Percorrer por autor "Andreoli, Cristina"
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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.
- Regulatory practices on the genotoxicity testing of nanomaterials and outlook for the futurePublication . Andreoli, Cristina; Dusinska, Maria; Bossa, Cecilia; Battistelli, Chiara Laura; Silva, Maria João; Louro, HenriquetaHighlights: - Genotoxicity testing of chemicals requires multiple tests to cover key endpoints; - NMs have distinct properties that require adaptations of conventional testing; - Approaches for genotoxicity testing of the NMs reviewed show challenges; - The level of harmonization between different frameworks is debated; - New approach methodologies are underlined to support NMs'regulation.
- The hCOMET project: International database comparison of results with the comet assay in human biomonitoring. Baseline frequency of DNA damage and effect of main confoundersPublication . Milić, Mirta; Ceppi, Marcello; Bruzzone, Marco; Azqueta, Amaya; Brunborg, Gunnar; Godschalk, Roger; Koppen, Gudrun; Langie, Sabine; Møller, Peter; Teixeira, João Paulo; Alija, Avdulla; Anderson, Diana; Andrade, Vanessa; Andreoli, Cristina; Asllani, Fisnik; Bangkoglu, Ezgi Eyluel; Barančoková, Magdalena; Basaran, Nursen; Boutet-Robinet, Elisa; Buschini, Annamaria; Cavallo, Delia; Costa Pereira, Cristiana; Costa, Carla; Costa, Solange; Da Silva, Juliana; Del Boˊ, Cristian; Dimitrijević Srećković, Vesna; Djelić, Ninoslav; Dobrzyńska, Malgorzata; Duračková, Zdenka; Dvořáková, Monika; Gajski, Goran; Galati, Serena; García Lima, Omar; Giovannelli, Lisa; Goroshinskaya, Irina A.; Grindel, Annemarie; Gutzkow, Kristine B.; Hernández, Alba; Hernández, Carlos; Holven, Kirsten B.; Ibero-Baraibar, Idoia; Ottestad, Inger; Kadioglu, Ela; Kažimirová, Alena; Kuznetsova, Elena; Ladeira, Carina; Laffon, Blanca; Lamonaca, Palma; Lebailly, Pierre; Louro, Henriqueta; Mandina Cardoso, Tania; Marcon, Francesca; Marcos, Ricard; Moretti, Massimo; Moretti, Silvia; Najafzadeh, Mojgan; Nemeth, Zsuzsanna; Neri, Monica; Novotna, Bozena; Orlow, Irene; Paduchova, Zuzana; Pastor, Susana; Perdry, Hervé; Spremo-Potparević, Biljana; Ramadhani, Dwi; Riso, Patrizia; Rohr, Paula; Rojas, Emilio; Rossner, Pavel; Safar, Anna; Sardas, Semra; Silva, Maria João; Sirota, Nikolay; Smolkova, Bozena; Staruchova, Marta; Stetina, Rudolf; Stopper, Helga; Surikova, Ekaterina I.; Ulven, Stine M.; Ursini, Cinzia Lucia; Valdiglesias, Vanessa; Valverde, Mahara; Vodicka, Pavel; Volkovova, Katarina; Wagner, Karl-Heinz; Živković, Lada; Dušinská, Maria; Collins, Andrew R.; Bonassi, StefanoThe alkaline comet assay, or single cell gel electrophoresis, is one of the most popular methods for assessing DNA damage in human population. One of the open issues concerning this assay is the identification of those factors that can explain the large inter-individual and inter-laboratory variation. International collaborative initiatives such as the hCOMET project - a COST Action launched in 2016 - represent a valuable tool to meet this challenge. The aims of hCOMET were to establish reference values for the level of DNA damage in humans, to investigate the effect of host factors, lifestyle and exposure to genotoxic agents, and to compare different sources of assay variability. A database of 19,320 subjects was generated, pooling data from 105 studies run by 44 laboratories in 26 countries between 1999 and 2019. A mixed random effect log-linear model, in parallel with a classic meta-analysis, was applied to take into account the extensive heterogeneity of data, due to descriptor, specimen and protocol variability. As a result of this analysis interquartile intervals of DNA strand breaks (which includes alkali-labile sites) were reported for tail intensity, tail length, and tail moment (comet assay descriptors). A small variation by age was reported in some datasets, suggesting higher DNA damage in oldest age-classes, while no effect could be shown for sex or smoking habit, although the lack of data on heavy smokers has still to be considered. Finally, highly significant differences in DNA damage were found for most exposures investigated in specific studies. In conclusion, these data, which confirm that DNA damage measured by the comet assay is an excellent biomarker of exposure in several conditions, may contribute to improving the quality of study design and to the standardization of results of the comet assay in human populations.