Khara Grieger

Modeling approaches for characterizing and evaluating environmental exposure to engineered nanomaterials in support of risk-based decision making.

As the use of engineered nanomaterials becomes more prevalent, the likelihood of unintended exposure to these materials also increases. Given the current scarcity of experimental data regarding fate, transport, and bioavailability, determining potential environmental exposure to these materials requires an in depth analysis of modeling techniques that can be used in both the near- and long-term. Here, we provide a critical review of traditional and emerging exposure modeling approaches to highlight the challenges that scientists and decision-makers face when developing environmental exposure and risk assessments for nanomaterials. We find that accounting for nanospecific properties, overcoming data gaps, realizing model limitations, and handling uncertainty are key to developing informative and reliable environmental exposure and risk assessments for engineered nanomaterials. We find methods suited to recognizing and addressing significant uncertainty to be most appropriate for near-term environmental exposure modeling, given the current state of information and the current insufficiency of established deterministic models to address environmental exposure to engineered nanomaterials.

Analysis of current research addressing complementary use of life-cycle assessment and risk assessment for engineered nanomaterials: have lessons been learned from previous experience with chemicals?

While it is generally agreed that successful strategies to address the health and environmental impacts of engineered nanomaterials (NM) should consider the well-established frameworks for conducting life-cycle assessment (LCA) and risk assessment (RA), scientific research, and specific guidance on how to practically apply these methods are still very much under development. This paper evaluates how research efforts have applied LCA and RA together for NM, particularly reflecting on previous experiences with applying these methods to chemicals. Through a literature review and a separate analysis of research focused on applying LCA and RA together for NM, it appears that current research efforts have taken into account some key “lessons learned” from previous experience with chemicals while many key challenges remain for practically applying these methods to NM. We identified two main approaches for using these methods together for NM: “LC-based RA” (traditional RA applied in a life-cycle perspective) and “RA-complemented LCA” (conventional LCA supplemented by RA in specific life-cycle steps). Hence, the latter is the only identified approach which genuinely combines LC- and RA-based methods for NM-risk research efforts to date as the former is rather a continuation of normal RA according to standard assessment procedures (e.g., REACH). Both these approaches along with recommendations for using LCA and RA together for NM are similar to those made previously for chemicals, and thus, there does not appear to be much progress made specific for NM. We have identified one issue in particular that may be specific for NM when applying LCA and RA at this time: the need to establish proper dose metrics within both methods.

A relative ranking approach for nano-enabled applications to improve risk-based decision making: a case study of Army materiel

Assessing the health and environmental risks of engineered nanomaterials (ENMs) continues to be a challenging endeavor. Due to extensive challenges related to applying traditional risk assessment frameworks to ENMs, decision making regarding the use of ENMs in products and applications may need to rely on structured decision support tools such as risk ranking approaches. This study examines the use of one risk ranking tool that incorporates both quantitative and qualitative information regarding the potential human health risks of ENMs, focused primarily on worker and soldier health. Using a case study involving Army materiel (i.e., equipment), a relative risk ranking algorithm is proposed that accounts for not only the physicochemical characteristics of the ENMs, but also the characteristics of the Army materiel. In this way, the resulting risk potential for soldiers and workers is not solely based on the inherent characteristics of the ENMs but is also influenced within the context of the technology being developed. Among other important findings, the results from applying this risk ranking algorithm in this case study suggest that inhalation from accidental exposures to carbon nanotubes and copper flakes incorporated into energy and obscurant materiel by Army workers rank highest relative to the other items evaluated in this baseline assessment. As the presence of data gaps was one of the greatest challenges to applying this risk ranking algorithm, future applications may benefit from reliance on a continually revised database that may be updated in real time and possibly synced with publically available databases in order to use the most current and comprehensive set(s) of data available.

Operationalization and application of “early warning signs” to screen nanomaterials for harmful properties

In 2001 the European Environment Agency (EEA) published a report that analyzed 14 cases of technological developments that later on turned out to have negative side-effects and they identified 12 “late lessons” for current and future policy-makers to bear in mind when initiating new technological endeavors. This paper explores how the first lesson – “Acknowledge and respond to ignorance, uncertainty and risk in technology appraisal” could be applied to screen nanomaterials. In cases of ignorance, uncertainty and risk, the EEA recommends paying particular attention to important warning signs such as novelty, persistency, whether materials are readily dispersed in the environment, and whether they bioaccumulate or lead to potentially irreversible action. Through an analysis of these criteria using five well-known nanomaterials (titanium dioxide, carbon nanotubes, liposomes, poly(lactic-co-glycolic acid) and nanoscale zero-valent iron), it was found that only nanoTiO2 fulfils all the five criteria. Depending on the length of the nanotubes, carbon nanotubes fulfil 3 or 4 criteria whereas liposomes, poly(lactic-co-glycolic acid), nanoscale zero-valent iron fulfil only one criteria. Finally, we discuss how these warning signs can be used by different stakeholders such as nanomaterial researchers and developers, companies and regulators to design benign nanomaterials, communicate what is known about nano-risks and decide on whether to implement precautionary regulatory measures.

A web-based tool to engage stakeholders in informing research planning for future decisions on emerging materials.

Prioritizing and assessing risks associated with chemicals, industrial materials, or emerging technologies is a complex problem that benefits from the involvement of multiple stakeholder groups. For example, in the case of engineered nanomaterials (ENMs), scientific uncertainties exist that hamper environmental, health, and safety (EHS) assessments. Therefore, alternative approaches to standard EHS assessment methods have gained increased attention. The objective of this paper is to describe the application of a web-based, interactive decision support tool developed by the U.S. Environmental Protection Agency (U.S. EPA) in a pilot study on ENMs. The piloted tool implements U.S. EPAs comprehensive environmental assessment (CEA) approach to prioritize research gaps. When pursued, such research priorities can result in data that subsequently improve the scientific robustness of risk assessments and inform future risk management decisions. Pilot results suggest that the tool was useful in facilitating multi-stakeholder prioritization of research gaps. Results also provide potential improvements for subsequent applications. The outcomes of future CEAWeb applications with larger stakeholder groups may inform the development of funding opportunities for emerging materials across the scientific community (e.g., National Science Foundation Science to Achieve Results [STAR] grants, National Institutes of Health Requests for Proposals).

A framework for One Health research

Abstract The need for multidisciplinary research to address todays complex health and environmental challenges has never been greater. The One Health (OH) approach to research ensures that human, animal, and environmental health questions are evaluated in an integrated and holistic manner to provide a more comprehensive understanding of the problem and potential solutions than would be possible with siloed approaches. However, the OH approach is complex, and there is limited guidance available for investigators regarding the practical design and implementation of OH research. In this paper we provide a framework to guide researchers through conceptualizing and planning an OH study. We discuss key steps in designing an OH study, including conceptualization of hypotheses and study aims, identification of collaborators for a multi-disciplinary research team, study design options, data sources and collection methods, and analytical methods. We illustrate these concepts through the presentation of a case study of health impacts associated with land application of biosolids. Finally, we discuss opportunities for applying an OH approach to identify solutions to current global health issues, and the need for cross-disciplinary funding sources to foster an OH approach to research.

The role of alternative testing strategies in environmental risk assessment of engineered nanomaterials

Within toxicology there is a pressure to find new test systems and organisms to replace, reduce and refine animal testing. In nanoecotoxicology the need for alternative testing strategies (ATS) is further emphasized as the validity of tests and risk assessment practices developed for dissolved chemicals are challenged. Nonetheless, standardized whole organism animal testing is still considered the gold standard for environmental risk assessment. Advancing risk analysis of engineered nanomaterials (ENMs) through ATS was discussed in September 2014 at an international Society for Risk Analysis (SRA) workshop in Washington, D.C. and serves as the point of departure for this paper. Here we present the main outcomes by describing and defining the use of ATS for ENMs as well as discussing its future role in environmental risk science. We conclude that diversity in testing should be encouraged to avoid “selective ignorance” and that, through an iterative process with low-tier and high-tier testing, data-generation can be validated to ensure relevant endpoints. Furthermore, simplified screening of ENMs could enable early decision-making on material design, while complex multispecies studies should be utilized to skip uncertain environmental extrapolations and give rise to more accurate risk analysis.

Data dialogues: critical connections for designing and implementing future nanomaterial research

Individuals and organizations in the engineered nanomaterial (ENM) community have increasingly recognized two related but distinct concerns: (1) Discordant data due to differences in experimental design (e.g., material characteristics, experimental model, and exposure concentration) or reporting (e.g., dose metric and material characterization details), and (2) a lack of data to inform decisions about ENM environmental, health, and safety (EHS). As one way to help address these issues, this Commentary discusses the important role of “data dialogues” or structured discussions between ENM researchers in EHS fields (e.g., toxicology, exposure science, and industrial hygiene) and decision makers who use the data researchers’ collect. The importance of these structured discussions is examined here in the context of barriers, solutions, and incentives: barriers to developing research relevant for human and ecological risk assessments; potential solutions to overcome such barriers; and incentives to help implement these or other solutions. These barriers, solutions, and incentives were identified by a group of expert stakeholders and ENM community members at the December 2013 Society for Risk Analysis panel discussion on research needed to support decision making for multiwalled carbon nanotubes. Key topics discussed by experts and ENM community members include: (1) The value of researchers collaborating with EHS decision makers (e.g., risk analysts, product developers, and regulators) to design research that can inform ENM EHS-related decisions (e.g., occupational exposure limits and product safety determinations), (2) the importance of funding incentives for such collaborative research, (3) the need to improve mechanisms for data sharing within and between sectors (e.g., academia, government, and industry), and (4) the critical need to educate the “next generation” of nanotechnology researchers in EHS topics (e.g., risk assessment, risk management). In presenting these outcomes, this Commentary is not intended to conclude the conversation that took place in December 2013 but rather to support a broader dialogue that helps ensure important risk assessment questions are answered for ENMs.

Application and Testing of Risk Screening Tools for Nanomaterial Risk Analysis

The field of engineered nanomaterial (ENM) risk analysis has matured significantly in the past decade. While there is a suite of new, emerging tools to evaluate ENM risks and make decisions regarding these risks, there has not yet been thorough testing of these tools. This analysis applies and tests three risk screening tools (NanoRiskCat, LICARA nanoSCAN, NanoGRID) using a common case study focused on ENMs designed for water treatment technologies, compares results generated, and highlights key lessons learned and best practices for stakeholders involved in developing and/or applying ENM risk screening tools. NanoRiskCat was found to be most useful for providing a visual aid to characterize the potential exposure and health impact profiles of the ENMs, while LICARA nanoSCAN was most useful for providing guidance on proceeding with ENM-enabled innovations. NanoGRID was helpful for characterizing data on potential ENM exposure and hazards and providing detailed guidance for subsequent laboratory-based testing. At the same time, several key challenges were identified during tool application and testing phases, ranging from minor inconveniences to more complex, foundational issues. Key lessons learned and potential best practices gleaned from this analysis include: i) risk screening tools can be used together in a complementary manner; ii) risk managers and other users should be clear on the selection of underlying data and impacts on results; iii) multidisciplinary teams are essential for tool completion; and iv) continued testing and validation of emerging risk analysis tools for ENMs is a continued research need.

International Implications of Labeling Foods Containing Engineered Nanomaterials

To provide greater transparency and comprehensive information to consumers regarding their purchase choices, the European Parliament and the Council have mandated via Regulation 1169/2011 that foods containing engineered nanomaterials (ENMs) be labeled. This review covers the main concerns related to the use of ENMs in foods and the potential impacts that this type of food labeling might have on diverse stakeholder groups, including those outside the European Union (EU), e.g., in the United States. We also provide recommendations to stakeholders for overcoming existing challenges related to labeling foods containing ENMs. The revised EU food labeling requirements will likely result in a number of positive developments and a number of challenges for stakeholders in both EU and non-EU countries. Although labeling of foods containing ENMs will likely improve transparency, provide more information to facilitate consumer decisions, and build trust among food safety authorities and consumers, critical obstacles to the successful implementation of these labeling requirements remain, including the need for (i) harmonized information requirements or regulations between countries in different regions of the world, (ii) clarification of the regulatory definitions of the ENMs to be used for food labeling, (iii) robust techniques to detect, measure, and characterize diverse ENMs in food matrices, and (iv) clarification of the list of ENMs that may be exempt from labeling requirements, such as several food additives used for decades. We recommend that food industries and food safety authorities be more proactive in communicating with the public and consumer groups regarding the potential benefits and risks of using ENMs in foods. Efforts should be made to improve harmonization of information requirements between countries to avoid potential international trade barriers.