Flavouring group evaluation 418 (FGE. 418): 3‐[3‐(2‐isopropyl‐5‐methyl‐cyclohexyl)‐ureido]‐butyric acid ethyl ester
Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of 3‐[3‐(2‐isopropyl‐5‐methyl‐cyclohexyl)‐ureido]‐butyric acid ethyl ester [FL‐no: 16.136] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. The substance has not been r...
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2025-01-01
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| Online Access: | https://doi.org/10.2903/j.efsa.2025.9201 |
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| author | EFSA Panel on Food Additives and Flavourings (FAF) Laurence Castle Monica Andreassen Gabriele Aquilina Maria Bastos Polly Boon Biagio Fallico Reginald FitzGerald Maria Jose Frutos Fernandez Bettina Grasl‐Kraupp Ursula Gundert‐Remy Rainer Gürtler Eric Houdeau Marcin Kurek Henriqueta Louro Patricia Morales Sabina Passamonti Romualdo Benigni Kevin Chipman Eugenia Cordelli Gisela Degen Karl‐Heinz Engel Paul Fowler Maria Carfí Gabriele Gagliardi Agnieszka Mech Salvatore Multari Carla Martino |
| author_facet | EFSA Panel on Food Additives and Flavourings (FAF) Laurence Castle Monica Andreassen Gabriele Aquilina Maria Bastos Polly Boon Biagio Fallico Reginald FitzGerald Maria Jose Frutos Fernandez Bettina Grasl‐Kraupp Ursula Gundert‐Remy Rainer Gürtler Eric Houdeau Marcin Kurek Henriqueta Louro Patricia Morales Sabina Passamonti Romualdo Benigni Kevin Chipman Eugenia Cordelli Gisela Degen Karl‐Heinz Engel Paul Fowler Maria Carfí Gabriele Gagliardi Agnieszka Mech Salvatore Multari Carla Martino |
| author_sort | EFSA Panel on Food Additives and Flavourings (FAF) |
| collection | DOAJ |
| description | Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of 3‐[3‐(2‐isopropyl‐5‐methyl‐cyclohexyl)‐ureido]‐butyric acid ethyl ester [FL‐no: 16.136] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. The substance has not been reported to occur naturally and it is chemically synthesised. The information provided on the manufacturing process, the composition and the stability of [FL‐no: 16.136] was considered sufficient. The chronic dietary exposure to [FL‐no: 16.136] estimated using the added portions exposure technique (APET) is calculated to be 860 μg/person per day for a 60‐kg adult and 540 μg/person per day for a 15‐kg 3‐year‐old child. [FL‐no: 16.136] did not show genotoxic effects in bacterial mutagenicity and mammalian cell micronucleus assays in vitro. No ADME studies on [FL‐no: 16.136] were provided. In a prenatal developmental toxicity study, no maternal or fetal toxicity was observed in rats dosed up to 1000 mg/kg body weight (bw) per day. In a 90‐day toxicity study in rats, no adverse effects were observed. In this study, the Panel considered that the NOAEL is 777 and 923 mg/kg bw per day (the highest dose tested) for male and female rats, respectively. Considering the lowest NOAEL of 777 mg/kg bw per day, as a reference point, adequate margins of exposure of 55 × 103 and 21 × 103 were calculated for adults and children, respectively, when considering the chronic APET dietary exposure estimates. The Panel concluded that the use of 3‐[3‐(2‐isopropyl‐5‐methylcyclohexyl)‐ureido]‐butyric acid ethyl ester [FL‐no: 16.136] as a flavouring substance under the proposed conditions of use does not raise a safety concern at the dietary exposure estimates calculated using the APET approach. |
| format | Article |
| id | doaj-art-b64e4c8624464371955f42346b239930 |
| institution | Kabale University |
| issn | 1831-4732 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | EFSA Journal |
| spelling | doaj-art-b64e4c8624464371955f42346b2399302025-01-31T12:06:04ZengWileyEFSA Journal1831-47322025-01-01231n/an/a10.2903/j.efsa.2025.9201Flavouring group evaluation 418 (FGE. 418): 3‐[3‐(2‐isopropyl‐5‐methyl‐cyclohexyl)‐ureido]‐butyric acid ethyl esterEFSA Panel on Food Additives and Flavourings (FAF)Laurence CastleMonica AndreassenGabriele AquilinaMaria BastosPolly BoonBiagio FallicoReginald FitzGeraldMaria Jose Frutos FernandezBettina Grasl‐KrauppUrsula Gundert‐RemyRainer GürtlerEric HoudeauMarcin KurekHenriqueta LouroPatricia MoralesSabina PassamontiRomualdo BenigniKevin ChipmanEugenia CordelliGisela DegenKarl‐Heinz EngelPaul FowlerMaria CarfíGabriele GagliardiAgnieszka MechSalvatore MultariCarla MartinoAbstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of 3‐[3‐(2‐isopropyl‐5‐methyl‐cyclohexyl)‐ureido]‐butyric acid ethyl ester [FL‐no: 16.136] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. The substance has not been reported to occur naturally and it is chemically synthesised. The information provided on the manufacturing process, the composition and the stability of [FL‐no: 16.136] was considered sufficient. The chronic dietary exposure to [FL‐no: 16.136] estimated using the added portions exposure technique (APET) is calculated to be 860 μg/person per day for a 60‐kg adult and 540 μg/person per day for a 15‐kg 3‐year‐old child. [FL‐no: 16.136] did not show genotoxic effects in bacterial mutagenicity and mammalian cell micronucleus assays in vitro. No ADME studies on [FL‐no: 16.136] were provided. In a prenatal developmental toxicity study, no maternal or fetal toxicity was observed in rats dosed up to 1000 mg/kg body weight (bw) per day. In a 90‐day toxicity study in rats, no adverse effects were observed. In this study, the Panel considered that the NOAEL is 777 and 923 mg/kg bw per day (the highest dose tested) for male and female rats, respectively. Considering the lowest NOAEL of 777 mg/kg bw per day, as a reference point, adequate margins of exposure of 55 × 103 and 21 × 103 were calculated for adults and children, respectively, when considering the chronic APET dietary exposure estimates. The Panel concluded that the use of 3‐[3‐(2‐isopropyl‐5‐methylcyclohexyl)‐ureido]‐butyric acid ethyl ester [FL‐no: 16.136] as a flavouring substance under the proposed conditions of use does not raise a safety concern at the dietary exposure estimates calculated using the APET approach.https://doi.org/10.2903/j.efsa.2025.92013‐[3‐(2‐Isopropyl‐5‐methyl‐cyclohexyl)‐ureido]‐butyric acid ethyl esterFGE.418FlavouringFL‐no: 16.136 |
| spellingShingle | EFSA Panel on Food Additives and Flavourings (FAF) Laurence Castle Monica Andreassen Gabriele Aquilina Maria Bastos Polly Boon Biagio Fallico Reginald FitzGerald Maria Jose Frutos Fernandez Bettina Grasl‐Kraupp Ursula Gundert‐Remy Rainer Gürtler Eric Houdeau Marcin Kurek Henriqueta Louro Patricia Morales Sabina Passamonti Romualdo Benigni Kevin Chipman Eugenia Cordelli Gisela Degen Karl‐Heinz Engel Paul Fowler Maria Carfí Gabriele Gagliardi Agnieszka Mech Salvatore Multari Carla Martino Flavouring group evaluation 418 (FGE. 418): 3‐[3‐(2‐isopropyl‐5‐methyl‐cyclohexyl)‐ureido]‐butyric acid ethyl ester EFSA Journal 3‐[3‐(2‐Isopropyl‐5‐methyl‐cyclohexyl)‐ureido]‐butyric acid ethyl ester FGE.418 Flavouring FL‐no: 16.136 |
| title | Flavouring group evaluation 418 (FGE. 418): 3‐[3‐(2‐isopropyl‐5‐methyl‐cyclohexyl)‐ureido]‐butyric acid ethyl ester |
| title_full | Flavouring group evaluation 418 (FGE. 418): 3‐[3‐(2‐isopropyl‐5‐methyl‐cyclohexyl)‐ureido]‐butyric acid ethyl ester |
| title_fullStr | Flavouring group evaluation 418 (FGE. 418): 3‐[3‐(2‐isopropyl‐5‐methyl‐cyclohexyl)‐ureido]‐butyric acid ethyl ester |
| title_full_unstemmed | Flavouring group evaluation 418 (FGE. 418): 3‐[3‐(2‐isopropyl‐5‐methyl‐cyclohexyl)‐ureido]‐butyric acid ethyl ester |
| title_short | Flavouring group evaluation 418 (FGE. 418): 3‐[3‐(2‐isopropyl‐5‐methyl‐cyclohexyl)‐ureido]‐butyric acid ethyl ester |
| title_sort | flavouring group evaluation 418 fge 418 3 3 2 isopropyl 5 methyl cyclohexyl ureido butyric acid ethyl ester |
| topic | 3‐[3‐(2‐Isopropyl‐5‐methyl‐cyclohexyl)‐ureido]‐butyric acid ethyl ester FGE.418 Flavouring FL‐no: 16.136 |
| url | https://doi.org/10.2903/j.efsa.2025.9201 |
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