Informace o publikaci

New approach methodologies to facilitate and improve the hazard assessment of non-genotoxic carcinogens-a PARC project

Autoři	AUDEBERT Marc ASSMANN Ann-Sophie AZQUETA Amaya BABICA Pavel BENFENATI Emilio BORTOLI Sylvie BOUWMAN Peter BRAEUNING Albert BURGDORF Tanja COUMOUL Xavier DEBIZET Kloe DUSINSKA Maria ERTYCH Norman FAHRER Joerg FETZ Verena LE HEGARAT Ludovic DE CERAIN Adela Lopez HEUSINKVELD Harm J. HOGEVEEN Kevin JACOBS Miriam N. LUIJTEN Mirjam RAITANO Giuseppa RECOULES Cynthia RUNDEN-PRAN Elise SALEH Mariam SOVADINOVÁ Iva STAMPAR Martina THIBOL Lea TOMKIEWICZ Celine VETTORAZZI Ariane VAN DE WATER Bob NAOUALE El Yamani ZEGURA Bojana OELGESCHLAEGER Michael
Rok publikování	2023
Druh	Článek v odborném periodiku
Časopis / Zdroj	FRONTIERS IN TOXICOLOGY
Fakulta / Pracoviště MU	Přírodovědecká fakulta
Citace
www	https://www.frontiersin.org/articles/10.3389/ftox.2023.1220998/full
Doi	http://dx.doi.org/10.3389/ftox.2023.1220998
Klíčová slova	non-genotoxic carcinogens; NGTxC; new approach methodologies; NAM; PARC
Přiložené soubory	2304022.pdf
Popis	Carcinogenic chemicals, or their metabolites, can be classified as genotoxic or non-genotoxic carcinogens (NGTxCs). Genotoxic compounds induce DNA damage, which can be detected by an established in vitro and in vivo battery of genotoxicity assays. For NGTxCs, DNA is not the primary target, and the possible modes of action (MoA) of NGTxCs are much more diverse than those of genotoxic compounds, and there is no specific in vitro assay for detecting NGTxCs. Therefore, the evaluation of the carcinogenic potential is still dependent on long-term studies in rodents. This 2-year bioassay, mainly applied for testing agrochemicals and pharmaceuticals, is time-consuming, costly and requires very high numbers of animals. More importantly, its relevance for human risk assessment is questionable due to the limited predictivity for human cancer risk, especially with regard to NGTxCs. Thus, there is an urgent need for a transition to new approach methodologies (NAMs), integrating human-relevant in vitro assays and in silico tools that better exploit the current knowledge of the multiple processes involved in carcinogenesis into a modern safety assessment toolbox. Here, we describe an integrative project that aims to use a variety of novel approaches to detect the carcinogenic potential of NGTxCs based on different mechanisms and pathways involved in carcinogenesis. The aim of this project is to contribute suitable assays for the safety assessment toolbox for an efficient and improved, internationally recognized hazard assessment of NGTxCs, and ultimately to contribute to reliable mechanism-based next-generation risk assessment for chemical carcinogens.
Související projekty:	Partnership for the Assessment of Risks from Chemicals