Supplementary Information (SI) Figure Legend SI Figure 1: Panelists and discussants in the December 2013 symposium built on previous work to identify research priorities for multiwalled carbon nanotube (MWCNT) risk assessment and management. The previously identified MWCNT research priorities are depicted here schematically with more information on the comprehensive environmental assessment (CEA) process used to identify the research priorities, and the priorities themselves, available in reports (RTI International 2012; U.S. EPA 2013). Briefly, areas in red are considered the highest priorities for research that informs MWCNT risk assessment and management. Areas in yellow, orange and green are respectively lower priority areas. The subset of high research priorities (i.e., areas in red) that panelists focused on in the December 2013 symposium are listed in tables. SI Tables The following tables summarize information that experts presented in the December 2013 Society for Risk Analysis Symposium. Topic-areas for each table correspond with areas that a separate group of experts identified as high research priorities for MWCNT during the 2012 CEA (SI Figure 1). The second column of each table contains an example of the specific research questions that experts identified during the 2012 CEA. Experts in the 2013 SRA Symposium used these questions as a starting point to discuss next steps for MWCNT research; however, in some instances, symposium experts modified the questions developed in 2012 to reflect their understanding or perspective of the topic area. Additional information on the development of the original questions is available in summary reports (RTI International 2012; U.S. EPA 2013). Note that Columns 3 through 6 of each table contain examples developed by panelists in preparation for the December 2013 SRA symposium. References included in Column 3 were identified as relevant examples by Commentary authors as a resource for readers. As such, information in each table is not intended to be comprehensive. SI Table 1: Product Life Cycle Research for Multiwalled Carbon Nanotubes (MWCNTs): Product Manufacturing Release Rate Research area Key research questions for MWCNT flame retardants What research related to this question is currently underway? Who is doing that research? What are barriers to initiating or continuing research related to this question? What incentives could encourage more research related to this question? Product Life Cycle 1. What is the step in manufacturing that poses the greatest risk of release to the environment? Example products: Academic and agency research groups, including: Intellectual property Public-private partnerships Product Manufacturing– Release Rate 2. What is the step in manufacturing that poses the greatest risk of occupational exposure? CNT nanocomposites, epoxy, coatings, including for brakes (Hirth et al. 2013; Schlagenhauf et al. 2012a; Schlagenhauf et al. 2012b) Example release processes: Abrasion, degradation (Huang et al. 2012) Example conditions/ settings: Manufacturing facilities Lab-simulated natural environments (e.g., representative temperatures, relative humidities, ultraviolet light) (Orlov et al. 2012) Example analytical methods: Detection method development (Ulrich et al. 2012) University of Iowa University of Illinois State University of New York at Stony Brook U.S. Environmental Protection Agency BASF: The Chemical Company Centers for Disease Control/ National Institute of Occupational Health Swiss Federal Institute for Materials Testing and Research/ Institute of Environmental Engineering, ETH Zurich Regulatory uncertainty Proprietary information Research dollars and scientific interest Limitations in current instrumentation Funded work on a specific “project” basis that is relevant to BOTH an academic or agency researcher and a developer/marketer (e.g., nanoproduct company) Job opportunities More industry consortia, or similar, organizations that provide research venues that provide collaborative research and reporting, which enhances scientific robustness of resulting data Table 2: Environmental Transport, Transformation, and Fate Research for MWCNTs: Wastewater Persistence Research Area Key research questions for MWCNT flame retardants What research related to this question is currently underway? Who is doing that research? What are barriers to initiating or continuing research related to this question? What incentives could encourage more research related to this question? Environmental Transport, Transformation, and Fate: Persistence in Wastewater 1. How does the degree of functionalization and changes in wastewater treatment processes affect the rate of transformation? Most research is centered on ENM types other than CNTs (Kiser et al. 2009) NIST group Standards/methods for conducting tests, and applicability of available methods Finding interested stakeholders Center for Environmental Implications of Nanotechnology, Duke University (e.g., Wiesner group) Identifying key MWCNT or environmental properties that most affect fate and transport, and relating laboratory experiments to real- world environmental conditions Standardized methods/criteria EMPA (Swiss Federal Laboratories for Materials Science and Technology) (e.g., Gottschalk and Nowack groups) Techniques for detection and analysis 2. What are the transformation byproducts from MWCNT and flame-resistant fibers? Analytics for other ENM types more straightforward (Kaegi et al. 2011; Lecoanet et al. 2004) Most research is done by government labs and universities, focused on a very small subset of the overall topic (Gottschalk et al. 2009; Nowack 2010) Environmental media are complex; lab tests tend to simplify simulated systems so they can be more well defined (and controlled) (Chen et al. 2010) Arizona State University (e.g., Westerhoff group) Johns Hopkins University group Interested stakeholders Identifying applications with potential releases Identify and prioritize key properties Development of reliable and costefficient detection and analysis methods for CNTs that have quick turnaround times Table 3: Human Exposure and Dose Research for MWCNTs: Occupational Inhalation and Absorption Research Area Key research questions for MWCNT flame retardants What research related to this question is currently underway? Who is doing that research? What are barriers to initiating or continuing research related to this question? What incentives could encourage more research related to this question? Human exposure 1. What research has been started to connect human occupational exposures and design of relevant (dose-level) studies? Occupational exposure studies are growing (Methner et al. 2009) Government and academic (and some private) research organizations, such as: Availability of standardized MWCNTs MWCNT manufacturing and applications (Shvedova et al. 2003) Multi-metric approach still needed (Donaldson et al. 2006) NIOSH-West Virginia University partnership NSF Centers Brown University, Oregon Nanoscience and Microtechnologies Institute (ONAMI) -Netherlands Organisation for Applied Scientific Research (TNO) Demonstrating the effect of design on biological response: safer design? Occupational – Inhalation And Toxicokinetics: Human – Absorption 2. What principles are being evaluated to design safer nanomaterials? 3. Are the metrics adequate to characterize the exposure/dose level? Inhalation is a key exposure route; respirable fraction is a main focus (Schulte et al. 2010) Low-dose studies Better characterization studies Private-public collaborators, such as: European Chemical Industry Council (CEFIC) Long-range Research Initiative (LRI) to develop criteria for safe design NIOSH partnerships with private companies to translate or link (human) exposure data to dose data from animal bioassays Lack of access to occupational settings Changes in MWCNT properties along the life cycle: yes, no, or maybe? Unknown significance of agglomeration in air Removing (at least reducing) uncertainty for regulators Linking occupational exposure experience to toxicology and risk assessments for accurate risk characterization Effective risk management measures Table 4a: Human Toxicity Research for MWCNT: Non-cancer health impacts Research Area Key research questions for MWCNT flame retardants What research related to this question is currently underway? Who is doing that research? What are barriers to initiating or continuing research related to this question? What incentives could encourage more research related to this question? Human health 1. Conduct acute and chronic rodent bioassay studies after inhalational exposure at relevant doses using well-characterized material Evaluation of dermal and eye irritation and skin sensitization due to carbon nanotubes (Ema et al. 2011) National Institute of Advanced Science and TechnologyJapan (e.g., Ema, Nakanishi) Identifying product formulations, including physicochemical properties of the nano-product and each component part Establishment of consortia groups with pooled funds available to conduct consuming studies Non-cancer 2. Perform experiments to test impacts of exposure on immune-compromised individuals Biocompatibility of nanoparticles and nanotubes (Parvinzadeh Gashti et al. 2012) Acute pulmonary dose-response to inhaled MWCNTs (Li et al. 2012; Porter et al. 2010) Interaction between CNTs and human cells (Tsuchiya et al. 2014) Islamic Azad University – Iran (e.g., Gashti, Almasian) Beihang UniversityChina (e.g., Li) and Tsinghua University (e.g.,Cui) NIOSH- U.S.: (e.g., Porter, Castranova) Research dollars to perform studies on the nanoproduct over dose and time and include appropriate controls Venues to publicize and present findings as well as to communicate to nonscientific community Tokai UniversityJapan (e.g., Tsuchiya, Kimura) NIEHS Nano Consortium a In the December 2013 SRA Symposium, the presentation on MWCNT research related to human health focused on examples of ongoing work within one particular research consortium rather than providing information specific to each column in Table 4. As such, examples in Table 4 were developed by Commentary authors as a resource for readers. 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