Following a request from the European Commission, the EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF Panel) 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 Scientific Panel was asked to evaluate flavouring substances using the procedure referred to in Commission Regulation EC No 1565/2000 (hereafter ‘the Procedure’).
The Flavouring Group Evaluation (FGE) 213 concerns 26 substances, corresponding to subgroup 2.7 of FGE.19. Twenty-three of the substances are α,β-unsaturated alicyclic ketones [Flavour Information System (FL)-nos: 07.008, 07.010, 07.014, 07.041, 07.047, 07.056, 07.057, 07.075, 07.076, 07.080, 07.083, 07.089, 07.108, 07.109, 07.117, 07.118, 07.119, 07.120, 07.127, 07.136, 07.168, 07.200 and 07.224] and three are precursors for such ketones [FL-nos: 02.106, 09.305 and 09.525].
In the first version of FGE.213 the Panel concluded that the genotoxicity concern for ethyl maltol [FL-no: 07.047], 3-ethylcyclopentan-1,2-dione [FL-no: 07.057] and the nine structurally related substances [FL-nos: 07.117, 07.118, 07.119, 07.120, 07.056, 07.168, 07.075, 07.076 and 07.080] could be ruled out and the 11 substances could accordingly be evaluated through the Procedure.
For maltol [FL-no: 07.014], a micronucleus assay after oral application was required in addition to an in vivo comet assay in order to clarify the genotoxic potential. The outcome would also be applicable to maltyl isobutyrate [FL-no: 09.525].
The remaining 13 substances (including two precursors of a ketone) [FL-nos: 02.106, 07.008, 07.010, 07.041, 07.083, 07.089, 07.108, 07.109, 07.127, 07.136, 07.200, 07.224 and 09.305] could not be evaluated through the Procedure. Accordingly, additional data on genotoxicity were required for representatives of these 13 substances.
The Flavour Industry informed that it no longer supports the representative flavouring substance, piperitenone oxide [FL-no: 16.044], for which the Panel requested additional data. In FGE.213Rev1, one additional substance has been included in subgroup 2.7, tr-1-(2,6,6-trimethyl-1-cyclohexen-1-yl)but-2-en-1-one [FL-no: 07.224], which is structurally related to the other substances for which the genotoxic potential could not be ruled out.
In FGE.213Rev1, the Panel evaluated the new data submitted by the Flavour Industry in response to the data request presented in FGE.213. Based on these new data, the Panel concluded that the genotoxicity concern could be ruled out for the representative substances β-ionone [FL-no: 07.008], β-damascone [FL-no: 07.083], nootkatone [FL-no: 07.089], 2,6,6-trimethylcyclohex-2-en-1,4-dione [FL-no: 07.109] and the nine substances that they represent [FL-nos: 02.106, 07.010, 07.041, 07.108, 07.127, 07.136, 07.200, 07.224 and 09.305].
In the case of maltol, positive results were observed in an in vitro micronucleus assay in human peripheral blood lymphocytes and in an in vivo micronucleus assay in mouse bone marrow after intraperitoneal application. Maltol was also tested in rats (administered by gavage) in a combined bone marrow micronucleus assay and comet assay in liver. Both tests showed negative results, but no clinical signs and no bone marrow toxicity were observed. To investigate the systemic exposure, plasma bioanalysis was performed, but results were inconsistent. Owing to the intended use of maltol as a food-flavouring agent, the in vivo study performed with administration of maltol by gavage is considered more relevant than the study performed by intraperitoneal application. Therefore, the Panel concluded in Revision 1 of this FGE that for maltol [FL-no: 07.014] and maltyl isobutyrate [FL-no: 09.525] the concern for genotoxicity could not be ruled out.
The Flavour Industry has submitted a new plasma bioanalysis for maltol, which is evaluated in the present revision of FGE.213 (FGE.213Rev2). The Panel considered this new plasma bioanalysis and concluded that it seems justifiable to assume that animals were systemically exposed to maltol and that the bone marrow was exposed in the in vivo micronucleus assay. Therefore, the negative result of the in vivo micronucleus assay can be considered reliable and, accordingly, the concern for genotoxicity for maltol [FL-no: 07.014] and for maltyl isobutyrate [FL-no: 09.525] in food is ruled out; both substances were evaluated by JECFA before 2000 and no EFSA consideration is required.
Moreover, the Panel reconsidered the available data on p-mentha-1,4(8)-dien-3-one [FL-no: 07.127], based on new data on the structurally related substance pulegone and concluded that additional genotoxicity data are needed to rule out the concern for genotoxicity on p-mentha-1,4(8)-dien-3-one [FL-no: 07.127].