EFSA Panel on food contact materials, enzymes, flavourings and processing aids (CEF); Scientific Opinion on Flavouring Group Evaluation 23, Revision 2 (FGE.23Rev2): Aliphatic, alicyclic and aromatic ethers including anisole derivatives from chemical groups 15, 16, 22, 26 and 30

Abstract

The European Food Safety Authority (EFSA) asked the Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (the Panel) to provide scientific advice to the Commission 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 requested to evaluate 19 flavouring substances in the Flavouring Group Evaluation 23, Revision 2 (FGE.23Rev2), using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. These 19 flavouring substances belong to chemical groups 15, 16, 22, 26 and 30, Annex I of the Commission Regulation (EC) No 1565/2000. The present Flavouring Group Evaluation deals with 19 candidate substances, which are aliphatic, alicyclic and aromatic ethers including anisole derivatives. Four of the candidate substances are aliphatic ethers, one is an alicyclic ether, three are alicyclic hydrocarbons with an ether side chain, two are ethers containing a benzene moiety, eight are phenol ethers and one is a naphthol ether. Five of the 19 candidate substances possess one or more chiral centres and three can exist as geometrical isomers. For one substance [FL-no: 03.022] Industry has informed that it occurs as a mixture of E- & Z-isomers, however, the composition of the mixture has to be specified. Two of the flavouring substances are classified into structural class I, seven are classified into structural class II and 10 are classified into structural class III. Ten of the substances in the present group have been reported to occur naturally in a wide range of food items. In its evaluation, the Panel as a default used the “Maximised Survey-derived Daily Intake” (MSDI) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Panel examined the information provided by the European Flavouring Industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate the intake by regular consumers of products flavoured at the use level reported by the Industry, especially in those cases where the annual production values were reported to be small. In consequence, the Panel had reservations about the data on use and use levels provided and the intake estimates obtained by the MSDI approach. In the absence of more precise information that would enable the Panel to make a more realistic estimate of the intakes of the flavouring substances, the Panel has decided also to perform an estimate of the daily intakes per person using a “modified Theoretical Added Maximum Daily Intake” (mTAMDI) approach based on the normal use levels reported by Industry. In those cases where the mTAMDI approach indicated that the intake of a flavouring substance might exceed its corresponding threshold of concern, the Panel decided not to carry out a formal safety assessment using the Procedure. In these cases the Panel requires more precise data on use and use levels. According to the default MSDI approach, the 19 flavouring substances in this group have intakes in Europe from 0.011 to 49 micrograms/capita/day, which are below the threshold of concern value for structural class I of 1800 micrograms/person/day, for structural class II of 540 micrograms/person/day and for structural class III of 90 micrograms/person/day. On the basis of the reported annual production in Europe (MSDI approach), the combined intake of the two candidate substances belonging to structural class I, of the seven candidate substances belonging to structural class II and of the 10 candidate substances belonging to structural class III, would result in combined intakes of approximately 1.2, 52 and 26 micrograms/capita/day, respectively. These values are lower than the thresholds of concern for structural class I, II or III substances. The estimated total combined intakes of the candidate and supporting substances (in Europe) are approximately 2800, 1300 and 130 micrograms/capita/day for structural class I, II and III substances, respectively. The combined daily per capita intake of 2800 micrograms exceeds the threshold of concern of 1800 micrograms/person/day for structural class I substances. The supporting substances were evaluated at the 51st JECFA meeting, where it was noted that although the combined intake exceeds the threshold for structural class I the substances are expected to be efficiently metabolised and would not saturate the metabolic pathways. The Panel agreed with this view and concluded that the combined intake of about 1.2 micrograms/capita/day for the candidate substances in structural class I is negligible compared to the combined intake of 2800 micrograms/capita/day of the supporting substances. Likewise the total combined intake of the seven candidate substances and ten supporting substances from structural class II is approximately 1300 micrograms/capita/day, which exceeds the threshold of concern for a compound belonging to structural class II of 540 micrograms/person/day. The supporting substances in structural class II were evaluated at the 61st JECFA meeting, where it was noted that although the combined intake exceeds the threshold, the substances are expected to be efficiently metabolised and would not saturate the metabolic pathways. The Panel agreed with this view and concluded that the combined intake of about 52 micrograms/capita/day for the candidate substances in structural class II is negligible compared to the combined intake of 1250 micrograms/capita/day of the supporting substances. The total combined intake of candidate and supporting substances of structural class III is 130 micrograms/capita/day, which is above the threshold of concern for structural class III of 90 micrograms/capita/day. The supporting substances were evaluated by the JECFA at the 59th and 61st meetings, where it was noted that although the combined intake exceeds the threshold for the structural class, the substances are expected to be efficiently metabolised and would not saturate the metabolic pathways. The Panel agreed with this view and concluded that the combined intake of about 26 micrograms/capita/day for the candidate substances in structural class III is minor compared to the combined intake of 100 micrograms/capita/day of the supporting substances. For the substances in this group, the available data on genotoxicity do not give rise to safety concern. According to the available data on supporting substances, it is expected that all 19 candidate substances in this group [FL-no: 02.247, 02.248, 03.008, 03.011, 03.012, 03.015, 03.016, 03.020, 03.022, 03.024, 04.059, 04.067, 04.068, 04.069, 04.075, 04.079, 04.084, 08.127 and 09.687] would be metabolised to innocuous products at the reported levels of intake as flavouring substances. It was noted that no repeated dose toxicity studies have been provided for any of the candidate substances and only a few studies were available on supporting substances. However, these toxicological data were consistent with the conclusions in the present Flavouring Group Evaluation using the Procedure. It was concluded that on the basis of the default MSDI approach the 19 candidate substances would not give rise to safety concerns at estimated levels of intake arising from their use as flavouring substances. When the estimated intakes were based on the mTAMDI approach they were 3200 micrograms/person/day for the two flavouring substances belonging to structural class I and for six of the seven flavouring substances belonging to structural class II, for the remaining flavouring substance from class II it is 14000 micrograms/person/day. These intakes are above the threshold of concern for structural class I of 1800 micrograms/person/day and for structural class II of 540 micrograms/person/day. For eight of the ten candidate substances belonging to structural class III the mTAMDI are 3200 or 3900 micrograms/person/day, which are above the threshold of concern of 90 microgram/person/day. For one substance from structural class III the mTAMDI of 58 micrograms/person/day is below the threshold. This substance is also expected to be metabolised to innocuous products. For one substance the mTAMDI could not be estimated as no use levels have been provided. Thus, for 17 of the 19 flavouring substances considered in this Opinion the intakes, estimated on the basis of the mTAMDI, exceed the relevant threshold for their structural class, to which the flavouring substances have been assigned. Therefore, for these 17 substances, and for [FL-no: 02.248] for which use levels are missing, more reliable exposure data are required. On the basis of such additional data, these flavouring substances should be reconsidered along the steps of the Procedure. Following this procedure additional toxicological data might become necessary. In order to determine whether the conclusion for the 19 candidate substances can be applied to the materials of commerce, it is necessary to consider the available specifications. Specifications including purity criteria and identity for the materials of commerce have been provided for all 19 flavouring substances. Information on the stereoisomeric composition is missing for one of the substances [FLno: 03.022], as Industry has informed that it occurs as a mixture of E- & Z-isomers, however, the composition of the mixture has to be specified. Thus, the final evaluation of the materials of commerce cannot be performed for this substance, pending further information. The remaining 18 substances [FL-no: 02.247, 02.248, 03.008, 03.011, 03.012, 03.015, 03.016, 03.020, 03.024, 04.059, 04.067, 04.068, 04.069, 04.075, 04.079, 04.084, 08.127 and 09.687] would present no safety concern at the estimated levels of intake based on the MSDI approach.