The European Food Safety Authority (EFSA) asked the Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (the Panel) to advise 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 63 flavouring substances in the Flavouring Group Evaluation 10, Revision 3 (FGE.10Rev3), using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. These flavouring substances belong to chemical groups 9, 13 and 30, Annex I of the Commission Regulation (EC) No 1565/2000.
The present revision of FGE.10, FGE.10Rev3, includes the assessment of two additional candidate substances [FL-no: 09.951 and 10.170].
The flavouring substances are alcohols, aldehydes, acetals, carboxylic acids and esters containing additional oxygenated functional groups and lactones.
Thirty-six of the candidate substances possess one or more chiral centres and eight can exist as geometrical isomers due to the presence and the position of a double bond. For five of these substances [FL-no: 10.038, 10.040, 10.059, 10.063 and 10.170] the stereoisomeric composition / composition of mixture has not been specified sufficiently.
Fifty-five candidate substances belong to structural class I, six belong to structural class II, and two belong to structural class III according to the decision tree approach presented by Cramer et al. (1978).
Fifty of the flavouring substances in the present group 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” (MSDI) 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.
The candidate substances which have been assigned to structural class I have estimated European daily per capita intakes (MSDI) ranging from 0.0012 to 1500 microgram. The candidate substances from structural class II have MSDIs ranging from 0.0012 to 1.2 microgram and the two candidate substances assigned to structural class III have estimated European daily per capita intakes of 0.011 and 1.2 microgram (Table 6.1). These intakes are below the thresholds of concern of 1800, 540 and 90 microgram/person/day for structural class I , II and III, respectively.
The combined estimated daily per capita intake as flavourings of the 55 candidate substances assigned to structural class I is 1600 microgram, which does not exceed the threshold of concern for a substance belonging to structural class I of 1800 microgram/person/day. Likewise, the combined estimated daily per capita intake as flavouring of the six candidate substances assigned to structural class II is 1.2 microgram, which does not exceed the threshold of concern for a substance belonging to structural class II of 540 microgram/person/day.
For 5-pentyl-3H-furan-2-one [FL-no: 10.170], the flavour Industry informs that the commercial product is a mixture of two structural isomers – 2/3 is the named compound (5-pentyl-3H-furan-2-one) and 1/3 is the structural isomer - 5-pentyl-5H-furan-2-one. This latter isomer is identical to [FL-no: 10.054], which is an alpha, beta-unsaturated alcohol (after hydrolysis of the lactone), allocated to subgroup 4.1 of FGE.19 (FGE.217). The Panel concluded that 5-pentyl-3H-furan-2-one [FL-no: 10.170] should not be evaluated through the Procedure until the additional gentoxicity data for [FL-no: 10.054] are available, as stated in FGE 217.
The Panel reconsidered the fact that 1-hydroxypropan-2-one [FL-no: 07.169] is an endogenous metabolite of acetone. Acetone is endogenously formed from the degradation of body fat/fatty acids and occurs in the blood of healthy humans not exposed to external sources of acetone in amounts of approximately 4 - 12 mg/person, corresponding to 0.7 to 2 mg/l blood. Under these conditions, the majority of the acetone in blood would be metabolised to 1-hydroxypropan-2-one, which is rapidly further metabolised to endogenous compounds (methylglyoxal, pyruvate and glucose) in the methylglyoxal pathway. The estimated exposure of 0.22 microgram/capita/day is considerably lower than that resulting from the metabolism of acetone and would not significantly add to the internal exposure to 1-hydroxypropan-2-one in the body and would not perturb the normal catabolism of the compound to innocuous endogenous products. The Panel therefore decided that further genotoxicity data are not required and that the substance could be taken through the Procedure.
For the remaining candidate substances, the genotoxic potential cannot be assessed adequately, however, from the limited data available there were no indications that genotoxicity for these substances should give rise to safety concern. So, 62 substances are evaluated through the Procedure in the present revision of FGE.10.
It can be anticipated that, at the estimated levels of intake as flavouring substances, 59 of the alcohols, aldehydes, acetals, carboxylic acids and esters with an additional oxygenated functional group and aliphatic lactones included in the present FGE are generally hydrolysed and completely metabolised to innocuous products, many of which are endogenous in humans. For three of the flavouring substances [FL-no: 02.242, 06.097 and 09.824], it cannot be concluded that they are metabolised to innocuous products. Adequate margins of safety could be established for these three substances in step B4 of the Procedure.
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 was considered that on the basis of the default MSDI approach that the flavouring substances, to which the Procedure have been applied, would not give rise to safety concerns at the estimated levels of intake arising from their use as flavouring substances.
The mTAMDI for the flavouring substances, for which use levels information is available, range from 800 to 5100 microgram/person/day. For 58 of these substances the mTAMDI is above the threshold of concern of their structural classes and for three substances the mTAMDI is below the threshold. The three flavouring substances which have mTAMDI intake estimates below the threshold of concern for their structural class are also expected to be metabolised to innocuous products. For two flavouring substances use levels have not been provided and no mTAMDI could be estimated. Thus, for 60 flavouring substances, further information is required. This would include more reliable intake data and then, if required, additional toxicological data.
Thus, in conclusion, 62 of the 63 flavouring substances were evaluated through the Procedure (based
on the MSDI approach), as one flavouring substance, 5-pentyl-3H-furan-2-one [FL-no: 10.170] could not be evaluated through the Procedure until adequate genotoxicity data become available.
In order to determine whether the conclusion for the candidate substances evaluated using the Procedure can be applied to the materials of commerce, it is necessary to consider the available specifications. Specifications including complete purity criteria and identity for the materials of commerce have been provided for 58 flavouring substances. For four substances [FL-no: 10.038, 10.040, 10.059 and 10.063] information on composition of mixture and / or stereoisomerism has not been specified sufficiently. For one substance [FL-no: 10.063] an identity test is missing.
Thus, the final evaluation of the materials of commerce cannot be performed for four substances [FL-no: 10.038, 10.040, 10.059 and 10.063], pending further information.
For the remaining 58 candidate substances [FL-no: 02.132, 02.198, 02.242, 05.149, 06.088, 06.090, 06.095, 06.097, 06.102, 06.135, 07.169, 08.053, 08.082, 08.090, 08.103, 08.113, 09.333, 09.345 - 09.354, 09.360, 09.502, 09.558, 09.565, 09.580, 09.590, 09.601, 09.626, 09.629, 09.633, 09.634, 09.644, 09.683, 09.815, 09.824, 09.832, 09.833, 09.862, 09.874, 09.916, 09.951, 10.039, 10.045, 10.047 - 10.049, 10.052, 10.055, 10.058, 10.068 and 10.168] the Panel concluded that they would present no safety concern at the estimated levels of intake based on the MSDI approach.