Periodic Reporting for period 3 - NanoInformaTIX (Development and Implementation of a Sustainable Modelling Platform for NanoInformatics.)
Reporting period: 2022-03-01 to 2023-02-28
NanoInformaTIX aims to develop, validate and implement a sustainable informatics framework, based on modelling of the entire life cycle, for the risk assessment of ENM and for informing safer design of quality products. This Sustainable NanoInformatics Framework (SNF) will be co-implemented with stakeholders to ensure a user-friendly interface for industry, regulators, researchers and civil society, providing cost-effective safety assessment guidance.
To do so, we assemble a consortium that has unmatched access the most advanced models and thoroughly curated data: NanoInformaTIX will further develop and extend existing models - some created in recent modelling projects. NanoInformaTIX will integrate validated models: Materials modelling, Exposure modelling, Bio-distribution modelling: Physiologically-Based Pharmacokinetics (PBPK), Dose-Response modelling: Quantitative-Structure-Activity Relationships (QSAR) and Systems Biology modelling to support the prediction of the potential (eco)-toxicity of ENM during each stage of their lifecycle. NanoInformaTIX will use existing, curated data from (i) Completed EU projects, established databases and from ongoing projects in North American, China, South Africa and (iv) peer reviewed literature, after careful scrutiny of data quality. NanoInformaTIX will use the data to validate the modelling, following the OECD validation principles.
Objective 1: Database
Objective 2: Material Modelling
Objective 3. Fate-Exposure Modelling
Objective 4: Dose-Response Modelling
Objective 5: Integration/linking of Models
Objective 6: Model validation
Objective 7: Development of the SNF
To do so, we assemble a consortium that has unmatched access the most advanced models and thoroughly curated data: NanoInformaTIX will further develop and extend existing models - some created in recent modelling projects. NanoInformaTIX will integrate validated models: Materials modelling, Exposure modelling, Bio-distribution modelling: Physiologically-Based Pharmacokinetics (PBPK), Dose-Response modelling: Quantitative-Structure-Activity Relationships (QSAR) and Systems Biology modelling to support the prediction of the potential (eco)-toxicity of ENM during each stage of their lifecycle. NanoInformaTIX will use existing, curated data from (i) Completed EU projects, established databases and from ongoing projects in North American, China, South Africa and (iv) peer reviewed literature, after careful scrutiny of data quality. NanoInformaTIX will use the data to validate the modelling, following the OECD validation principles.
Objective 1: Database
Objective 2: Material Modelling
Objective 3. Fate-Exposure Modelling
Objective 4: Dose-Response Modelling
Objective 5: Integration/linking of Models
Objective 6: Model validation
Objective 7: Development of the SNF
Predicting safety of engineered nanomaterials (ENM) stands on understanding the ultimate nature of what makes a material toxic; this ranges from its sources, fate, exposure, dose and response. All of these are closely interconnected. There is a vast amount of data on physico-chemical, toxicological and ecotoxicological properties of ENM generated the last decades and new data coming from research; yet information is not fully available: a comprehensive insight is still lacking. NanoInformaTIX is developing a Sustainable Nanoinformatics Framework (SNF) platform for risk management of engineered nanomaterials (ENM) in industrial manufacturing. Our mission is to integrate these existing and emerging data into efficient user-friendly interfaces to enhance accessibility and usability of the Nanoinformatics models to industry, regulators, and civil society, thus supporting sustainable manufacturing of ENM-based products.
This mission can only be accomplished from fundamental knowledge on all stages of ENM lifecycle. Understanding materials fate in the environment and in our bodies, understanding how they interact among themselves in environment and our body, is achieved by integrating knowledge onto the SNF, and by knowing the rationale behind behaviour. This is the reason to have a WP devoted to describing the materials themselves, their structures and defects, and how these shapes how they interact with their environment (eco and body). During these months, the different groups in the different WP’s have interacted closely, meeting regularly, to address the key pillars on which NanoInformaTIX SNF stands.
Currently, NanoInformaTIX has
- Integrated data from existing databases of terminated/ongoing projects, established protocols to import data from NIOSH, a FAIRification workflow has been developed to facilitate data files import. It is also incorporating new descriptors generated by computational chemistry in the project and with validation data.
- We have developed a comprehensive description of nanomaterials through computational modeling, delivering parameters not readily available through experimentation an delivering new descriptors to better understand the fate of materials in the environment and biological media.
- We have modelled the fate and biodistribution in humans and in the environment, modelling uptake and biodistribution in mammals and in aquatic species and the fate and behaviour of nanomaterials in fresh and ocean water mesocosms. The models in human and environmental systems describe size-specific material flow models to predict releases to the environment, fate model of nanomaterials in oceans and in rivers, an integrated model on exposure to airborne nanomaterials in indoor species and a physiologically based pharmacokinetic model to predict biodistribution of nanomaterials in humans.
- The models above serve to develop representation of NM considering what determines their mobility in different media and to develop dose-response models for in vitro toxicity data. We also develop an in vivo dose-response modelling and its extrapolation to in vivo.
- Omics technologies (system biology) are being used to molecularly understand the nature of adverse outcomes and their pathways.
- Different experimental tests improve and validate models and integrate in a chain of models that engage into the ultimate goal, which is the sustainable nanoinformatics platform.
- The DSS is being developed and will enable the predictive knowledge to optimise engineered nanomaterials to be safer-by-design through the understanding of what makes a material toxic.
This mission can only be accomplished from fundamental knowledge on all stages of ENM lifecycle. Understanding materials fate in the environment and in our bodies, understanding how they interact among themselves in environment and our body, is achieved by integrating knowledge onto the SNF, and by knowing the rationale behind behaviour. This is the reason to have a WP devoted to describing the materials themselves, their structures and defects, and how these shapes how they interact with their environment (eco and body). During these months, the different groups in the different WP’s have interacted closely, meeting regularly, to address the key pillars on which NanoInformaTIX SNF stands.
Currently, NanoInformaTIX has
- Integrated data from existing databases of terminated/ongoing projects, established protocols to import data from NIOSH, a FAIRification workflow has been developed to facilitate data files import. It is also incorporating new descriptors generated by computational chemistry in the project and with validation data.
- We have developed a comprehensive description of nanomaterials through computational modeling, delivering parameters not readily available through experimentation an delivering new descriptors to better understand the fate of materials in the environment and biological media.
- We have modelled the fate and biodistribution in humans and in the environment, modelling uptake and biodistribution in mammals and in aquatic species and the fate and behaviour of nanomaterials in fresh and ocean water mesocosms. The models in human and environmental systems describe size-specific material flow models to predict releases to the environment, fate model of nanomaterials in oceans and in rivers, an integrated model on exposure to airborne nanomaterials in indoor species and a physiologically based pharmacokinetic model to predict biodistribution of nanomaterials in humans.
- The models above serve to develop representation of NM considering what determines their mobility in different media and to develop dose-response models for in vitro toxicity data. We also develop an in vivo dose-response modelling and its extrapolation to in vivo.
- Omics technologies (system biology) are being used to molecularly understand the nature of adverse outcomes and their pathways.
- Different experimental tests improve and validate models and integrate in a chain of models that engage into the ultimate goal, which is the sustainable nanoinformatics platform.
- The DSS is being developed and will enable the predictive knowledge to optimise engineered nanomaterials to be safer-by-design through the understanding of what makes a material toxic.
NanoInformaTIX is not simply another framework. Specifically, it will provide an easily accessible nanomaterials safety data/model software platform tool to predict adverse outcomes from material-characteristics. This platform, built with stakeholders’ inputs, is validated through an iterative approach with independent datasets for validation. The validation of the system will help to secure the user confidence in the predictions of human and environmental toxicological hazards throughout a ENM material life cycle.
The validated accessible framework provided by NanoInformaTIX for predicting human and environmental ENM toxicological hazards will also assist SME by shortening the time to market by offering a tool for them to assess the potential hazards of their materials and the opportunity to explore solutions to modify their products (the Safe-by-Design module of the framework). In fact, SME sometimes have very narrow technical expertise (e.g. about material modelling, machine learning, etc.) and are likely to have difficulty in contextualising their role in a larger context such as toxicological potential of ENM. The NanoInformaTIX framework will facilitate access to SME which technical tools and requirements are more pertinent and impactful for their products.
The NanoInformaTIX framework will be a vital tool for SME in the safe-by-design of their materials, Especially, since the performance of this framework is entirely in silico. This will allow the material design time and cost to be reduced considerably and consequently shorten the time to market for the SME products.
The demand for an informatics tool to help SME in designing their ENM is there and established a market for such a tool. NanoInformaTIX's impact on this market is twofold, (1) NanoInformaTIX supplies such a tool as the solution to SME need; (2) NanoInformaTIX makes the tool sustainable by delivering a business plan to maintain and upgrade the SNF beyond the lifetime of the project. The availability of NanoInformaTIX as the first tool to be used by SME (and also regulators and civil society) regarding the design and regulatory assessment of ENM will be a tremendous contribution and impact on nanotechnology.
The validated accessible framework provided by NanoInformaTIX for predicting human and environmental ENM toxicological hazards will also assist SME by shortening the time to market by offering a tool for them to assess the potential hazards of their materials and the opportunity to explore solutions to modify their products (the Safe-by-Design module of the framework). In fact, SME sometimes have very narrow technical expertise (e.g. about material modelling, machine learning, etc.) and are likely to have difficulty in contextualising their role in a larger context such as toxicological potential of ENM. The NanoInformaTIX framework will facilitate access to SME which technical tools and requirements are more pertinent and impactful for their products.
The NanoInformaTIX framework will be a vital tool for SME in the safe-by-design of their materials, Especially, since the performance of this framework is entirely in silico. This will allow the material design time and cost to be reduced considerably and consequently shorten the time to market for the SME products.
The demand for an informatics tool to help SME in designing their ENM is there and established a market for such a tool. NanoInformaTIX's impact on this market is twofold, (1) NanoInformaTIX supplies such a tool as the solution to SME need; (2) NanoInformaTIX makes the tool sustainable by delivering a business plan to maintain and upgrade the SNF beyond the lifetime of the project. The availability of NanoInformaTIX as the first tool to be used by SME (and also regulators and civil society) regarding the design and regulatory assessment of ENM will be a tremendous contribution and impact on nanotechnology.