Résumé
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 the 48 flavouring substances in this Flavouring Group Evaluation 06, Revision 2 (FGE.06Rev2), using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. These 48 flavouring substances belong to chemical groups 1 and 4, Annex I of the Commission Regulation (EC) No 1565/2000.
The present Flavouring Group Evaluation deals with 48 straight- and branched-chain unsaturated primary alcohols, aldehydes, carboxylic acids and esters.
Eight of the 48 flavouring substances possess a chiral centre [FL-no: 02.170, 02.175, 05.143, 09.341, 09.612, 09.871, 09.872 and 09.938].
Thirty-one of the 48 substances can exist as geometrical isomers [FL-no: 02.152, 02.195, 02.222, 02.234, 05.061, 05.082, 05.203, 05.217, 05.218, 05.220, 08.074, 08.102, 09.377, 09.567, 09.569, 09.572, 09.575, 09.638, 09.640, 09.643, 09.672, 09.673, 09.674, 09.831, 09.838, 09.855, 09.884, 09.885, 09.928, 09.937 and 09.939]. For 13 of these substances [FL-no: 02.152, 02.222, 05.061, 05.203, 05.218, 08.074, 08.102, 09.377, 09.640, 09.674, 09.831, 09.884, 09.885] no indication has been given that one of the possible isomers has preponderance in the commercial flavouring material.
Forty-six candidate substances are classified into structural class I. The remaining two substances [FL-no: 05.143 and 09.884] are classified into structural class II.
Thirty-eight of the flavouring substances in the present group have been reported to occur naturally in a wide range of food items.
According to the default MSDI approach, the 48 flavouring substances in this group have intakes in Europe from 0.001 to 120 microgram/capita/day, which are below the thresholds of concern value for both structural class I (1800 microgram/person/day) and structural class II (540 microgram/person/day) substances.
On the basis of the reported annual production volumes in Europe (MSDI approach), the combined intake of the 46 candidate substances belonging to structural class I and of the two candidate substances belonging to structural class II would result in a total intake of approximately 255 and 0.7 microgram/capita/day, respectively. These values are below the thresholds of concern for structural class I and class II substances of 1800 and 540 microgram/person/day, respectively. The total combined estimated intake of 65 of the 70 supporting substances for which European annual production data are available and of the 46 candidate substances from structural class I is approximately 6700 microgram/capita/day, which exceeds the threshold of concern for structural class I (1800 microgram/person/day). However, the substances are expected to be efficiently metabolised and are not expected to saturate the metabolic pathways.
For the substances in this group the limited data available do not give rise to safety concern with respect to genotoxicity and carcinogenicity.
Except for hex-3-enyl 2-ethylbutyrate [FL-no: 09.884] the candidate substances are expected to be metabolised to innocuous substances at the estimated levels of use as flavouring substances. One of the hydrolysis products of [FL-no: 09.884], 2-ethylbutyric acid, showed teratogenic potential in one mouse subcutaneous single-dose study, and is structurally related to valproic acid, which is a known teratogen. However, an additional study in which 2-ethylbutyric acid was given by gavage to pregnant rats showed a NOAEL of 200 mg/kg bw/day of 2-ethylbutyric acid. This dose is more than 4 x 10(7) times higher than the MSDI for 2-ethylbutyric acid arising from the intake of the candidate substance, [FL-no: 09.884]. Accordingly, the candidate substance [FL-no: 09.884] does not pose a safety concern with respect to teratogenicity when used at the level of intake as flavouring substance estimated on the basis of the MSDI approach.
It was noted that where toxicity data were available they were consistent with the conclusions in the present flavouring group evaluation using the Procedure.
It is considered that on the basis of the default MSDI approach these 48 candidate substances would not give rise to safety concerns at the estimated levels of intake arising from their use as flavouring substances.
When the estimated intakes were based on the mTAMDI approach they ranged from 36 to 40000 microgram/person/day for the 45 flavouring substances from structural class I for which data have been provided. Thus, the intakes were all above the threshold of concern for structural class I of 1800 microgram/person/day, except for nine flavouring substances [FL-no: 05.061, 05.174, 05.082, 05.203, 05.217, 05.218, 05.220, 09.937 and 09.939]. The estimated intakes of the two flavouring substances assigned to structural class II, based on the mTAMDI are 1600 and 3900 microgram/person/day, which is above the threshold of concern for structural class II of 540 microgram/person/day. The nine substances [FL-no: 05.061, 05.174, 05.082, 05.203, 05.217, 05.218, 05.220, 09.937 and 09.939], which have mTAMDI intake estimates below the threshold of concern for structural class I, are also expected to be metabolised to innocuous products. Thus, for 38 of the 48 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. For one substance [FL-no: 09.647] no use levels were provided. Therefore, for these 39 substances more reliable exposure data are required. On the basis of such additional data, these flavouring substances should be reconsidered along the steps of the Procedure. Subsequently, additional data might become necessary.
In order to determine whether the conclusion for the 48 candidate substances can be applied to the material of commerce, it is necessary to consider the available specifications. Adequate specifications including complete purity criteria and identity for the materials of commerce have been provided for 46 of the 48 flavouring candidate substances. An ID test is missing for [FL-no: 09.938] and a boiling point is lacking for [FL-no: 09.674]. Otherwise the specifications are adequate for all 48 candidate substances, except that information on composition of stereoisomeric mixture has not been specified sufficiently for 13 of the substances [FL-no: 02.152, 02.222, 05.061, 05.203, 05.218, 08.074, 08.102, 09.377, 09.640, 09.674, 09.831, 09.884 and 09.885].
Thus, the final evaluation of the materials of commerce cannot be performed for 14 substances [FL-no: 02.152, 02.222, 05.061, 05.203, 05.218, 08.074, 08.102, 09.377, 09.640, 09.674, 09.831, 09.884, 09.885 and 09.938], pending further information. The remaining 34 substances [FL-no: 02.125, 02.138, 02.170, 02.175, 02.176, 02.195, 02.201, 02.234, 05.082, 05.143, 05.174, 05.217, 05.220, 08.100, 09.341, 09.368, 09.567, 09.569, 09.572, 09.575, 09.612, 09.638, 09.643, 09.672, 09.673, 09.838, 09.855, 09.871, 09.872, 09.897, 09.898, 09.928, 09.937 and 09.939] would present no safety concern at the levels of intake estimated on the basis of the MSDI approach.