Periodic Reporting for period 1 - DIAGONAL (Development and scaled Implementation of sAfe by design tools and Guidelines for multicOmponent aNd hArn nanomateriaLs)
Okres sprawozdawczy: 2021-05-01 do 2022-10-31
The overall objective of DIAGONAL is to bring Safe-and-sustainable-by-Design (SSbD) knowledge and tools to a development stage which can be implemented in the MCNMs and HARNs related industries, relying on experimental (in-vitro) and modelling (in-silico) research, to study specific hazard and exposure properties that MCNMs & HARNs exhibit along their life cycle, with emphasis in the interactions between NM constituents, with other particles and the environment, as well as their release rate and fate. While hazard and exposure determination will allow gaining understanding on the MCNMs & HARNs behaviour and evolution, multi-scale modelling will answer the questions "what are they?" and "where do they go?", through novel predictors for properties estimation, resulting from additive and/or synergistic interactions between components, as well as system-dependent properties. Ultimately, the obtained results will serve as basis to provide adapted or novel risk management guidelines, ready to use SbD tools and strategies to increase nanomaterials safety, including Sustainable-by-Design considerations and recommendations for risk governance.
DIAGONAL partners are involved in current R&D projects (NMBP-12-2017, NMBP-13-2018, NMBP-14-2018, NMBP-15-2019), networks (e.g. NanoSafety Cluster and EMMC) and working groups (e.g. OECD - WPMN and BNCT). The project will establish cooperation lines with the US nanosafety research community involving a US partner and integrating renowned US institutions on its advisory board, guaranteeing resource-efficient working plans, aligned with current EU and international efforts in the nanosafety field, and facilitating the use of existing reference platforms and databases.
7 industrial cases producing or using MCNMs/HARNs will participate providing data from scaled up scenarios, validating models, and implementing the novel SbD approaches and tools developed in the project. Exploitation activities and connection with Open Innovation Test Beds will allow mainstreaming SbD among targeted industries.
DIAGONAL partners are involved in current R&D projects (NMBP-12-2017, NMBP-13-2018, NMBP-14-2018, NMBP-15-2019), networks (e.g. NanoSafety Cluster and EMMC) and working groups (e.g. OECD - WPMN and BNCT). The project will establish cooperation lines with the US nanosafety research community involving a US partner and integrating renowned US institutions on its advisory board, guaranteeing resource-efficient working plans, aligned with current EU and international efforts in the nanosafety field, and facilitating the use of existing reference platforms and databases.
7 industrial cases producing or using MCNMs/HARNs will participate providing data from scaled up scenarios, validating models, and implementing the novel SbD approaches and tools developed in the project. Exploitation activities and connection with Open Innovation Test Beds will allow mainstreaming SbD among targeted industries.
Specific databases and platforms DIAGONAL (SciNote, NanoPharos and EnalosCloud Platform) have been prepared, as well as the upgrade of SimpleBox4Nano model to create a specific version for MCNMs. The progress on the Dynamic modelling approach has been presented (PBK models, D3.4) which will be used to develop predictive modelling of accumulation dynamics of MCNMs and HARNs in biota. From the in-silico approach, the following methodologies were also stablished:
• methodology for theoretical framework for predicting the oxidative stress potential of MCNMs (related publications: 10.1080/17435390.2022.2080609 / 10.3390/ijms232113196)
• multiscale computational methodology for the study of MCNMs considered by project demonstrators (carbon-based NMs, ZnO, Ag NWs).
Additionally, Ambassadors’ meetings with NMBP-16 projects are progressing in the topics of Computational studies of nanomaterials (quantum dots) & Preparation of the IATA Template for MCNMs.
The physicochemical characteristics of selected MCNMs and HARNs, including their individual components and their transformation and degradation products are being assessed, and seven demonstrator’s reports describing the obtained results are in preparation. Exposure Scenarios (ES) on them have been defined, as well as the monitoring procedure to perform the monitoring campaigns (already started). Human toxicity testing of the MCNMs and HARNs, as well as their transformation products is being carried out applying the different advanced and realistic human in vitro models. Similarly, ecotoxicology assessment for which toxicokinetic and toxicodynamic experiments will be conducted are being performed for both MCNM and HARNs. For environmental LCA in particular, characterization factors are being developed for the materials under study adapting USETox methodology.
Risk Management and Risk Governance related tasks already identified the legal framework applicable to the related materials and applications; Regarding RG, the development on the definition of the nano-safety assessment framework is being monitored.
Finally, the communication, dissemination and exploitation activities within DIAGONAL have been transversally integrated, including all project partners. In this regard, the collaboration achieved among NMBP-16 projects, stakeholders’ identification and co-organization of dedicated events is a significant achievement.
• methodology for theoretical framework for predicting the oxidative stress potential of MCNMs (related publications: 10.1080/17435390.2022.2080609 / 10.3390/ijms232113196)
• multiscale computational methodology for the study of MCNMs considered by project demonstrators (carbon-based NMs, ZnO, Ag NWs).
Additionally, Ambassadors’ meetings with NMBP-16 projects are progressing in the topics of Computational studies of nanomaterials (quantum dots) & Preparation of the IATA Template for MCNMs.
The physicochemical characteristics of selected MCNMs and HARNs, including their individual components and their transformation and degradation products are being assessed, and seven demonstrator’s reports describing the obtained results are in preparation. Exposure Scenarios (ES) on them have been defined, as well as the monitoring procedure to perform the monitoring campaigns (already started). Human toxicity testing of the MCNMs and HARNs, as well as their transformation products is being carried out applying the different advanced and realistic human in vitro models. Similarly, ecotoxicology assessment for which toxicokinetic and toxicodynamic experiments will be conducted are being performed for both MCNM and HARNs. For environmental LCA in particular, characterization factors are being developed for the materials under study adapting USETox methodology.
Risk Management and Risk Governance related tasks already identified the legal framework applicable to the related materials and applications; Regarding RG, the development on the definition of the nano-safety assessment framework is being monitored.
Finally, the communication, dissemination and exploitation activities within DIAGONAL have been transversally integrated, including all project partners. In this regard, the collaboration achieved among NMBP-16 projects, stakeholders’ identification and co-organization of dedicated events is a significant achievement.
Scientific gaps on MCNMs and HARNs are being covered by a thorough analysis from the physicochemical and toxicology perspective thanks to the advanced technologies available in the Consortium. The application of multiple characterisations on all NMs under scope, some of them novel as SERS or HIM-SIMS, is providing information for the understanding of the risks that these NMs may pose. The analyses (identification, monitoring, quantification and measuring) on the degradation products along the life-cycle for MCNMs/HARNS is also being addressed. The toxicity assessments also include potential mixture effects.
The development of more complex nanomaterials in several dimensions, such as multiscale materials with targeted structures from nm over µm to mm, nano-bio-conjugates, responsive (active) materials, multicomponent formulations with adjuvants and polymers, inorganic-organic composites, self-organised structures, etc. have received less attention than spherical particles with some additional research on selected fibres and 2D materials. DIAGONAL, together with the NMBP-16 Projects are working in the definition of “multicomponent nanomaterial” (MCNM), which should be the first step towards the development of guidelines for their adequate exposure and hazard assessment. The three NMBP-16 projects stablished an Ambassadors Task Force dedicated to work on the definition of the MCNM concept.
From the in-silico perspective, also initial grouping strategies were developed into the NMBP-16 ambassadors group using quantum dots as case study by performing a quantitative similarity assessment, based on the dissolution behavior and surface reactivity. The focus was hazard endpoints evaluation, grouping and read across of this case study, characterized by multiple metal components and diverse surface chemistry. Methods to assess similarity via pairwise comparison and ranking respect were developed. This methodology is planned to the MCNMs considered in this work belonging to to five different types: i) carbon-based, ii) metal oxides, iii) Ti-based, iv) CeO2 / ZrO2 based and v) silver nanowires. Independent studies were carried out for each category. The developed grouping strategy is expected to be valuable in assessing the inhalation toxicity MCNMs considered in this work.
Furthermore, DIAGONAL is working on the adaptation and improvement of the current guidelines for exposure and hazard assessment of MCNMs and HARNs following methodologies as per described by OECD TGs/DGs, ECHA SOPs or standards like ISO. This will enable the critical review of their sustainability to evaluate physic-chemical properties, as well as hazard and exposure characteristics of MCNMs and HARNs for the ongoing work with the Malta Initiative.
The development of more complex nanomaterials in several dimensions, such as multiscale materials with targeted structures from nm over µm to mm, nano-bio-conjugates, responsive (active) materials, multicomponent formulations with adjuvants and polymers, inorganic-organic composites, self-organised structures, etc. have received less attention than spherical particles with some additional research on selected fibres and 2D materials. DIAGONAL, together with the NMBP-16 Projects are working in the definition of “multicomponent nanomaterial” (MCNM), which should be the first step towards the development of guidelines for their adequate exposure and hazard assessment. The three NMBP-16 projects stablished an Ambassadors Task Force dedicated to work on the definition of the MCNM concept.
From the in-silico perspective, also initial grouping strategies were developed into the NMBP-16 ambassadors group using quantum dots as case study by performing a quantitative similarity assessment, based on the dissolution behavior and surface reactivity. The focus was hazard endpoints evaluation, grouping and read across of this case study, characterized by multiple metal components and diverse surface chemistry. Methods to assess similarity via pairwise comparison and ranking respect were developed. This methodology is planned to the MCNMs considered in this work belonging to to five different types: i) carbon-based, ii) metal oxides, iii) Ti-based, iv) CeO2 / ZrO2 based and v) silver nanowires. Independent studies were carried out for each category. The developed grouping strategy is expected to be valuable in assessing the inhalation toxicity MCNMs considered in this work.
Furthermore, DIAGONAL is working on the adaptation and improvement of the current guidelines for exposure and hazard assessment of MCNMs and HARNs following methodologies as per described by OECD TGs/DGs, ECHA SOPs or standards like ISO. This will enable the critical review of their sustainability to evaluate physic-chemical properties, as well as hazard and exposure characteristics of MCNMs and HARNs for the ongoing work with the Malta Initiative.