novel behavior of nanomaterials in relation to human and environmental health and safety concerns,¹⁰⁰ and the second emphasizes accountability and giving the public a voice in making decisions about new technologies that will affect them and the fabric of their community.

In general, when the social impacts of a new technology are considered, ethics and fundamental research and development are treated as separate. Such an approach keeps facts and values separate, posits risks and benefits that are measurable and scalable, and assumes that uncertainty can be understood and managed scientifically.¹⁰¹ But because nanotechnology is a potentially disruptive emerging technology, addressing its impacts on society will require a different approach. For example, to understand the structure, function, and effects of nanomaterials will require collaborations between chemists and toxicologists, as well as social scientists who desire to address the ethical and policy issues related to use of nanotechnology. Ensuring responsible development of nanotechnology will depend on taking an integrated approach to ethical issues that will also involve the public in thinking through the implications of nanotechnology.¹⁰² Plato’s observation that “the discoverer of an art is not the best judge of the good or harm which will accrue to those who practice it”¹⁰³ seems a succinct reminder of the value of informed outside review and societal participation in decision making about the introduction of significant new technologies into our environment.

Efforts to stimulate the public’s participation can contribute to greater transparency in decision making and help forestall misinterpretation of information and subsequent confusion and fear of the unknown that can lead, in turn, to mistrust of both industry and government.¹⁰⁴ With the proper level of education, communication, and involvement, members of the public invited into the decision process take part as stakeholders in the outcome of future developments in a new technology. In the committee’s view, public awareness and informed understanding of the risks and benefits of nanotechnology are thus extremely important, and they can be addressed in a variety of ways.

Among recent studies and activities pertinent to involvement of the public, the committee mentions two as illustrative:

• Informed Public Perceptions of Nanotechnology and Trust in Government,¹⁰⁵ from the Woodrow Wilson International Center for Scholars Project on Emerging Nanotechnologies, presents the results of a study conducted in May and June of 2005 of individuals’ perceptions of government, nanotechnology, and regulation. Provided with information on nanotechnology and on U.S. regulatory and policy decision making relevant to nanotechnology, participating private citizens in Cleveland, Dallas, and Spokane, Washington, provided responses that included the following concerns:

  • Concern about the existence of hundreds of nanotechnology-enabled products in the marketplace and the expenditure of billions of dollars of taxpayer money on nanotech R&D about which people want to be kept informed and to have a role in decision making; while major benefits are anticipated, “government should not be making these decisions alone,” especially with regard to medicine and food;

  • Concern about ensuring effective regulation, reflecting the feeling that voluntary safety standards applied to industry would not be sufficient to manage the potential risks associated with nanotechnology;

  • Concern that political pressure has interfered with protections for public safety and that regulatory agencies, although they were thought to be trying to ensure public safety, were being restrained by outside pressure from providing appropriate levels of protection; and

  • Concern based on industry’s track record on past safety issues, arising in areas ranging from drugs to genetically engineered crops that industry has pushed products to market without adequate safety testing.

• In the United Kingdom, engagement of the public was sought via “Nanojury UK,”an interesting approach in which 20 lay people received briefings on nanotechnology and after several months reported back with four recommendations for the UK government involving funding for the development

and availability of nano-enabled medicines; support for nanotechnologies that bring jobs to the UK by investment in education, training, and research; the need for scientists to learn to communicate better with the general public; and labeling for products containing manufactured nanoparticles to enable consumer awareness.¹⁰⁶

Under the NNI multiple approaches have been sought to address ethical and societal aspects of the responsible development of nanotechnology, including education and public engagement. A study funded by the NSF and the Nanoscale Interdisciplinary Research Team (NIRT) at the University of South Carolina, entitled “From Laboratory to Society: Developing an Informed Approach to Nanoscale Science and Technology,” focused on engaging the public in a dialog and providing educational resources to increase understanding of opportunities and risks involved with this new technology.¹⁰⁷ Two NSF-sponsored Centers for Nanotechnology in Society established recently under the NNI at the University of California, Santa Barbara and Arizona State University will provide a network of social scientists, economists, and nanotechnology researchers to address societal implications of nanotechnology.

Public perceptions are also influenced by the media’s coverage of a technology. A report by Laing from Comex Research pointed to a general lack of coverage of nanotechnology by both Canadian and U.S. media,¹⁰⁸ and one by Friedman and Egolf of Lehigh University concluded that the number of newspaper articles about health and environmental risks was low in both the U.S. and British media,¹⁰⁹ suggesting yet another approach to improving knowledge and stimulating awareness and public participation.

Based on its examination of currently reported research on environmental, health, and safety impacts of nanotechnology and the current status of regulation in this regard, the committee reached the following conclusions:

Conclusion. Notwithstanding the results of early research on the health and environmental risks of engineered nanomaterials, it is not possible yet to make a rigorous assessment of the level of risk posed by this class of materials. Further risk assessment protocols have to be developed, and more research is required to enable assessment of potential EHS risks from nanomaterials. The committee acknowledges that increased research on (1) health and environment implications and on (2) legal, societal, and ethical impacts will add to the cost of the development of nanotechnology. However, the committee concluded that the need for more EHS data requires an expanded

research effort that will complement the important dialog on these issues that is being facilitated. At the same time, there is some evidence that engineered nanomaterials can have adverse effects on the health of laboratory animals. Reproducible and well-characterized EHS data will inform the development of rigorous risk-based guidelines and best practices, but until that information becomes available it is prudent to employ some precautionary measures to protect the health and safety of workers, the public, and the environment.

Conclusion. Addressing the ethical and social impact of nanotechnology will require an integrated approach among scientists, engineers, social scientists, toxicologists, policymakers, and the public. Various studies have documented their participants’ desire to learn more about the risks and benefits of nanotechnology and their willingness to participate in decision-making and regulatory processes to realize the full potential of nanotechnology.

Assessment of the need for standards, guidelines, or strategies for ensuring the responsible development of nanotechnology is particularly challenging, given the unique characteristics and properties of nanoscale materials, the relative lack of data about potential risks posed by specific substances, and the convergence of nanotechnology with biotechnology, information technology, and cognitive science—each embodying its own set of compelling economic, societal, and ethical issues. The workshop discussions held during this study reflected the complexity of these issues. It was evident that participants saw in the development of nanotechnology a potential for addressing some of our most pressing societal problems—from treating cancer to meeting growing energy needs. At the same time, applications in health care and other areas present a clear potential for unintended and unexpected risks, as well as second-order consequences.¹¹⁰ Some of these unexpected consequences may be beneficial, leading to innovations in currently unrelated fields. However, the possibility of unintended effects that may raise public concern demands proactive attention. Responsible development of these new converging technologies requires careful attention to social and ethical dimensions of their development and use. Sound guidelines and standards are imperative to minimize, for example, health and ecological risks.

There have been pockets of increased funding for EHS-related research. In the FY 2007 budget, President Bush proposed $8.6 million for nanotechnology research within EPA’s Office of Research and Development, compared with the $4.6 million in the FY 2006 budget.¹¹¹ But although nanotechnology research benefited, there was a 4 percent cut in EPA’s overall FY 2007 budget. As previously discussed, on March 16, 2006, 14 grants totaling $5 million were awarded to universities through EPA’s Science to Achieve Results research program in partnership with NSF and

NIOSH.¹¹² These grants focus on the investigation of potential health and environmental effects of manufactured nanomaterials.

At the same time, a coalition of companies, NGOs, and the NanoBusiness Alliance trade group has called on Congress to increase funding for EHS research in nanotechnology. In FY 2006, 3.7 percent of the NNI budget was targeted for EHS research, with another 4 percent targeted toward research on ethical, legal, and social implications.¹¹³

It is also imperative that all stakeholders be involved in the risk assessment process. Given the rapid progress of nanotechnology, stewardship is essential in the form of addressing EHS issues, using nanotechnology for improving public health and environmental remediation, and managing nanotechnology-related risks. The responsibility lies with all stakeholders to make well-informed decisions that will lead to both realizing the benefits and mitigating the risks of nanotechnology.

In summary, the committee believes that EHS research needs to be accelerated and improved if the potential of nanotechnology is to be realized. In that regard, the committee offers the following recommendation:

Recommendation. To help ensure the responsible development of nanotechnology, the committee recommends that research on the environmental, health, and safety effects of nanotechnology be expanded. Assessing the effects of engineered nanomaterials on public health and the environment requires that the research conducted be well defined and reproducible and that effective methods be developed and applied to (1) estimate the exposure of humans, wildlife, and other ecological receptors to source material; (2) assess effects on human health and ecosystems of both occupational and environmental exposure; and (3) characterize, assess, and manage the risks associated with exposure.

The NNI’s establishment of the NEHI Working Group has provided for exchange of information among agencies that support nanotechnology research and those responsible for regulation and guidelines related to nanoproducts. The NEHI Working Group also is helping to facilitate the identification, prioritization, and implementation of research and other activities required for responsible research on and development, utilization, and oversight of nanotechnology, including research methods to enable life cycle analysis. The working group has also served as a central focus for communication of information related to research on EHS implications of nanotechnology to other government agencies and nongovernment parties. The committee believes that such a government entity should continue to work with all stakeholders to proceed in an efficient and coordinated manner in addressing the responsible development of nanotechnology.

Finally, the committee emphasizes that EHS research that yields reproducible results and statistically reliable data will enable more informed discussions about how to (1) develop and disseminate EHS guidelines and best practices for R&D laboratories (including teaching institutions) and (2) regularly assess the adequacy and effectiveness of regulatory standards and policies for manufacturing facilities suc as industrial plants.