Scientific Opinion on Flavouring Group Evaluation 305 (FGE.305): L-Methionylglycine of chemical group 34

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Article
Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids
EFSA Journal
EFSA Journal 2013;11(4):3150 [31 pp.].
doi
10.2903/j.efsa.2013.3150
Panel members at the time of adoption
Ulla Beckman Sundh, Mona-Lise Binderup, Claudia Bolognesi, Leon Brimer, Laurence Castle, Alessandro Di Domenico, Karl-Heinz Engel, Roland Franz, Nathalie Gontard, Rainer Gürtler, Trine Husøy, Klaus-Dieter Jany, Martine Kolf-Clauw, Catherine Leclercq, Wim Mennes, Maria Rosaria Milana, Iona Pratt, Kettil Svensson, Maria de Fatima Tavares Poças, Fidel Toldra and Detlef Wölfle
Acknowledgements

The Panel wishes to thank the members of the Working Groups on Flavourings: Ulla Beckman Sundh, Leon Brimer, Wilfried Bursch, Angelo Carere, Karl-Heinz Engel, Henrik Frandsen, Rainer Gürtler, Frances Hill, Trine Husøy, John Christian Larsen, 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: 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-2010-01503
Adopted
19 March 2013
Published
5 April 2013
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 one flavouring substance, the dipeptide L-methionylglycine [FL-no: 17.037], in the Flavouring Group Evaluation 305, using the Procedure in Commission Regulation (EC) No 1565/2000. The substance was considered not to have genotoxic potential. The substance was evaluated through a stepwise approach (the Procedure) that integrates information on the structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that for the flavouring substance, evaluated through the Procedure, no appropriate NOAEL was available and additional data are required. The present evaluation of the candidate substance L-methionylglycine [FL-no: 17.037] is only applicable for its use in foods that are not heated or intended to be heated. Besides the safety assessment of the flavouring substance, the specifications for the material of commerce have also been considered. Adequate specifications including complete purity criteria and identity for the material of commerce have been provided for the candidate substance.

Summary

Following a request from the European Commission the 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 Panel was requested to evaluate one flavouring substance, the dipeptide L-methionylglycine [FL-no: 17.037], in the Flavouring Group Evaluation 305 (FGE.305), using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. This flavouring substance belongs to chemical group 34, Annex I of the Commission Regulation (EC) No 1565/2000.

The candidate substance possesses one chiral centre and the optical isomer has been specified.

The candidate substance belongs to structural class III and has not been reported to occur naturally in any food items according to TNO.

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 intake in Europe for the candidate substance L-methionylglycine [FL-no: 17.037] is 1.2 µg/capita/day.

No data on genotoxicity has been submitted for the candidate substance. However, consideration of the chemical structure does not give rise to safety concern with respect to genotoxicity.
No information has been provided on hydrolysis of the candidate substance L-methionylglycine [FL-no: 17.037] under physiological conditions. Without information about the potential for hydrolysis of the candidate substance L-methionylglycine [FL-no: 17.037] and without any studies that show the fate of the substance in vitro and/or in vivo, it is not possible to predict whether it will be absorbed as a dipeptide or not, nor its distribution or potential bioactivity after absorption. Since such information is lacking, rapid metabolism of the dipeptide to innocuous metabolites cannot be anticipated. Therefore, evaluation of the candidate substance proceeds via the B-side to step B4 of the Procedure, at which step no adequate study from which a No Observed Adverse Effect Level (NOAEL) was available. So, the Panel concluded that additional data are required for the candidate substance L-methionylglycine [FL-no: 17.037].

When the estimated intake was based on the mTAMDI, it was 24000 µg/person/day, which is above the threshold for structural class III of 90 µg/person/day.

The Panel noted the high discrepancy between MSDI and mTAMDI. The hypothetical nature of the MSDI, which is based on anticipated volumes of production, leads to a high uncertainty in the safety evaluation of this substance when based on the MSDI. The Panel will therefore not be in a position to conclude on the absence of safety concern for this specific substance unless a more refined dietary exposure estimate based on use levels is provided.

The Panel further noted that the nature of the candidate substance and the proposed intended uses indicated by Industry suggests that the candidate substance ma be a flavour precursor. The present evaluation of the candidate substance L-methionylglycine [FL-no: 17.037] is only applicable for its use in foods that are not heated or intended to be heated.

Adequate specifications, including purity criteria and identity for the material of commerce, have been provided for the candidate substance.

For the candidate substance L-methionylglycine [FL-no: 17.037] additional data are required, as no adequate study was available from which a NOAEL could be established.

Keywords
Flavourings, food safety, L-methionylglycine, dipeptide, amino acid
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Number of Pages
31