Duan Shu-Min, Zhang Yong-Liang, Gao Yan-Jun, Lyu Li-Zhi, Wang Yun
Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, 100191, China.
J Nanosci Nanotechnol. 2021 Oct 1;21(10):5014-5025. doi: 10.1166/jnn.2021.19351.
: Titanium dioxide (TiO₂), consisting of nanoparticles and sub-microparticles, were widely used as food additive and consumed by people every day, which has aroused a public safety concern. Some studies showed TiO₂ can be absorbed by intestine and then distributed to different tissues after oral intake, which is supposed to affect the content of various elements in the body whereas led to tissue damage. However, knowledge gaps still exist in the impact of TiO₂ on the disorder of elemental homeostasis. Thus, this study aimed to explore the oral toxicity of TiO₂ by assessing its influence on elemental homeostasis and tissues injury. : ICR mice were fed with normal feed, TiO₂ nanoparticles (NPs)-mixed feed or TiO₂ submicron particles (MPs)-mixed feed (1% mass fraction TiO₂ NPs or MPs were mixed in commercial pellet diet) for 1, 3, and 6 months. Particles used in this study were characterized. The distribution of Ti and other 23 elements, the correlation among elements, and pathological change in the liver, kidney, spleen and blood cells of the mice was determined. : Ti accumulation only appeared in blood cells of mice treated with TiO₂ MPs-mixed feed for 6 months, but TiO₂ cause 12 kinds of elements (boron, vanadium, iron, cobalt, copper, zinc, selenium, sodium, calcium, magnesium, silicon, phosphorus) content changed in organ tissue. The changed kinds of elements in blood cells (6 elements), liver (7 elements) or kidney (6 elements) were more than in the spleen (1 element). The TiO₂ NPs induced more elements changed in blood cells and liver, and the TiO₂ MPs induced more elements changed in kidney. Significantly positive correlation between Ti and other elements was found in different organs except the liver. Organ injuries caused by TiO₂ NPs were severer than TiO₂ MPs. Liver exhibited obvious pathological damage which became more serious with the increase of exposure time, while kidney and spleen had slight damages. : These results indicated long-time dietary intake of TiO₂ particles could induce element imbalance and organ injury. The liver displayed more serious change than other organs, especially under the treatment with TiO₂ NPs. Further research on the oral toxicity of TiO₂ NPs should pay more attention to the health effects of element imbalances using realistic exposure methods.
二氧化钛（TiO₂）由纳米颗粒和亚微米颗粒组成，作为食品添加剂被广泛使用且人们每日都会摄入，这引发了公众对其安全性的担忧。一些研究表明，口服摄入后TiO₂可被肠道吸收，然后分布到不同组织中，这可能会影响体内各种元素的含量并导致组织损伤。然而，关于TiO₂对元素稳态紊乱的影响仍存在知识空白。因此，本研究旨在通过评估TiO₂对元素稳态和组织损伤的影响来探讨其口服毒性。
将ICR小鼠分别用正常饲料、TiO₂纳米颗粒（NPs）混合饲料或TiO₂亚微米颗粒（MPs）混合饲料（在商业颗粒饲料中混合1%质量分数的TiO₂ NPs或MPs）喂养1、3和6个月。对本研究中使用的颗粒进行了表征。测定了小鼠肝脏、肾脏、脾脏和血细胞中Ti及其他23种元素的分布、元素之间的相关性以及病理变化。
Ti的蓄积仅出现在用TiO₂ MPs混合饲料处理6个月的小鼠血细胞中，但TiO₂导致器官组织中12种元素（硼、钒、铁、钴、铜、锌、硒、钠、钙、镁、硅、磷）含量发生变化。血细胞（6种元素）、肝脏（7种元素）或肾脏（6种元素）中元素变化的种类多于脾脏（1种元素）。TiO₂ NPs诱导血细胞和肝脏中更多元素发生变化，而TiO₂ MPs诱导肾脏中更多元素发生变化。除肝脏外不同器官中Ti与其他元素之间均存在显著正相关。TiO₂ NPs引起的器官损伤比TiO₂ MPs更严重。肝脏表现出明显的病理损伤，且随着暴露时间的增加而加重，而肾脏和脾脏有轻微损伤。
这些结果表明，长期通过饮食摄入TiO₂颗粒可导致元素失衡和器官损伤。肝脏的变化比其他器官更严重，尤其是在TiO₂ NPs处理下。关于TiO₂ NPs口服毒性的进一步研究应采用实际暴露方法，更多关注元素失衡对健康的影响。
