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Following a request from the European Commission, the European Food Safety Authority (EFSA)'s Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids, upon a re-evaluation, has deemed flavoring substance 3-acetyl-2,5-dimethylthiophene from Flavoring Group Evaluation (FGE) 19 subgroup 5.2 to be genotoxic.
3-Acetyl-2,5-dimethylthiophene is used as a flavoring to give food a burnt nutty flavor and can also occur naturally in boiled and cooked meats. The substance is produced by a small number of manufacturers and present in a limited number of foods, mainly some savory products, confectionaries and fine bakery wares. Overall usage is low (total annual use in the EU is reported to be 2.3 kg). While no exposure assessment has been carried out by EFSA, the possible risk to consumers who may have been exposed to this substance in food is expected to be very small, the organization stated.
From November 27 through 29, 2007, EFSA discussed the flavoring group evaluation 19 including flavoring substances which are alpha, beta-unsaturated aldehydes or ketones or precursors thereof. It says these structures are "considered to be a structural alert for genotoxicity."
3-Acetyl-2,5-dimethylthiophenebelongs to subgroup 5.2 in the FGE.19. In 2013, the CEF panel concluded in its scientific opinion on FGE.224 (EFSA, 2013) that for the substance 3-acetyl-2,5-dimethylthiophene [FL-no 15.024] no conclusion could be taken due to the lack of data on genotoxicity. The missing data has now been submitted by the European Flavour Association to the European Commission which asked EFSA to evaluate this new information.
The data submitted consisted of an in vitro bacterial mutation assay and an in vivo Muta Mice study which were performed in compliance with Good Laboratory Practice and according to the OECD Guideline 471 and 488, respectively. The panel said the bacterial mutation assay showed a dose-dependent positive outcome in the strains TA98, TA100 and TA102 in presence of Aroclor induced rat liver S9-mix (at non toxic concentrations), indicating that the mutagenicity observed in this assay is due to a metabolite of the substance.
In addition, an in vivo study in Muta Mice was performed monitoring mutant frequency in liver and duodenum, and counting of micronucleated reticulocytes in the peripheral blood. Results from this study showed a dose dependent increase in the mutant frequency for liver, while no dose-related effects where observed for mutant frequency in duodenum nor was an increase in micronucleated reticulocytes observed.
The panel said the results of the in vivo study further support the hypothesis that the mutagenicity observed is due to a metabolite of the 3-acetyl-2,5-dimethylthiophene. It concluded that 3-acetyl-2,5-dimethylthiophene is mutagenic both in vitro and in vivo and that therefore its use as flavoring substance raises a safety concern.