Periodic Reporting for period 1 - NanoQSAR (Structure-activity relationship modelling of REACH-relevant endpoints to predict the toxicity of engineered nanomaterials)
Reporting period: 2021-07-15 to 2023-07-14
Nanotechnology is among the fastest growing and most promising technologies in our current society, promoting the development of smart and innovative products and improving processes in a several industry sectors, including composites, colouring, ceramics, electronics, nutrition, cosmetics, energy, optics, automotive, etc. Thus, the development and spread of new engineered nanomaterials (ENMs) is growing in the industrial field and, consequently, in the direct use by the public. As with any new material or substance introduced in the market, it is crucial to evaluate their properties and particularly their toxic effects. The toxicity of ENMs is a complex issue, because it is not only determined by the chemical composition but also by properties like the particle size and shape, global charge and surface area. The significant knowledge gaps in the toxicokinetic and toxic mechanism of ENMs further strength the need of identifying nano-specific indicators of toxicity and developing approaches for toxicity prediction and risk assessment. Nanomaterials (NMs) toxicity depends on the structure of the particles and it is not significant if it was specifically produced to have that particular structure (engineered), formed by humans (incidental) or created in the environment by natural causes (natural).
Quantitative structure–activity (or toxicity) relationship (QSAR) approaches paradigm has only recently been used to predict biological effects of NMs, with only few quantitative nano-structure activity relationships models described in the literature. Hence, the nanoQSAR focus is the application of the QSAR paradigm to identify high concern NMs and predict relevant endpoints for risk assessment, reducing the cost and timescale derived from the use of in vivo or in vitro assays.
These are the objectives of the project:
- To develop a set of nanoQSAR models to predict physicochemical, toxicological and environmental effects of relevant metal oxide (MOx) nanoparticles and quantum dots (QDs).
- The validation of robust nanoQSAR models for regulatory purposes in the field of nanotoxicology according to OECD principles
- To validate the nanoQSAR models using as input parameters experimental data from running or recently completed projects funded under EU programs.
- To provide new computational derived information on the physicochemical, toxicological, ecotoxicological and environmental endpoints for REACH.
- To implement the nanoQSAR models in a computational platform allowing for the fast and cheap evaluation of the toxicological profiles of NMs for regulatory purposes.
Quantitative structure–activity (or toxicity) relationship (QSAR) approaches paradigm has only recently been used to predict biological effects of NMs, with only few quantitative nano-structure activity relationships models described in the literature. Hence, the nanoQSAR focus is the application of the QSAR paradigm to identify high concern NMs and predict relevant endpoints for risk assessment, reducing the cost and timescale derived from the use of in vivo or in vitro assays.
These are the objectives of the project:
- To develop a set of nanoQSAR models to predict physicochemical, toxicological and environmental effects of relevant metal oxide (MOx) nanoparticles and quantum dots (QDs).
- The validation of robust nanoQSAR models for regulatory purposes in the field of nanotoxicology according to OECD principles
- To validate the nanoQSAR models using as input parameters experimental data from running or recently completed projects funded under EU programs.
- To provide new computational derived information on the physicochemical, toxicological, ecotoxicological and environmental endpoints for REACH.
- To implement the nanoQSAR models in a computational platform allowing for the fast and cheap evaluation of the toxicological profiles of NMs for regulatory purposes.
Work performed:
- A set of nanoQSAR models has been developed, in order to predict physicochemical, toxicological and environmental effects of relevant metal oxide (MOx) nanoparticles and quantum dots (QDs).
- The robustness of such nanoQSAR models has been validated for regulatory purposes in the field of nanotoxicology according to OECD principles. To validate the nanoQSAR models experimental data from running or recently completed projects funded under EU programs have been used as input parameters .
- The nanoQSAR models have been implemented in a computational platform allowing for the fast and cheap evaluation of the toxicological profiles of NMs for regulatory purposes.
Exploitation and dissemination actions:
- A webpage has been created in the company’s website specific for the NanoQSAR project (https://protoqsar.com/nanoqsar/(opens in new window)) with information about the details of the project and updates of its evolution. Furthermore, a specific module for nanoQSAR models named ProtoNANO is included in the website of ProtoPRED (https://protopred.protoqsar.com/(opens in new window)).
- A specific page devoted to NanoQSAR, (https://www.youtube.com/playlist?list=PL9JKQBLNHdePRhyOHLq2T6U5qu9s1D3Q2(opens in new window)) has been incorporated to the corporate YouTube channel of ProtoQSAR (https://www.youtube.com/@protoqsar3075(opens in new window)). This list includes two videos developed by the researcher as a part of the NanoQSAR project.
- The presentation of the project in different technical events and outreach events.
- Scientifc manuscript: Moncho, S., Serrano-Candelas, E., de Julián, J. V., & Gozalbes, R. “Nano-QSAR, a review: On the identification of nanomaterials for Nano-QSAR models.”
- A set of nanoQSAR models has been developed, in order to predict physicochemical, toxicological and environmental effects of relevant metal oxide (MOx) nanoparticles and quantum dots (QDs).
- The robustness of such nanoQSAR models has been validated for regulatory purposes in the field of nanotoxicology according to OECD principles. To validate the nanoQSAR models experimental data from running or recently completed projects funded under EU programs have been used as input parameters .
- The nanoQSAR models have been implemented in a computational platform allowing for the fast and cheap evaluation of the toxicological profiles of NMs for regulatory purposes.
Exploitation and dissemination actions:
- A webpage has been created in the company’s website specific for the NanoQSAR project (https://protoqsar.com/nanoqsar/(opens in new window)) with information about the details of the project and updates of its evolution. Furthermore, a specific module for nanoQSAR models named ProtoNANO is included in the website of ProtoPRED (https://protopred.protoqsar.com/(opens in new window)).
- A specific page devoted to NanoQSAR, (https://www.youtube.com/playlist?list=PL9JKQBLNHdePRhyOHLq2T6U5qu9s1D3Q2(opens in new window)) has been incorporated to the corporate YouTube channel of ProtoQSAR (https://www.youtube.com/@protoqsar3075(opens in new window)). This list includes two videos developed by the researcher as a part of the NanoQSAR project.
- The presentation of the project in different technical events and outreach events.
- Scientifc manuscript: Moncho, S., Serrano-Candelas, E., de Julián, J. V., & Gozalbes, R. “Nano-QSAR, a review: On the identification of nanomaterials for Nano-QSAR models.”
There are platforms in the market for the prediction of physicochemical, toxicological and ecotoxicological properties of small molecules for regulatory purposes, such as QSAR ToolBox, VEGA, DEREK, TOPKAT and ToxCast, but these tools are not specifically focus in the nanomaterials (NM), for this reason it is needed a new platform specialized in nanoQSAR models, like our ProtoPRED tool. The NanoQSAR project include a compendium of robust and validated Quantitative Structure Activity Relationships (QNTR) models adapted to nanomaterials to predict relevant endpoints.
The expected results are: The development of nanoQSAR models to predict physicochemical, toxicological and environmental effects of relevant metal oxide (MOx) nanoparticles and QDs, in order to allow future investigations related with effects of nanomaterials and the validation of the models; To provide new computational derived information on the physicochemical, toxicological, ecotoxicological and environmental endpoints for REACH; The implementation of the nanoQSAR models in a computational platform allowing for the fast and cheap evaluation of the toxicological profiles of NMs for regulatory purposes.
To fortify the EU’s scientific and technological bases and the European Research Area (ERA), the NanoQSAR project has potential scientific impact. From one side, the project has allowed to reinforce the computing systems through the development of nanoQSAR models in the field of nanotoxicology. On the other side, NanoQSAR project has expanded the knowledge of the physicochemical, toxicological and environmental effects of relevant metal oxide (MOx) nanoparticles and QDs.
NanoQSAR project will have a potential societal impact, as it would improve the quality of life of citizens, given that the project has helped to reach a better understanding of the potential harmful effects of NMs on human health and the environment by studying the knowledge gaps in the toxicokinetic and toxic mechanism of NMs. Finally, the application of computational methods, in combination with in vitro validation, has contributed to reduce animal testing in the traditional laboratory assays following the 3Rs principle.
Finally, NanoQSAR project will have an important economic/technological impact and will boost Europe’s innovation capacity, competitiveness, and jobs by providing new computational information on the physicochemical, toxicological, ecotoxicological and environmental endpoints for REACH. Computational models help with the compliance of rules as set out in the European directives for registration and labelling of compounds, like REACH, BPR, CLP, etc. These internationally regulations promote the use of the computational techniques as alternative methods, that have the guarantee of the OECD principles. Regarding the REACH legislation for nanomaterials, the ProtoPRED platform will be attractive to manufacturers and importers of NMs as a non-testing tool for risk assessment. Moreover, NanoQSAR project has contributed to increasing efficiency, decreasing costs and increasing profits, as allow us to work in a virtual environment.
The expected results are: The development of nanoQSAR models to predict physicochemical, toxicological and environmental effects of relevant metal oxide (MOx) nanoparticles and QDs, in order to allow future investigations related with effects of nanomaterials and the validation of the models; To provide new computational derived information on the physicochemical, toxicological, ecotoxicological and environmental endpoints for REACH; The implementation of the nanoQSAR models in a computational platform allowing for the fast and cheap evaluation of the toxicological profiles of NMs for regulatory purposes.
To fortify the EU’s scientific and technological bases and the European Research Area (ERA), the NanoQSAR project has potential scientific impact. From one side, the project has allowed to reinforce the computing systems through the development of nanoQSAR models in the field of nanotoxicology. On the other side, NanoQSAR project has expanded the knowledge of the physicochemical, toxicological and environmental effects of relevant metal oxide (MOx) nanoparticles and QDs.
NanoQSAR project will have a potential societal impact, as it would improve the quality of life of citizens, given that the project has helped to reach a better understanding of the potential harmful effects of NMs on human health and the environment by studying the knowledge gaps in the toxicokinetic and toxic mechanism of NMs. Finally, the application of computational methods, in combination with in vitro validation, has contributed to reduce animal testing in the traditional laboratory assays following the 3Rs principle.
Finally, NanoQSAR project will have an important economic/technological impact and will boost Europe’s innovation capacity, competitiveness, and jobs by providing new computational information on the physicochemical, toxicological, ecotoxicological and environmental endpoints for REACH. Computational models help with the compliance of rules as set out in the European directives for registration and labelling of compounds, like REACH, BPR, CLP, etc. These internationally regulations promote the use of the computational techniques as alternative methods, that have the guarantee of the OECD principles. Regarding the REACH legislation for nanomaterials, the ProtoPRED platform will be attractive to manufacturers and importers of NMs as a non-testing tool for risk assessment. Moreover, NanoQSAR project has contributed to increasing efficiency, decreasing costs and increasing profits, as allow us to work in a virtual environment.