Periasamy Vaiyapuri Subbarayan, Athinarayanan Jegan, Al-Hadi Ahmed M, Juhaimi Fahad Al, Mahmoud Mohamed H, Alshatwi Ali A
Nanobiotechnology and Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food Science and Agriculture, Riyadh, Saudi Arabia.
Human Nutrition Department, National Research Centre Dokki, Cairo, Egypt.
Environ Toxicol Pharmacol. 2015 Jan;39(1):176-86. doi: 10.1016/j.etap.2014.11.021. Epub 2014 Dec 5.
Food grade TiO2 (E171) is a synthetic additive, and widely used as a coloring agent in many foods, pharmaceutical and personal care products. A few reports have highlighted that insoluble particulates (less than 200nm) of food grade TiO2 are found in many foods and confectionary products. However, information regarding the physico-chemical properties (i.e., size and shape)-based food grade TiO2 nanotoxicity related human health issues are limited. The main goal of this study is to examine the presence of nano-sized particulates and its structural characteristics of food grade- TiO2 materials and to assess the acute cellular uptake and metabolic stress induced by these particulates in human lung fibroblast (WI-38) cells. The results of transmission electron microscopy, energy dispersive X-ray spectroscopy, and X-ray diffraction studies indicated that about food grade TiO2 sample contains spherical shaped particulate forms in the nano-scale range, <100nm. The intracellular oxidative stress in human lung fibroblast cells (WI-38) was assessed through studies investigating the cellular uptake of the particles, changes in nuclear and cytoplasmic morphology, intracellular ROS, mitochondrial trans-membrane potential, the cell cycle and the expression of genes linked to metabolic stress markers. Altogether our data clearly indicate that primary metabolic stress indicators such as changes in the intracellular ROS, the dose-dependent loss of the mitochondrial membrane potential, alterations in cell cycle progression (G2/M>S>G0/G1) and changes in the TNF and CYP1A gene expression pattern are linked to cellular stress. Thus, food grade TiO2 as nano-scaled contaminants could not only be potential human health risk factors, suggesting that safety considerations with special respect to a few crucial factors such as size, and shape should be considered and regulated by food regulators.
食品级二氧化钛（E171）是一种合成添加剂，广泛用作许多食品、药品和个人护理产品中的着色剂。一些报告强调，在许多食品和糖果产品中发现了食品级二氧化钛的不溶性颗粒（小于200纳米）。然而，关于基于物理化学性质（即尺寸和形状）的食品级二氧化钛纳米毒性与人类健康问题的信息有限。本研究的主要目的是检查食品级二氧化钛材料中纳米级颗粒的存在及其结构特征，并评估这些颗粒在人肺成纤维细胞（WI-38）中引起的急性细胞摄取和代谢应激。透射电子显微镜、能量色散X射线光谱和X射线衍射研究结果表明，食品级二氧化钛样品中约含有纳米级范围内（<100纳米）的球形颗粒形式。通过研究颗粒的细胞摄取、细胞核和细胞质形态变化、细胞内活性氧、线粒体跨膜电位、细胞周期以及与代谢应激标志物相关的基因表达，评估了人肺成纤维细胞（WI-38）中的细胞内氧化应激。我们的数据清楚地表明，主要的代谢应激指标，如细胞内活性氧的变化、线粒体膜电位的剂量依赖性丧失、细胞周期进程的改变（G2/M>S>G0/G1）以及TNF和CYP1A基因表达模式的变化，都与细胞应激有关。因此，食品级二氧化钛作为纳米级污染物不仅可能是潜在的人类健康风险因素，这表明食品监管机构应考虑并规范一些关键因素（如尺寸和形状）的安全性。
