Scientific Opinion on Flavouring Group Evaluation 13, Revision 2 (FGE.13Rev2): Furfuryl and furan derivatives with and without additional side-chain substituents and heteroatoms from chemical group 14

2015

EFS2

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) 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 (JECFA), and to decide whether further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. 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 present consideration concerns a group of 28 furan-substituted compounds evaluated by the JECFA. This revision of FGE.67 is due to new data on toxicity for 3-(-methyl-2-furyl) butanal .058] providing an appropriate NOAEL for the evaluation of candidate substance ]. The Panel concluded that 11 substances [FLnos: 13.006, 13.021, 13.022, 13.023, 13.024, 13.031, 13.047, 13.058, 13.074, 13.116 and 13.190] do not give rise to safety concerns at the levels of dietary intake, estimated on the basis of the MSDI approach. However, based on mTAMDI calculations, for these eleven candidate substances, except .058], more reliable intake data are required for a re-evaluation. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered, which for all candidate substances are adequate. For 17 substances 13.052, 13.054, 13.059, 13.061, 13.066, 13.069, 13.070, 13.083, 13.101, 13.103, 13.105, 13.106, 13.123, 13.138, 13.148 and 13.163] a concern for genotoxicity was raised and therefore these were not evaluated using the Procedure. The Panel noted further that for 7 of these 17 substances 13.052, 13.054, 13.059, 13.061, 13.069 The 28 candidate substances considered in this FGE 13.021, 13.022, 13.023, 13.024, 13.031, 13.045, 13.047, 13.052, 13.054, 13.058, 13.059, 13.061, 13.066, 13.069, 13.070, 13.074, 13.083, 13.101, 13.103, 13.105, 13.106, 13.116, 13.123, 13.138, 13.148, 13.163 and 13.190] have been allocated to various subgroups, based on their chemical structures. These substances are structurally related to the group of 27 furfuryl and furan derivatives evaluated by EFSA in FGE.13Rev2. Part of the substances is also structurally related to a group of 33 sulphur-substituted furan derivatives used as flavouring agents, evaluated by EFSA in FGE.65Rev1 and another part is structurally related to 14 furfuryl derivatives evaluated in FGE.66Rev1.The Panel agrees with the JECFA for 17 of the substances 13.052, 13.054, 13.059, 13.061, 13.066, 13.069, 13.070, 13.083, 13.101, 13.103, 13.105, 13.106, 13.123, 13.138, 13.148 and 13.163] that these substances cannot be evaluated through the Procedure, based on concerns with respect to genotoxicity.On the basis of the new data on toxicity for 3-(5-methyl-2-furyl) butanal .058] an appropriate NOAEL of 5.9mg/kg bw per day was derived, supporting the evaluation of this candidate...

Section: Efsa Considerationsmentioning

confidence: 99%

mentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 67 Revision 2 (FGE.67Rev2): Consideration of 28 furan‐substituted compounds evaluated by JECFA at the 55th, 65th and 69th meetings (JECFA, 2001, 2006a, 2009b)

2015

EFS2

“…These metabolites are all expected to be excreted in the urine. A more detailed discussion on the metabolism of sulphur compounds can be found in FGE.13Rev2 (EFSA CEF Panel, 2011b).…”

Section: Metabolism Of Substances In Subgroup A-imentioning

confidence: 99%

“…To a very small extent ring C-oxidation may be followed by ring cleavage to yield alpha-diketone and thioamide fragments. The acyl-substituted thiazoles 15.039,15.085 and 15.116] may also be expected to undergo keto-reduction, possibly followed by conjugation, similar to acyl derivatives of furanes (EFSA CEF Panel, 2011b) and pyrazines (EFSA CEF Panel, 2011a).…”

Section: A-subgroups (Substances With Aromatic Ring Structures)mentioning

confidence: 99%

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

2013

EFS2

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...

“…The Panel concluded that all the substances in the JECFA flavouring group of sulfur-substituted furan derivatives are structurally related to a group of sulfur-containing furane derivatives evaluated within the group of 'Furfuryl and furan derivatives with and without additional side-chain substituents and heteroatoms from chemical group 14 evaluated by EFSA in the Flavouring Group Evaluation 13, Revision 2 (FGE.13Rev2; (EFSA CEF Panel, 2011).…”

Section: Efsa Considerationsmentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 65, Revision 1 (FGE.65Rev1): Consideration of sulfur‐substituted furan derivatives used as flavouring agents evaluated by JECFA (59th meeting) structurally related to a subgroup of substances within the group of ‘Furfuryl and furan derivatives with and without additional side‐chain substituents and heteroatoms from chemical group 14’ evaluated by EFSA in FGE.13Rev2 (2011)

2015

EFS2

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 substances are evaluated through a stepwise approach that integrates information on structure‐activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. FGE.65 concerns a group of 33 sulfur‐substituted furan derivatives evaluated by the JECFA at their 59th meeting. The Panel concluded in FGE.65 that the evaluation could not be finalised for four of the 33 substances [FL‐no: 13.056, 13.160, 13.193 and 13.194] due to lack of toxicity data. In the present revision of FGE.65, the toxicity data requested in FGE.65 for [FL‐no: 13.160] have now become available. These toxicity data are also considered to cover the evaluation of [FL‐no: 13.193 and 13.194], but not [FL‐no: 13.056]. Based on the new data the Panel agrees with the JECFA conclusion, ‘No safety concern at estimated levels of intake as flavouring substances’ based on the MSDI approach for 32 of the furan derivatives. For one substance [FL‐no: 13.056] a request for additional toxicity data still remains. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered and for all 33 substances, the information is adequate.