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

J 2023

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

AUDEBERT, Marc; Ann-Sophie ASSMANN; Amaya AZQUETA; Pavel BABICA; Emilio BENFENATI et al.

Základní údaje

Originální název

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

Autoři

Vydání

FRONTIERS IN TOXICOLOGY, LAUSANNE, FRONTIERS MEDIA SA, 2023, 2673-3080

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30108 Toxicology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.600

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/23:00131493

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

non-genotoxic carcinogens; NGTxC; new approach methodologies; NAM; PARC

Štítky

143180, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 25. 8. 2023 10:24, Mgr. Michaela Hylsová, Ph.D.

Anotace

V originále

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.

Návaznosti

101057014, interní kód MU

Název: Partnership for the Assessment of Risks from Chemicals (Akronym: PARC)

Investor: Evropská unie, Partnership for the Assessment of Risks from Chemicals, Klastr 1 - Zdraví

Přiložené soubory

2304022.pdf

Citovat

AUDEBERT, Marc; Ann-Sophie ASSMANN; Amaya AZQUETA; Pavel BABICA; Emilio BENFENATI; Sylvie BORTOLI; Peter BOUWMAN; Albert BRAEUNING; Tanja BURGDORF; Xavier COUMOUL; Kloe DEBIZET; Maria DUSINSKA; Norman ERTYCH; Joerg FAHRER; Verena FETZ; Ludovic LE HEGARAT; Adela Lopez DE CERAIN; Harm J. HEUSINKVELD; Kevin HOGEVEEN; Miriam N. JACOBS; Mirjam LUIJTEN; Giuseppa RAITANO; Cynthia RECOULES; Elise RUNDEN-PRAN; Mariam SALEH; Iva SOVADINOVÁ; Martina STAMPAR; Lea THIBOL; Celine TOMKIEWICZ; Ariane VETTORAZZI; Bob VAN DE WATER; El Yamani NAOUALE; Bojana ZEGURA a Michael OELGESCHLAEGER. New approach methodologies to facilitate and improve the hazard assessment of non-genotoxic carcinogens-a PARC project. FRONTIERS IN TOXICOLOGY. LAUSANNE: FRONTIERS MEDIA SA, 2023, roč. 5, July 2023, s. 1-12. ISSN 2673-3080. Dostupné z: https://doi.org/10.3389/ftox.2023.1220998.

@article{2304022,
   author = {Audebert, Marc and Assmann, AnnandSophie and Azqueta, Amaya and Babica, Pavel and Benfenati, Emilio and Bortoli, Sylvie and Bouwman, Peter and Braeuning, Albert and Burgdorf, Tanja and Coumoul, Xavier and Debizet, Kloe and Dusinska, Maria and Ertych, Norman and Fahrer, Joerg and Fetz, Verena and Le Hegarat, Ludovic and de Cerain, Adela Lopez and Heusinkveld, Harm J. and Hogeveen, Kevin and Jacobs, Miriam N. and Luijten, Mirjam and Raitano, Giuseppa and Recoules, Cynthia and RundenandPran, Elise and Saleh, Mariam and Sovadinová, Iva and Stampar, Martina and Thibol, Lea and Tomkiewicz, Celine and Vettorazzi, Ariane and van de Water, Bob and Naouale, El Yamani and Zegura, Bojana and Oelgeschlaeger, Michael},
   article_location = {LAUSANNE},
   article_number = {July 2023},
   doi = {https://doi.org/10.3389/ftox.2023.1220998},
   keywords = {non-genotoxic carcinogens; NGTxC; new approach methodologies; NAM; PARC},
   language = {eng},
   issn = {2673-3080},
   journal = {FRONTIERS IN TOXICOLOGY},
   title = {New approach methodologies to facilitate and improve the hazard assessment of non-genotoxic carcinogens-a PARC project},
   url = {https://www.frontiersin.org/articles/10.3389/ftox.2023.1220998/full},
   volume = {5},
   year = {2023}
}

TY  - JOUR
ID  - 2304022
AU  - 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
PY  - 2023
TI  - New approach methodologies to facilitate and improve the hazard assessment of non-genotoxic carcinogens-a PARC project
JF  - FRONTIERS IN TOXICOLOGY
VL  - 5
IS  - July 2023
SP  - 1-12
EP  - 1-12
PB  - FRONTIERS MEDIA SA
SN  - 26733080
KW  - non-genotoxic carcinogens
KW  - NGTxC
KW  - new approach methodologies
KW  - NAM
KW  - PARC
UR  - https://www.frontiersin.org/articles/10.3389/ftox.2023.1220998/full
N2  - 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.
ER  -

AUDEBERT, Marc; Ann-Sophie ASSMANN; Amaya AZQUETA; Pavel BABICA; Emilio BENFENATI; Sylvie BORTOLI; Peter BOUWMAN; Albert BRAEUNING; Tanja BURGDORF; Xavier COUMOUL; Kloe DEBIZET; Maria DUSINSKA; Norman ERTYCH; Joerg FAHRER; Verena FETZ; Ludovic LE HEGARAT; Adela Lopez DE CERAIN; Harm J. HEUSINKVELD; Kevin HOGEVEEN; Miriam N. JACOBS; Mirjam LUIJTEN; Giuseppa RAITANO; Cynthia RECOULES; Elise RUNDEN-PRAN; Mariam SALEH; Iva SOVADINOVÁ; Martina STAMPAR; Lea THIBOL; Celine TOMKIEWICZ; Ariane VETTORAZZI; Bob VAN DE WATER; El Yamani NAOUALE; Bojana ZEGURA a Michael OELGESCHLAEGER. New approach methodologies to facilitate and improve the hazard assessment of non-genotoxic carcinogens-a PARC project. \textit{FRONTIERS IN TOXICOLOGY}. LAUSANNE: FRONTIERS MEDIA SA, 2023, roč.~5, July 2023, s.~1-12. ISSN~2673-3080. Dostupné z: https://doi.org/10.3389/ftox.2023.1220998.

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