Scientific Opinion on Flavouring Group Evaluation 21, Revision 4 (FGE.21Rev4): Thiazoles, thiophenes, thiazoline and thienyl derivatives from chemical groups 29 and 30

Abstract

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 59 flavouring substances in the Flavouring Group Evaluation 21, Revision 4, using the Procedure in Commission Regulation (EC) No 1565/2000. This revision is made due to the inclusion of the assessment of new toxicity data on one supporting substance 5,6-dihydro-2,4,6-tris(2-methylpropyl)-4H-1,3,5-dithiazine , which is considered to be structurally related to the candidate substances 2-butyl-4-methyl(4H)pyrrolidino[1,2d]-1,3,5-dithiazine .042], dihydro-2,4,6-triethyl-1,3,5(4H)-dithiazine .054], 2,4-dimethyl(4H)pyrrolidino[1,2e]-1,3,5-dithiazine .055], 4,6-dimethyl-2-(1-methylethyl)dihydro-1,3,5-dithiazine .057], 2-isobutyldihydro-4,6-dimethyl-1,3,5-dithiazine [FLno: 15.079] and ethyl thialdine . Furthermore, new in vitro genotoxicity studies have become available on the supporting substance 2-acetyl-2-thiazoline .010], which is considered to be structurally related to and a supportive substance for 2-methyl-2-thiazoline . Eighteen of the original 59 candidate substances 15.042, 15.043, 15.064, 15.070, 15.072, 15.077, 15.088, 15.090, 15.091, 15.092, 15.094, 15.099, 15.106, 15.107, 15.114, 15.129 and 15.133], for which additional data were requested, are no longer supported by Industry for use as flavouring substances in Europe and will therefore not be considered any further. Therefore, FGE.21Rev4 will only deal with 41 candidate substances. Two of the substances, 3-thiazolines, 2,4-dimethyl-3-thiazoline .060] and 2-isobutyl-3-thiazoline [FLno: 15.119], were considered to have genotoxic potential. The remaining 39 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 32 flavouring substances 15.039, 15.044, 15.050, 15.051, 15.052, 15.054, 15.055, 15.057, 15.058, 15.061, 15.062, 15.063, 15.067, 15.068, 15.069, 15.071, 15.078, 15.079, 15.080, 15 All candidate substances are five-or six-member sulphur-containing heterocyclic compounds, some of which also contain nitrogen. They have been divided into two main groups, those with an aromatic ring (33 candidate substances) (Group A) and those with a non-aromatic ring structure (eight candidate substances) (Group B). All are ring-substituted with one or more of the substituents alkyl, alkenyl, aryl, alcohol, keto and thio. For assessment purposes, the following further subdivision of groups (A) and (B) has been made: Thirty-four of the candidate substances belong to structural class II and seven belong to structural class III.Thirty-one of the candidate substances have been reported to occur naturally in a wide range of foods.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. Howev...

Flavouring Group Evaluation 21 Revision 6 (FGE.21Rev6): thiazoles, thiophenes, thiazoline and thienyl derivatives from chemical groups 29 and 30

“…In FGE.21Rev4 (EFSA CEF Panel, 2013a ), based on experimental data on the supporting substance 2‐acetyl‐2‐thiazoline [FL‐no: 15.010], the CEF Panel concluded that 2‐methyl‐2‐thiazoline [FL‐no: 15.086] does not give rise to concern with respect to genotoxicity and it can accordingly be evaluated using the Procedure. In the same opinion, it was indicated that no data were provided for the substances in subgroup B‐III, because their evaluation was not supported by Industry (EFSA CEF Panel, 2013a ). Therefore, no genotoxicity data were available for the evaluation of 2,4‐dimethyl‐3‐thiazoline [FL‐no: 15.060] and 2‐isobutyl‐3‐thiazoline [FL‐no: 15.119].…”

“…Therefore, no further data were submitted (DG SANCO, 2012, 2013) and these substances will not be considered any further (the 18 substances are listed in Table 2 ). Therefore, in FGE.21Rev4, the CEF Panel evaluated 41 substances (EFSA CEF Panel, 2013a ).…”

“…The substance 2‐methyl‐2‐thiazoline [FL‐no: 15.086] in subgroup B‐II was evaluated in FGE.21Rev4 (EFSA CEF Panel, 2013a ), based on additional data on the supporting substance 2‐acetyl‐2‐thiazoline [FL‐no: 15.010] from FGE.93Rev1 (EFSA CEF Panel, 2013c ).…”