Scientific opinion on genotoxicity testing strategies applicable to food and feed safety assessment

Abstract

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.

Genotoxicity Expert Panel review: weight of evidence evaluation of the genotoxicity of glyphosate, glyphosate-based formulations, and aminomethylphosphonic acid

“…Genetic toxicology tests relied upon by most regulatory bodies to support decisions focus on a set of core endpoints that are known to be involved either in direct activation of genes responsible for neoplastic initiation in somatic cells or alteration of the genetic information in germ cells (EFSA 2011;ICH 2011;Kirkland et al 2011). Therefore, the endpoints given the greatest weight in Table 1 include gene mutation and chromosomal aberrations. MN formation in vivo was also assigned a high weight (Table 1), as it is considered an indication of chromosome breakage but could also result from aneuploidy (KirschVolders et al 2003).…”

“…IARC did not consider the chemical structure of glyphosate in its mechanistic section; however, IARC Monograph Section 5.3 states that glyphosate is not electrophilic. Many guidelines recommend that the presence of structural alerts be considered in evaluation of or testing for genotoxicity (Cimino 2006;Eastmond et al 2009;EFSA 2011;ICH 2011). As reported in Kier and Kirkland (2013) analysis of the glyphosate structure by DEREK software identified no structural alerts for chromosomal damage, genotoxicity, mutagenicity, or carcinogenicity.…”

Guidance on the assessment of the safety of feed additives for the consumer

“…Details on how the Comprehensive Database is used are published in the Guidance of EFSA (EFSA, 2011). For each EU country and age class, only the latest survey available in the Comprehensive Database will be used.…”

Scientific Opinion on Flavouring Group Evaluation 77, Revision 2 (FGE.77Rev2): Consideration of Pyridine, Pyrrole and Quinoline Derivatives evaluated by JECFA (63rd meeting) structurally related to Pyridine, Pyrrole, Indole and Quinoline Derivatives evalu

“…The negative results of these two studies are not sufficient to overrule the concern on the genotoxic potential of 6-methylquinoline, which was observed in vitro, induction of gene mutations in bacterial cells, chromosome aberrations and sister chromatid exchanges (SCE) in cultured mammalian cells after metabolic activation (S9). Therefore, in line with the requirements in the EFSA guidance document (EFSA Scientific Committee, 2012) further in vivo testing is recommended with a more appropriate and sensitive assay, i.e. a Comet assay with liver as target organ to alleviate the concern for genotoxicity of 6-methylquinoline.…”