The Panel on Food Additives and Flavourings of the European Food Safety Authority was requested to evaluate the genotoxic potential of flavouring substances from subgroup 3.2 of FGE.19 in the Flavouring Group Evaluation 215, Revision 1 (FGE.215Rev1). In FGE.215, the Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids concluded that the concern for genotoxicity could not be ruled out and requested in vivo data for the two representative substances 4‐phenylbut‐3‐en‐2‐one [FL‐no: 07.024] and 1‐(4‐methoxyphenyl)pent‐1‐en‐3‐one [FL‐no: 07.030]. The Flavour Industry has provided additional genotoxicity studies for both representative substances [FL‐no: 07.024] and [FL‐no: 07.030]. Based on these new data, the Panel concluded that the concern for genotoxicity is ruled out for the representative substance [FL‐no: 07.024] and for the structurally related substances 4‐phenylbut‐3‐en‐2‐ol [FL‐no: 02.066] and 3‐methyl‐4‐phenylbut‐3‐en‐2‐one [FL‐no: 07.027] which can accordingly be evaluated through the Procedure in FGE.69. For the representative substance 1‐(4‐methoxyphenyl)pent‐1‐en‐3‐one [FL‐no: 07.030], the Panel concluded that [FL‐no: 07.030] is aneugenic in vitro. For such substances, there is currently no agreed follow‐up strategy to finalise their safety assessment. The Panel is aware that the EFSA Scientific Committee is going to address this issue and a statement clarifying the assessment of in vitro aneugenic substances is under preparation. The Panel concluded therefore that, for the time being, the representative substance 1‐(4‐methoxyphenyl)pent‐1‐en‐3‐one [FL‐no: 07.030] and the structurally related substances vanillylidene acetone [FL‐no: 07.046] and 1‐(4‐methoxyphenyl)‐4‐methylpent‐1‐en‐3‐one [FL‐no: 07.049] cannot be evaluated through the Procedure. The Panel further concluded that 4‐(2,3,6‐trimethylphenyl)but‐3‐en‐2‐one [FL‐no: 07.206] is to be considered as a stand‐alone substance due to the presence of the methyl groups, therefore, in vitro genotoxicity data were requested for [FL‐no: 07.206]. Industry communicated that the evaluation of [FL‐no: 07.206] is not supported any longer, therefore additional data were not submitted.

The food processing contaminants 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), 5‐hydroxymethylfurfural (HMF) and 2,5 dimethylfuran (DMF) are potentially both mutagenic and carcinogenic in vitro and/or in vivo, although data on DMF is lacking. The PHIP metabolite N‐hydroxy‐PhIP and HMF are bioactivated by sulfotransferases (SULTs). The substrate specificity and tissue distribution of SULTs differs between species. A single oral dose of PhIP, HMF or DMF was administered to wild‐type (wt) mice and mice expressing human SULT1A1/1A2 (hSULT mice). DNA damage was studied using the in vivo alkaline single cell gel electrophoresis (SCGE) assay. No effects were detected in wt mice. In the hSULT mice, PhIP and HMF exposure increased the levels of DNA damage in the liver and kidney, respectively. DMF was not found to be genotoxic. The observation of increased DNA damage in hSULT mice compared with wt mice supports the role of human SULTs in the bioactivation of N‐hydroxy‐PhIP and HMF in vivo. Environ. Mol. Mutagen. 56:709–714, 2015. © 2015 The Authors. Environmental and Molecular Mutagenesis Published by Wiley Periodicals, Inc.

Humans express sulfotransferases (SULTs) of the SULT1A subfamily in many tissues, whilst the single SULT1A gene present in rodents is mainly expressed in liver. The food processing contaminants, 5-hydroxymethylfurfural (HMF) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), are bioactivated by human SULT1A1 and SULT1A2. FVB multiple intestinal neoplasia (Min) mice, which spontaneously develop tumors and flat aberrant crypt foci (ACF) in intestine, were crossed with transgenic FVB mice expressing human SULT1A1 and 1A2 (hSULT) in several tissues, giving rise to wild-type and Min mice with and without hSULT. One-week-old Min mice with or without hSULT were given HMF (375 or 750 mg/kg bw) or saline by gavage three times a week for 11 wk. In another experiment, the F1 generation received subcutaneous injections of 50 mg/kg bw PhIP or saline 1 wk before birth, and 1, 2, and 3 wk after birth. HMF did not affect the formation of tumors, but may have induced some flat ACF (incidence 15-20%) in Min mice with and without hSULT. No control mouse developed any flat ACF. With the limitation that these putative effects were weak, they were unaffected by hSULT expression. The carcinogenic effect of PhIP increased in the presence of hSULT, with a significant increase in both incidence (31-80%) and number of colonic tumors (0.4-1.3 per animal). Thus, intestinal expression of human SULT1A1 and 1A2 might increase the susceptibility to compounds bioactivated via this pathway implying that humans might be more susceptible than conventional rodent models.

The Panel on Food Additives and Flavourings (FAF Panel) of the European Food Safety Authority was requested to evaluate the genotoxic potential of the flavouring substances from subgroup 1.2.1 of FGE.19 in the Flavouring Group Evaluation 204 (FGE.204). In the present revision of this FGE (FGE.204Rev1), the FAF Panel evaluated new data provided by Industry following a request from the former Panel on Food Contact materials, Enzymes, Flavourings and Processing Aids (CEF Panel). This request followed from positive results in an in vitro micronucleus test for clastogenicity and a negative result, but with no proof of bone marrow exposure, in an in vivo micronucleus assay for the representative substance 7-methyl-3-octenone-2 ]. Subsequently, the Industry submitted an in vivo comet assay which was considered equivocal in the liver. The study was repeated confirming that 7-methyl-3-octenone-2 [FL-no: 07.177] did not induce primary DNA damage in the liver and duodenum. Based on the available data, the Panel concluded that the concern for genotoxicity can be ruled out for ] and the 15 structurally related substances

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