Toxicological Threshold Of Concern Research Articles

Scientific Opinion on Flavouring Group Evaluation 63, Revision 4 (FGE.63Rev4): consideration of aliphatic secondary saturated and unsaturated alcohols, ketones and related esters evaluated by JECFA (59th and 69th meetings) structurally related to flavouring substances evaluated by EFSA in FGE.07Rev6.

The EFSA Panel on Food Additives and Flavourings was requested to evaluate 43 flavouring substances assigned to the Flavouring Group Evaluation 63 (FGE.63), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Twenty‐nine substances have already been considered in FGE.63 and its revisions ([FL‐no: 02.023, 02.099, 02.104, 02.136, 02.155, 02.252, 07.015, 07.069, 07.081, 07.099, 07.100, 07.101, 07.102, 07.114, 07.123, 07.151, 07.190, 07.240, 07.247, 07.249, 07.256, 09.281, 09.282, 09.657, 09.658, 09.923, 09.924, 09.925 and 09.936]). The remaining 14 flavouring substances have been cleared with respect to genotoxicity in FGE.204Rev1 ([FL‐no: 02.102, 02.193, 07.044, 07.048, 07.082, 07.104, 07.105, 07.106, 07.107, 07.121, 07.139, 07.177, 07.188 and 07.244]) and they are considered in this revision 4 of FGE.63. The substances were evaluated through a stepwise approach that integrates information on the structure–activity relationships, intake from current uses, toxicological threshold of concern (TTC) and available data on metabolism and toxicity. The Panel concluded that none of these 43 substances gives rise to safety concerns at their levels of dietary intake, when estimated on the basis of the ‘Maximised Survey‐derived Daily Intake’ (MSDI) approach. Besides the safety assessment of the flavouring substances, the specifications for the materials of commerce have also been considered and found adequate for 43 flavouring substances. However, for 14 of these flavouring substances in the present revision and for 10 of the substances in the previous revision (FGE.63Rev3), the ‘modified Theoretical Added Maximum Daily Intakes’ (mTAMDIs) values are equal to or above the TTCs for their structural classes (I and II). For 15 substances previously evaluated in FGE.63Rev3, use levels are still needed to calculate the mTAMDI estimates. Therefore, in total for 39 flavouring substances, more data on uses and use levels should be provided to finalise their safety evaluations.

Scientific Opinion on Flavouring Group Evaluation 7, Revision 6 (FGE.07Rev6): saturated and unsaturated aliphatic secondary alcohols, ketones and esters of secondary alcohols and saturated linear or branched-chain carboxylic acids from chemical group 5.

The EFSA Panel on Food Additives and Flavourings was requested to evaluate 55 flavouring substances assigned to the Flavouring Group Evaluation 07 (FGE.07), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Fifty‐three substances have already been considered in FGE.07 and its revisions. This revision 6 includes two additional substances which have been cleared with respect to genotoxicity in FGE.201Rev2 (4‐methyl‐3‐hepten‐5‐one [FL‐no: 07.261]) and FGE.204Rev1 (non‐2‐en‐4‐one, [FL‐no: 07.187]). The substances were evaluated through a stepwise approach that integrates information on the structure–activity relationships, intake from current uses, toxicological threshold of concern (TTC) and available data on metabolism and toxicity. The Panel concluded that none of the 55 substances gives rise to safety concerns at their levels of dietary intake, when estimated on the basis of the ‘Maximised Survey‐derived Daily Intake’ (MSDI) approach. Besides the safety assessment of the flavouring substances, the specifications for the materials of commerce have also been considered and found adequate. Normal and maximum use levels were available for all flavouring substances. For 52 substances, including the newly included substances [FL‐no: 07.187 and 07.261], their ‘modified Theoretical Added Maximum Daily Intakes’ (mTAMDIs) estimates were above the TTC for their structural classes (I and II). Therefore, for these 52 flavouring substances, more detailed data on uses and use levels should be provided to finalise their safety evaluations.

Scientific Opinion on Flavouring Group Evaluation 13 Revision 3 (FGE.13Rev3): furfuryl and furan derivatives with and without additional side-chain substituents and heteroatoms from chemical group 14.

The Panel on Food additives and Flavourings of the EFSA was requested to update Flavouring Group Evaluation 13 using the Procedure as outlined in Commission Regulation (EC) No 1565/2000, to include an evaluation of the flavouring substances 2‐ethyl‐5‐methylfuran [FL‐no: 13.125] and 2‐octylfuran [FL‐no: 13.162]. FGE.13 revision 3 (FGE.13Rev3) deals with 26 flavourings substances of which 24 have been already evaluated to be of no safety concern. For [FL‐no: 13.125] and [FL‐no: 13.162], a concern for genotoxicity was raised in FGE.13Rev1. This concern could be ruled out based on new genotoxicity data on supporting substances in FGE.67Rev3. Subsequently, [FL‐no: 13.125 and 13.162] were evaluated, through a stepwise approach that integrates intake from current uses, toxicological threshold of concern (TTC), and available data on metabolism and toxicity, along the B‐side of the Procedure, making use of a BMDL of 8.51 mg/kg body weight (bw) per day. The Panel derived this BMDL from an oral subchronic toxicity study with the supporting substance 2‐pentylfuran [FL‐no: 13.059]. Using this BMDL, for [FL‐no: 13.125 and 13.162], adequate margins of safety were calculated based on the MSDI approach. The Panel concluded that the 26 candidate substances in FGE.13Rev3 do not give rise to safety concerns at their levels of dietary intake, when estimated on the basis of the MSDI approach. Adequate specifications for the materials of commerce have been provided for all 26 substances. Data on uses and use levels are needed for [FL‐no: 13.130]. For 21 flavouring substances [FL‐no: 13.011, 13.102, 13.108, 13.113, 13.114, 13.122, 13.125, 13.127, 13.129, 13.132, 13.133, 13.135, 13.136, 13.139, 13.141, 13.143, 13.146, 13.149, 13.162, 13.178 and 13.185], the mTAMDI intake estimates are above the TTC for their structural class and more reliable data on uses and use levels are required to finalise their evaluation.

Analysis of PBT and PET cyclic oligomers in extracts of coffee capsules and food simulants by a HPLC-UV/FLD method

A HPLC-UV/FLD method was validated for the quantification of six polyethylene terephthalate (PET) and four polybutylene terephthalate (PBT) oligomers. PBT oligomers are EU regulated, while the PET ones are considered non-intentionally added substances (NIAS). LOQs were higher than 0.4 and 3.5 μg kg−1 for the simulants and in the polymer extracts, respectively. Recoveries ranged from 95 to 114 % with RSDs below 12%. Migration testing of PBT and polypropylene coffee capsules were performed with H2O and simulant C, and extracts were obtained with accelerated solvent extraction (ASE). For the latter legislative limits weren’t surpassed. As no migration limits are existing for the analytes, both EFSA’s toxicological threshold of concern (TTC) and sum of oligomers approaches were applied. The majority of oligomers were below the TTC (90 µg/person/day), but the limit value of 50 µg/kg food was surpassed for some capsules, which indicates a significant intake in both single and multiple consumption.

Scientific Opinion on Flavouring Group Evaluation 91, Revision 3 (FGE.91Rev3): consideration of aliphatic, aromatic and α,β-unsaturated sulfides and thiols evaluated by JECFA (53rd, 61st, 68th and 76th meetings), structurally related to substances in FGE.08Rev5.

The EFSA Panel on Food Additives and Flavourings was requested to evaluate 49 flavouring substances assigned to the Flavouring Group Evaluation 91 (FGE.91), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Forty‐four substances have been considered in FGE.91 and its revisions (FGE.91Rev1 and FEG.91Rev2). With regard to the remaining five flavouring substances considered in this revision 3 of FGE.91: two ([FL‐no: 12.065 and 12.079]) have been cleared with respect to genotoxicity in FGE.201Rev2; two ([FL‐no: 12.169 and 12.241]) were originally allocated to FGE.74Rev4 and one ([FL‐no: 12.304]) to FGE.08Rev5. The Panel considered the flavouring substance [FL‐no: 12.169] representative for the tertiary monothiols [FL‐no: 12.038, 12.085, 12.137, 12.138, 12.145, 12.252, 12.259, 12.241 and 12.304]. The substances were evaluated through a stepwise approach that integrates information on the structure–activity relationships, intake from current uses, toxicological threshold of concern (TTC), and available data on metabolism and toxicity. The Panel concluded that none of these 49 substances gives rise to safety concerns at their levels of dietary intake, estimated on the basis of the ‘Maximised Survey‐derived Daily Intake’ (MSDI) approach. The specifications for the materials of commerce have also been considered and found adequate for all 49 flavouring substances. For five substances [FL‐no: 12.077, 12.162, 12.265, 12.267 and 17.036], evaluated through the Procedure in FGE.91Rev2, no normal and maximum use levels are available. For 10 substances [FL‐no: 12.065, 12.038, 12.079, 12.108, 12.139, 12.264, 12.274, 12.252, 12.284 and 12.304], the modified Theoretical Added Maximum Daily Intake (mTAMDI) intake estimates are above the TTC for their structural class. Therefore, for these 15 substances, more detailed data on uses and use levels should be provided in order to refine their exposure assessments and to finalise their safety evaluations.

Scientific Opinion on Flavouring Group Evaluation 72, Revision 2 (FGE.72Rev2): consideration of aliphatic, branched-chain saturated and unsaturated alcohols, aldehydes, acids and related esters evaluated by JECFA (61st, 68th and 69th meetings) and structurally related to flavouring substances in FGE.05Rev3.

The EFSA Panel on Food Additives and Flavourings was requested to evaluate 31 flavouring substances assigned to the Flavouring Group Evaluation 72 (FGE.72), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Twenty‐three substances have already been considered in FGE.72 and FGE.72Rev1 ([FL‐no: 02.011, 02.012, 02.027, 02.029, 02.058, 02.076, 02.109, 05.020, 05.021, 05.124, 05.148, 05.169, 08.036, 08.044, 08.047, 08.055, 08.064, 08.070, 08.079, 09.273, 09.408, 09.931 and 16.001]). The remaining eight flavouring substances have been cleared with respect to genotoxicity in FGE.200Rev1 ([FL‐no: 05.114]) and FGE.201Rev2 ([FL‐no: 02.174, 05.033, 05.090, 05.095, 05.105, 05.107 and 05.126]) and they are considered in this revision 2 of FGE.72. The substances were evaluated through a stepwise approach that integrates information on the structure–activity relationships, intake from current uses, toxicological threshold of concern (TTC), and available data on metabolism and toxicity. The Panel concluded that none of these 31 substances gives rise to safety concerns at their levels of dietary intake, estimated on the basis of the ‘Maximised Survey‐derived Daily Intake’ (MSDI) approach. Besides the safety assessment of the flavouring substances, the specifications for the materials of commerce have also been considered and found adequate for all 31 flavouring substances. For 21 substances, evaluated through the Procedure in the previous revision (FGE.72Rev1), no normal and maximum use levels are available. For four substances, the modified Theoretical Added Maximum Daily Intake (mTAMDI) intake estimates are equal to ([FL‐no: 05.090]) or above ([FL‐no: 05.107, 05.105, 05.033]) the TTC for their structural class. Therefore, for these 25 substances more detailed data on uses and use levels should be provided in order to refine their exposure assessments and to finalise their safety evaluations.

Scientific Opinion on Flavouring Group Evaluation 71 Revision 1 (FGE.71Rev1): consideration of aliphatic, linear, α,β‐unsaturated alcohols, aldehydes, carboxylic acids, and related esters evaluated by JECFA (63rd and 69th meeting) structurally related to flavouring substances evaluated in FGE.05Rev3

The EFSA Panel on Food Additives and Flavourings was requested to evaluate 39 flavouring substances assigned to the Flavouring Group Evaluation 71 (FGE.71), using the Procedure in Commission Regulation (EC) No 1565/2000. Nine substances have already been considered in FGE.71 [FL‐no: 08.054, 08.073, 08.123, 09.037, 09.156, 09.157, 05.158, 09.235, 09.239]. The remaining 30 substances [FL‐no: 02.020, 02.050, 02.090, 02.112, 02.137, 02.156, 02.210, 05.037, 05.060, 05.070, 05.073, 05.076, 05.078, 05.102, 05.109, 05.150, 05.171, 05.179, 09.276, 09.277, 09.303, 09.385, 09.394, 09.395, 09.396, 09.397, 09.398, 09.399, 09.678 and 09.841] have been cleared with respect to genotoxicity in FGE.200Rev1 and they are considered in this revision. The substances were evaluated through a stepwise approach that integrates information on the structure–activity relationships, intake from current uses, toxicological threshold of concern (TTC), and available data on metabolism and toxicity. The Panel concluded that none of the 39 substances gives rise to safety concerns at their levels of dietary intake, estimated on the basis of the ‘Maximised Survey‐derived Daily Intake’ (MSDI) approach. Besides the safety assessment of the flavouring substances, the specifications for the materials of commerce have also been considered and found adequate, except for [FL‐no: 08.073 and 09.235]. For these two substances, data on the composition of the stereoisomeric mixture should be requested. Normal and maximum use levels should be provided for nine flavouring substances [FL‐no: 08.054, 08.073, 08.123, 09.037, 09.156, 09.157, 05.158, 09.235, 09.239]. For two flavouring substances [FL‐no: 02.020 and 05.076], the ‘modified Theoretical Added Maximum Daily Intake’ (mTAMDI) estimates are above the TTC for their structural class I. Therefore, additional information on uses and use levels should be provided for these eleven substances in order to finalise their evaluation.

Scientific Opinion on Flavouring Group Evaluation 73, Revision 5 (FGE.73Rev5): consideration of alicyclic alcohols, aldehydes, acids and related esters evaluated by JECFA (59th, 63rd and 86th meeting) and structurally related to substances evaluated in FGE.12Rev5

The EFSA Panel on Food Additives and Flavourings was requested to evaluate 24 flavouring substances assigned to the Flavouring Group Evaluation 73 (FGE.73), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Twenty-three substances have already been considered in FGE.73 and its four revisions ([FL-no: 02.114, 02.141, 05.098, 05.112, 08.067, 09.289, 09.488, 09.534, 09.615, 05.119, 05.123, 08.034, 08.060, 09.028, 09.536, 05.104, 09.034, 09.712, 09.305, 02.060, 02.091, 09.278, 09.302]). The remaining substance myrtenal [FL-no: 05.106] has been cleared with respect to genotoxicity in FGE.208Rev3 and is considered in this revision 5 of FGE.73. The substances were evaluated through a stepwise approach that integrates information on the structure–activity relationships, intake from current uses, toxicological threshold of concern (TTC), and available data on metabolism and toxicity. The Panel concluded that none of these 24 substances gives rise to safety concerns at their levels of dietary intake, estimated on the basis of the ‘Maximised Survey-derived Daily Intake’ (MSDI) approach. Besides the safety assessment of the flavouring substances, the specifications for the materials of commerce have also been considered and found adequate for 23 substances. For [FL-no: 09.278], the stereoisomeric composition is not specified. For two substances [FL-no: 09.034, and 09.712], the modified Theoretical Added Maximum Daily Intake (mTAMDI) estimates are above the TTC for their structural class (I). For 17 substances evaluated through the Procedure, no normal and maximum use levels are available. Therefore, for these 19 substances, more detailed data on uses and use levels should be provided in order to refine their exposure assessments and to finalise their safety evaluations.

Scientific Opinion on Flavouring Group Evaluation 61 Revision 2 (FGE.61Rev2): consideration of aliphatic acetals evaluated by JECFA (57th, 63rd and 68th meetings) structurally related to acetals evaluated by EFSA in FGE.03Rev2.

The EFSA Panel on Food Additives and Flavourings was requested to evaluate 12 flavouring substances attributed to the Flavouring Group Evaluation 61 (FGE.61), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Nine substances have already been considered in FGE.61 and FGE.61Rev1 [FL‐no: 06.001, 06.004, 06.005, 06.008, 06.009, 06.015, 06.028, 06.037, 06.081]. The remaining three substances [FL‐no: 06.025, 06.031 and 06.072] have been cleared with respect to genotoxicity in FGE.200Rev1 and are considered in this revision 2 of FGE.61. The substances were evaluated through a stepwise approach that integrates information on the structure–activity relationships, intake from current uses, toxicological threshold of concern (TTC), and available data on metabolism and toxicity. The Panel concluded that none of the 12 substances gives rise to safety concerns at their levels of dietary intake, estimated on the basis of the ‘Maximised Survey‐derived Daily Intake’ (MSDI) approach. Besides the safety assessment of the flavouring substances, the specifications for the materials of commerce have also been considered and found adequate. For nine flavouring substances [FL‐no: 06.001, 06.004, 06.005, 06.008, 06.009, 06.015, 06.028, 06.037 and 06.081], use levels are still needed to calculate the modified Theoretical Added Maximum Daily Intake (mTAMDI) values in order to identify those flavouring substances that need more refined exposure assessment and to finalise the evaluation accordingly.

Scientific Opinion on Flavouring Group Evaluation 70, Revision 1 (FGE.70Rev1): consideration of aliphatic, linear, α,β‐unsaturated, di‐ and trienals and related alcohols, acids and esters evaluated by JECFA (61st‐68th‐69th meeting)

The EFSA Panel on Food Additives and Flavourings was requested to evaluate 29 flavouring substances attributed to the Flavouring Group Evaluation 70 (FGE.70), using the Procedure in Commission Regulation (EC) No 1565/2000. Seven substances have already been considered in FGE.70 [FL‐no: 08.085, 09.194, 09.260, 09.300, 09.371, 09.639 and 09.840]. The remaining 22 substances [FL‐no: 02.049, 05.058, 05.111, 05.120, 05.172, 09.947, 02.139, 02.153, 02.162, 02.188, 05.057, 05.064, 05.071, 05.084, 05.101, 05.108, 05.125, 05.127, 05.140, 05.141, 05.173 and 09.573] have been cleared with respect to genotoxicity in FGE.200Rev1 and FGE.203Rev2 and are considered in this revision. The substances were evaluated through a stepwise approach that integrates information on the structure–activity relationships, intake from current uses, toxicological threshold of concern (TTC), and available data on metabolism and toxicity. The Panel concluded that none of the 29 substances gives rise to safety concerns at their levels of dietary intake, estimated on the basis of the ‘Maximised Survey‐derived Daily Intake’ (MSDI) approach. Besides the safety assessment of the flavouring substances, the specifications for the materials of commerce have also been considered and found adequate, except for [FL‐no: 09.371 and 09.840]. For these two substances, data on the composition of the stereoisomeric mixture should be requested. Data on the identity and contents of secondary components should be requested for [FL no: 09.260]. Normal and maximum use levels should be provided for seven flavouring substances [FL‐no: 08.085, 09.194, 09.260, 09.300, 09.371, 09.639 and 09.840]. For six flavouring substances [FL‐no: 05.057, 05.058, 05.111, 05.120, 05.172 and 09.947] further information is required based on the comparison of the ‘modified Theoretical Added Maximum Daily Intakes’ (mTAMDIs) with the TTCs. This includes more reliable data on use and use levels and then, if required, additional toxicological data.

Scientific Opinion on Flavouring Group Evaluation 5, Revision 3 (FGE.05Rev3): Branched‐ and straight‐chain unsaturated aldehydes, dienals, unsaturated and saturated carboxylic acids and related esters with saturated and unsaturated aliphatic alcohols and a phenylacetic acid related ester from chemical groups 1, 2, 3, 5 and 15

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate 54 flavouring substances attributed to the Flavouring Group Evaluation 05 (FGE.05), using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. This Revision 3 includes 17 additional substances which have been cleared with respect to genotoxicity in FGE.200Rev1 ([FL‐no: 02.192, 02.231, 05.072, 05.144, 05.184, 05.189, 05.190, 05.191, 05.195, 09.247, 09.400, 09.866, 09.948]) and in FGE.203Rev2 ([FL‐no: 05.081, 05.186, 05.194, 05.196]). The substances were evaluated through a stepwise approach that integrates information on the structure–activity relationships, intake from current uses, toxicological threshold of concern (TTC), and available data on metabolism and toxicity. The Panel concluded that none of the 54 substances gives rise to safety concern at their levels of dietary intake, estimated on the basis of the ‘Maximised Survey‐derived Daily Intake’ (MSDI) approach. Besides the safety assessment of the flavouring substances, the specifications for the materials of commerce have also been considered and found adequate, except for 10 substances ([FL‐no: 08.072, 08.083, 08.101, 08.119, 08.120, 09.181, 09.329, 09.335, 09.379 and 09.637]) for which quantitative figures on the composition of stereoisomeric mixtures are missing and for [FL‐no: 09.578] complete specifications should be provided. Normal and maximum use levels were not available for [FL‐no: 08.072, 08.083, 08.101, 08.119, 08.120, 09.287, 09.326 and 09.578]. Except for flavouring substances [FL‐no: 05.072, 05.081, 05.186, 05.194, 05.196, 09.934 and 09.942], more reliable intake data should be requested for all the 46 flavouring substances, for which use levels were submitted, as their modified Theoretical Added Maximum Daily Intake (mTAMDI) exposure estimates are above the threshold of concern for structural classes I and II. This would include more reliable intake data and then, if required, additional toxicological data.

Scientific Opinion on Flavouring Group Evaluation 7, Revision 5 (FGE.07Rev5): saturated and unsaturated aliphatic secondary alcohols, ketones and esters of secondary alcohols and saturated linear or branched-chain carboxylic acids from chemical group 5.

The EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids was requested to evaluate 53 flavouring substances attributed to the Flavouring Group Evaluation 07, including four new substances but‐3‐en‐2‐ol, non‐1‐en‐e‐ol, hex‐1‐en‐3‐one and 1‐nonene‐3‐one [FL‐nos: 02.131, 02.187, 07.161 and 07.210] in this Revision 5, using the Procedure in Commission Regulation (EC) No 1565/2000. None of the 53 substances was considered to have genotoxic potential. The substances were evaluated through a stepwise approach that integrates information on the structure–activity relationships, intake from current uses, toxicological threshold of concern (TTC), and available data on metabolism and toxicity. The Panel concluded that all 53 substances do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the ‘Maximised Survey‐derived Daily Intake’ (MSDI) approach. Besides the safety assessment of the flavouring substances, the specifications for the materials of commerce have also been considered and found adequate. For 50 substances, further information is required based on comparison of the ‘modified Theoretical Added Maximum Daily Intakes’ (mTAMDIs) with the TTCs. This would include more reliable intake data and then, if required, additional toxicological data.

Scientific Opinion on Flavouring Group Evaluation 63, Revision 3 (FGE.63Rev3): aliphatic secondary alcohols, ketones and related esters evaluated by JECFA (59th and 69th meetings) structurally related to saturated and unsaturated aliphatic secondary alcohols, ketones and esters of secondary alcohols and saturated linear or branched-chain carboxylic acids evaluated by EFSA in FGE.07Rev4.

The EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids 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 1565/20001. The present consideration concerns a group of 29 aliphatic secondary alcohols, ketones and related esters evaluated by JECFA at the 59th and 69th meetings in 2002 and 2008. This revision is made due to the inclusion of nine additional substances cleared for genotoxicity concern in FGE.205 Revision 1. The substances were 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. The Panel agrees with the application of the Procedure as performed by JECFA for all 29 substances considered in this FGE. For all substances, the Panel concludes that there is ‘no safety concern at the estimated levels of intake as flavouring substances based on the MSDI approach’. For all 29 substances, the specifications for the materials of commerce have also been considered and found adequate. Ten out of the 14 substances for which use levels became available exceed the modified theoretical added maximum daily intake (mTAMDI) and more reliable exposure data are required to finalise their evaluation. On the basis of such data, additional toxicological data might become necessary. For 15 substances, use levels are needed to calculate the mTAMDIs in order to identify those flavouring substances that need more refined exposure assessment to finalise the evaluation.

Scientific opinion on Flavouring Group Evaluation 313, (FGE.313): α,β‐unsaturated 3(2H)‐furanone derivatives from chemical group 13

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of EFSA was requested to evaluate three flavouring substances, 2,5-dimethyl-4-ethoxyfuran-3(2H)-one [FL-no: 13.117], 2,5-dimethylfuran-3(2H)-one [FL-no: 13.119] and 4-Acetyl-2,5-dimethylfuran-3(2H)-one [FL-no: 13.175] in the Flavouring Group Evaluation 313 (FGE.313), using the Procedure in Commission Regulation (EC) No 1565/2000. The substances were considered in FGE.220, and revisions hereof, not to have genotoxic potential. They were evaluated through a stepwise approach 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 the two flavouring substances [FL-no: 13.117, 13.119] do not give rise to safety concerns at their level of dietary intake, estimated on the basis of the Maximised Survey-derived Daily Intake (MSDI) approach. For the flavouring substance [FL-no: 13.175], toxicity data are required. Besides the safety assessment of the flavouring substance, the specifications for the materials of commerce have also been considered. Adequate specifications including complete purity criteria and identity for the materials of commerce have been provided for the three flavouring substances. The Panel concluded that for 2,5-dimethyl-4-ethoxyfuran-3(2H)-one [FL-no: 13.117], 2,5-dimethylfuran-3(2H)-one [FL-no: 13.119] and 4-acetyl-2,5-dimethylfuran-3(2H)-one [FL-no: 13.175] for which the Modified Theoretical Added Maximum Daily Intakes (mTAMDIs) are above the thresholds for their structural class, more reliable exposure data are required for a re-evaluation.

Scientific Opinion on Flavouring Group Evaluation 75, Revision 1 (FGE.75Rev1): Consideration of tetrahydrofuran derivatives evaluated by JECFA (63rd meeting) structurally related to tetrahydrofuran derivatives evaluated by EFSA in FGE.33 (2008)

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) of the EFSA 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 10 tetrahydrofuran derivatives and one furanone derivative evaluated by the JECFA at the 63rd meeting in 2004. This revision is made due to additional toxicity data have become available for anhydrolinalool oxide (5) [FL-no: 13.097]. The substances were 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. The JECFA concluded all the 11 tetrahydrofuran derivatives at step A3. The Panel agrees with the application of the Procedure as performed by the JECFA for 10 of the 11 substances. For the remaining substance [FL-no: 13.097] the Panel did not find that it could be metabolised to innocuous products and should accordingly be evaluated via the B-side of the Procedure scheme. A no observed adverse effect level (NOAEL) of 52 mg/kg body weight was derived from a 90-day study in rats and compared with an exposure estimate of 0.9 μg/ capita / per day for anhydrolinalool oxide a margin of safety of 3.5 × 106 was calculated. Accordingly, the Panel agrees with the JECFA conclusion ‘No safety concern at estimated level of intake as flavouring substances’ based on the maximised survey-derived daily intake (MSDI) approach. The specifications for the materials of commerce have also been considered and for all 11 substances, the information is adequate.

Flavouring Group Evaluation 51, Revision 2 (FGE.51Rev2): Consideration of alicyclic ketones and secondary alcohols and related esters evaluated by JECFA (59th meeting) structurally related to alicyclic ketones secondary alcohols and related esters in FGE.09Rev6 (2015)

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF Panel) 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 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 24 alicyclic ketones and secondary alcohols and related esters evaluated by JECFA (59th meeting in 2002 and 63rd meeting in 2004). This revision is made due to inclusion of four additional substances cleared for genotoxicity concern compared to the previous version [FL-no: 07.033, 07.094, 07.112 and 07.140]. The Panel concluded for 23 substances that these do not give rise to safety concerns at the levels of dietary intake, estimated on the basis of the MSDI approach [FL-no: 02.209, 07.034, 07.035, 07.045, 07.094, 07.095, 07.098, 07.112, 07.126, 07.129, 07.140, 07.148, 07.149, 07.172, 07.179, 07.180, 07.257, 09.027, 09.140, 09.160, 09.230, 09.464 and 09.930]. However, for all substances use levels are needed to calculate the mTAMDIs in order to identify those flavouring substances that need more refined exposure assessment and to finalise the evaluation. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have been considered and are adequate for 21 substances. For [FL-no: 07.094 and 07.112], information on the solubility in water and ethanol is missing. The chemical identity could not be unambiguously confirmed for substance [FL-no: 07.033]. Therefore the Panel could not consider the JECFA evaluation of this substance and information as to its chemical identity should be submitted.

Scientific Opinion on Flavouring Group Evaluation 99 Revision 1 (FGE.99Rev1): Consideration of furanone derivatives evaluated by the JECFA (63rd, 65th and 69th meetings)

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 (the 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 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 six furanone derivatives evaluated by the JECFA at their 63rd, 65th and 69th meetings. This revision of FGE.99 includes the assessment of the 2,5-dimethyl-4-methoxyfuran-3(2H)-one [FL-no: 13.089] cleared for genotoxicity concern compared to the previous version. The Panel concluded that none of the six substances gives rise to safety concerns at the levels of dietary intake, estimated on the basis of the MSDI approach [FL-nos: 13.010, 13.084, 13.085, 13.089, 13.099 and 13.176]. The specifications of the materials of commerce have also been considered and are adequate for all candidate substances in this FGE. However, for all substances use levels are required to calculate the mTAMDIs in order to identify those flavouring substances that need more refined exposure assessment and to finalise the evaluation.

Scientific Opinion on Flavouring Group Evaluation 9, Revision 6 (FGE.09Rev6): Secondary alicyclic saturated and unsaturated alcohols, ketones and esters containing secondary alicyclic alcohols from chemical group 8 and 30, and an ester of a phenol derivative from chemical group 25

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 22 flavouring substances in the Flavouring Group Evaluation 9, Revision 6, using the Procedure in Commission Regulation (EC) No 1565/2000. None of the substances was considered to have genotoxic potential. 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 revision of FGE.09 includes the assessment of one additional flavouring substance, trans-3-methyl-2-(2-pentenyl)-2-cyclopenten-1-one [FL-no: 07.219]. The Panel concluded that the 22 substances [FL-nos: 02.070, 02.075, 02.135, 02.167, 06.136, 07.059, 07.109, 07.202, 07.203, 07.219, 07.255, 09.154, 09.355, 09.520, 09.618, 09.619, 09.621, 09.843, 09.870, 09.929, 09.935 and 09.949] do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. However, based on mTAMDI calculations, for 11 flavouring substances [FL-nos: 07.059, 07.109, 07.202, 07.203, 09.154, 09.520, 09.618, 09.619, 09.843, 09.935 and 09.949] more reliable exposure data are required for a re-evaluation. For two substances [FL-nos: 07.219 and 09.929] no use levels are available and these should be submitted. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have been considered. Specifications, including complete purity criteria and identity for the materials of commerce, have been provided for all candidate substances.

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)

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 [FL-no: 13.058] providing an appropriate NOAEL for the evaluation of candidate substance [FL-no: 13.058]. The Panel concluded that 11 substances [FL-nos: 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 [FL-no: 13.058], 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 [FL-nos: 13.045, 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 [FL-nos: 13.045, 13.052, 13.054, 13.059, 13.061, 13.069 and 13.083], use levels have not yet been submitted.

Scientific Opinion on Flavouring Group Evaluation 21, Revision 5 (FGE.21Rev5): Thiazoles, thiophenes, thiazoline and thienyl derivatives from chemical groups 29 and 30

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 41 flavouring substances in Flavouring Group Evaluation 21, Revision 5, using the Procedure in Commission Regulation (EC) No 1565/2000. This revision was carried out because of the inclusion of the assessment of new toxicity data on the candidate substances, 5-ethylthiophene-2-carbaldehyde [FL-no: 15.074] and 2-pentylthiophene [FL-no: 15.096]. These data on 5-ethylthiophene-2-carbaldehyde [FL-no: 15.074] should cover 2-acetylthiophene [FL-no: 15.040] and 2-propionylthiophene [FL-no: 15.097]. These data on 2-pentylthiophene [FL-no: 15.096] should cover 2-butylthiophene [FL-no: 15.045], 2-hexylthiophene [FL-no: 15.076] and 2-octylthiophene [FL-no: 15.093]. For two of the substances [FL-no: 15.060 and 15.119] the Panel concluded that additional genotoxicity data are required. 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 the 39 flavouring substances [FL-no: 15.038, 15.039, 15.040, 15.044, 15.045, 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, 15.074, 15.076, 15.078, 15.079, 15.080, 15.082, 15.084, 15.085, 15.086, 15.087, 15.089, 15.093, 15.096, 15.097, 15.098, 15.108, 15.115, 15.116, 15.118 and 15.135] do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the Maximised Survey-derived Daily Intake (MSDI) approach. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered. Adequate specifications, including complete purity criteria and identity for the materials of commerce, have been provided for all 41 candidate substances.