Guidance on aneugenicity assessment.
Résumé
The EFSA Scientific Committee was asked to provide guidance on the most appropriatein vivotests tofollow up on positivein vitroresults for aneugenicity, and on the approach to risk assessment forsubstances that are aneugenic but not clastogenic nor causing gene mutations. The ScientificCommittee confirmed that the preferred approach is to perform anin vivomammalian erythrocytemicronucleus test with a relevant route of administration. If this is positive, it demonstrates that thesubstance is aneugenicin vivo. A negative result with evidence that the bone marrow is exposed tothe test substance supports a conclusion that aneugenic activity is not expressedin vivo. If there is noevidence of exposure to the bone marrow, a negative result is viewed as inconclusive and furtherstudies are required. The liver micronucleus assay, even though not yet fully validated, can providesupporting information for substances that are aneugenic following metabolic activation. Thegastrointestinal micronucleus test, conversely, to be further developed, may help to assess aneugenicpotential at the initial site of contact for substances that are aneugenicin vitrowithout metabolicactivation. Based on the evidence in relation to mechanisms of aneugenicity, the Scientific Committeeconcluded that, in principle, health-based guidance values can be established for substances that areaneugenic but not clastogenic nor causing gene mutations, provided that a comprehensivetoxicological database is available. For situations in which the toxicological database is not sufficient toestablish health-based guidance values, some approaches to risk assessment are proposed. TheScientific Committee recommends further development of the gastrointestinal micronucleus test, andresearch to improve the understanding of aneugenicity to support risk assessment.
Domaines
Sciences du Vivant [q-bio]
Fichier principal
EFSA Journal - 2021 - - Guidance on aneugenicity assessment.pdf (2.79 Mo)
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