Opinion on genotoxicity testing strategies


Genotoxicity, testing strategies
First published in the EFSA Journal
30 September 2011
13 September 2011
Last Updated
3 October 2012. This version replaces the previous one/s.
Opinion of the Scientific Committee/Scientific Panel

The Scientific Committee reviewed the current state-of-the-science on genotoxicity testing and provided a commentary and recommendations on genotoxicity testing strategies. A step-wise approach is recommended for the generation and evaluation of data on genotoxic potential, beginning with a basic battery of in vitro tests, comprising a bacterial reverse mutation assay and an in vitro micronucleus assay. Consideration should be given to whether specific features of the test substance might require substitution of one or more of the recommended in vitro tests by other in vitro or in vivo tests in the basic battery. In the event of negative in vitro results, it can be concluded that the substance has no genotoxic potential. In case of inconclusive, contradictory or equivocal results, it may be appropriate to conduct further testing in vitro. In case of positive in vitro results, review of the available relevant data on the test substance and, where necessary, an appropriate in vivo study to assess whether the genotoxic potential observed in vitro is expressed in vivo is recommended. Suitable in vivo tests are the mammalian erythrocyte micronucleus test, transgenic rodent assay, and Comet assay. The approach to in vivo testing should be step-wise. If the first in vivo test is positive, no further testing is necessary and the substance should be considered as an in vivo genotoxin. If the test is negative, it may be possible to conclude that the substance is not an in vivo genotoxin. However, in some cases, a second in vivo test may be necessary (e.g. if the first test is negative but more than one endpoint in the in vitro tests are positive, an in vivo test on a second endpoint may be necessary). The combination of assessing different endpoints in different tissues in the same animal in vivo should also be considered.

Panel members at the time of adoption
Boris Antunović, Susan Barlow, Andrew Chesson, Albert Flynn, Anthony Hardy, Michael-John Jeger, Ada Knaap, Harry Kuiper, John-Christian Larsen, David Lovell, Birgit Noerrung, Iona Pratt, Ivonne Rietjens, Josef Schlatter, Vittorio Silano, Frans Smulders and Philippe Vannier
scientific.committee [at] efsa.europa.eu
EFSA Journal 2011;9(9):2379 [69 pp.].
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