Guidance on aneugenicity assessment

EFSA Scientific Committee (SC)

Research output: Contribution to journalComment/debateResearchpeer-review

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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.

Original languageEnglish
Article numbere06770
JournalEFSA Journal
Issue number8
Number of pages27
Publication statusPublished - Aug 2021

Bibliographical note

Funding Information:
The EFSA Scientific Committee wishes to acknowledge the following hearing experts for the views provided to this scientific output: Roland Froetschl, Bodo Haas, Uta Herbst, David Kirkland, Christina Tlustos; the observer Frank Le Curieux (European Chemicals Agency - ECHA); the experts Maria Dusinska and Ursula Gunder-Remy for the critical review of the manuscript; the EFSA staff Sara De Berardis, Christina Kyrkou and Esraa Elewa.

Publisher Copyright:
© 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.


  • Aneugenicity
  • Genotoxicity in vivo and in vitro
  • Micronucleus test


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