Scientific Opinion on Flavouring Group Evaluation 304, Revision 1 (FGE.304Rev1): Four carboxamides from Chemical Groups 30

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Article
Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids
EFSA Journal
EFSA Journal 2014;12(7):3769 [35 pp.].
doi
10.2903/j.efsa.2014.3769
Panel members at the time of adoption
Claudia Bolognesi, Laurence Castle, Jean-Pierre Cravedi, Karl-Heinz Engel, Paul Fowler, Roland Franz, Konrad Grob, Rainer Gürtler, Trine Husøy, Wim Mennes, Maria Rosaria Milana, André Penninks, Franz Roland, 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 Working Group on Flavourings: Ulla Beckman Sundh, Leon Brimer, Angelo Carere, Karl-Heinz Engel, Henrik Frandsen, Rainer Gürtler, Frances Hill, Trine Husøy, Wim Mennes, Gerard Mulder and Harriet Wallin for the preparatory work on this scientific opinion and the hearing experts: Vibe Beltoft, Pia Lund and Karin Nørby and EFSA staff: Annamaria Rossi and Kim Rygaard Nielsen 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-2013-00860
Adopted
3 July 2014
Published
22 July 2014
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 four flavouring substances in the Flavouring Group Evaluation 304, Revision 1 (FGE.304Rev1) using the Procedure in Commission Regulation (EC) No 1565/2000. This revision is made due to a re-evaluation of one flavouring substance N-(2-(pyridine-2-yl)ethyl)-3-p-menthanecarboxamide [FL-no: 16.118], as a 90-day dietary rat study has become available. One of the original five flavouring substances [FL-no: 16.124], for which additional data were requested, is no longer supported by the Industry for use as flavouring substance in Europe and will therefore not be considered any further in FGE.304Rev1. Therefore, FGE.304Rev1 will deal with four flavouring substances. None of the four substances were considered to have genotoxic potential. The substances were evaluated through a stepwise approach (the Procedure) that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that the four substances [FL-no: 16.117, 16.118, 16.123 and 16.125] do not give rise to safety concern at their levels of dietary intake, estimated on the basis of the MSDI approach. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered. Specifications including complete purity criteria and identity for the materials of commerce have been provided for all four candidate substances.

Summary

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 asked to evaluate four flavouring substances in the Flavouring Group Evaluation 304, Revision 1 (FGE.304Rev1), using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. These four carboxamides [FL-no: 16.117, 16.118, 16.123 and 16.125] belong to chemical group 30, Annex I of the Commission Regulation (EC) No 1565/2000.

The present Flavouring Group Evaluation deals with four carboxamides. Since the publication of the previous version, FGE.304, one of the original five candidate substances [FL-no: 16.124], for which additional data were required, is no longer supported by Industry for use as flavouring substance in Europa and will therefore not be considered any further. This revision of FGE.304, FGE.304Rev1, therefore only deals with four candidate substances N-p-benzeneacetonitrile-menthanecarboxamide [FL-no: 16.117], N-(2-(pyridine-2-yl)ethyl)-3-p-menthanecarboxamide [FL-no: 16.118], (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)cyclohexanecarboxamide [FL-no: 16.123] and (2S,5R)-N-[4-(2-amino-2-oxoethyl)phenyl]-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide [FL-no: 16.125].
Further, the present revision of FGE.304, FGE.304Rev1, includes the assessment of new toxicity data on N-(2-(pyridine-2-yl)ethyl)-3-p-menthanecarboxamide [FL-no: 16.118] for which additional data were required.

The four flavouring substances possess chiral centres. All substances have been presented with specification of the stereoisomeric composition.

All candidate substances were assigned to structural class III, according to the decision tree approach presented by Cramer et al., 1978.

None of the candidate substances have been reported to occur naturally.

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.

Genotoxicity data are available for three substances. The Panel concluded that the data available do not give rise to safety concern with respect to genotoxicity for any of the candidate substances.
On the basis of the available data, the hydrolysis of the candidate substances cannot be excluded. However, owing to the lack of further data, the candidate substances cannot be anticipated to be metabolised to innocuous products.

According to the default MSDI approach, the three flavouring substances [FL-no: 16.118, 16.123 and 16.125] in this group have intakes in Europe from 6.1 to 61 µg/capita/day, which are below the threshold of concern value for structural class III of 90 µg/person/day. For the remaining substance [FL-no: 16.117] the intake of 120 µg/capita/day is above the threshold of concern. However, an adequate NOAEL of 100 mg/kg body weight/day exists from a 90-day study with this candidate substance [FL-no: 16.117], which provides a margin of safety of 5 x 104. This substance is structurally related to the two substances [FL-no: 16.123 and 16.125] for which a margin of safety of 3.3 x 105, based on the combined estimated daily per capita intake, can be calculated. For the remaining candidate substance [FL-no: 16.118] a 90-day study has become available and a NOAEL to provide adequate margin of safety of 5000 is derived. Therefore, the four substances [FL-no: 16.117, 16.118, 16.123 and 16.125] are not anticipated to pose a safety concern when used as flavouring substances at the estimated levels of intake, based on the MSDI approach.

In order to determine whether the conclusion for the four flavouring substances can be applied to the materials of commerce, it is necessary to consider the available specifications. Adequate specifications including complete purity criteria and identity for the materials of commerce have been provided for all the flavouring substances evaluated through the Procedure. Thus, the final evaluation of the materials of commerce can be performed for all four substances.

In conclusion, for all substances [FL-no: 16.117, 16.118, 16.123 and 16.125], the Panel concluded that they would present no safety concern at the estimated levels of intake based on the MSDI approach.

However, when the estimated intakes were based on the mTAMDI approach, they ranged from 150 to 7800 µg/person/day for the four candidate substances from structural class III, which are above the threshold of concern for structural class III of 90 µg/person/day. Therefore more reliable exposure data are required for these substances [FL-no: 16.117, 16.118, 16.123 and 16.125]. On the basis of such additional data, these flavouring substances should be reconsidered using the Procedure. Subsequently, additional data might become necessary.

Keywords
FGE.304, carboxamides, flavourings, food safety
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Number of Pages
35