1. Guidance on aneugenicity assessment
- Author
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EFSA Scientific Committee (SC), More, Simon John, Bampidis, Vasileios, Bragard, Claude, Halldorsson, Thorhallur Ingi, Hernández-Jerez, Antonio F, Hougaard Bennekou, Susanne, Koutsoumanis, Kostas, Lambré, Claude, Machera, Kyriaki, Naegeli, Hanspeter, Nielsen, Søren Saxmose, Schlatter, Josef, Schrenk, Dieter, Turck, Dominique, Younes, Maged, Aquilina, Gabriele, Bignami, Margherita, Bolognesi, Claudia, Crebelli, Riccardo, Gürtler, Rainer, Marcon, Francesca, Nielsen, Elsa, Vleminckx, Christiane, Carfì, Maria, Martino, Carla, Maurici, Daniela, Parra Morte, Juan, Rossi, Annamaria, Benford, Diane, and University of Zurich
- Subjects
Veterinary (miscellaneous) ,Aneugenicity ,2405 Parasitology ,TP1-1185 ,Genotoxicity in vivo and in vitro ,Plant Science ,Gene mutation ,Bioinformatics ,Microbiology ,Clastogen ,In vitro ,Micronucleus test ,1110 Plant Science ,In vivo ,medicine ,TX341-641 ,1106 Food Science ,Nutrition. Foods and food supply ,business.industry ,Chemical technology ,Cros1223 ,genotoxicity in vivo and in vitro ,2404 Microbiology ,10079 Institute of Veterinary Pharmacology and Toxicology ,aneugenicity ,3401 Veterinary (miscellaneous) ,micronucleus test ,Scientific Opinion ,medicine.anatomical_structure ,570 Life sciences ,biology ,Animal Science and Zoology ,Parasitology ,Bone marrow ,1103 Animal Science and Zoology ,Genotoxicity ,business ,Risk assessment ,Food Science - Abstract
The EFSA Scientific Committee was asked to provide guidance on the most appropriate in vivo tests to follow up on positive in vitro results for aneugenicity, and on the approach to risk assessment for substances that are aneugenic but not clastogenic nor causing gene mutations. The Scientific Committee confirmed that the preferred approach is to perform an in vivo mammalian erythrocyte micronucleus test with a relevant route of administration. If this is positive, it demonstrates that the substance is aneugenic in vivo. A negative result with evidence that the bone marrow is exposed to the test substance supports a conclusion that aneugenic activity is not expressed in vivo. If there is no evidence of exposure to the bone marrow, a negative result is viewed as inconclusive and further studies are required. The liver micronucleus assay, even though not yet fully validated, can provide supporting information for substances that are aneugenic following metabolic activation. The gastrointestinal micronucleus test, conversely, to be further developed, may help to assess aneugenic potential at the initial site of contact for substances that are aneugenic in vitro without metabolic activation. Based on the evidence in relation to mechanisms of aneugenicity, the Scientific Committee concluded that, in principle, health‐based guidance values can be established for substances that are aneugenic but not clastogenic nor causing gene mutations, provided that a comprehensive toxicological database is available. For situations in which the toxicological database is not sufficient to establish health‐based guidance values, some approaches to risk assessment are proposed. The Scientific Committee recommends further development of the gastrointestinal micronucleus test, and research to improve the understanding of aneugenicity to support risk assessment., This publication is linked to the following EFSA Supporting Publications article: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2021.EN-6814/full
- Published
- 2021