Use of rosemary extracts as a food additive1 Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food
Use of rosemary extracts as a food additive1 Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food
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DOI：
10.2903/j.efsa.2008.721
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发表时间：
2008-06-01
期刊：
影响因子：
3.3
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中科院分区：
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应委员会的要求，食品添加剂、调味品、加工助剂和食品接触材料小组 (AFC) 被要求就迷迭香提取物用作抗氧化剂时的安全性提供科学意见。迷迭香提取物源自迷迭香，含有多种已被证明具有抗氧化功能的化合物。这些化合物主要属于酚酸、黄酮类、二萜类和三萜类。目前的意见涉及使用多种溶剂提取技术制备的迷迭香提取物。这些将按申请人提供的首字母缩略词命名，如下：F62：通过丙酮提取从干燥迷迭香叶中生产的迷迭香提取物，D74：通过超临界二氧化碳提取干燥迷迭香叶制备的迷迭香提取物，AR：从迷迭香部分脱臭乙醇提取物制备的迷迭香提取物，ARD：从迷迭香脱臭乙醇提取物制备的提取物，RES：脱色和脱色的提取物使用己烷和乙醇两步提取获得的脱臭迷迭香提取物。提取物的主要抗氧化成分是酚类二萜鼠尾草酚和鼠尾草酸。专家组建议修改请愿人提出的规格，以反映安全测试中使用的提取物的规格，涉及鼠尾草酚和鼠尾草酸以及抗氧化剂/挥发性比率。本意见考虑的五种迷迭香提取物中的四种，（D74， AR、ARD 和 RES）进行了遗传毒性测试。在原核和真核测试系统中进行了多项体外遗传毒性研究，并使用迷迭香提取物 RES 进行了体内小鼠微核测试。专家组的结论是，这些不会引起迷迭香提取物遗传毒性方面的安全问题。抗氧化剂迷迭香提取物对大鼠的急性和亚慢性毒性较低。对所有五种溶剂提取物（D74、AR、ARD、F62、RES）的亚慢性研究表明，高剂量这些迷迭香提取物的唯一作用是相对肝脏重量略有增加。这种效应已被证明是可逆的，可能是 I 期和 II 期酶诱导的结果。该效应并不伴随血浆天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和碱性磷酸酶（AP）水平的升高。考虑到肝脏变化的程度低、可逆性和性质，以及血浆 ALT、AST 和 AP 没有增加，专家组得出结论，报告的肝脏重量轻微增加，伴有最小的小叶中心肥大和微粒体酶诱导，代表一种适应性反应，不存在毒理学问题。总体而言，对测试的不同迷迭香提取物（包括 AR、ARD、RES 和 D74）的大鼠进行 90 天喂养研究，揭示了 NOAEL值范围为 180 至 400 毫克提取物/千克体重/天当量，具体取决于相应提取物的鼠尾草酚和鼠尾草酸含量，至 20-60 毫克/千克体重/天鼠尾草酚加鼠尾草酸。迷迭香提取物的毒理学数据不足以建立数值 ADI，因为毒性数据集不提供生殖毒性研究或长期研究。另一方面，现有数据，包括 90 天研究中没有对生殖器官产生影响以及缺乏遗传毒性，并没有引起人们的担忧。对成人和学龄前儿童（1.5 至 4.5 岁）的鼠尾草酚加鼠尾草酸膳食暴露量进行了估计，平均值分别为 0.04 和 0.11 毫克鼠尾草酚加鼠尾草酸/公斤体重/天，0.10和 0.20 毫克鼠尾草酚加鼠尾草酸/公斤体重/天，第 95 个百分位数和 97.5 个百分位值分别为 0.12 和 0.23 毫克鼠尾草酚加鼠尾草酸/公斤体重/天。专家小组指出，在 90 天大鼠研究中，所有五种提取物（180 至 400 毫克提取物/公斤体重/天）的 NOAEL 范围之间的界限相当于20-60 毫克/公斤体重/天的鼠尾草酚加鼠尾草酸，成人膳食暴露估计值的平均摄入量将在 5001500 之间，第 95 个百分位值将在 200-600 之间，第 97.5 个百分位值将在 167-500 之间。对于学龄前儿童来说，这些差距将分别达到至少 182-546、100-300 和 87-261。专家组指出，这些安全边际是最坏情况估计值，因为不同研究的 NOAEL 通常是测试的最高剂量水平，并且饮食暴露的估计是保守的。因此，专家组认为，安全边际足够高，可以得出结论，拟议用途和使用水平导致的饮食暴露不存在安全问题。专家组指出，为了达到这些饮食暴露水平，高水平消费者需要选择完全由含有迷迭香提取物的食品组成的饮食。允许的。事实上，并非所有加工食品都含有添加的抗氧化剂，而且这些提取物似乎不太可能在每个类别的所有拟议食品中以最大使用水平使用，或者一些消费者总是系统地选择所有含有迷迭香提取物的食品。根据确定的安全边际，专家组得出结论，按拟议用途和使用水平使用迷迭香提取物不会引起安全问题。
Following a request from the Commission, the Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC) was asked to deliver a scientific opinion on the safety in use of rosemary extracts when used as an antioxidant.Rosemary extracts are derived from Rosmarinus officinalis L. and contain several compounds which have been proven to exert antioxidative functions. These compounds belong mainly to the classes of phenolic acids, flavonoids, diterpenoids and triterpenes.The present opinion refers to rosemary extracts prepared using several solvent extraction techniques. These will be named by the acronyms provided by the petitioner and are as follows:F62: rosemary extract produced from dried rosemary leaves by acetone extraction,D74: rosemary extract prepared by extraction of dried rosemary leaves by means of supercritical carbon dioxide,AR: rosemary extract prepared from a partially deodorised ethanolic extract of rosemary,ARD: extract prepared from a deodorised ethanolic extract of rosemary,RES: extract which is a decolourised and deodorised rosemary extract obtained by a two-step extraction using hexane and ethanol.The principal antioxidative components of the extracts are the phenolic diterpenes carnosol and carnosic acid.The Panel suggests to modify the specifications proposed by the petitioner to reflect the specifications of the extracts that were used in the safety testing, with respect to carnosol and carnosic acid and the antioxidant/volatile ratio.Four of the five rosemary extracts considered in the present opinion, (D74, AR, ARD, and RES) were tested for genotoxicity. Several in vitro genotoxicity studies were performed in both prokaryotic and eukaryotic test systems and an in vivo mouse micronucleus test performed with rosemary extract RES. The Panel concluded that these do not give rise to safety concerns with respect to genotoxicity of the rosemary extracts.Antioxidant rosemary extracts have low acute and sub-chronic toxicity in the rat. Sub-chronic studies on all five solvent extracts (D74, AR, ARD, F62, RES) reveal that the only effect at high doses of these rosemary extracts is a slight increase in relative liver weight. This effect has been shown to be reversible and may be the result of Phase I and II enzyme induction. The effect was not accompanied by increases in plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (AP). Considering the low magnitude, reversibility and the nature of the hepatic changes, and the absence of increases in plasma ALT, AST and AP, the Panel concludes that the minor increase in the liver weight reported, accompanied by minimal centrilobular hypertrophy and microsomal enzyme induction, represent an adaptive response and are not of toxicological concern.Overall, the 90-day feeding studies in rats with the different rosemary extracts tested, including AR, ARD, RES and D74, reveal NOAEL values in the range of 180 to 400 mg extract/kg body weight/day equivalent, depending on the carnosol and carnosic acid content of the respective extracts, to 20-60 mg/kg bw/day of carnosol plus carnosic acid.The toxicological data on the rosemary extracts are insufficient to establish a numerical ADI, because the toxicity data set does not provide reproductive toxicity studies or a long term study. On the other hand, the existing data, including the absence of effects in the 90-day studies on reproductive organs and lack of genotoxicity, do not give reason for concern.Dietary exposure to carnosol plus carnosic acid has been estimated for adults and pre-school children (aged 1.5 to 4.5 years) and amounts to mean values of respectively 0.04 and 0.11 mg carnosol plus carnosic acid/kg bw/day, 0.10 and 0.20 mg carnosol plus carnosic acid/kg bw/day at the 95th percentiles and 97.5th percentile values of 0.12 and 0.23 mg carnosol plus carnosic acid/kg bw/day.The Panel notes that the margin between the NOAEL range in the 90-day rat studies with all five extracts of 180 to 400 mg extract/kg bw/day equivalent to 20-60 mg/kg bw/day of carnosol plus carnosic acid, and the dietary exposure estimates for adults would amount between 5001500 for the mean intake values, between 200-600 for the 95th percentile values and between 167-500 for the 97.5th percentile values. For pre-school children these margins would amount to respectively at least 182-546, 100-300 and 87-261. The Panel notes that these margins of safety are worst case estimates since the NOAELs from the different studies were generally the highest dose levels tested, and that the estimates of dietary exposure were conservative.Therefore the Panel is of the opinion that the margin of safety is high enough to conclude that dietary exposure resulting from the proposed uses and use levels are not of safety concern.The Panel notes that to achieve these levels of dietary exposure, high level consumers would need to select a diet that was entirely composed of foods containing rosemary extracts for those food categories in which it was permitted. In reality not all processed foods will contain added antioxidants and it seems unlikely that these extracts would be used at the maximum usage level in all the proposed food in each category or that some consumers would systematically always choose all foods containing rosemary extract.Based on the margins of safety identified, the Panel concluded that the use of rosemary extracts at the proposed uses and use levels would not be of safety concern.