Safety assessment of titanium dioxide (E171) as a food additive.
Safety assessment of titanium dioxide (E171) as a food additive.
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DOI：
10.2903/j.efsa.2021.6585
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发表时间：
2021-05
期刊：
影响因子：
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通讯作者：
Wright M
中科院分区：
文献类型：
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作者：
EFSA Panel on Food Additives and Flavourings (FAF);Younes M;Aquilina G;Castle L;Engel KH;Fowler P;Frutos Fernandez MJ;Fürst P;Gundert-Remy U;Gürtler R;Husøy T;Manco M;Mennes W;Moldeus P;Passamonti S;Shah R;Waalkens-Berendsen I;Wölfle D;Corsini E;Cubadda F;De Groot D;FitzGerald R;Gunnare S;Gutleb AC;Mast J;Mortensen A;Oomen A;Piersma A;Plichta V;Ulbrich B;Van Loveren H;Benford D;Bignami M;Bolognesi C;Crebelli R;Dusinska M;Marcon F;Nielsen E;Schlatter J;Vleminckx C;Barmaz S;Carfí M;Civitella C;Giarola A;Rincon AM;Serafimova R;Smeraldi C;Tarazona J;Tard A;Wright M
本意见涉及食品添加剂二氧化钛(E-171)的最新安全评估，其依据是专家小组认为可靠的新的相关科学证据，包括使用纳米二氧化钛(NPs)获得的数据和一代生殖毒性扩展研究(EOGRT)的数据。按数量计算，E-171中不到50%的组成颗粒具有最小外部尺寸&100 nm。此外，专家小组还注意到，组成颗粒<lt；30纳米的颗粒在数量上不到颗粒的1%。因此，专家小组认为，对30纳米二氧化钛的研究与E-171的安全评估没有多大关系。专家小组的结论是，虽然胃肠道对二氧化钛颗粒的吸收较低，但它们可能会在体内积聚。对全身和器官毒性的研究没有显示出不良反应，无论是E-171每天1,000毫克/公斤体重(BW)剂量，还是二氧化钛纳米粒(>；30 nm)最高测试剂量100 mg/kg体重(BW)。在EOGRT研究中测试的最高剂量1,000毫克E171/kg bw的剂量下，没有观察到对生殖和发育毒性的影响。然而，观察到E-171的潜在免疫毒性和炎症，以及纳米二氧化钛的潜在神经毒性，以及E-171可能诱导的异常隐窝病灶，可能会产生不良反应。关于遗传毒性，专家小组得出结论，二氧化钛颗粒有可能导致DNA链断裂和染色体损伤，但不会导致基因突变。无论是在体外还是在体内进行遗传毒性测试，都没有观察到二氧化钛颗粒的物理化学性质与结果之间的明显相关性。因此，不能排除E-171中可能存在的对二氧化钛颗粒遗传毒性的担忧。遗传毒性的几种作用模式可能是并行运行的，而由二氧化钛颗粒引发的不同分子机制的相对贡献尚不清楚。至于是否可以假定采取门槛行动模式，则存在不确定性。此外，无法确定与遗传毒性相关的二氧化钛颗粒大小的截止值。目前还没有适当设计的研究来研究纳米二氧化钛的潜在致癌作用。根据所有现有证据，不能排除对遗传毒性的担忧，考虑到许多不确定因素，专家小组得出结论，E-171用作食品添加剂时不再被认为是安全的。
The present opinion deals with an updated safety assessment of the food additive titanium dioxide (E 171) based on new relevant scientific evidence considered by the Panel to be reliable, including data obtained with TiO2 nanoparticles (NPs) and data from an extended one‐generation reproductive toxicity (EOGRT) study. Less than 50% of constituent particles by number in E 171 have a minimum external dimension < 100 nm. In addition, the Panel noted that constituent particles < 30 nm amounted to less than 1% of particles by number. The Panel therefore considered that studies with TiO2 NPs < 30 nm were of limited relevance to the safety assessment of E 171. The Panel concluded that although gastrointestinal absorption of TiO2 particles is low, they may accumulate in the body. Studies on general and organ toxicity did not indicate adverse effects with either E 171 up to a dose of 1,000 mg/kg body weight (bw) per day or with TiO2 NPs (> 30 nm) up to the highest dose tested of 100 mg/kg bw per day. No effects on reproductive and developmental toxicity were observed up to a dose of 1,000 mg E 171/kg bw per day, the highest dose tested in the EOGRT study. However, observations of potential immunotoxicity and inflammation with E 171 and potential neurotoxicity with TiO2 NPs, together with the potential induction of aberrant crypt foci with E 171, may indicate adverse effects. With respect to genotoxicity, the Panel concluded that TiO2 particles have the potential to induce DNA strand breaks and chromosomal damage, but not gene mutations. No clear correlation was observed between the physico‐chemical properties of TiO2 particles and the outcome of either in vitro or in vivo genotoxicity assays. A concern for genotoxicity of TiO2 particles that may be present in E 171 could therefore not be ruled out. Several modes of action for the genotoxicity may operate in parallel and the relative contributions of different molecular mechanisms elicited by TiO2 particles are not known. There was uncertainty as to whether a threshold mode of action could be assumed. In addition, a cut‐off value for TiO2 particle size with respect to genotoxicity could not be identified. No appropriately designed study was available to investigate the potential carcinogenic effects of TiO2 NPs. Based on all the evidence available, a concern for genotoxicity could not be ruled out, and given the many uncertainties, the Panel concluded that E 171 can no longer be considered as safe when used as a food additive.