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The NNI was proposed in 2000, and its original plan incorporated environmental, health, and safety (EHS) and other broader societal issues. 1,2 The NNI was subsequently authorized by Congress under the 2003 21st Century Nanotechnology Research and Development Act (15 USC §7501) to provide a multiagency framework to ensure U.S. leadership in the emerging fields of nanotechnology and to address “ethical, legal, environmental, and other appropriate societal concerns.”3 Since the launch of the NNI, global competition has intensified. Nanoscience has transformed from an emerging area of stand-alone research to a technology integrated with both established and pioneering technologies, and one that is fueling real-world applications.
The NNI recognized the importance of understanding the potential impacts of nanotechnology integration into diverse markets and sectors. A well-coordinated nanotechnology-related EHS (nanoEHS) research effort is vital to U.S. innovation and economic competitiveness.4 The ongoing NNI investments reflect a sustained emphasis on broad, fundamental research in nanoscience to oversee the translation of nanotechnology into technological breakthroughs that benefit the American people.4 Promoting the responsible development of nanotechnology has been one of the NNI’s primary goals since its inception, encompassing both nanoEHS and ethical, legal, and societal implications (ELSI) research and policy. The vision of responsible development has been instrumental in developing societal awareness and acceptance of engineered nanomaterials (ENMs) and nanotechnology-enabled products and applications.5,6 The 2021 NNI Strategic Plan maintains this vision of responsible development of nanotechnology as a core goal that underpins all other goals and facilitates public confidence and technology adoption.7 From Federal fiscal year (FY) 2005 through FY 2021, NNI agencies cumulatively have allocated over $1.3 billion to nanoEHS. Within the NNI, these nanoEHS research activities developed and funded by Federal agencies are coordinated through the NEHI Working Group, which supports the NNI’s efforts to establish nanoEHS as a central and intentionally coordinated component of the overall nanotechnology research strategy and framework. 8
The NNI’s nanoEHS research and coordination activities were initially driven, in part, by concerns within the EHS community about the health implications of ENMs as new forms of ambient, ultrafine particles (UFPs, ranging in size from 5 nm to 100 nm).9–12 Early nanoEHS research studies indicated that size, surface area, surface chemistry, and other physicochemical properties might be predictors of particle toxicity. 13–15 These findings generated interest in potential hazard (toxicity) and risk from exposure to ENMs based on their increased reactivity compared to larger forms of the same materials. Other early questions investigated by the Federal community included differentiating ambient and anthropogenic particles from ENMs. Efforts to address that question are exemplified by a National Institute of Standards and Technology (NIST)-led activity that developed methods to detect stable isotope-enriched silver nanoparticles in a standard estuarine sediment. 16 Understanding real-world exposures to engineered nanoparticles required a transition away from using pristine or as-synthesized ENMs and overcoming limitations in the conduct of early studies. These drawbacks included the lack of information on nanoparticle characterization and transformations, and uncertainty regarding appropriate study protocols and standards, biologically relevant doses, and routes of exposures. NEHI representatives from multiple agencies including the National Science Foundation, National Institutes of Health (NIH) as well as the Environmental Protection Agency (EPA) were early champions for dedicated nanoEHS research studies, and these research topics and questions provided the blueprint for the development and evolution of the NNI nanoEHS research strategy.17,18
A 2006 NNI review of research needs19 was followed by the first formal NNI nanoEHS research strategy, published in 2008. The 2008 NNI Research Strategy provided a structure for fostering concurrent research on multiple fronts such as fundamental research on materials, hazard, and exposure, and the development of reasonable strategies to mitigate/manage potential human health risks based on UFP research.20 After publication of the 2008 strategy, the NNI held stakeholder workshops and received input from academic researchers, consumers, environmental nonprofits, and industry groups to update the research strategy. In 2011, the NNI published an updated EHS research strategy, which addressed the significant input received over the intervening years. The 2011 document had many common elements with the 2008 strategy, but also addressed critiques set out in a 2009 National Academies report.21 The six key areas of the 2011 NNI EHS Research Strategy—human health, environmental health, exposure, measurement and metrology, informatics and modeling, and risk assessment and management—remain the core research areas supported by NNI agencies. With the publication of these research strategies, the NNI and its NEHI Working Group realized a new level of cooperation and urgency that has since been a major driver of interdisciplinary/cross-sector approaches. In 2014, NNI participating agencies reported on progress towards the goals set out in the 2011 strategy.22
During the past decade, the research supported by the NEHI participating agencies has included understanding the interactions between ENMs and biological systems. Research in this area is central to the translation of nanotechnology into biomedical applications. Research centers such as the National Science Foundation (NSF)- and EPA-funded Centers for Environmental Implications of Nanotechnology, led by Duke University and the University of California at Los Angeles, have contributed to substantial progress in understanding the impacts of nanomaterials. NIEHS has sponsored two Nanomaterials Health Implications Research consortia . Over a decade, these collaborative research efforts supported by NIEHS advanced the prediction of potential health effects arising from real-world scenarios. Nanotechnology’s prominence in drug delivery (e.g., nanocapsules and nanoemulsions) continues to grow. In 2017, the Food and Drug Administration (FDA) published the draft form of the FDA’s Guidance for Industry—Drug Products, Including Biological Products that Contain Nanomaterials , which generally follows a product-focused approach to risk evaluation. After addressing public comments, FDA published the Guidance in final form in 2022.23
The NNI has supported the emergence of an international community of collaborative nanoEHS researchers. By advancing tools, methods, and standards for robust health and safety evaluation, these cooperative efforts have fostered the safe and responsible development of nanotechnology in many regions of the world. For example, NNI agencies have provided contributions and leadership within the Organisation for Economic Cooperation and Development (OECD) for programs to develop nanoEHS assessment tools and methodologies. The Indo-U.S. Science and Technology Forum has boosted cooperation in the areas of consumer and drug-related standards, information exchange, and training. The U.S.-EU nanoEHS Communities of Research (CORs) were established in 2011. Since then, a series of trans-Atlantic workshops has promoted communication and cooperation between the United States and the European Union on nanoEHS research and regulation. (See U.S.-EU Nanotechnology Communities of Research for additional information on the CORs.) NEHI has recognized the value of, and is proactively sharing, the tools, methods, and approaches from the study of ENMs to emerging contaminants of concern. NNI researchers have led initiatives such as the 2021 Asia Pacific Economic Cooperation (APEC) Nanoplastics in Marine Debris workshop, which aimed to broaden the research connections of U.S. scientists with researchers in other APEC economies who are also tackling this rapidly emerging issue. Information and resources from the workshop are available at https://www.wrcgroup.com/resources/apec-nanoplastics-workshop/
In summary, much has been accomplished, but many questions from 2011 remain incompletely answered, and new questions and issues have arisen with the advent of increasingly complex ENMs and nanotechnology-enabled products. NEHI is working to identify current critical issues in nanoEHS and how these should the NNI’s strategy going forward.
Bibliography
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