Scientific Opinion on Flavouring Group Evaluation 77, Revision 1 (FGE.77Rev1): Consideration of Pyridine, Pyrrole and Quinoline Derivatives evaluated by JECFA (63rd meeting) structurally related to Pyridine, Pyrrole, Indole and Quinoline Derivatives evaluated by EFSA in FGE.24Rev2 (2013)

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Article
Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids
EFSA Journal
EFSA Journal 2014;12(2):3586 [50 pp.].
doi
10.2903/j.efsa.2014.3586
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, 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, 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-2012-00699
EFSA-Q-2013-00355
EFSA-Q-2013-00556
EFSA-Q-2013-00602
EFSA-Q-2013-00816
Adopted
29 January 2014
Published
19 February 2014
Affiliation
European Food Safety Authority (EFSA), Parma, Italy
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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 consider evaluations of flavouring substances assessed since 2000 by the Joint FAO/WHO Expert Committee on Food Additives (the JECFA), and to decide whether further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. The present consideration concerns a group of 22 pyridine, pyrrole and quinoline derivatives evaluated by the JECFA (63rd meeting). The revision of this consideration is made since additional toxicity data have become available for isoquinoline [FL-no: 14.001], pyrrole [FL-no: 14.041] and 2-acetylpyrrole [FL-no: 14.047]. The toxicity data on 2-acetylpyrrole should also cover 2-propionylpyrrole [FL-no: 14.068]. Further, additional genotoxicity data on 6-methylquinoline [FL-no: 14.042] have become available. The Panel concluded that for 6-methylquinoline [FL-no: 14.042], the new genotoxicity data did not clear the concern with respect to genotoxicity in vitro and accordingly the substance is not evaluated through the Procedure. For 18 substances [FL-no: 14.001, 14.004, 14.007, 14.030, 14.038, 14.039, 14.041, 14.047, 14.058, 14.059, 14.060, 14.061, 14.065, 14.066, 14.068, 14.071, 14.072 and 14.164] considered in this FGE, the Panel agrees with the JECFA conclusion, “No safety concern at estimated levels of intake as flavouring substances” based on the MSDI approach. For three substances [FL-no: 13.134, 14.045 and 14.046], additional toxicological data are still required. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been evaluated, and the information is considered adequate for all the substances.

Summary

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 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 CEF Panel was requested to consider the Joint FAO/WHO Expert Committee on Food Additives (the JECFA) evaluations of flavouring substances assessed since 2000, and to decide whether no further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. These flavouring substances are listed in the Register, which was adopted by Commission Decision 1999/217/EC and its consecutive amendments.

In the previous version of Flavouring Group Evaluation 77 (FGE.77), EFSA considered 22 flavouring substances from a group of flavouring substances consisting of pyridine, pyrrole and quinoline derivatives evaluated by the JECFA at its 63rd meeting.

This revision is made due to new 90-day studies provided for isoquinoline [FL-no: 14.001], pyrrole [FL-no: 14.041] and 2-acetylpyrrole [FL-no: 14.047]. The data on 2-acetylpyrrole should also cover 2-propionylpyrrole [FL-no: 14.068]. Further, additional genotoxicity data on 6-methylquinoline [FL-no: 14.042] have also become available.

The present consideration therefore concerns these additional data and will be considered in relation to the European Food safety Authority (EFSA) evaluation of 24 pyridine, pyrrole, indole and quinoline derivatives evaluated in the Flavouring Group Evaluation 24, Revision 2 (FGE.24Rev2).

The JECFA evaluated two substances [FL-no: 13.134 and 14.030] via the B-side of the Procedure and 20 substances via the A-side.

The Panel agrees with the way the application of the Procedure has been applied by the JECFA for four of the 22 substances. Three of these four substances, methyl nicotinate [FL-no: 14.071], indole [FL-no: 14.007] and 3-methylindole [FL-no: 14.004], were evaluated by the JECFA on the A-side of the Procedure, as they were anticipated to be metabolised to innocuous products. For these three substances, EFSA agreed no safety concern at step A3 of the Procedure, as the intake is below the threshold of the structural class. For the fourth substance, 2-pyridine methanethiol [FL-no: 14.030], for which EFSA agrees with the JECFA that it should be evaluated through the B-side of the Procedure, a NOAEL was derived from a 90-day study.

The Panel concluded, contrary to the JECFA, that 6-methylquinoline [FL-no: 14.042] (evaluated via the B-side by the JECFA) should not be evaluated through the Procedure due to concern with respect to genotoxicity in vitro.

Also for 1-furfurylpyrrole [FL-no: 13.134], EFSA disagree with the JECFA, as the 90-day feeding study in rats was considered a poorly reported old study, the quality of which cannot be assessed.

For the remaining 16 substances the Panel, in contrast to the JECFA, did not anticipate that they will be metabolised to innocuous products and accordingly concluded that they should be evaluated along the B-side of the Procedure. However, in FGE.77, for 10 [FL-no: 14.038, 14.039, 14.058, 14.059, 14.060, 14.061, 14.065, 14.066, 14.072 and 14.164] of these 16 JECFA-evaluated pyridine derivatives evaluated via the B-side of the Procedure by EFSA, NOAELs could be derived to provide adequate margins of safety and the Panel agrees with the JECFA conclusion “no safety concern at estimated levels of intake as flavouring substances” based on the MSDI approach.

In previous version of FGE.77 it was concluded that for pyrrole and the five pyrrole derivatives as well as for isoquinoline [FL-no: 13.134, 14.001, 14.041, 14.045, 14.046, 14.047 and 14.068], No Observed Adverse Effect Levels (NOAELs) could not be derived as such or for structurally related substances. Accordingly, additional toxicological data were required for these seven substances in FGE.77.

Since publication of FGE.77, three 90-day studies have become available for isoquinoline [FL-no: 14.001], pyrrole [FL-no: 14.041] and 2-acetylpyrrole [FL-no: 14.047] and NOAELs to provide adequate margin of safety are derived to cover these three substances as well as the structurally related 2-propionylpyrrole [FL-no: 14.068].

So, in total, for 15 substances [FL-no: 14.001, 14.030, 14.038, 14.039, 14.041, 14.047, 14.058, 14.059, 14.060, 14.061, 14.065, 14.066, 14.068, 14.072 and 14.164], evaluated via the B-side of the Procedure by EFSA, NOAELs could be derived to provide adequate margins of safety.

In order to determine whether the conclusion for the 22 JECFA evaluated 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 tests are available for the 22 JECFA- evaluated substances.

Thus, for three substances [FL-no: 13.134, 14.045 and 14.046] the Panel has reservations as additional toxicological data are still required. For one substance, 6-methylquinoline [FL-no: 14.042], the Panel concluded that the Procedure should not be applied until adequate genotoxicity data become available. For the remaining 18 JECFA evaluated pyridine, pyrrole and quinoline derivatives [FL-no: 14.001, 14.004, 14.007, 14.030, 14.038, 14.039, 14.041, 14.047, 14.058, 14.059, 14.060, 14.061, 14.065, 14.066, 14.068, 14.071, 14.072 and 14.164] the Panel agrees with the JECFA conclusion “no safety concern at estimated levels of intake as flavouring substances” based on the MSDI approach.

Keywords
pyridine, FGE.77, pyrrole, quinoline, JECFA, 63rd meeting, FGE.24Rev2
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Number of Pages
50