Elena Semenzin

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

Abstract 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 (ζ potential = +46.5 mV) 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 (ζ potential = −16.2 mV) showed the cytotoxicity, a long blood circulation, as well as bioaccumulation in spleen (34.33 µg/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.

Sustainable nanotechnology decision support system: bridging risk management, sustainable innovation and risk governance

The significant uncertainties associated with the (eco)toxicological risks of engineered nanomaterials pose challenges to the development of nano-enabled products toward greatest possible societal benefit. This paper argues for the use of risk governance approaches to manage nanotechnology risks and sustainability, and considers the links between these concepts. Further, seven risk assessment and management criteria relevant to risk governance are defined: (a) life cycle thinking, (b) triple bottom line, (c) inclusion of stakeholders, (d) risk management, (e) benefit–risk assessment, (f) consideration of uncertainty, and (g) adaptive response. These criteria are used to compare five well-developed nanotechnology frameworks: International Risk Governance Council framework, Comprehensive Environmental Assessment, Streaming Life Cycle Risk Assessment, Certifiable Nanospecific Risk Management and Monitoring System and LICARA NanoSCAN. A Sustainable Nanotechnology Decision Support System (SUNDS) is proposed to better address current nanotechnology risk assessment and management needs, and makes. Stakeholder needs were solicited for further SUNDS enhancement through a stakeholder workshop that included representatives from regulatory, industry and insurance sectors. Workshop participants expressed the need for the wider adoption of sustainability assessment methods and tools for designing greener nanomaterials.

Frameworks and tools for risk assessment of manufactured nanomaterials.

Commercialization of nanotechnologies entails a regulatory requirement for understanding their environmental, health and safety (EHS) risks. Today we face challenges to assess these risks, which emerge from uncertainties around the interactions of manufactured nanomaterials (MNs) with humans and the environment. In order to reduce these uncertainties, it is necessary to generate sound scientific data on hazard and exposure by means of relevant frameworks and tools. The development of such approaches to facilitate the risk assessment (RA) of MNs has become a dynamic area of research. The aim of this paper was to review and critically analyse these approaches against a set of relevant criteria. The analysis concluded that none of the reviewed frameworks were able to fulfill all evaluation criteria. Many of the existing modelling tools are designed to provide screening-level assessments rather than to support regulatory RA and risk management. Nevertheless, there is a tendency towards developing more quantitative, higher-tier models, capable of incorporating uncertainty into their analyses. There is also a trend towards developing validated experimental protocols for material identification and hazard testing, reproducible across laboratories. These tools could enable a shift from a costly case-by-case RA of MNs towards a targeted, flexible and efficient process, based on grouping and read-across strategies and compliant with the 3R (Replacement, Reduction, Refinement) principles. In order to facilitate this process, it is important to transform the current efforts on developing databases and computational models into creating an integrated data and tools infrastructure to support the risk assessment and management of MNs.

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.

Review of decision analytic tools for sustainable nanotechnology

Nanotechnology innovation is hampered by data gaps and knowledge limitations in evaluating the risks and impacts of nano-enabled products. “Sustainable nanotechnology” is a growing concept in the literature, which calls for a comprehensive evaluation of the risks and impacts of nanotechnology at an early stage of nano-enabled product life cycle. ‘One such method to frame sustainable nanotechnology is the triple bottom line (TBL) approach, which comprises the environmental, economic, and societal “pillars” that contribute to the overall sustainability of a nano-enabled product. For the context of nanotechnology, risk analysis (RA), life cycle assessment (LCA), and multi-criteria decision analysis (MCDA) are frequently called upon to support sustainable nanotechnology governance. This paper provides a systematic review of these tools in the context of sustainable nanotechnology. The results indicate a growing number of applications for these tools with LCA contributing to the environmental and economic pillars, and RA contributing to the environmental pillar. MCDA provides the structural scaffold and mathematical techniques necessary to integrate RA and LCA within the TBL, and also provides the means to address uncertainty of early-stage nanotechnology assessment. Using these tools, integrated sustainability assessment could provide a viable means for industry and regulators to make near-term decisions about complex nanotechnology problems.

DSS-ERAMANIA: Decision Support System for Site-Specific Ecological Risk Assessment of Contaminated Sites

The DSS-ERAMANIA is a decision support system implementing a site-specific Ecological Risk Assessment (ERA) procedure and supporting the experts and the decision makers in the assessment of contaminated soils. It was developed according to a Triad approach, where the results provided by a set of measurement endpoints are evaluated and integrated to support the assessment and characterization of ecosystem impairment (i.e. assessment endpoint) caused by the soil contamination. In the Triad approach, the measurement endpoints refer to three Lines Of Evidence (LOE): environmental chemistry, ecotoxicology and ecology, whose integration should pragmatically reduce the uncertainty in the risk estimation. For the DSS, a framework including three subsequent investigation levels (i.e. tiers) was implemented, that enables the completion of the risk assessment once the provided answer is unequivocal as characterized by a relatively small uncertainty, ensuring at the same time an adequate financial investment. The DSS includes two modules: “Comparative Tables” and “Integrated Ecological Risk Indexes”, both based on Multi Criteria Decision Analysis (MCDA). Module 1 (“Comparative Tables”) aims at comparing the different measurement endpoints belonging to each LOE (i.e. bioavailability tools, toxicity tests and ecological observations) to guide the expert/decision maker in the choice of the suitable set of tests to be applied to the case study for each tier of investigation. Module 2 (“Integrated Ecological Risk Indexes”) provides qualitative and quantitative tools allowing the assessment of terrestrial ecosystem impairment (i.e. the impairment occurring on biodiversity and functional diversity of the terrestrial ecosystem) by integrating complementary information obtained by the application of the measurement endpoints selected in the first module. The two modules were implemented in a software application and validated using the Acna di Cengio contaminated site (located in Savona province, Italy). The objectives, functionalities and structure of the DSS-ERAMANIA will be presented and the main outcomes of the DSS application to the case study will be discussed.

Species sensitivity weighted distribution for ecological risk assessment of engineered nanomaterials: The n-TiO2 case study

Societal concerns about the environmental risks of engineered nanomaterials (ENMs) have recently increased, but nano-ecological risk assessments are constrained by significant gaps in basic information on long-term effects and exposures, for example. An approach to the ecological risk assessment of ENMs is proposed that can operate in the context of high uncertainty. This approach further develops species sensitivity weighted distribution (SSWD) by including 3 weighting criteria (species relevance, trophic level abundance, and nanotoxicity data quality) to address nano-specific needs (n-SSWD). The application of n-SSWD is illustrated for nanoscale titanium dioxide (n-TiO2 ), which is available in different crystal forms; it was selected because of its widespread use in consumer products (e.g., cosmetics) and the ample availability of data from ecotoxicological studies in the literature (including endpoints for algae, invertebrates, bacteria, and vertebrates in freshwater, saltwater, and terrestrial compartments). The n-SSWD application resulted in estimation of environmental quality criteria (hazard concentration affecting 5% and 50% of the species) and ecological risk (potentially affected fraction of species), which were then compared with similar results obtained by applying the traditional species sensitivity distribution (SSD) approach to the same dataset. The n-SSWDs were also built for specific trophic levels (e.g., primary producers) and taxonomic groups (e.g., algae), which helped to identify the most sensitive organisms. These results showd that n-SSWD is a valuable risk tool, although further testing is suggested.

Integrated Risk Assessment for WFD Ecological Status classification applied to Llobregat river basin (Spain). Part II - Evaluation process applied to five environmental Lines of Evidence.

Many indicators and indices related to a variety of biological, physico-chemical, chemical, and hydromorphological water conditions have been recently developed or adapted by scientists in order to support water managers in the Water Framework Directive (WFD) implementation. In this context, the achievement of a comprehensive and reliable Ecological Status classification of water bodies across Europe is hampered by the lack of harmonised procedures for selecting an appropriate set of indicators and integrating heterogeneous information in a flexible way. To this purpose, an Integrated Risk Assessment (IRA)(2) methodology was developed based on the Weight of Evidence approach. This method analyses and combines a set of environmental indicators grouped into five Lines of Evidence (LoE), i.e. Biology, Chemistry, Ecotoxicology, Physico-chemistry and Hydromorphology. The whole IRA methodology has been implemented as a specific module into a freeware GIS (Geographic Information System)-based Decision Support System, named MODELKEY DSS. This paper focuses on the evaluation of the four supporting LoE (i.e. Chemistry, Ecotoxicology, Physico-chemistry and Hydromorphology), and includes a procedure for a comparison of each indicator with proper thresholds and a subsequent integration process to combine the obtained output with the LoE Biology results in order to provide a single score expressing the Ecological Status classification. The approach supports the identification of the most prominent stressors, which are responsible for the observed alterations in the river basin under investigation. The results provided by the preliminary testing of the IRA methodology through application of the MODELKEY DSS to the Llobregat case study are finally reported and discussed.

Supporting decision-making for sustainable nanotechnology

AbstractUnderstanding 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 Systems for Contaminated Land Management: A Review

The aim of this review is to introduce and compare some of the latest progress in the development of decision support systems (DSSs) for the management of contaminated sites.