Supporting Decision Making for Sustainable Nanotechnology

Understanding how stakeholders manage risks associated with nanomaterials is a key input to the design of strategies and tools to achieve safe and sustainable nanomanufacturing. The paper presents some results of a study aiming firstly to inform the development of a software decision support tool. Further, we seek also to understand existing tools used by stakeholders as a source of capabilities and potential adaptation into decision support framework and tools. Central research questions of this study are: How is collective decision-making on risk management and sustainable nanomaterials organised? Which aspects are taken into account in this collective decision-making? And what role can a decision support tool play in such decision-making? The paper analyses 13 responses to a questionnaire survey held among participants in a meeting in October 2013 and a series of 27 semi-structured telephone interviews conducted from January until April 2014 with decision-makers from mainly European industry and regulators involved in risk management and sustainable manufacturing of nanomaterials. Findings from the study on the social organisation of collective decision-making, aspects taken into account in decisions and potential role of decision support tools are presented.Understanding how stakeholders manage risks associated with nanomaterials is a key input to the design of strategies and tools to achieve safe and sustainable nanomanufacturing. The paper presents some results of a study aiming firstly to inform the development of a software decision support tool. Further, we seek also to understand existing tools used by stakeholders as a source of capabilities and potential adaptation into decision support framework and tools. Central research questions of this study are: How is collective decision-making on risk management and sustainable nanomaterials organised? Which aspects are taken into account in this collective decision-making? And what role can a decision support tool play in such decision-making? The paper analyses 13 responses to a questionnaire survey held among participants in a meeting in October 2013 and a series of 27 semi-structured telephone interviews conducted from January until April 2014 with decision-makers from mainly European industry and regulators involved in risk management and sustainable manufacturing of nanomaterials. Findings from the study on the social organisation of collective decision-making, aspects taken into account in decisions and potential role of decision support tools are presented

Decision Support for International Agreements Regulating Nanomaterials

Nanomaterials are handled in global value chains for many different products, albeit not always recognisable as nanoproducts. The global market for nanomaterials faces an uncertain future, as the international dialogue on regulating nanomaterials is still ongoing and risk assessment data are being collected. At the same time, regulators and civil society organisations complain about a lack of transparency about the presence of nanomaterials on the market. In the project on Sustainable nanotechnologies (SUN, www.sun-fp7.eu), a Decision Support System (SUNDS) has been developed, primarily for confidential use by risk and sustainability managers inside a company or consortium. In this article, we formulate a scenario concerning a potential role for an open access decision support system in negotiations on international agreements regulating trade in nanomaterials. The scenario includes design rules for decision support systems as well as procedures for use of such a system in stakeholder dialogue and policy-making on governance of these and other emerging technologies. This article incorporates analysis of results of stakeholder engagement on nanomaterials as well as literature and internet sources suggested by these stakeholders

Comparing mental models of prospective users of the sustainable nanotechnology decision support system

Mental modelling analysis can be a valuable tool in understanding and bridging cognitive values in multi-stakeholders' communities. It is especially true in situation of emerging risks where significant uncertainty and competing objectives could result in significant difference in stakeholder perspective on the use of new materials and technologies. This paper presents a mental modelling study performed among prospective users of an innovative decision support system for safe and sustainable development of nano-enabled products. These users included representatives of industry and regulators, as well as several insurance specialists and researchers. We present methodology and tools for comparing stakeholder views and objectives in the context of developing a decision support system

Concern-Driven Integrated Toxicity Testing Strategies for Nanomaterials - Report of the NanoSafety Cluster Working Group 10

Bringing together topic-related European Union-(EU)-funded projects, the so-called “NanoSafety Cluster” aims at identifying key areas for further research on risk assessment procedures for nanomaterials (NM). The outcome of NanoSafety Cluster Working Group 10, this commentary presents a vision for concern-driven integrated approaches for the (eco-)toxicological testing and assessment (IATA) of NM. Such approaches should start out by determining concerns, i.e. specific information needs for a given NM based on realistic exposure scenarios. Recognized concerns can be addressed in a set of tiers using standardized protocols for NM preparation and testing. Tier 1 includes determining physico-chemical properties, non-testing (e.g. structure activity relationships) and evaluating existing data. In tier 2, a limited set of in vitro and in vivo tests are performed that can either indicate that the risk of the specific concern is sufficiently known or indicate the need for further testing, including details for such testing. Ecotoxicological testing begins with representative test organisms followed by complex test systems. After each tier, it is evaluated whether the information gained permits assessing the safety of the NM so that further testing can be waived. By effectively exploiting all available information, IATA allow accelerating the risk assessment process and reducing testing costs and animal use (in line with the 3Rs principle implemented in EU Directive 2010/63/EU). Combining material properties, exposure, biokinetics, and hazard data, information gained with IATA can be used to recognize groups of NM based upon similar modes-of-action. Grouping of substances in return should form integral part of the IATA themselves

The MARINA Risk Assessment Strategy: A Flexible Strategy for Efficient Information Collection and Risk Assessment of Nanomaterials

An engineered nanomaterial (ENM) may actually consist of a population of primary particles, aggregates and agglomerates of various sizes. Furthermore, their physico-chemical characteristics may change during the various life-cycle stages. It will probably not be feasible to test all varieties of all ENMs for possible health and environmental risks. There is therefore a need to further develop the approaches for risk assessment of ENMs. Within the EU FP7 project Managing Risks of Nanoparticles (MARINA) a two-phase risk assessment strategy has been developed. In Phase 1 (Problem framing) a base set of information is considered, relevant exposure scenarios (RESs) are identified and the scope for Phase 2 (Risk assessment) is established. The relevance of an RES is indicated by information on exposure, fate/kinetics and/or hazard; these three domains are included as separate pillars that contain specific tools. Phase 2 consists of an iterative process of risk characterization, identification of data needs and integrated collection and evaluation of data on the three domains, until sufficient information is obtained to conclude on possible risks in a RES. Only data are generated that are considered to be needed for the purpose of risk assessment. A fourth pillar, risk characterization, is defined and it contains risk assessment tools. This strategy describes a flexible and efficient approach for data collection and risk assessment which is essential to ensure safety of ENMs. Further developments are needed to provide guidance and make the MARINA Risk Assessment Strategy operational. Case studies will be needed to refine the strategy

How can we justify grouping of nanoforms for hazard assessment? Concepts and tools to quantify similarity

The risk of each nanoform (NF) of the same substance cannot be assumed to be the same, as they may vary in their physicochemical characteristics, exposure and hazard. However, neither can we justify a need for more animal testing and resources to test every NF individually. To reduce the need to test all NFs, (regulatory) information requirements may be fulfilled by grouping approaches. For such grouping to be acceptable, it is important to demonstrate similarities in physicochemical properties, toxicokinetic behaviour, and (eco)toxicological behaviour. The GRACIOUS Framework supports the grouping of NFs, by identifying suitable grouping hypotheses that describe the key similarities between different NFs. The Framework then supports the user to gather the evidence required to test these hypotheses and to subsequently assess the similarity of the NFs within the proposed group. The evidence needed to support a hypothesis is gathered by an Integrated Approach to Testing and Assessment (IATA), designed as decision trees constructed of decision nodes. Each decision node asks the questions and provides the methods needed to obtain the most relevant information. This White paper outlines existing and novel methods to assess similarity of the data generated for each decision node, either via a pairwise analysis conducted property-by-property, or by assessing multiple decision nodes simultaneously via a multidimensional analysis. For the pairwise comparison conducted property-by-property we included in this White paper: • A Bayesian model assessment which compares two sets of values using nested sampling. This approach is new in NF grouping. • A Arsinh-Ordered Weighted Average model (Arsinh-OWA) which applies the arsinh transformation to the distance between two NFs, and then rescales the result to the arsinh of a biologically relevant threshold before grouping using OWA based distance. This approach is new in NF grouping. • An x-fold comparison as used in the ECETOC NanoApp. • Euclidean distance, which is a highly established distance metric. The x-fold, Bayesian and Arsinh-OWA distance algorithms performed comparably in the scoring of similarity between NF pairs. The Euclidean distance was also useful, but only with proper data transformation. The x-fold method does not standardize data, and thus produces skewed histograms, but has the advantage that it can be implemented without programming knowhow. A range of multidimensional evaluations, using for example dendrogram clustering approaches, were also investigated. Multidimensional distance metrics were demonstrated to be difficult to use in a regulatory context, but from a scientific perspective were found to offer unexpected insights into the overall similarity of very different materials. In conclusion, for regulatory purposes, a property-by-property evaluation of the data matrix is recommended to substantiate grouping, while the multidimensional approaches are considered to be tools of discovery rather than regulatory methods

Demonstrating approaches to chemically modify the surface of Ag nanoparticles in order to influence their cytotoxicity and biodistribution after single dose acute intravenous administration

With the advance in material science and the need to diversify market applications, silver nanoparticles (AgNPs) are modified by different surface coatings. However, how these surface modifications influence the effects of AgNPs on human health is still largely unknown. We have evaluated the uptake, toxicity and pharmacokinetics of AgNPs coated with citrate, polyethylene glycol, polyvinyl pyrolidone and branched polyethyleneimine (Citrate AgNPs, PEG AgNPs, PVP AgNPs and BPEI AgNPs, respectively). Our results demonstrated that the toxicity of AgNPs depends on the intracellular localization that was highly dependent on the surface charge. BPEI AgNPs ( potential=+46.5mV) induced the highest cytotoxicity and DNA fragmentation in Hepa1c1c7. In addition, it showed the highest damage to the nucleus of liver cells in the exposed mice, which is associated with a high accumulation in liver tissues. The PEG AgNPs ( potential=-16.2mV) showed the cytotoxicity, a long blood circulation, as well as bioaccumulation in spleen (34.33 mu g/g), which suggest better biocompatibility compared to the other chemically modified AgNPs. Moreover, the adsorption ability with bovine serum albumin revealed that the PEG surface of AgNPs has an optimal biological inertia and can effectively resist opsonization or non-specific binding to protein in mice. The overall results indicated that the biodistribution of AgNPs was significantly dependent on surface chemistry: BPEI AgNPs>Citrate AgNPs=PVP AgNPs>PEG AgNPs. This toxicological data could be useful in supporting the development of safe AgNPs for consumer products and drug delivery applications

A framework for grouping and read-across of nanomaterials- supporting innovation and risk assessment

According to some legislation grouping can streamline data gap filling for the hazard assessment of substances. The GRACIOUS Framework aims to facilitate the application of grouping of nanomaterials or nanoforms (NFs), in a regulatory context and to support innovation. This includes using grouping to enable read-across from (a) source(s), for which data and information exist, to a similar target NF where information is lacking. The Framework provides an initial set of hypotheses for the grouping of NFs which take into account the identity and use(s) of the NFs, as well as the purpose of grouping. Initial collection of basic information allows selection of an appropriate pre-defined grouping hypothesis and a tailored Integrated Approach to Testing and Assessment (IATA), designed to generate new evidence to support acceptance or rejection of the hypothesis. Users needing to develop their own user-defined hypothesis (and IATA) are also supported by the Framework. In addition, the IATA guides acquisition of the information needed to support read-across. This approach gathers information to render risk assessment more efficient, affordable, as well as reducing the use of test animals