GenoQSAR · Genotoxicity prediction by means of QSAR methods for regulatory purposes
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-10-01 → 2023-09-30
- EU contribution
- €172,932
- Participants
- 1
- Scheme
- MSCA-IF
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Results in brief
Genotoxicity prediction by means of QSAR methods for regulatory purposes
The EU's regulatory framework for chemical substances has undergone significant revisions due to growing concerns about safeguarding human health and the environment. The European Chemicals Agency (ECHA) is implementing the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) legislation. This legislation mandates the chemical industry to assess the toxicity of substances in use, even if they have not undergone prior regulatory testing. However, the REACH regulation has faced criticism from both societal and industrial sectors, primarily due to ethical and economic concerns. The evaluation of chemical toxicity traditionally involves expensive, time-consuming, and ethically contentious animal experiments. As a response, the REACH regulation actively promotes the adoption of alternative methods, emphasizing that animal testing should be a last resort, only employed when no other scientifically reliable methods are available to assess the impact on humans or the environment. Non-testing methods, particularly computational (in silico) tools, have become increasingly prominent. Among these tools, Quantitative Structure-Activity Relationships (QSAR) modelling stands out as a well-established approach in drug design, toxicology, industrial, and environmental chemistry. Importantly, these methods hold regulatory recognition for hazard and risk assessment, as well as for classification and labelling. These have been the objectives of the project: - Development of novel QSAR models to predict different in vitro and in vivo endpoints for human toxicity. An attempt has been made to develop some specific models for nanomaterials. All the models fit the regulatory principles of the OECD. - Development of a decisional workflow, using models for different endpoints, to obtain a “consensus” score for the prediction of genotoxicity. This workflow follows the guidelines delivered by REACH for the genotoxicity assessment. - Implementation of the human toxicology models, as well as the decisional workflow, in a computational platform allowing fast and cheap evaluation of the toxicological properties by the end-users.
Data: CORDIS, © European Union
Project objective
The concern to protect human health and the environment has prompted significant changes in EU regulation on chemicalsubstances. The European Chemicals Agency (ECHA) plays the role in implementing the Registration, Evaluation,Authorization and Restriction of Chemicals (REACH) legislation, that requires industry to evaluate the toxicity of chemicalsubstances that are in use but have never been subjected to regulatory testing.REACH regulation has also raised strong criticism and concern from society and industrials because of ethical and economicreasons. The toxicity evaluation of chemicals requires costly, time-consuming and ethically questionable animalexperiments. As consequence, this European regulation promotes scientific innovation and encourages the use of resultsgenerated by alternative methods, including especially non-testing methods (NTMs), also referred to as in silico tools.Among them, “Quantitative Structure-Activity Relationships” (QSAR) methods are one of the most recognized machinelearning methods in drug design, toxicology, industrial and environmental chemistry. Nowadays, they can be included inintegrated testing strategies (ITS), to provide information for hazard and risk assessment, classification and labelling.We propose the development of an ensemble of QSAR predictive models for several parameters related with the differentkinds of genotoxicity damage. These chemoinformatic will be implemented on a proprietary computational technologicalplatform. Particular attention will be also payed to the generation of models for nanomaterials, taking into account their highand growing impact nowadays on industry in general.The QSAR models and integration algorithms will be characterized bytheir reliability, and will be developed according to the rules set out by the OECD, therefore guaranteeing their validity inREACH.
Original text from CORDIS.
Participants
- PROTOQSAR 2000 SL · ValenciaCoordinatorSpain
Links
Data: CORDIS, © European Union