Percorrer por autor "Alivernini, Silvia"
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- Analysis and evaluation of genotoxicity and carcinogenicity assessment in EU legislation to improve regulatory implementation of NAMs: A focus on in silico approachesPublication . Bossa, Cecília; Raitano, Giuseppa; Benfenati, Emilio; Alivernini, Silvia; Andreoli, Cristina; Aquilina, G.; Attias, L.; Dusinska, Maria; El Yamani, N.; Louro, Henriqueta; Marcon, Francesca; Rundèn-Pran, E.; Russo, Maria Teresa; Silva, Maria João; Battistelli, Chiara LauraGenotoxicity and carcinogenicity are key endpoints for the risk assessment of all types of substances. Research on alternatives to animal testing for these endpoints has been active for decades, leading to the development of short-term in vitro tests that are integrated into current testing strategies. Nevertheless, high relevance is still devoted to data from in vivo studies. In parallel, progress in the comprehension of mechanisms underpinning genotoxicity and genotoxic carcinogenicity processes, together with the analysis of the great wealth of experimental data produced, allowed the discovery of structural determinants utilized in quantitative and qualitative structure-activity relationships and enabling in silico predictions of these endpoints. Presented here is a case study part of the collective effort carried out within the European Partnership for the Assessment of Risks from Chemicals (PARC) to address the challenges associated with innovation in chemical risk assessment, including the phasing out of animal testing through the introduction of New Approach Methodologies (NAMs) [1,2]. The case study aims to analyze current practices of the regulatory evaluation of genotoxicity and carcinogenicity hazard in several EU frameworks, in order to highlight needs and challenges in the actual or potential use of NAMs as well as short-and long- term goals towards the overcoming of animal testing. Among other NAMs, we are focusing on the role of in silico approaches highlighting strategies to increase the regulatory application and acceptance of QSAR based approaches. To this aim, the OECD QSAR Assessment Framework [3,4] has been identified as a suitable tool for evaluating the models and their predictions and will be applied to selected case studies. Moreover, a list of human relevant carcinogens has been developed as reference chemicals to evaluate and possibly refine in silico methodologies supporting a human-centric paradigm shift in toxicology.
- A regulatory perspective on the applicability of NAMs in genotoxicity and carcinogenicity assessment in EU: current practices and future directionsPublication . Bossa, Cecilia; Alivernini, Silvia; Andreoli, Cristina; Aquilina, Gabriele; Attias, Leonello; Benfenati, Emilio; Dusinska, Maria; El Yamani, Naouale; Louro, Henriqueta; Marcon, Francesca; Raitano, Giuseppa; Rundén-Pran, Elise; Russo, Maria Teresa; Silva, Maria João; Battistelli, Chiara LauraNew Approach Methodologies (NAMs) are gaining significant momentum globally to reduce animal testing and enhance the efficiency and human relevance of chemical safety assessment. Even with substantial EU commitment from regulatory agencies and the academic community, the full regulatory adoption of NAMs remains a distant prospect. This challenge is further complicated by the fact that the academic world, oriented toward NAMs development, and regulatory agencies, focused on practical application, frequently operate in separate spheres. Addressing this disconnect, the present paper, developed within the European Partnership for the Assessment of Risks from Chemicals (PARC), provides a clear overview of both the available non-animal tests and current evaluation practices for genotoxic and carcinogenic hazard assessment, while simultaneously highlighting existing regulatory needs, gaps, and challenges toward greater human health protection and the replacement of animal testing through NAMs adoption. The analysis reveals a complex landscape: while the EU is deeply committed to developing and adopting NAMs, as outlined in its Chemical Strategy for Sustainability and supported by initiatives like PARC, prescriptive regulations such as Classification, Labelling and Packaging (CLP) and Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) still heavily mandate in vivo animal data for hazard classification, particularly for germ cell mutagenicity and carcinogenicity. This reliance creates a "too-short-blanket-problem," where efforts to reduce animal testing may impact human health protection because of the current in vivo-based classification criteria. In contrast, sectors such as cosmetics and certain European Food Safety Authority (EFSA)-regulated products demonstrate greater flexibility toward progressive integration of NAMs. While the deep mechanistic understanding of genotoxicity and carcinogenicity has significantly advanced the integration of alternatives to animal tests into regulatory chemical hazard assessment, their broader and full implementation faces considerable challenges due to both scientific complexities (i.e., the development and validation of fit-for-purpose NAMs) and existing legislative provisions.