Anticipating technology risk (WP1)
Aim: To anticipate as early as possible any nanotechnology related risks and manage its maturation before it becomes a threat.
Current status: Delphi first stage interviews/survey have been undertaken, with analysis and initial results presented to the consortium, with responses from industry, research, policy makers, insurers, regulators and citizens. The project has also undertaken a review of available horizon scanning tools and is compiling a list of those relevant to CaLIBRAte priorities. The project also delivered a SUN project-caLIBRAte stakeholders workshop, with over 150 participants from over 100 countries, and also participated in the Safe by Design workshop in Bilbao. A second questionnaire is under development to focus on the most challenging aspects of risk governance.
Exposure and risk assessment models in humans (WP2)
Aim: To develop and calibrate stage-gate specific integrated occupational and consumer specific dose-dependent hazard, exposure and risk assessment models (HRA models).
Criteria will be developed and applied to selected candidate HRA and exposure models/tools at the various gates of the stage-gate model. The work aims to ensure that selections of combinations of these models can ultimately be applied for reliable human risk assessment at any of the possible different stages of MN synthesis/MN-based product development. A further ambition, specifically for calibration and benchmarking, is the successful incorporation of new data from newer technologies and models. Biomarkers and mode-of-action data (adverse outcome pathways) will be selected for inclusion in these approaches, based upon omics data derived from in vivo studies.
Current status: The project has reviewed available models, with 5 models identified (NanoSafer CB, LICARA NanoScan, Swiss Precutionary Matrix, Guidenano, ECETOC TRA). The review provided a recommendation of selection of models at each stage gate of the innovation process. The selection of these models will be ised in interaction with other WPs in the project.
Exposure and risk assessment models in the environment (WP3)
Aim: caLIBRAte aims to identify which criteria from existing environmental risk assessment models and tools are important in making decisions with respect to environmental issues at the various gates of the stage-gate model and identify those models and tools with highest value for a certain stakeholder group.
For certain stakeholders a risk-banding approach is most useful while other requite a full environmental risk assessment. The applicability of the available models and tools will be evaluated based on these criteria and a systematic overview of the possibilities and limitations will be obtained. With the results from the calibration of the tools within the project, the team will refine selected tools to incorporate the newest developments in research, industry and regulators with respect to MNs. Tools developed with a certain use in mind will be adapted to specific decisions makers by fine-tuning or improving certain aspects. This will allow the tools to evolve further than anticipated by their creators. It will incorporate innovative hazard and risk assessment methods based on in-vitro tests, high throughput screening or omics techniques.
Current status: The project has completed a review of environmental exposure, hazard and risk assessment models. A fully quantitative assessment scheme has been designed that allows models to be assess, not just based on specific criteria, but comprehensively across a range of different strebgths and weaknesses. Results can now support the selection of models for gap analyses and assessment for structure and parameterisation.
Databases have been systematically scanned for relevant nano- and environmental-related data sets (HTS, omics) and metadata of each data set listed in a data collation table. The coverage of particles/organisms was assessed and quality criteria were defined plus suitable data sets selected. A statistical platform has been established to analyze the data and ensure reliable quality control, normalization and annotation of each data set.
Risk evaluation, mitigation and communication (WP4)
Aim: To engage stakeholders in a structured dialogue, where uncertainty in assessment results will be addressed through the use of the Delphi-group format.
The public will first be engaged in elaborating on their information needs and possible behavioural intentions, which will then be validated with different citizens. Individuals participating in this step will first encounter a stimulus without accompanying information, which in turn trigger their responses to be uncoloured and represent a real need. Validation of findings will employ an ambitious method step through conducting quantitative surveys. fed into the risk characterization and evaluation, which provides input on the evidence- and value based components of making a judgment about a risk. It will bring together the different phases of a risk governance cycle up until the point of making a judgement on the tolerability and acceptability of the risk.
Current status: A number of events had been co-organised by caLIBRAte to date in support of this work, including:
- A SUN-caLIBRAte workshop was held in Venice in March 2017 and the project supported AIRI in the development and conducting of the Delphi questionnaire with stakeholders
- caLIBRAte participated in a Safe by Design (SbD) workshop in Bilbao in April, where it was determined that SbD was a tool more suited to industry than regulators, with industry concerns about cost and liability from such platforms
- caLIBRAte co-organised an SRA Policy Forum "Risk governance for Key Enabling Technologies" on March 2-3, bringing more than 150 delegates from US, Asia and Europe
The project completed a literature review to refine criteria and procedures for risk evaluation, mitigation and communication in the context of the risk governance of manufactured nanomaterials.
Data management (WP5)
Aim: To establish a unique, integrated, data management system containing data on NM properties and behaviour, to identify gaps in the current information and to generate new data for model calibration in order to improve the quality of the risk assessment and risk governance of NMs.
Experiences from previous and ongoing EU-projects and national programmes will be used to develop a set of data (format) requirements to build the data model, which is the backbone of the database. Existing data will be gathered through collaborations with other projects, made possible by partners of caLIBRAte involved in them. These collaborations will allow sharing of information on NM characterization, toxicity (both in vivo and in vitro), as well as on experiences and plans on attempts to group nanomaterials. Data and information gaps will be identified by comparing the available data with the information needed for calibration of the selected risk assessment models. Activities will be designed and performed to address these gaps.
Current status: Requirements for the data to be collected and stored in the caLIBRAte database have been listed, considering the input and output parameters of the selected models. In addition, minimal compulsory entries for physiochemicals properties and toxicology have been defined in this list. To collect information on the contents of nanosafety databases, a questionnaire was prepared and launched together with the NanoSafety Cluster Working Group on Databases. The responses have formed the basis for the gap analysis.
An eNanomapper-caLIBRAte database has been established and currently contains NANoREG1 data plus a subset of MARINA data, with data collection ongoing.
A comprehensive review on the pulmonary toxicity of different nanomaterials has also been initiated focusing on 13 nanomaterials: Silver; carbon (graphene, carbon black, carbon nanotubes), cerium oxide, copper, cobalt, iron (FeO, Fe2O3, Fe3O4), manganese, nickel oxide, silicium (silica), titanium dioxide, zinc and zirconium. From a bulk of more than 1000 scientific articles, ca. 350 scientific articles have been reviewed in full length.
A strategy and method for quality assessment has been developed based on previous initiatives. From the gap analysis, a preliminary result was extracted from the detailed survey that there may be a gap in human exposure and release to the environment for all nanomaterials. An access database (called ‘gap base’) that links nanomaterials with model requirements and relevant databases has been designed. The gap base will help identify gaps in data for the use of the models but can also be used to point out where the information can be found for model parameter and each NM.
A test and synthesis strategy was developed to enable the materials required for in vivo and in vitro experiments and ecotoxicological testing of the surface area and porosity hypothesis as well as the higher generation nanoparticle doping and coating issues for model development and testing.
Exposure casestudies (WP6)
Aim: To establish a state-of-the art suite and generate new value-chain casestudies on exposure (and effects linked in database) of NM and NM-enabled products along their lifecycle with data, to support model development, calibration and caLIBRAte framework demonstration.
The project will comprehensively inventory firstly the existing value-chain case-studies and associated data sets, with more more than 40 case studies so far that can be contributed directly into the project, covering from NMs synthesis scenarios to product end-of life. According to the outcomes from the gap analysis plus the model input parameters and data formats identified to required by the human and environmental risk assessment models and tools proposed for the caLIBRAte risk governance framework, the project will identify the casestudies that can be applied directly into the caLIBRate framework, identifying and prioritizing critical scenarios for experimental determination of exposure/release. Thus, experiments will provide industriallyrelevant outputs by conducting release estimates directly relevant to the case studies. Two new casestudies will also be generated through the product value chain by (1) selecting an scenario of early stage to late R&D and product launch and, and by (2) selecting a comprehensive example involving a long-implemented industrial NM application in NMs.
Current status: 50 case studies and associated experimental work have been selected, bringing in work from a large number of EU-funded projects. These cover release and/or emission of nanomaterials from nan-enabled products towards different compartments (e.g. indoor air or WWTP) as well as worker exposure during handling/manufacturing operations performed at industrial settings, where pristine NMs or product-containing NMs are synthesized or manufactured.
In addition, 8 companies have been contacted for the generation of new case studies.
Performance testing, calibration and testing (WP7)
Aim: To advance risk assessment significantly beyond the state of the art
The project will identify which segments that is recommended for potential improvement of existing qualitative to quantitative risk-assessment and -management models for MN and MN-enabled products as well as the SUN and GUIDEnano decision support tools and subsequently subject the refined models to final sensitivity analysis, calibration or benchmarking and documentation of their performance. It will also improve the quality of the risk assessment and risk governance of MNs and MN-enabled products through the sensitivity testing analysis, performance testing, calibration and final demonstration as best possible for the different model and tool types. Finally, the project will adjust the models to user needs based on a.o. input from stakeholders. The required input will be obtained as a result of a workshop focusing in particular on the potential (key users from industry, insurance, regulation and consumer organizations and NGOs).
Current status: Information on 14 models has been collated (9 HRA and 5 ERA), including input data requirements and their classification based on input type. In addtion, the operational requirements (platform, input data formats, output data formats) have been mapped. Preparatory work has been undertaken for automated running of tools (for sensitivity testing) and work initiated to develop a model performance testing strategy with regard to their ability to identify and rank nanomaterial hazard.
Nano risk governance framework and 'system of systems' (WP8)
Aim: To consolidate the caLIBRAte Nano-Risk Governance framework by developing the System of Systems (SoS) sustainable platform
The SoS architecture will consist of different interactive functional systems (e.g. horizon scanning tools, different simple to advanced risk prioritization, control banding and quantitative predictive models for human and environmental risk assessment, -analysis, management etc.,). The framework models will be linked to the 10 steps of the ERMF framework (ISO 31000 and IRGC) and support the Cooper-style stage gate innovation model as a special interface for different stakeholders. The platform will host and integrate not only single models and tools developed in WP1-4 and tested and calibrated in WP7, but also the stakeholders and data/information/knowledge generated in the project and support the interaction with the global web of knowledge. The developed Nano-Risk Governance framework SoS, is envisaged to be recognized and accepted by the multidisciplinary stakeholders participating in the decision making process for Nanotechnology related risks.
Current status: The project has undertaken initial survey and interviews with primary outcomes from stakeholders indicating that current guidance and regulations linked to nano are not sufficient, and identified unregulated ares, including end of life products. The project is now moving on to identify key user requirements from the system of systems and starting to create the web-based architecture.