Scientific Opinion on Flavouring Group Evaluation 3, Revision 2 (FGE.03Rev2): Acetals of branched-and straight-chain aliphatic saturated primary alcohols and branched-and straight-chain saturated or unsaturated aldehydes, an ester of a hemiacetal and an orthoester of formic acid, from chemical groups 1, 2 and 4

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate one flavouring substance, acetaldehyde ethyl isopropyl acetal [FL-no: 06.137], structurally related to the 58 flavouring substances in the Flavouring Group Evaluation 03, in a Revision 2, using the Procedure in Commission Regulation (EC) No 1565/2000. None of the substances were considered to have genotoxic potential. The new substance was along with the remaining 58 substances 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 as for the other already evaluated substances that the substance [FL-no: 06.137] do not give rise to safety concern at its level of dietary intake, estimated on the basis of the MSDI approach. Besides the safety assessment of this flavouring substance, the specifications for the materials of commerce have also been considered, and since the publication of FGE.03Rev1 additional information on chirality on 30 substances is made available and has been incorporated into the present Revision 2 of FGE. 03. (C) European Food Safety Authority, 2011 The European Food Safety Authority (EFSA) asked the Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (the Panel) to provide 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 Panel was requested to evaluate 59 flavouring substances in the Flavouring Group Evaluation 03, Revision 2 (FGE.03Rev2), using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. These 59 flavouring substances belong to chemical groups 1, 2 and 4, Annex I of the Commission Regulation (EC) No 1565/2000. The present Flavouring Group Evaluation deals with 57 acetals of branched- and straight-chain aliphatic saturated primary alcohols and branched- and straight-chain saturated or unsaturated aldehydes, one orthoester of formic acid and one ester of a hemiacetal. Thirty-three of the 59 flavouring substances possess one or more chiral centres. For all of these substances the stereoisomeric composition has been specified. One of the 59 substances can exist as a geometrical isomer [FL-no:06.063] and no indication has been given that one of the possible isomers has preponderance in the commercial flavouring material. Fifty-eigth of the flavouring substances are classified into structural class I and the orthoester [FL-no:06.096] into structural class III. Forty-three of the substances in the present group of 59 substances have been reported to occur naturally in a wide range of food items. In its evaluation, the Panel as a default used the "Maximised Survey-derived Daily Intakes" (MSDIs) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Panel examined the information provided by the European Flavouring Industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate the intake by regular consumers of products flavoured at the use level reported by the Industry, especially in those cases where the annual production values were reported to be small. In consequence, the Panel had reservations about the data on use and use levels provided and the intake estimates obtained by the MSDI approach. In the absence of more precise information that would enable the Panel to make a more realistic estimate of the intakes of the flavouring substances, the Panel has decided also to perform an estimate of the daily intakes per person using a "modified Theoretical Added Maximum Daily Intake" (mTAMDI) approach based on the normal use levels reported by Industry. In those cases where the mTAMDI approach indicated that the intake of a flavouring substance might exceed its corresponding threshold of concern, the Panel decided not to carry out a formal safety assessment using the Procedure. In these cases the Panel requires more precise data on use and use levels. According to the default MSDI approach, the 59 flavouring substances have intakes in Europe from 0.001 to 14 microgram/capita/day, which are below the threshold of concern value for structural class I of 1800 microgram/person/day. Likewise the estimated level of intake for the orthoester [FL-no: 06.096] of 0.013 microgram/capita/day is below the threshold of concern for structural class III of 90 microgram/person/day. Adequately reported genotoxicity studies are only available for one of the flavouring substances. These studies do not give rise to safety concern with respect to genotoxicity of the flavouring substance in this Flavouring Group Evaluation. Consideration was given to methanol, formaldehyde, ethanol and acetaldehyde that are potential hydrolysis products of several of the acetals in the present Flavouring Group Evaluation. Because of the natural occurrence in food and the endogenous formation in humans of considerably larger amounts of these compounds, their formation from hydrolysis of the acetals were not considered to be of safety concern with respect to genotoxicity at their estimated levels of intakes, based on the MSDI approach. The 59 candidate substances are expected to be metabolised to innocuous products. There are no toxicological studies available on the 59 flavouring substances or on structurally related acetals other than data on acute toxicity. On the basis of the default MSDI approach the Panel concluded that the 57 acetals, the orthoester and the ester of a hemiacetal would not give rise to safety concerns at levels of intake arising from their use as flavouring substances. When the estimated intakes were based on the mTAMDI approach they ranged from 3 to 9500 microgram/person/day for the 58 substances from structural class I. For 16 of the substances the intakes were above the threshold of concern for structural class I of 1800 microgram/person/day. For the one substance from structural class III [FL-no:06.096] the mTAMDI is 1600 microgram/person/day, which is above the threshold of concern for structural class III of 90 microgram/person/day. Thus, for 17 of the 59 flavouring substances considered in this Opinion, the intakes, estimated on the basis of the mTAMDI, exceed the relevant threshold for their structural class to which the flavouring substance has been assigned. Therefore, for these 17 substances more reliable exposure data are required. On the basis of such additional data, these flavouring substances should be reconsidered using the Procedure. Subsequently, additional data might become necessary. In order to determine whether this evaluation could be applied to the materials of commerce, it is necessary to consider the available specifications. Adequate specifications including complete purity criteria and identity tests for the materials of commerce have been provided for 42 of the 59 flavouring candidate substances. The specifications are not adequate for 17 substances [FL-no: 03.023, 06.041, 06.042, 06.043, 06.045, 06.046, 06.047, 06.063, 06.105, 06.106, 06.107, 06.109, 06.115, 06.123, 06.124, 06.128 and 06.129] as identity tests are lacking and for one of substances [ FL- no: 06.063] has the stereoisomeric composition to be specified. Thus, the final evaluation of the materials of commerce cannot be performed for 17 substances ([FL-no: 03.023, 06.041, 06.042, 06.043, 06.045, 06.046, 06.047, 06.063, 06.105, 06.106, 06.107, 06.109, 06.115, 06.123, 06.124, 06.128, 06.129]), pending further information. For the remaining 42 substances [FL-no: 06.044, 06.048, 06.049, 06.050, 06.051, 06.052, 06.053, 06.054, 06.055, 06.057, 06.058, 06.059, 06.061, 06.062, 06.064, 06.065, 06.066, 06.067, 06.069, 06.070, 06.071, 06.073, 06.074, 06.075, 06.076, 06.079, 06.082, 06.083, 06.084, 06.085, 06.086, 06.091, 06.092, 06.096, 06.100, 06.111, 06.114, 06.125, 06.127, 06.130, 06.131 and 06.137] the Panel concluded that they would present no safety concern at the levels of intake estimated on the basis of the MSDI approach.