Periodic Reporting for period 1 - POTENTIAL (Platform Optimisation To Enable NanomaTerIAL safety assessment for rapid commercialisation)
Okres sprawozdawczy: 2023-01-01 do 2024-06-30
The development of advanced nanomaterials (Ad-NMs) in the industry will increasingly impact industry and employment. In addition, to foreseeing their economic and production impact, it is necessary to plan protocols to define their impact in terms of health for producers, direct consumers, and the eventual fallout on global and environmental health. In line with this need, the primary objective of the project is to develop reliable and accessible protocols for the quantification of the possible impact of four different categories of Ad-NMs on environmental and biological matrices. To address this ambitious challenge, POTENTIAL will generate an integrated platform that will provide a series of protocols suitable for monitoring the behavior of a wide range of Ad-NMs, from synthesis to interaction with biological matrices of increasing biological complexity. By dividing the work plan into four distinct but very related phases, the protocols in the validation and development phase will be tested using very different materials and, within the same family, materials with small differences (graphene, quantum dots, biomedical nanocarriers and nano-microplastics). The protocols will concern post-synthesis characterization, their behavior in biological and ecological matrices, and the impact on simple and complex living systems. POTENTIAL will engage in silico modeling activities to identify key nano-bio/eco interactions of Ad-NMs in physiological and biological media. This strategy will provide descriptors to develop algorithms for similarity assessment as a basis for enabling the approaches. The platform will finally adopt grouping and read-across approaches that meet regulatory requirements for risk assessment. These methods will be integrated into a methodological framework for the quantitative classification of health and environmental risk.
Below is also an overview of the work carried out and the main achievents obtained whithin the 5 specific objectives (OBJ).
OBJ1-Provide standardised protocols for quantification and characterisation of intrinsic and extrinsic Ad-NMs properties in complex matrices by the development of imaging protocols.
Studies aimed at the development of protocols for the visualization of imaging protocols in biological matrices at different levels of complexity have been carried out. The production of protocols of advanced microscopies, such as Raman Micro-Spectrometry combined with confocal microscopy and Super-Resolution Imaging Microscopy, is proceeding, and the results achieved are reliable and robust. The optimization of alternative approaches, e.g. High-Resolution Transmission Electron Microscopy and Cyto-Viva, furthermore, has started.
OBJ2-Develop protocols to trace changes in NM properties along their lifecycle and methodologies for accelerated life testing of the Ad-NMs and NMPs.
Protocols and methods were developed for assessing the Ad-NM physical-chemical properties of Ad-NMs and NMPs in biological fluids.
OBJ3 -Develop cost-effective protocols for the quantitative determination of the environmental and health hazard of Ad-NMs reinforcing the 3Rs criteria.
Studies were performed to characterize and develop an integrated platform for determining the acute and sub-acute toxicity of Ad-NMs and MNPs. In particular, we employed 2D and 3D human cellular models to recapitulate the interaction of the materials with intestinal and lung epithelia in vitro, a plant cellular model for ecotoxicity studies in vitro, and two animal models that can provide information on organ penetration and function.
OBJ4-Generate grouping and read-across approaches to support risk assessment and SSbD decision making
We have compiled an inventory of both established and enhanced properties of Ad-NMs that are known to affect their health and ecological risks. We reviewed the existing similarity assessment methods for chemicals and nanomaterials and prioritized methods such as weighted ordered weighted average and machine learning approaches such as Histogram-based Gradient Boosting Classification to be further advanced in POTENTIAL. In addition, the relevance of the state-of-the-art approaches for grouping nanoforms (e.g. grouping hypotheses, IATA) has been assessed for their relevance to addressing the novel properties and interactions of Ad-NMs with a focus on the POTENTIAL case studies.
OBJ5 Create a crosstalk with project results to international regulatory bodies for standardization and formal validation
We are actively exchanging information with the other sister projects, CHIASMA, and the EFSA grant NAMS4NANO. We have exchanged information, protocols, and approaches. POTENTIAL significantly contributed to the NanoSafety Cluster “Roadmap Safe and Sustainable Advanced and Innovative Materials 2024-2030“ and, more specifically, to the chapter on ‘harmonization and standardization’.
OBJ1-Provide standardised protocols for quantification and characterisation of intrinsic and extrinsic Ad-NMs properties in complex matrices by the development of imaging protocols.
Studies aimed at the development of protocols for the visualization of imaging protocols in biological matrices at different levels of complexity have been carried out. The production of protocols of advanced microscopies, such as Raman Micro-Spectrometry combined with confocal microscopy and Super-Resolution Imaging Microscopy, is proceeding, and the results achieved are reliable and robust. The optimization of alternative approaches, e.g. High-Resolution Transmission Electron Microscopy and Cyto-Viva, furthermore, has started.
OBJ2-Develop protocols to trace changes in NM properties along their lifecycle and methodologies for accelerated life testing of the Ad-NMs and NMPs.
Protocols and methods were developed for assessing the Ad-NM physical-chemical properties of Ad-NMs and NMPs in biological fluids.
OBJ3 -Develop cost-effective protocols for the quantitative determination of the environmental and health hazard of Ad-NMs reinforcing the 3Rs criteria.
Studies were performed to characterize and develop an integrated platform for determining the acute and sub-acute toxicity of Ad-NMs and MNPs. In particular, we employed 2D and 3D human cellular models to recapitulate the interaction of the materials with intestinal and lung epithelia in vitro, a plant cellular model for ecotoxicity studies in vitro, and two animal models that can provide information on organ penetration and function.
OBJ4-Generate grouping and read-across approaches to support risk assessment and SSbD decision making
We have compiled an inventory of both established and enhanced properties of Ad-NMs that are known to affect their health and ecological risks. We reviewed the existing similarity assessment methods for chemicals and nanomaterials and prioritized methods such as weighted ordered weighted average and machine learning approaches such as Histogram-based Gradient Boosting Classification to be further advanced in POTENTIAL. In addition, the relevance of the state-of-the-art approaches for grouping nanoforms (e.g. grouping hypotheses, IATA) has been assessed for their relevance to addressing the novel properties and interactions of Ad-NMs with a focus on the POTENTIAL case studies.
OBJ5 Create a crosstalk with project results to international regulatory bodies for standardization and formal validation
We are actively exchanging information with the other sister projects, CHIASMA, and the EFSA grant NAMS4NANO. We have exchanged information, protocols, and approaches. POTENTIAL significantly contributed to the NanoSafety Cluster “Roadmap Safe and Sustainable Advanced and Innovative Materials 2024-2030“ and, more specifically, to the chapter on ‘harmonization and standardization’.
Results relevant to the scientific impacts were released. Protocols for the Ad-NMs characterization, their behavior in complex matrices, and their acute toxicity in 2D cellular models were established. The data obtained were shared with the partners in charge of developing in vitro and in silico models to support similarity assessment, grouping, and read-across of information for risk assessment and SSbD. All the project’s beneficiaries participated in meetings and congresses to present the results obtained within the project.
At this stage of the project, its economic impact cannot be established.
Different actions were performed to increase the general population's awareness of Ad-NMs and NMPs, thus delivering the social impact of POTENTIAL. To this end, the communication and dissemination activities were particularly relevant.
At this stage of the project, its economic impact cannot be established.
Different actions were performed to increase the general population's awareness of Ad-NMs and NMPs, thus delivering the social impact of POTENTIAL. To this end, the communication and dissemination activities were particularly relevant.