A Decision Support System for preclinical assessment of nanomaterials in medical products: the REFINE DSS.

The application of nanomaterials in medicine has led to novel pharmaceuticals and medical devices that have demonstrated a strong potential for increasing the efficacy/performance and safety of therapeutic and diagnostic procedures to address a wide range of diseases. However, the successful translation of these technologies from their inception (proof-of-concept) to clinical practice has been challenged by substantial gaps in the scientific and technical capacity of R&D companies, especially SMEs, to keep up with the ever-evolving regulatory expectations in the emerging area of nanomedicine. To address these challenges, the EU Horizon 2020 project REFINE has developed a Decision Support System (DSS) to support developers of nanotechnology-enabled health products in bringing their products to the clinic. The REFINE DSS has been developed to support experts, innovators, and regulators in the implementation of intelligent testing strategies (ITS) for efficient preclinical assessment of nanotechnology-enabled health products. The DSS applies logical rules provided by REFINE experts which generate prioritized lists of assays to be performed (i.e. ITSs) for physicochemical characterisation and for immunotoxicological endpoints. The DSS has been tested against several case studies and was validated by internal project experts as well as external ones.

Risk Management Framework for Nano-Biomaterials Used in Medical Devices and Advanced Therapy Medicinal Products.

The convergence of nanotechnology and biotechnology has led to substantial advancements in nano-biomaterials (NBMs) used in medical devices (MD) and advanced therapy medicinal products (ATMP). However, there are concerns that applications of NBMs for medical diagnostics, therapeutics and regenerative medicine could also pose health and/or environmental risks since the current understanding of their safety is incomplete. A scientific strategy is therefore needed to assess all risks emerging along the life cycles of these products. To address this need, an overarching risk management framework (RMF) for NBMs used in MD and ATMP is presented in this paper, as a result of a collaborative effort of a team of experts within the EU Project BIORIMA and with relevant inputs from external stakeholders. The framework, in line with current regulatory requirements, is designed according to state-of-the-art approaches to risk assessment and management of both nanomaterials and biomaterials. The collection/generation of data for NBMs safety assessment is based on innovative integrated approaches to testing and assessment (IATA). The framework can support stakeholders (e.g., manufacturers, regulators, consultants) in systematically assessing not only patient safety but also occupational (including healthcare workers) and environmental risks along the life cycle of MD and ATMP. The outputs of the framework enable the user to identify suitable safe(r)-by-design alternatives and/or risk management measures and to compare the risks of NBMs to their (clinical) benefits, based on efficacy, quality and cost criteria, in order to inform robust risk management decision-making.

Use of multiple indicators to compare sustainability performance of organic vs conventional vineyard management.

The wine sector is paying more attention to sustainable wine production practices, but this topic is highly debated because organic viticulture aims to a reduction of environmental impacts, while conventional viticulture ensures an increase of yield. This work provides an economic and environmental comparison using different indicators whereas no previous studies on viticulture have faced on both aspects of sustainability. Two distinct vineyards within the same case study farm were considered, where conventional and organic viticulture practices were applied for 5 years. For each type of production, we calculated the economic benefit and environmental indicators such as the Water Footprint, Carbon Footprint, and an indicator of environmental performance associated with the vineyard phase ("Vineyard Management" or "Vigneto" indicator part of the Italian VIVA certification framework). This latter considers six sub-indicators investigating pesticides management, fertilizers management, organic matter content, soil compaction, soil erosion, and landscape quality. The multi criteria approach is a novel framework assessing sustainability on vineyard management using environmental indicators from VIVA calculator and the economic aspect. Main results showed that organic management in viticulture can be applied without having economic losses and with the benefit of better preserving the natural capital.

Controlling the risks of nano-enabled products through the life cycle: The case of nano copper oxide paint for wood protection and nano-pigments used in the automotive industry.

The widespread use of engineered nanomaterials (ENMs) in consumer products and the overwhelming uncertainties in their ecological and human health risks have raised concerns regarding their safety among industries and regulators. There has been an ongoing debate over the past few decades on ways to overcome the challenges in assessing and mitigating nano-related risks, which has reached a phase of general consensus that nanotechnology innovation should be accompanied by the application of the precautionary principle and best practice risk management, even if the risk assessment uncertainties are large. We propose a quantitative methodology for selecting the optimal risk control strategy based on information about human health and ecological risks, efficacy of risk mitigation measures, cost and other contextual factors. The risk control (RC) methodology was developed in the European FP7 research project SUN and successfully demonstrated in two case studies involving real industrial nano-enabled products (NEPs): nano-scale copper oxide (CuO) and basic copper carbonate (Cu2(OH)2CO3) used as antimicrobial and antifungal coatings and impregnations for the preservation of treated wood, and two nanoscale pigments used for colouring plastic automotive parts (i.e. red organic pigment and carbon black). The application of RC for human health risks showed that although nano-related risks could easily be controlled in automotive plastics case study with modifications in production technology or specific type of engineering controls, nano-related risks due to sanding and sawing copper oxide painted wood were non-acceptable in the use lifecycle stage and would need the identification of a more effective risk control strategy.

Risk Governance of Nanomaterials: Review of Criteria and Tools for Risk Communication, Evaluation, and Mitigation.

Nanotechnologies have been increasingly used in industrial applications and consumer products across several sectors, including construction, transportation, energy, and healthcare. The widespread application of these technologies has raised concerns regarding their environmental, health, societal, and economic impacts. This has led to the investment of enormous resources in Europe and beyond into the development of tools to facilitate the risk assessment and management of nanomaterials, and to inform more robust risk governance process. In this context, several risk governance frameworks have been developed. In our study, we present and review those, and identify a set of criteria and tools for risk evaluation, mitigation, and communication, the implementation of which can inform better risk management decision-making by various stakeholders from e.g., industry, regulators, and the civil society. Based on our analysis, we recommend specific methods from decision science and information technologies that can improve the existing risk governance tools so that they can communicate, evaluate, and mitigate risks more transparently, taking stakeholder perspectives and expert opinion into account, and considering all relevant criteria in establishing the risk-benefit balance of these emerging technologies to enable more robust decisions about the governance of their risks.

Comparison of Water-focused Life Cycle Assessment and Water Footprint Assessment: The case of an Italian wine.

In recent decades, the debate on how to implement and measure sustainability in food production gained increasing importance and interest for agriculture. In the wine sector, producers are increasingly pursuing sustainable practices, including measures for water preservation from degradation and overuse. But methodologies for assessing and communicating the impacts on water resources need to be understood in detail to guide the selection of the most appropriate management practices, support environmental labelling and promote environmental-friendly products to consumers. This work focuses on the impacts on water resources associated with the production of Italian wine by comparing two methodologies: the Water-focused Life Cycle Assessment and the "Water" indicator included in the Italian "VIVA" certification framework, which is based on the Water Footprint Assessment. The two methodologies address the impact on freshwater consumption and degradation from a life cycle perspective. VIVA is based on a water balance method that reflects a volumetric measure of water consumption, while the LCA-based approach investigates both the freshwater consumption and depletion using different impact indicators. The study goal is to compare the two methodologies to understand how their outcomes can support and improve the management of water-related issues in wine production. One main conclusion is that the WATER indicator within VIVA framework can provide more precise recommendations for the optimal management of water use during the vineyard phase, while LCA approach highlights impact hotspots related to both direct and indirect use of water resources (e.g., it points out the relevant contribution of the bottling stage to different impact indicators). The comparative application of both methodologies can provide useful insights into the water-related impacts of different wine production processes and stages and support a comprehensive assessment of the best management practices, unless the differences in the methodological approaches and goals are well understood by assessors.

Quantitative human health risk assessment along the lifecycle of nano-scale copper-based wood preservatives.

The use of nano-scale copper oxide (CuO) and basic copper carbonate (Cu2(OH)2CO3) in both ionic and micronized wood preservatives has raised concerns about the potential of these substances to cause adverse humans health effects. To address these concerns, we performed quantitative (probabilistic) human health risk assessment (HHRA) along the lifecycles of these formulations used in antibacterial and antifungal wood coatings and impregnations by means of the EU FP7 SUN project's Decision Support System (SUNDS, www.sunds.gd). The results from the risk analysis revealed inhalation risks from CuO in exposure scenarios involving workers handling dry powders and performing sanding operations as well as potential ingestion risks for children exposed to nano Cu2(OH)2CO3 in a scenario involving hand-to-mouth transfer of the substance released from impregnated wood. There are, however, substantial uncertainties in these results, so some of the identified risks may stem from the safety margin of extrapolation to fill data gaps and might be resolved by additional testing. Our stochastic approach successfully communicated the contribution of different sources of uncertainty in the risk assessment. The main source of uncertainty was the extrapolation from short to long-term exposure, which was necessary due to the lack of (sub)chronic in vivo studies with CuO and Cu2(OH)2CO3. Considerable uncertainties also stemmed from the use of default inter- and intra-species extrapolation factors.

An Information System for Brownfield Regeneration: providing customised information according to stakeholders' characteristics and needs.

In the EU brownfield presence is still considered a widespread problem. Even though, in the last decades, many research projects and initiatives developed a wealth of methods, guidelines, tools and technologies aimed at supporting brownfield regeneration. However, this variety of products had and still has a limited practical impact on brownfield revitalisation success, because they are not used in their entire potential due to their scarce visibility. Also, another problem that stakeholders face is finding customised information. To overcome this non-visibility and not-sufficient customisation of information, the Information System for Brownfield Regeneration (ISBR) has been developed, based on Artificial Neural Networks, which allows understanding stakeholders' information needs by providing tailored information. The ISBR has been tested by stakeholders from the EU project TIMBRE case studies, located in the Czech Republic, Germany, Poland and Romania. Data gained during tests allowed to understand stakeholders' information needs. Overall, stakeholders showed to be concerned first on remediation aspects, then on benchmarking information, which are valuable to improve practices in the complex field of brownfield regeneration, and then on the relatively new issue of sustainability applied to brownfield regeneration and remediation. Mature markets confirmed their interest for remediation-related aspects, highlighting the central role that risk assessment plays in the process. Emerging markets showed to seek information and tools for strategic and planning issues, like brownfield inventories and georeferenced data sets. Results led to conclude that a new improved platform, combining the ISBR functionalities with geo-referenced ones, would be useful and could represent a further research application.

Points of attention in designing tools for regional brownfield prioritization.

The regeneration of brownfields has been increasingly recognized as a key instrument in sustainable land management, since free developable land (or so called "greenfields") has become a scare and more expensive resource, especially in densely populated areas. However, the complexity of these sites requires considerable efforts to successfully complete their revitalization projects, thus requiring the development and application of appropriate tools to support decision makers in the selection of promising sites where efficiently allocate the limited financial resources. The design of effective prioritization tools is a complex process, which requires the analysis and consideration of critical points of attention (PoAs) which has been identified considering the state of the art in literature, and lessons learned from previous developments of regional brownfield (BF) prioritization processes, frameworks and tools. Accordingly, we identified 5 PoAs, namely 1) Assessing end user needs and orientation discussions, 2) Availability and quality of the data needed for the BF prioritization tool, 3) Communication and stakeholder engagement 4) Drivers of regeneration success, and 5) Financing and application costs. To deepen and collate the most recent knowledge on the topics from scientists and practitioners, we organized a focus group discussion within a special session at the AquaConSoil (ACS) conference 2017, where participants were asked to add their experience and thoughts to the discussion in order to identify the most significant and urgent points of attention in BF prioritization tool design. The result of this assessment is a comprehensive table (Table 2), which can support problem owners, investors, service providers, regulators, public and private land managers, decision makers etc. in the identification of the main aspects (sub-topics) to be considered and their relative influences and in the comprehension of the general patterns and challenges to be faced when dealing with the development of BF prioritization tools.

Probabilistic approach for assessing infants' health risks due to ingestion of nanoscale silver released from consumer products.

Silver nanoparticles (n-Ag) are widely used in consumer products and many medical applications because of their unique antibacterial properties. Their use is raising concern about potential human exposures and health effects. Therefore, it is informative to assess the potential human health risks of n-Ag in order to ensure that nanotechnology-based consumer products are deployed in a safe and sustainable way. Even though toxicity studies clearly show the potential hazard of n-Ag, there have been few attempts to integrate hazard and exposure assessments to evaluate risks. The underlying reason for this is the difficulty in characterizing exposure and the lack of toxicity studies essential for human health risk assessment (HHRA). Such data gaps introduce significant uncertainty into the risk assessment process. This study uses probabilistic methods to assess the relative uncertainty and potential risks of n-Ag exposure to infants. In this paper, we estimate the risks for infants potentially exposed to n-Ag through drinking juice or milk from sippy cups or licking baby blankets containing n-Ag. We explicitly evaluate uncertainty and variability contained in available dose-response and exposure data in order to make the risk characterization process transparent. Our results showed that individual margin of exposures for oral exposure to sippy cups and baby blankets containing n-Ag exhibited minimal risk.

Comparison of international approaches to sustainable remediation.

Since mid-to-late 2000s growing interest for sustainable remediation has emerged in initiatives from several international and national organisations as well as other initiatives from networks and forums. This reflects a realisation that risk-management activities can about bring environmental, social, and economic impacts (positive or negative) in addition to achieving risk-based remediation goals. These ideas have begun to develop as a new discipline of "sustainable remediation". The various initiatives have now published a number of frameworks, standards, white papers, road maps and operative guidelines. The similarities and differences in the approaches by these outputs and general trends have been identified. The comparison is based on a set of criteria developed in discussion with members of these various initiatives, and identifies a range of similarities between their publications. Overall the comparison demonstrates a high level of consensus across definitions and principles, which leads to the conclusion that there is a shared understanding of what sustainable remediation is both across countries and stakeholder groups. Publications do differ in points of detail, in particular about the operational aspects of sustainable remediation assessment. These differences likely result from differences in context and legal framework. As this analysis was carried out its findings were debated with members of the various international initiatives, many of whom have been included as authors. Hence the outcomes described in this paper can be seen as the result of a sort of multi-level debate among international experts (authors) and so can offer a starting point to new sustainable remediation initiatives (for example in other countries) that aim to start developing their own documents.

Targeted selection of brownfields from portfolios for sustainable regeneration: User experiences from five cases testing the Timbre Brownfield Prioritization Tool.

Prioritizing brownfields for redevelopment in real estate portfolios can contribute to more sustainable regeneration and land management. Owners of large real estate and brownfield portfolios are challenged to allocate their limited resources to the development of the most critical or promising sites, in terms of time and cost efficiency. Authorities worried about the negative impacts of brownfields - in particular in the case of potential contamination - on the environment and society also need to prioritize their resources to those brownfields that most urgently deserve attention and intervention. Yet, numerous factors have to be considered for prioritizing actions, in particular when adhering to sustainability principles. Several multiple-criteria decision analysis (MCDA) approaches and tools have been suggested in order to support these actors in managing their brownfield portfolios. Based on lessons learned from the literature on success factors, sustainability assessment and MCDA approaches, researchers from a recent EU project have developed the web-based Timbre Brownfield Prioritization Tool (TBPT). It facilitates assessment and prioritization of a portfolio of sites on the basis of the probability of successful and sustainable regeneration or according to individually specified objectives. This paper introduces the challenges of brownfield portfolio management in general and reports about the application of the TBPT in five cases: practical test-uses by two large institutional land owners from Germany, a local and a regional administrative body from the Czech Republic, and an expert from a national environmental authority from Romania. Based on literature requirements for sustainability assessment tools and on the end-users' feedbacks from the practical tests, we discuss the TBPT's strengths and weaknesses in order to inform and give recommendations for future development of prioritization tools.

Timbre Brownfield Prioritization Tool to support effective brownfield regeneration.

In the last decade, the regeneration of derelict or underused sites, fully or partly located in urban areas (or so called "brownfields"), has become more common, since free developable land (or so called "greenfields") has more and more become a scare and, hence, more expensive resource, especially in densely populated areas. Although the regeneration of brownfield sites can offer development potentials, the complexity of these sites requires considerable efforts to successfully complete their revitalization projects and the proper selection of promising sites is a pre-requisite to efficiently allocate the limited financial resources. The identification and analysis of success factors for brownfield sites regeneration can support investors and decision makers in selecting those sites which are the most advantageous for successful regeneration. The objective of this paper is to present the Timbre Brownfield Prioritization Tool (TBPT), developed as a web-based solution to assist stakeholders responsible for wider territories or clusters of brownfield sites (portfolios) to identify which brownfield sites should be preferably considered for redevelopment or further investigation. The prioritization approach is based on a set of success factors properly identified through a systematic stakeholder engagement procedure. Within the TBPT these success factors are integrated by means of a Multi Criteria Decision Analysis (MCDA) methodology, which includes stakeholders' requalification objectives and perspectives related to the brownfield regeneration process and takes into account the three pillars of sustainability (economic, social and environmental dimensions). The tool has been applied to the South Moravia case study (Czech Republic), considering two different requalification objectives identified by local stakeholders, namely the selection of suitable locations for the development of a shopping centre and a solar power plant, respectively. The application of the TBPT to the case study showed that it is flexible and easy to adapt to different local contexts, allowing the assessors to introduce locally relevant parameters identified according to their expertise and considering the availability of local data.

Risk-based prioritization methodology for the classification of groundwater pollution sources.

Water management is one of the EU environmental priorities and it is one of the most serious challenges that today's major cities are facing. The main European regulation for the protection of water resources is represented by the Water Framework Directive (WFD) and the Groundwater Directive (2006/118/EC) which require the identification, risk-based ranking and management of sources of pollution and the identification of those contamination sources that threaten the achievement of groundwater's good quality status. The aim of this paper is to present a new risk-based prioritization methodology to support the determination of a management strategy for the achievement of the good quality status of groundwater. The proposed methodology encompasses the following steps: 1) hazard analysis, 2) pathway analysis, 3) receptor vulnerability analysis and 4) relative risk estimation. Moreover, by integrating GIS functionalities and Multi Criteria Decision Analysis (MCDA) techniques, it allows to: i) deal with several sources and multiple impacted receptors within the area of concern; ii) identify different receptors' vulnerability levels according to specific groundwater uses; iii) assess the risks posed by all contamination sources in the area; and iv) provide a risk-based ranking of the contamination sources that can threaten the achievement of the groundwater good quality status. The application of the proposed framework to a well-known industrialized area located in the surroundings of Milan (Italy) is illustrated in order to demonstrate the effectiveness of the proposed framework in supporting the identification of intervention priorities. Among the 32 sources analyzed in the case study, three sources received the highest relevance score, due to the medium-high relative risks estimated for Chromium (VI) and Perchloroethylene. The case study application showed that the developed methodology is flexible and easy to adapt to different contexts, thanks to the possibility to introduce specific relevant parameters identified according to expert judgment and data availability.

Regional risk assessment approaches to land planning for industrial polluted areas in China: the Hulunbeier region case study.

The rapid industrial development and urbanization processes that occurred in China over the past 30years has increased dramatically the consumption of natural resources and raw materials, thus exacerbating the human pressure on environmental ecosystems. In result, large scale environmental pollution of soil, natural waters and urban air were recorded. The development of effective industrial planning to support regional sustainable economy development has become an issue of serious concern for local authorities which need to select safe sites for new industrial settlements (i.e. industrial plants) according to assessment approaches considering cumulative impacts, synergistic pollution effects and risks of accidental releases. In order to support decision makers in the development of efficient and effective regional land-use plans encompassing the identification of suitable areas for new industrial settlements and areas in need of intervention measures, this study provides a spatial regional risk assessment methodology which integrates relative risk assessment (RRA) and socio-economic assessment (SEA) and makes use of spatial analysis (GIS) methodologies and multicriteria decision analysis (MCDA) techniques. The proposed methodology was applied to the Chinese region of Hulunbeier which is located in eastern Inner Mongolia Autonomous Region, adjacent to the Republic of Mongolia. The application results demonstrated the effectiveness of the proposed methodology in the identification of the most hazardous and risky industrial settlements, the most vulnerable regional receptors and the regional districts which resulted to be the most relevant for intervention measures since they are characterized by high regional risk and excellent socio-economic development conditions.

Regional risk assessment for contaminated sites part 3: spatial decision support system.

Large scale (e.g. regional or national) assessments of contaminated sites may be very costly in terms of investigation and methodological (i.e. risk assessment procedures) requirements and may produce a quantity of information that usually discourages examination by decision-makers. Moreover, most of the existing tools effectively support local environmental risk assessment and management, but lack the capabilities of larger scale analysis, not mentioning the absence of the relevant component of socio-economic prioritization. To respond to the concerns and the management needs of experts and decision makers, the Spatial decision support sYstem for Regional rIsk Assessment of Degraded land (SYRIADE DSS) was developed and is presented according to its three modules: Regional Risk Assessment, Socio-economic Assessment and Integrated Assessment, respectively. The system allows to rank potentially contaminated sites for priority of investigation, when no information on characterization and risk by site specific methodologies is available. This GIS-based system embeds an innovative spatial and relative risk assessment procedure, and proposes the integrated analysis of different data (environmental and socio-economic) for the concerned sites, eliciting when necessary experts' knowledge and stakeholders' values (through Multi Criteria Decision Analysis, MCDA, methodologies). The application to a Polish case-study shows the performance and the flexibility of the system in investigating and mapping (potentially) contaminated sites at the regional scale.

Regional risk assessment for contaminated sites part 2: ranking of potentially contaminated sites.

Environmental risks are traditionally assessed and presented in non spatial ways although the heterogeneity of the contaminants spatial distributions, the spatial positions and relations between receptors and stressors, as well as the spatial distribution of the variables involved in the risk assessment, strongly influence exposure estimations and hence risks. Taking into account spatial variability is increasingly being recognized as a further and essential step in sound exposure and risk assessment. To address this issue an innovative methodology which integrates spatial analysis and a relative risk approach was developed. The purpose of this methodology is to prioritize sites at regional scale where a preliminary site investigation may be required. The methodology aimed at supporting the inventory of contaminated sites was implemented within the spatial decision support sYstem for Regional rIsk Assessment of DEgraded land, SYRIADE, and was applied to the case-study of the Upper Silesia region (Poland). The developed methodology and tool are both flexible and easy to adapt to different regional contexts, allowing the user to introduce the regional relevant parameters identified on the basis of user expertise and regional data availability. Moreover, the used GIS functionalities, integrated with mathematical approaches, allow to take into consideration, all at once, the multiplicity of sources and impacted receptors within the region of concern, to assess the risks posed by all contaminated sites in the region and, finally, to provide a risk-based ranking of the potentially contaminated sites.

A spatial risk assessment methodology to support the remediation of contaminated land.

When soil and groundwater contaminations occur over large areas, remediation measures should be spatially prioritized on the basis of the risk posed to human health and in compliance with technological and budget constraints. Within this scope, the application of human health risk assessment algorithms in a spatially resolved environment raises a number of methodological and technical complexities. In this paper, a methodology is proposed and applied in a case study to support the entire formulation process of remediation plans, encompassing hazard assessment, exposure assessment, risk characterisation, uncertainty assessment and allocation of risk reduction measures. In the hazard assessment, it supports the selection of Contaminants of Concern (CoC) with regard to both their average concentrations and peak concentrations, i.e. hot spots. In the exposure assessment, it provides a zoning of the site based on the geostatistical mapping of contaminant. In the risk characterisation, it generates vector maps of Risk Factors on the basis of the risk posed by multiple substances and allows the interrogation of most relevant CoC and exposure pathways for each zone of the site. It also supports the Monte Carlo based probabilistic estimation of the Risk Factors and generates maps of the associated uncertainty. In the risk reduction phase, it supports the formulation of remediation plans based on the stepwise spatial allocation of remediation interventions and the on-time simulation of risk reduction performances. The application of this methodology is fully supported by an easy-to-use and customized Geographical Information System and does not require high expertise for interpretation. The proposed methodology is the core module of a Decision Support System (DSS) that was implemented in the DESYRE software aimed at supporting the risk-based remediation of megasites.