DNA strand break by 2,5-dimethyl-4-hydroxy-3(2 H)-furanone, a fragnant compound in various foodstuffs

Hiramoto, Kazuyuki; Aso-o, Reiko; Ni-Iyama, H.; Hikage, S.; Kato, Tetsuta; Kikugawa, Kiyomi

doi:10.1016/s0165-1161(96)90005-9

Cited by 46 publications

(51 citation statements)

References 14 publications

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“…Positive results were obtained for 4-hydroxy-2,5-dimethylfuran-3(2H)-one [FLno: 13.010] in Salmonella typhimurium strains TA100, TA102, TA98 and TA97 at the highest dose tested (4000 µg/plate) with or without metabolic activation (Xing et al, 1988). In contrast, (Gilroy et al, 1978) and (Hiramoto et al, 1996b) reported positive results for this compound only in S. typhimurium strain TA100 when tested at concentrations of ≤ 10,000 µg/plate with or without metabolic activation. Similarly, 2-ethyl-4-hydroxy-5-methyl-3(2H)-furanone .084] and 4-hydroxy-5-methylfuran-3(2H)-one .085] produced positive results in S. typhimurium strain TA100 with or without metabolic activation (Hiramoto et al, 1996a;Li et al, 1998).…”

Section: Efsa Considerationsmentioning

confidence: 93%

See 1 more Smart Citation

Scientific Opinion on Flavouring Group Evaluation 99 Revision 1 (FGE.99Rev1): Consideration of furanone derivatives evaluated by the JECFA (63rd, 65th and 69th meetings)

Publication¹

2015

EFS2

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The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) of the European Food Safety Authority was requested to consider evaluations of flavouring substances assessed since 2000 by the Joint FAO/WHO Expert Committee on Food Additives (the JECFA), and to decide whether further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. The substances were evaluated through a stepwise approach that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The present consideration concerns a group of six furanone derivatives evaluated by the JECFA at their 63rd, 65th and 69th meetings. This revision of FGE.99 includes the assessment of the 2,5-dimethyl-4-methoxyfuran-3(2H)-one [FL-no: 13.089] cleared for genotoxicity concern compared to the previous version. The Panel concluded that none of the six substances gives rise to safety concerns at the levels of dietary intake, estimated on the basis of the MSDI approach 13.084, 13.085, 13.089, 13.099 and 13.176]. The specifications of the materials of commerce have also been considered and are adequate for all candidate substances in this FGE. However, for all substances use levels are required to calculate the mTAMDIs in order to identify those flavouring substances that need more refined exposure assessment and to finalise the evaluation.

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Section: Efsa Considerationsmentioning

confidence: 93%

“… Addition of metal chelating agents also inhibits DNA strand-breaking by depleting the metal ions required for this process; (Hiramoto et al, 1996a;Hiramoto et al, 1996b;Yamashita et al, 1998).…”

Section: +mentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 99 Revision 1 (FGE.99Rev1): Consideration of furanone derivatives evaluated by the JECFA (63rd, 65th and 69th meetings)

Publication¹

2015

EFS2

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“…Two studies showing micronucleus formation in peripheral blood cells were considered valid (Hiramoto et al, 1996b; in a third study similar evidence but of limited validity was obtained (Xing et al, 1988). The latter authors also reported an increase in sister chromatid exchanges (SCE) in mouse bone marrow, but the validity of that observation could not be assessed.…”

Section: -Hydroxy-25-dimethylfuran-3(2h)-one [Fl-no: 13010]mentioning

confidence: 99%

“…The EFSA Journal (2009) ON-1061, 14-23 (Hiramoto et al, 1996b) Valid. Positive in TA100 + and -S9; negative in TA98 (+/-S9).…”

Section: Flavouring Group Evaluation 220mentioning

confidence: 99%

Flavouring Group Evaluation 220: alpha, beta‐Unsaturated ketones and precursors from chemical subgroup 4.4 of FGE.19: 3(2H)‐Furanones

2009

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“…5) Data must be available on the substance or closely related substances to perform a safety evaluation. (Hiramoto et al, 1996b) Valid. Positive in TA100 (+/-S9); negative in TA 98 (+/-S9).…”

mentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 220, Revision 2 (FGE.220Rev1): α,β‐Unsaturated ketones and precursors from chemical subgroup 4.4 of FGE.19: 3(2H)‐Furanones

2013

EFS2

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The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate the genotoxic potential of 10 flavouring substances from subgroup 4.4 of FGE.19 in the Flavouring Group Evaluation 220 (FGE.220). FGE.220 is subdivided into two subgroups (subgroup 4.4a containing 13.117, 13.119, 13.157 and 13.175] and subgroup 4.4b containing [13.010, 13.084 and 13.085, 13.099 and 13.176]. For both subgroups the Panel concluded that the genotoxicity alert could not be ruled out based on the data available and accordingly additional genotoxicity data were requested. In FGE.220, Revision 1, the Panel concluded, based on new submitted data, that for the substances in subgroup 4.4b there is no concern for genotoxicity. The Flavour Industry has now provided additional genotoxicity studies for two representative substances of subgroup 4.4a, 2,5-dimethylfuran-3(2H)-one .119] and 4-acetyl-2,5-dimethylfuran-3(2H)-one . Based on the new data the Panel concluded that 2,5-dimethylfuran-3(2H)-one [FL-no: 13.119] does not give rise to concern with respect to genotoxicity. For 4-acetyl-2,5-dimethylfuran-3(2H)-one ] the concern for genotoxicity could not be ruled out and therefore the Panel requests a repetition of the submitted micronucleus study in the presence of S9-mix applying the same conditions and possibly in addition modified conditions, or a combined in vivo micronucleus and Comet assay, including analysis of liver. This is also applicable to 2,5-dimethyl-4-methoxyfuran-3(2H)-one [FLno:13.089] and 2,5-dimethyl-4-ethoxyfuran-3(2H)-one .117], which are covered by the representative substance 4-acetyl-2,5-dimethylfuran-3(2H)-one ]. The Flavour Industry has informed that 5-methylfuran-3(2H)-one ] is not in common use in the flavour industry and is no longer supported.

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DNA strand break by 2,5-dimethyl-4-hydroxy-3(2 H)-furanone, a fragnant compound in various foodstuffs

Cited by 46 publications

References 14 publications

Scientific Opinion on Flavouring Group Evaluation 99 Revision 1 (FGE.99Rev1): Consideration of furanone derivatives evaluated by the JECFA (63rd, 65th and 69th meetings)

Scientific Opinion on Flavouring Group Evaluation 99 Revision 1 (FGE.99Rev1): Consideration of furanone derivatives evaluated by the JECFA (63rd, 65th and 69th meetings)

Flavouring Group Evaluation 220: alpha, beta‐Unsaturated ketones and precursors from chemical subgroup 4.4 of FGE.19: 3(2H)‐Furanones

Scientific Opinion on Flavouring Group Evaluation 220, Revision 2 (FGE.220Rev1): α,β‐Unsaturated ketones and precursors from chemical subgroup 4.4 of FGE.19: 3(2H)‐Furanones

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