The European Food Safety Authority (EFSA) asked the Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (the Panel) to deliver a 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 one flavouring substance in the Flavouring Group Evaluation 300, Revision 1 using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. The flavouring substance belongs to chemical group 30, Annex I of the Commission Regulation (EC) No 1565/2000.
The present Flavouring Group Evaluation deals with one cyclo-aliphatic amide. This revision is made due to additional toxicity data that have become available on the substance cyclopropanecarboxylic acid (2-isopropyl-5-methyl-cyclohexyl)-amide [FL-no: 16.115].
The substance cyclopropanecarboxylic acid (2-isopropyl-5-methyl-cyclohexyl)-amide [FL-no: 16.115] possesses three chiral centres and has been presented with specification of the stereoisomeric composition.
The substance is assigned into structural class III, according to the decision tree approach presented by Cramer et al., 1978.
The substance in the present group has not been reported to occur naturally in food.
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. 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 also decided 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 results from the available limited genotoxicity studies do not raise a concern for genotoxicity and hence do not preclude the evaluation of the candidate substance in this FGE through the Procedure.
According to the default MSDI approach, the flavouring substance in this group has a total intake in Europe of 3 µg/capita/day, which is below the threshold of concern value for structural class III of 90 µg/person/day.
From the data available it is not possible to conclude that cyclopropanecarboxylic acid (2-isopropyl-5-methyl-cyclohexyl)-amide [FL-no: 16.115] would be metabolised to innocuous products at the reported levels of intake as flavouring substance. Therefore, the substance was evaluated along the B-side of the Procedure. Now a 90-day study on the candidate substance [FL-no: 16.115] has become available and a No Observed Adverse Effect Level NOAEL to provide an adequate margin of safety of 2.9 x 106 is derived. Therefore, the substance [FL-no: 16.115] is not anticipated to pose a safety concern when used as flavouring substance at the estimated levels of intake, based on the MSDI approach.
When the estimated intake was based on the mTAMDI approach it was 960 µg/person/day for this flavouring substance belonging to structural class III. The estimated intake for the candidate substance is above the threshold of concern of 90 µg/person/day. Thus, for the flavouring substance considered in this opinion the intake, estimated on the basis of the mTAMDI, exceed the relevant threshold for the structural class, to which the flavouring substance has been assigned. Therefore, for the substance more reliable exposure data is required. On the basis of such additional data, the flavouring substance should be reconsidered along the steps of the Procedure. Following this procedure additional toxicological data might become necessary.
In order to determine whether the conclusion for the candidate substance can be applied to the material of commerce, it is necessary to consider the available specifications. Specifications including purity criteria and identity for the material of commerce have been provided for the flavouring substance.
In conclusion, for the flavouring substance cyclopropanecarboxylic acid (2-isopropyl-5-methyl-cyclohexyl)-amide [FL-no: 16.115] the Panel considered that the substance would present no safety concern at the estimated level of intake estimated on the basis of the MSDI approach.