Castle Laurence, Andreassen Monica, Aquilina Gabriele, Bastos Maria, Boon Polly, Fallico Biagio, FitzGerald Reginald, Frutos Fernandez Maria Jose, Grasl-Kraupp Bettina, Gundert-Remy Ursula, Gürtler Rainer, Houdeau Eric, Kurek Marcin, Louro Henriqueta, Morales Patricia, Passamonti Sabina, Benigni Romualdo, Chipman Kevin, Cordelli Eugenia, Degen Gisela, Engel Karl-Heinz, Fowler Paul, Carfí Maria, Gagliardi Gabriele, Mech Agnieszka, Multari Salvatore, Martino Carla
EFSA J. 2025 Jan 31;23(1):e9201. doi: 10.2903/j.efsa.2025.9201. eCollection 2025 Jan.
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 × 10 and 21 × 10 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.
应要求，欧洲食品安全局食品添加剂和调味剂小组（FAF）根据欧盟法规（EC）No 1331/2008，评估3-[3-(2-异丙基-5-甲基环己基)-脲基]丁酸乙酯[FL编号：16.136]作为一种新型调味物质的安全性。该物质未被报道天然存在，是通过化学合成的。所提供的关于[FL编号：16.136]制造工艺、成分和稳定性的信息被认为是充分的。使用添加量暴露技术（APET）估算的[FL编号：16.136]慢性膳食暴露量，对于一名60千克的成年人，计算得出为每天860微克/人；对于一名15千克的3岁儿童，为每天540微克/人。[FL编号：16.136]在体外细菌致突变性试验和哺乳动物细胞微核试验中未显示出遗传毒性作用。未提供关于[FL编号：16.136]的吸收、分布、代谢和排泄（ADME）研究。在一项产前发育毒性研究中，给大鼠每日灌胃剂量高达1000毫克/千克体重，未观察到母体或胎儿毒性。在一项大鼠90天毒性研究中，未观察到不良反应。在该研究中，小组认为雄性和雌性大鼠的无观察到有害作用水平（NOAEL）分别为每天777和923毫克/千克体重（测试的最高剂量）。以每天777毫克/千克体重这个最低的NOAEL作为参考点，在考虑慢性APET膳食暴露估算值时，分别计算出成年人和儿童的充足暴露边际为55×10和21×10。小组得出结论，在使用APET方法计算的膳食暴露估算值下，按照提议的使用条件使用3-[3-(2-异丙基-5-甲基环己基)-脲基]丁酸乙酯[FL编号：16.136]作为调味物质不会引发安全担忧。
