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.