Scientific Opinion on the re-evaluation of aspartame (E 951) as a food additive
Scientific Opinion on the re-evaluation of aspartame (E 951) as a food additive
复制标题
DOI：
10.2903/j.efsa.2013.3496
复制
发表时间：
2013-12-01
期刊：
影响因子：
3.3
通讯作者：
Wright, Matthew
中科院分区：
文献类型：
--
作者：
Aguilar, Fernando;Crebelli, Riccardo;Wright, Matthew
EFSA ANS专家组提供了关于安替西泮（E 951）安全性的科学意见。阿斯巴甜是一种甜味剂，在欧盟被授权作为食品添加剂。在JECFA和SCF先前的评价中，根据动物慢性毒性确定每日允许摄入量为40毫克/千克体重/天。对原始报告、先前的评价、在公开呼吁后提供的额外文献和数据进行了评价。阿斯巴甜在胃肠道中迅速完全水解为苯丙氨酸、天冬氨酸和甲醇。慢性和发育毒性是动物数据库中的相关终点。根据动物慢性毒性研究，确定无观测不良效应水平为4000毫克/千克体重/天。不能排除在低于4000 mg/kg的剂量下动物发生发育毒性的可能性。根据MoA和证据权重分析，评估小组得出结论，动物的发育毒性可归因于苯丙氨酸。已知高血浆水平的苯丙氨酸会导致人类发育毒性。评估小组得出结论，关于发育毒性的人类数据更适合于风险评估。使用苯丙氨酸对正常、PKU杂合子或PKU纯合子个体给药后的人体数据，使用浓度-反应模型来确定苯丙氨酸给药对血浆苯丙氨酸的影响。在正常和PKU杂合子中，除了膳食苯丙氨酸外，摄入高达40 mg/kg bw/d ADI的甜菜碱不会导致血浆苯丙氨酸峰值浓度高于当前预防胎儿不良反应的临床指南。评估小组得出结论认为，按照目前的西莫司坦接触估计值或每日允许摄入量40毫克/千克体重/天，西莫司坦不存在安全问题。因此，没有理由修改阿替西泮的每日允许摄入量。目前对阿替西泮及其降解产物DKP的暴露低于其各自的ADI。ADI不适用于PKU患者。(C)欧洲食品安全局，2013年
The EFSA ANS Panel provides a scientific opinion on the safety of aspartame (E 951). Aspartame is a sweetener authorised as a food additive in the EU. In previous evaluations by JECFA and the SCF, an ADI of 40 mg/kg bw/day was established based on chronic toxicity in animals. Original reports, previous evaluations, additional literature and data made available following a public call were evaluated. Aspartame is rapidly and completely hydrolysed in the gastrointestinal tract to phenylalanine, aspartic acid and methanol. Chronic and developmental toxicities were relevant endpoints in the animal database. From chronic toxicity studies in animals, a NOAEL of 4000 mg/kg bw/day was identified. The possibility of developmental toxicity occurring at lower doses than 4000 mg/kg in animals could not be excluded. Based on MoA and weight- of- evidence analysis, the Panel concluded that developmental toxicity in animals was attributable to phenylalanine. Phenylalanine at high plasma levels is known to cause developmental toxicity in humans. The Panel concluded that human data on developmental toxicity were more appropriate for the risk assessment. Concentrationresponse modelling was used to determine the effects of aspartame administration on plasma phenylalanine using human data after phenylalanine administration to normal, PKU heterozygote or PKU homozygote individuals. In normal and PKU heterozygotes, aspartame intakes up to the ADI of 40 mg/kg bw/day, in addition to dietary phenylalanine, would not lead to peak plasma phenylalanine concentrations above the current clinical guideline for the prevention of adverse effects in fetuses. The Panel concluded that aspartame was not of safety concern at the current aspartame exposure estimates or at the ADI of 40 mg/kg bw/day. Therefore, there was no reason to revise the ADI of aspartame. Current exposures to aspartame - and its degradation product DKP - were below their respective ADIs. The ADI is not applicable to PKU patients. (C) European Food Safety Authority, 2013