Periodic Reporting for period 3 - HARMLESS (Advanced High Aspect Ratio and Multicomponent materials: towards comprehensive intelLigent tEsting and Safe by design Strategies)
Berichtszeitraum: 2024-02-01 bis 2025-04-30
Complex multi-component nanomaterials with different shapes such as fiber-like nanomaterials offer innovation potential and challenges in risk assessment and sustainability. These so-called advanced materials (AdMa) improve consumer products but raise concerns due to different degradation rates and toxicity profiles compared to their individual components. Previous Safe and Sustainable by Design (SSbD) projects focused on single-component materials. The current challenge is to develop SSbD approaches for integrating AdMa into real-world product development and understanding their impact on manufacturing, product performance, environment, and health.
The HARMLESS project aimed at making AdMa safer and more sustainable — from design to real-world use. The project combines modern lab methods, computer models, and big data tools to understand how tiny materials behave in our bodies and the environment.
Its goals are to:
1. Help companies design AdMa that are safer and environmentally more friendly from the start — saving time, money, and protecting people and nature.
2. Create user-friendly, practical tools and clear guidelines so that companies can easily assess the safety and sustainability of AdMa compared to conventional materials throughout a product’s life cycle.
3. Develop new ways to test and predict how materials might cause harm, without relying on animal testing.
4. Use huge amounts of available or newly generated data and smart software to spot potentially risky materials early and suggest safer alternatives.
5. Work closely with policymakers, industry, and the public to make sure the tools fit real needs and build trust in new materials.
In short, HARMLESS helps make future materials safer for people and the planet — while keeping innovation moving forward.
The HARMLESS project aimed at making AdMa safer and more sustainable — from design to real-world use. The project combines modern lab methods, computer models, and big data tools to understand how tiny materials behave in our bodies and the environment.
Its goals are to:
1. Help companies design AdMa that are safer and environmentally more friendly from the start — saving time, money, and protecting people and nature.
2. Create user-friendly, practical tools and clear guidelines so that companies can easily assess the safety and sustainability of AdMa compared to conventional materials throughout a product’s life cycle.
3. Develop new ways to test and predict how materials might cause harm, without relying on animal testing.
4. Use huge amounts of available or newly generated data and smart software to spot potentially risky materials early and suggest safer alternatives.
5. Work closely with policymakers, industry, and the public to make sure the tools fit real needs and build trust in new materials.
In short, HARMLESS helps make future materials safer for people and the planet — while keeping innovation moving forward.
The HARMLESS partners developed a modular, stepwise approach to safely and sustainably innovating AdMa that aligns with the industry's multi-phase product development process. The early stages provide general safety guidance based on the available information about AdMa and its intended use. Later stages identify critical knowledge gaps and recommend new approach methodologies (NAMs) that are cost-efficient and can acquire a harmonized dataset for environmental and health risk assessments. These assessments are conducted in the context of known risks from reference materials, using advanced computational modeling. In the latest stages, high-throughput toxicity screening and multi-omics analysis provide the most comprehensive risk assessment.
Bioinformatics and multiscale computational models, including quantitative structure–activity relationship (QSAR) models, were used to predict in vivo hazard potential for over 70 reference and case study materials from NAM data and to guide the design of safer materials. To cluster these materials in a more bio-mechanism-aware manner, HARMESS researchers mapped the community-accepted network of adverse outcome pathways (AOPs) (AOPwiki.org).
HARMLESS created advanced tools to manage and analyze big data sets of millions of data points for the over 70 materials in the eNanoMapper database, ensuring data are FAIR (Findable, Accessible, Interoperable, and Reusable). Automated data integration and visualization within eNanoMapper improved transparency and accessibility for regulatory and industrial stakeholders.
The tools were integrated into a user-friendly Decision Support System (DSS) to help companies apply Safe-and-Sustainable-by-Design (SSbD) principles during product innovation. Multiple industrial case studies demonstrated real-world applicability of the DSS with refined tools and workflows. An Early Warning System (EWS) was also developed to identify potential risks early in material innovation, providing timely input for regulators.
Main results:
• Mode-of-Action and AOP-based Integrated Approaches to Testing and Assessment (IATAs) were successfully established for a broad range of advanced and conventional materials.
• More than 40 NAMs providing data for ca. 200 parameters, including quantum-mechanical descriptors, were refined within this project.
• Large, multi-level datasets for health and environmental risk assessment were generated and made FAIR by uploading them to the eNanoMapper platform (enanomapper.adma.ai/projects/harmless; open access from November 2026).
• High-throughput in vitro toxicity scoring and transcriptomics analyses provided new mechanistic insights and enabled grouping and safety assessment of materials.
• The developed over 100 predictive models (e.g. QSAR) linking NAMs to the toxicity response of animals are essential for leveraging NAMs in health-related risk assessment.
• The user-friendly DSS offers a practical, stepwise workflow aligned with the SSbD strategy of the European Commission (DOI: 10.2760/879069) to support safer material design decisions from early- to late-stage product development.
• The HARMLESS Early Warning System was shown to align with international frameworks (e.g. OECD Early4AdMa) and demonstrated its value for improved regulatory preparedness through collaborative workshops with OECD on two HARMLESS case study materials.
• Extensive stakeholder engagement ensured that tools and methods are compatible with real-world industry needs and regulatory requirements.
• The DSS was effective in all four industry case studies, from ideation to laboratory phases leading to varied decisions: Stopping the project before scale-up (automotive catalysts by perovskites), renewed ideation (plant protection by imogolites), and continued marketing with proven safety and sustainability (paints with colloidal silica and insulation by aerogel-mats).
Bioinformatics and multiscale computational models, including quantitative structure–activity relationship (QSAR) models, were used to predict in vivo hazard potential for over 70 reference and case study materials from NAM data and to guide the design of safer materials. To cluster these materials in a more bio-mechanism-aware manner, HARMESS researchers mapped the community-accepted network of adverse outcome pathways (AOPs) (AOPwiki.org).
HARMLESS created advanced tools to manage and analyze big data sets of millions of data points for the over 70 materials in the eNanoMapper database, ensuring data are FAIR (Findable, Accessible, Interoperable, and Reusable). Automated data integration and visualization within eNanoMapper improved transparency and accessibility for regulatory and industrial stakeholders.
The tools were integrated into a user-friendly Decision Support System (DSS) to help companies apply Safe-and-Sustainable-by-Design (SSbD) principles during product innovation. Multiple industrial case studies demonstrated real-world applicability of the DSS with refined tools and workflows. An Early Warning System (EWS) was also developed to identify potential risks early in material innovation, providing timely input for regulators.
Main results:
• Mode-of-Action and AOP-based Integrated Approaches to Testing and Assessment (IATAs) were successfully established for a broad range of advanced and conventional materials.
• More than 40 NAMs providing data for ca. 200 parameters, including quantum-mechanical descriptors, were refined within this project.
• Large, multi-level datasets for health and environmental risk assessment were generated and made FAIR by uploading them to the eNanoMapper platform (enanomapper.adma.ai/projects/harmless; open access from November 2026).
• High-throughput in vitro toxicity scoring and transcriptomics analyses provided new mechanistic insights and enabled grouping and safety assessment of materials.
• The developed over 100 predictive models (e.g. QSAR) linking NAMs to the toxicity response of animals are essential for leveraging NAMs in health-related risk assessment.
• The user-friendly DSS offers a practical, stepwise workflow aligned with the SSbD strategy of the European Commission (DOI: 10.2760/879069) to support safer material design decisions from early- to late-stage product development.
• The HARMLESS Early Warning System was shown to align with international frameworks (e.g. OECD Early4AdMa) and demonstrated its value for improved regulatory preparedness through collaborative workshops with OECD on two HARMLESS case study materials.
• Extensive stakeholder engagement ensured that tools and methods are compatible with real-world industry needs and regulatory requirements.
• The DSS was effective in all four industry case studies, from ideation to laboratory phases leading to varied decisions: Stopping the project before scale-up (automotive catalysts by perovskites), renewed ideation (plant protection by imogolites), and continued marketing with proven safety and sustainability (paints with colloidal silica and insulation by aerogel-mats).
The HARMLESS project has provided substantial progress beyond the state of the art which is likely to create impact on several levels.
The main aspects are:
• The user-friendly DSS provides low-barrier access to the HARMLESS SSbD strategy for small and medium enterprises (SMEs) and industry to design safer and more sustainable products.
• The strong focus of HARMLESS on New Approach Methodologies (NAMs) and their in vivo anchorage reduces the need for animal toxicity studies, i.e. it contributes to the 3R policy (Replacement, Reduction, Refinement) for animal studies.
• The uniquely rich, FAIR, and open-access data ecosystem provided by HARMLESS substantially expanded the amount of publicly available, high-quality data that will support future risk assessment activities for nanomaterials.
• HARMLESS developed minimum requirements to evaluate human and environmental safety.
• HARMLESS has fostered consistency and coherence in SSbD initiatives by building on previous EU projects' concepts, data and infrastructure (e.g. eNanoMapper), establishing an external advisory board with non-European representatives, and spearheading alignment with our NMBP-16 sister projects (DIAGONAL, SUNSHINE) resulting in a complementary suite of tiered SSbD tools for innovators and regulators.
• The Early Warning System (EWS) enhances regulatory preparedness for AdMa and it was presented to the OECD member states.
• The DSS and EWS identify potential risks at an early stage of material innovation, providing timely input for both regulators and innovators.
• HARMLESS has improved the position of the four case study owners in the global market.
The main aspects are:
• The user-friendly DSS provides low-barrier access to the HARMLESS SSbD strategy for small and medium enterprises (SMEs) and industry to design safer and more sustainable products.
• The strong focus of HARMLESS on New Approach Methodologies (NAMs) and their in vivo anchorage reduces the need for animal toxicity studies, i.e. it contributes to the 3R policy (Replacement, Reduction, Refinement) for animal studies.
• The uniquely rich, FAIR, and open-access data ecosystem provided by HARMLESS substantially expanded the amount of publicly available, high-quality data that will support future risk assessment activities for nanomaterials.
• HARMLESS developed minimum requirements to evaluate human and environmental safety.
• HARMLESS has fostered consistency and coherence in SSbD initiatives by building on previous EU projects' concepts, data and infrastructure (e.g. eNanoMapper), establishing an external advisory board with non-European representatives, and spearheading alignment with our NMBP-16 sister projects (DIAGONAL, SUNSHINE) resulting in a complementary suite of tiered SSbD tools for innovators and regulators.
• The Early Warning System (EWS) enhances regulatory preparedness for AdMa and it was presented to the OECD member states.
• The DSS and EWS identify potential risks at an early stage of material innovation, providing timely input for both regulators and innovators.
• HARMLESS has improved the position of the four case study owners in the global market.