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Scientific Opinion on Flavouring Group Evaluation 301 (FGE.301): A sulphur substituted pyrimidin-derivative and its hydrochloride salt from Chemical Group 30
The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate two flavouring substances, 4-amino-5,6-dimethylthieno[2,3-d]pyrimidin-2(1H)-one [FL-no: 16.116] and 4-amino-5,6-dimethylthieno[2,3-d]pyrimidin-2(1H)-one hydrochloride [FL-no: 16.120] in the Flavouring Group Evaluation 301, using the Procedure in Commission Regulation (EC) No 1565/2000. None of the substances were 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 Panel concluded that the two substances [FL-no: 16.116 and 16.120] do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach.
© 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 two flavouring substances in the Flavouring Group Evaluation 301 (FGE.301), using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. These two flavouring substances belong to chemical group 30, Annex I of the Commission Regulation (EC) No 1565/2000.
The present Flavouring Group Evaluation deals with a sulphur substituted pyrimidin-derivative and its hydrochloride salt from chemical group 30.
The two flavouring substances (candidate substances) have no possibility for geometrical or optical isomers.
Both of the flavouring substances are classified into structural class III.
Neither of the substances in the present group has been reported to occur naturally in food items.
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 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 results for the available genotoxicity studies do not raise a concern for genotoxicity and hence do not preclude the evaluation of the two candidate substances in this FGE through the Procedure.
From the data available it is not possible to conclude that the two candidate substances in this group [FL-no: 16.116 and 16.120] would be metabolised to innocuous products at the reported levels of intake as flavouring substances.
According to the default MSDI approach, the two flavouring substances in this group have a total intake in Europe of 610 microgram/capita/day which is above the threshold of concern value for structural class III of 90 microgram/person/day. However, an adequate NOAEL exists of 10 microgram/kg bw/day from a 13-weeks study for the candidate substance 4-amino-5,6-dimethylthieno[2,3-d]pyrimidine-2(1H)-one hydrochloride [FL-no: 16.120] which provides a margin of safety of 5900.
When the estimated intakes were based on the mTAMDI approach they were 3600 and 4200 microgram/person/day for the two flavouring substances belonging to structural class III. These intakes are above the threshold of concern of 90 microgram/person/day for structural class III substances. Therefore, for these two 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. Following this procedure additional toxicological data might become necessary.
In order to determine whether the conclusion for the two candidate substances can be applied to the materials 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 both flavouring substances.
The Panel concluded that the two candidate substances 4-amino-5,6-dimethylthieno[2,3-d]pyrimidin-2(1H)-one [FL-no: 16.116] and 4-amino-5,6-dimethylthieno[2,3-d]pyrimidin-2(1H)-one hydrochloride [FL-no: 16.120] would present no safety concern at the estimated levels based on the MSDI approach.
Flavourings, pyrimidin-derivative, food, safety, FGE.301