Flavouring Group Evaluation 5: Esters of 23 branched-and straight-chain aliphatic saturated primary alcohols and of one secondary alcohol, and 24 branched-and straight-chain unsaturated carboxylic acids from chemical groups 1, 2, and 5 (Commission Regulation (EC) No 1565/2000 of 18 July 2000)
Flavouring Group Evaluation 5: Esters of 23 branched-and straight-chain aliphatic saturated primary alcohols and of one secondary alcohol, and 24 branched-and straight-chain unsaturated carboxylic acids from chemical groups 1, 2, and 5 (Commission Regulation (EC) No 1565/2000 of 18 July 2000)
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DOI：
10.2903/j.efsa.2005.204/full
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发表时间：
2005-07-01
期刊：
影响因子：
3.3
通讯作者：
Toldra, Fidel
中科院分区：
文献类型：
--
作者：
Anton, Robert;Barlow, Sue;Toldra, Fidel
食品添加剂、调味料、加工助剂和与食品接触的材料问题小组被要求就成员国食品中或食品上使用的化学定义的调味物质对人类健康的影响向委员会提供咨询意见。特别地，该小组被要求评估调味剂组评估FGE中的24种调味剂物质。使用欧盟委员会法规EC No 1565/2000中提到的程序。这24种调味物质属于欧盟委员会法规EC No 1565/2000附件I的化学组1、2和5。目前的调味基团评价涉及24种酯类，包括支链和直链饱和脂肪族伯醇（包括一个仲醇）和支链和直链不饱和羧酸。24种调味物质中有19种可以以几何异构体的形式存在。在其中11个案例中，没有迹象表明其中一种可能的异构体在商业调味材料中具有优势。此外，一种候选物质具有手性中心。其中21种物质属于结构类，3种物质属于结构类。据报道，目前这24种物质中有22种自然存在于各种食品中。在其评估中，专家小组默认使用最大调查衍生的每日摄入量（msdi）方法来估计欧洲人均调味物质的摄入量。然而，当小组审查欧洲调味工业提供的关于各种食品中使用水平的信息时，很明显，在许多情况下，MSDI方法严重低估了按行业报告的使用水平调味的产品的普通消费者的摄入量，特别是在那些报告的年产值很小的情况下。因此，评估小组对所提供的使用和使用水平数据以及MSDI方法所获得的摄入量估计数持保留意见。由于缺乏更精确的信息，使小组能够对调味物质的摄入量做出更现实的估计，小组还决定根据工业报告的正常使用量，使用改进的理论添加最大每日摄入量（mTAMDI）方法对每人的每日摄入量进行估计。在mTAMDI方法表明调味物质的摄入量可能超过其相应的关注阈值的情况下，小组决定不使用该程序进行正式的安全评估。在这些情况下，小组需要关于使用和使用水平的更精确数据。根据默认的MSDI方法，这组24种调味物质在欧洲的摄入量从0.0012微克/人/天到1.7微克/人/天，低于结构I类物质（1800微克/人/天）和结构II类物质（540微克/人/天）的关注值阈值。预计所有24种调味物质将参与共同的吸收、分布和代谢途径，并表现出相似的毒理学特性。本调味类评价中所包含的中短长度线性和支链醇和羧酸的数据以及这类化学物质的一般信息表明，它们从肠道中被迅速吸收、代谢和排泄，并且可以预期，该组的24个酯将在相对较短的时间内水解成相应的酸和醇。在这24种调味物质中有三种甲基丙烯酸酯，即甲基丙烯酸乙酯[FL-no: 09.375]、甲基丙烯酸甲酯[FL-no: 09.647]和2-甲基丙烯酸异丁基[FL-no: 09.586]。在一项为期60天的大鼠饮用水研究中，甲基丙烯酸乙酯的最低剂量为50 mg/kg体重/天。因此，不能设立一个不受影响的工作。正如欧盟风险评估报告所示，甲基丙烯酸甲酯同样具有神经毒性。然而，口服研究中没有足够的NOAEL用于甲基丙烯酸甲酯。对于异丁基2-甲基丙烯酸酯，既没有神经毒性研究，也没有其他重复剂量毒性研究。因此，需要额外的甲基丙烯酸乙酯[FL-no: 09.375]、甲基丙烯酸甲酯[FL-no: 09.647]和2-甲基丙烯酸异丁基[FL-no: 09.586]的毒性数据。遗传毒性资料有限，无法充分评估遗传毒性。然而，现有的数据以及候选物质的化学结构并没有引起对这类调味物质的遗传毒性的关注。据认为，根据默认的MSDI方法，24种物质中的21种在用作调味物质的估计摄入量下不会引起安全问题。对于三种调味物质，即甲基丙烯酸乙酯[FL-no: 09.375]、甲基丙烯酸甲酯[FL-no: 09.647]和2-甲基丙烯酸异丁酯[FL-no: 09.586]，由于需要额外的毒性数据，评估已被推迟。当根据mTAMDI估计摄入量时，21种结构类候选物质的摄入量范围为3400至3700微克/人/天，因此，摄入量高于结构类1800微克/人/天的关注阈值。对于被划分为结构II类的三种调味物质，基于mTAMDI的估计摄入量为3700微克/人/天，高于结构II类540微克/人/天的关注阈值。因此，根据mTAMDI估计的24种调味物质的摄入量超过了指定调味剂的结构类的阈值。因此，需要更可靠的暴露数据。在这些额外数据的基础上，这些调味物质应该在程序的步骤中重新考虑。按照这个程序，可能需要额外的毒理学数据。为了确定这种评价是否适用于商业材料，有必要考虑现有的规范。已为所有24种候选调味物质提供了适当的规格，包括完整的纯度标准和商用材料的鉴定测试，但需要为11种物质提供几何和光学异构的信息。因此，对这11种物质[FL-no: 09.324, 09.329, 09.330, 09.335, 09.372, 09.374, 09.379, 09.625, 09.637, 09.641和09.865]的商业材料不能进行最终的评估，等待进一步的规格信息。
The Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food is asked to advise the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Panel is asked to evaluate 24 flavouring substances in the Flavouring Group Evaluation FGE. 05, using the procedure as referred to in the Commission Regulation EC No 1565/2000. These 24 flavouring substances belong to chemical groups 1, 2, and 5 of Annex I of the Commission Regulation EC No 1565/2000.The present Flavouring Group Evaluation deals with 24 esters with branched-and straight-chain aliphatic saturated primary alcohols (including one secondary alcohol) and branched-and straightchain unsaturated carboxylic acids.Nineteen of the 24 flavouring substances can exist as geometrical isomers. In 11 of these cases, no indication has been given that one of the possible isomers has preponderance in the commercial flavouring material. In addition, one candidate substance possesses a chiral centre.Twenty-one of them belong to structural class I while three substances were assigned to structural class II.Twenty-two of the substances in the present group of 24 substances have been reported to occur naturally in a wide range of food items.In its evaluation, the Panel as a default used the Maximised Survey-derived Daily Intakes (MSDIs) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Panel examined the information provided by the European flavouring industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate the intake by regular consumers of products flavoured at the use level reported by the industry, especially in those cases where the annual production values were reported to be small. In consequence, the Panel had reservations about the data on use and use levels provided and the intake estimates obtained by the MSDI approach.In the absence of more precise information that would enable the Panel to make a more realistic estimate of the intakes of the flavouring substances, the Panel has decided also to perform an estimate of the daily intakes per person using a modified Theoretical Added Maximum Daily Intake(mTAMDI) approach based on the normal use levels reported by industry. In those cases where the mTAMDI approach indicated that the intake of a flavouring substance might exceed its corresponding threshold of concern, the Panel decided not to carry out a formal safety assessment using the Procedure. In these cases the Panel requires more precise data on use and use levels.According to the default MSDI approach, the 24 flavouring substances in this group have intakes in Europe from 0.0012 to 1.7 microgram/capita/day which are below the threshold of concern value for both structural class I (1800 microgram/person/day) and structural class II (540 microgram/person/day) substances.All 24 flavouring substances are expected to participate in common routes of absorption, distribution and metabolism, and exhibit similar toxicological properties. Data for short and medium length linear and branched-chain alcohols and the carboxylic acids included in the present Flavouring Group Evaluation and general information for this class of chemicals indicate that they are rapidly absorbed from the intestinal tract, metabolised and excreted, and it can be expected that the 24 esters of the group will be hydrolysed to their corresponding acids and alcohols in humans within a relatively short time.There are three methacrylates in this group of 24 flavouring substances, i.e. ethyl methacrylate [FLno: 09.375], methyl methacrylate [FL-no: 09.647], and isobutyl 2-methylprop-2-enoate [FL-no: 09.586]. Ethyl methacrylate induced neurotoxicity in a 60-day drinking water study in rats at 50 mg/kg body weight/day, the lowest dose tested. Accordingly, a NOAEL could not be established. Methyl methacrylate has a neurotoxic potential likewise, as shown in an EU Risk Assessment Report. However, an adequate NOAEL from an oral study is not available for methyl methacrylate. For isobutyl 2-methylprop-2-enoate, there are neither neurotoxicity studies nor other repeated dose toxicity studies. Therefore, additional toxicity data for ethyl methacrylate [FL-no: 09.375], methyl methacrylate [FL-no: 09.647], and isobutyl 2-methylprop-2-enoate [FL-no: 09.586] are required.Genotoxicity data are limited and the genotoxicity could not be assessed adequately. However, the available data as well as the chemical structures of the candidate substances do not raise concerns about genotoxicity for the flavouring substances in this group.It is considered that on the basis of the default MSDI approach 21 of the 24 substances would not give rise to safety concerns at the estimated levels of intake arising from their use as flavouring substances. For three flavouring substances, i.e. ethyl methacrylate [FL-no: 09.375], methyl methacrylate [FL-no: 09.647], and isobutyl-2-methylprop-2-enoate [FL-no: 09.586], the evaluation has been deferred as additional toxicity data are required.When the estimated intakes were based on the mTAMDI they ranged from 3400 to 3700 microgram/person/day for the 21 candidate substances from structural class I. Thus, the intakes were above the threshold of concern for structural class I of 1800 microgram/person/day. For each of the three flavouring substances assigned to structural class II, the estimated intake based on the mTAMDI is 3700 microgram/capita/day, which is above the threshold of concern for structural class II of 540 microgram/person/day.Thus, for the 24 flavouring substances the intakes estimated on the basis of the mTAMDI exceed the threshold for the structural class, for which the flavouring has been assigned. Therefore, more reliable exposure data are required. On the basis of such additional data, these flavouring substances should be reconsidered along the steps of the procedure. Following this procedure, additional toxicological data might become necessary.In order to determine whether this evaluation could be applied to the material of commerce, it is necessary to consider the available specifications.Adequate specifications including complete purity criteria and identity tests for the materials of commerce have been provided for all 24 candidate flavouring substances, except that information on geometrical and optical isomerism is needed for 11 substances. Thus, the final evaluation of thematerials of commerce cannot be performed for these 11 substances [FL-no: 09.324, 09.329, 09.330, 09.335, 09.372, 09.374, 09.379, 09.625, 09.637, 09.641, and 09.865], pending further information on specifications.