Heimbach J, Rieth S, Mohamedshah F, Slesinski R, Samuel-Fernando P, Sheehan T, Dickmann R, Borzelleca J
ENVIRON Corporation, 4350 N. Fairfax Drive, Arlington, VA 22203, USA.
Food Chem Toxicol. 2000 Jan;38(1):99-111. doi: 10.1016/s0278-6915(99)00125-8.
Iron EDTA [sodium iron (Fe(3+)) ethylenediaminetetraacetic acid (EDTA)], shown to have a significant beneficial effect on iron status by increasing iron bioavailability in human diets, has been proposed for use as a fortificant in certain grain-based products including breakfast cereals and cereal bars. This paper presents an assessment of the safety of iron EDTA for its intended uses in these products. Iron EDTA, like other EDTA-metal complexes, dissociates in the gastrointestinal tract to form iron, which is bioavailable, and an EDTA salt; absorption of the metal ion and EDTA are independent. Because of this dissociation, consideration of information on EDTA compounds other than iron EDTA is relevant to this safety assessment. EDTA compounds are poorly absorbed in the gastrointestinal tract and do not undergo significant metabolic conversion. They have a low degree of acute oral toxicity. EDTA compounds are not reproductive or developmental toxicants when fed with a nutrient-sufficient diet or minimal diets supplemented with zinc. In chronic toxicity studies, diets containing as much as 5% EDTA were without adverse effects. EDTA compounds were not carcinogenic in experimental animal bioassays and are not directly genotoxic. This lack of significant toxicity is consistent with a history of safe use of other EDTA compounds (CaNa(2)EDTA and Na(2)EDTA) approved by the FDA for use as direct food additives. An upper-bound estimated daily intake (EDI) of EDTA from iron EDTA (1.15mg/kg bw/day for the US population) is less than half the acceptable daily intake (ADI) for EDTA of 2. 5mg/kg bw/day established by JECFA. The data collected and published over the past 20 to 30 years demonstrate that iron EDTA is safe and effective for iron fortification of food products and meets the standard of "reasonable certainty of no harm". Based on the published record, iron EDTA may be regarded as generally recognized as safe (GRAS) for the intended food uses and maximum use levels.
乙二胺四乙酸铁钠[钠铁（Fe(3+)）乙二胺四乙酸（EDTA）]，通过提高人类饮食中铁的生物利用率，已被证明对铁营养状况有显著的有益作用，有人提议将其用作某些谷物类产品（包括早餐谷物和谷物棒）中的强化剂。本文对乙二胺四乙酸铁钠在这些产品中的预期用途进行了安全性评估。乙二胺四乙酸铁钠与其他EDTA金属络合物一样，在胃肠道中会解离形成具有生物利用性的铁和一种EDTA盐；金属离子和EDTA的吸收是相互独立的。由于这种解离，考虑除乙二胺四乙酸铁钠之外的其他EDTA化合物的信息与本次安全性评估相关。EDTA化合物在胃肠道中吸收很差，且不会发生显著的代谢转化。它们的急性经口毒性较低。当与营养充足的饮食或补充了锌的最低限度饮食一起喂食时，EDTA化合物不是生殖或发育毒性物质。在慢性毒性研究中，含有高达5% EDTA的饮食没有不良影响。EDTA化合物在实验动物生物测定中不具有致癌性，也没有直接的遗传毒性。这种缺乏显著毒性的情况与美国食品药品监督管理局（FDA）批准用作直接食品添加剂的其他EDTA化合物（CaNa₂EDTA和Na₂EDTA）的安全使用历史一致。乙二胺四乙酸铁钠的EDTA估计每日摄入量上限（美国人群为1.15mg/kg体重/天）不到食品添加剂联合专家委员会（JECFA）确定的EDTA每日可接受摄入量（ADI）2.5mg/kg体重/天的一半。过去20到30年收集和发表的数据表明，乙二胺四乙酸铁钠对食品进行铁强化是安全有效的，并且符合“无危害的合理确定性”标准。根据已发表的记录，乙二胺四乙酸铁钠对于预期的食品用途和最大使用量可被视为一般认为是安全的（GRAS）。
