Scientific Opinion on Flavouring Group Evaluation 220 Revision 3 (FGE.220Rev3): Consideration of genotoxic potential for α,β-unsaturated 3(2H)-Furanones from subgroup 4.4 of FGE.19

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Article
Panel on Food Additives and Nutrient Sources Added to Food
Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids
EFSA Journal
EFSA Journal 2015;13(5):4117 [37 pp.].
doi
10.2903/j.efsa.2015.4117
Panel members at the time of adoption
Claudia Bolognesi, Laurence Castle, Jean-Pierre Cravedi, Karl-Heinz Engel, Paul Fowler, Konrad Grob, Rainer Gürtler, Trine Husøy, Wim Mennes, Maria Rosaria Milana, André Penninks, Vittorio Silano, Andrew Smith, Maria de Fátima Tavares Poças, Christina Tlustos, Fidel Toldrá, Detlef Wölfle and Holger Zorn.
Acknowledgements

The Panel wishes to thank the members of the Genotoxicity Working Group on Flavourings: Mona-Lise Binderup, Claudia Bolognesi, Riccardo Crebelli, Rainer Gürtler, Natália Kovalkovičová, Francesca Marcon, Daniel Marzin and Pasquale Mosesso for the preparatory work on this scientific opinion and the hearing experts: Vibe Beltoft and Karin Nørby, and EFSA staff: Annamaria Rossi and Maria Carfi for the support provided to this scientific opinion.

Contact
Type
Opinion of the Scientific Committee/Scientific Panel
On request from
European Commission
Question Number
EFSA-Q-2014-00684
EFSA-Q-2014-00685
EFSA-Q-2014-00686
Adopted
7 mai 2015
Published
28 mai 2015
Affiliation
European Food Safety Authority (EFSA), Parma, Italy
Note
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Abstract

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate the genotoxic potential of 10 flavouring substances from FGE.19 subgroup 4.4, in the Flavouring Group Evaluation 220 (FGE.220). FGE.220 is subdivided into two subgroups: subgroup 4.4a containing [FL-no: 13.089, 13.117, 13.119, 13.157 and 13.175] and subgroup 4.4b containing [13.010, 13.084 and 13.085, 13.099 and 13.176]. For both subgroups the Panel concluded that the genotoxicity alert could not be ruled out based on the data available and accordingly additional genotoxicity data were requested. In FGE.220, Revision 1, the Panel concluded that for the substances in subgroup 4.4b there is no concern for genotoxicity. In FGE.220, Revision 2, the Panel evaluated genotoxicity studies on two representative substances of subgroup 4.4a: 2,5-dimethylfuran-3(2H)-one [FL-no:13.119] and 4-acetyl-2,5-dimethylfuran-3(2H)-one [FL-no: 13.175]. Based on the submitted data the Panel concluded that 2,5-dimethylfuran-3(2H)-one [FL-no: 13.119] does not give rise to concern with respect to genotoxicity. For 4-acetyl-2,5-dimethylfuran-3(2H)-one [FL-no: 13.175] the concern for genotoxicity could not be ruled out, therefore the Panel requested a repetition of the submitted micronucleus study in the presence of S9-mix, or a combined in vivo micronucleus and Comet assay, including analysis of the liver. The Flavour Industry has tested again 4-acetyl-2,5-dimethylfuran-3(2H)-one [FL-no: 13.175] in an in vitro micronucleus assay as was requested by the Panel. This new study is evaluated in FGE.220, Revision 3, where the Panel concluded that [FL-no: 13.175] does not give rise to concern with respect to genotoxicity and can be evaluated using the Procedure. This is also applicable to other two substances in subgroup 4.4a: 2,5-dimethyl-4-methoxyfuran-3(2H)-one [FL-no:13.089] and 2,5-dimethyl4-ethoxyfuran-3(2H)-one [FL-no:13.117]. Based on the available data the substances of this FGE are no longer of concern with respect to genotoxicity and can be evaluated through the Procedure.

Summary

Following a request from the European Commission, the EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) was asked to deliver a scientific opinion on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Panel was asked to evaluate 10 flavouring substances in Flavouring Group Evaluation 220 (FGE.220) using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000.

Flavouring Group Evaluation 220 (FGE.220) concerned 10 substances, corresponding to subgroup 4.4 of FGE.19. The 10 substances are α,β-unsaturated 3(2H)-furanones [FL-no: 13.010, 13.084, 13.085,13.089, 13.099, 13.117, 13.119, 13.157, 13.175 and 13.176]. The substances were further subdivided into two subgroups as five [FL-no: 13.089, 13.117, 13.119, 13.157 and 13.175] of the 10 substances can only exist as α,β-unsaturated ketones (subgroup 4.4a) while in the other five substances [13.010,13.084 and 13.085, 13.099 and 13.176], the α,β-double bond can be involved in keto-enol tautomerism (subgroup 4.4b). For both groups the Panel concluded that the genotoxicity alert could not be ruled out based on data available at that time, and accordingly additional genotoxicity data were requested for both groups.

Revision 1 of FGE.220 (FGE.220Rev1) concerned the evaluation of additional data submitted by Industry in response to the requested genotoxicity data in FGE.220 on the representative substance for subgroup 4.4b, 4-hydroxy-2,5-dimethylfuran-3(2H)-one [FL-no: 13.010]. The Panel concluded that for the substances [13.010, 13.084 and 13.085, 13.099 and 13.176] in subgroup 4.4b there is no concern for genotoxicity, and these substances were accordingly evaluated through the Procedure in FGE.99.

In FGE.220, Revision 2, genotoxicity data related to subgroup 4.4a were evaluated. The Flavour Industry informed that one of the representative substances, 5-methylfuran-3(2H)-one [FL-no: 13.157], is not in common use in the Flavour Industry and is no longer supported. As an alternative substance for testing within this subgroup, the Flavour Industry had proposed the structurally related substance 2,5-dimethylfuran-3(2H)-one [FL-no: 13.119]. Accordingly, additional genotoxicity data were submitted for 2,5-dimethylfuran-3(2H)-one [FL-no: 13.119] and 4-acetyl-2,5-dimethylfuran-3(2H)-one [FL-no: 13.175]. These data were examined by the Panel which concluded that 2,5-dimethylfuran-3(2H)-one [FLno:13.119] does not give rise to concern with respect to genotoxicity and can accordingly be evaluated using the Procedure. For 4-acetyl-2,5-dimethylfuran-3(2H)-one [FL-no: 13.175] the concern for genotoxicity could not be ruled out and therefore the Panel requested a repetition of the micronucleus study in the presence of S9-mix, applying the same conditions and possibly in addition modified conditions, or a combined in vivo micronucleus and Comet assay, including analysis of liver.

The Industry has tested again 4-acetyl-2,5-dimethylfuran-3(2H)-one [FL-no: 13.175] in an in vitro micronucleus assay in the presence of S9-mix (3+21 hours). These data are evaluated in the present Revision 3 of FGE.220 (FGE.220 Rev3). The available data suggest that 4-acetyl-2,5-dimethylfuran-3(2H)-one [FL-no: 13.175] did not induce reproducible statistically significant increase in micronucleated binucleate cells across replicate cultures indicating that the test substance can be considered negative for clastogenicity and aneugenicity. The Panel therefore concluded that [FL-no: 13.175] does not give rise to concern with respect to genotoxicity and accordingly can be evaluated using the Procedure. This is also applicable to 2,5-dimethyl-4-methoxyfuran-3(2H)-one [FL-no:13.089] and 2,5-dimethyl4-ethoxyfuran-3(2H)-one [FL-no:13.117] which are covered by the representative substance 4-acetyl2,5-dimethylfuran-3(2H)-one [FL-no:13.175].

Based on the available data all 9 substances of this FGE are no longer of concern with respect to genotoxicity and can be evaluated through the Procedure.

Keywords
α,β-unsaturated ketones, 3(2H)-furanones, flavouring substances, safety evaluation, FGE.220, FGE.19, subgroup 4.4
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Number of Pages
37