Food-grade titanium dioxide (E171), a white colourant widely used in ultra-processed food products, has been banned in the European Union. However, its usage is still permitted in medicines, and in several other countries. The estimated intake of E171 in children is higher than in adults, which led us to hypothesise that E171 induces differential effects depending on age, with adult mice being the most susceptible due to age, despite the lower dose. To evaluate the effects of oral administration of E171 on intestinal permeability, ileum, and colon histology, and how these effects impact anxious and depressive behaviour in young and adult mice of both sexes. Young and adult mice of both sexes C57BL/6 mice received 10 mg/kg E171/3 times per week for 3 months. E171 was administered orally in water by pipetting, while control groups only received drinking water, then intestinal permeability, histology and animal behaviour were analysed. E171 showed an amorphous shape, primary particles sized below 1 µm and anatase crystalline structure. Oral administration of E171 disrupted the intestinal permeability in adult male and female mice, but no effects were observed in young mice of both sexes. E171 promoted ileal adenoma formation in half of the adult female population, moreover hyperplastic crypts, and hyperplastic goblet cells at histological level in adult mice of both sexes. The colon presented hyperplastic goblet cells, hyperchromatic nuclei, increased proliferation and DNA damage in adult mice of both sexes. The anxiety and depressive behaviour were only altered in adult mice treated with E171, but no changes were detected in young animals of both sexes. Adult mice displayed higher susceptibility in all parameters analysed in this study compared to young mice of both sexes.

中文翻译：

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口服食品级二氧化钛 (E171) 会引起成年小鼠的肠道和行为改变，但对幼年小鼠的影响有限

食品级二氧化钛 (E171) 是一种广泛用于超加工食品的白色着色剂，已被欧盟禁止使用。然而，它在药物中和其他几个国家仍然被允许使用。儿童 E171 的估计摄入量高于成人，这使我们假设 E171 会根据年龄产生不同的影响，成年小鼠由于年龄而最容易受到影响，尽管剂量较低。评估口服 E171 对肠道通透性、回肠和结肠组织学的影响，以及这些影响如何影响年轻和成年雌性小鼠的焦虑和抑郁行为。两性的幼年和成年小鼠 C57BL/6 小鼠每周接受 10 mg/kg E171/3 次，持续 3 个月。通过移液将E171溶于水中口服，而对照组仅接受饮用水，然后分析肠道通透性、组织学和动物行为。E171 呈无定形形状，初级颗粒尺寸低于 1 µm，具有锐钛矿晶体结构。口服 E171 会破坏成年雄性和雌性小鼠的肠道通透性，但在幼年和雌性小鼠中均未观察到影响。E171促进一半成年雌性小鼠中回肠腺瘤的形成，此外，在两性成年小鼠的组织学水平上促进隐窝增生和杯状细胞增生。成年雌雄小鼠的结肠均呈现增生性杯状细胞、深染细胞核、增殖增加和 DNA 损伤。仅接受 E171 治疗的成年小鼠的焦虑和抑郁行为发生改变，但在两性幼年动物中均未检测到任何变化。与年轻小鼠相比，成年小鼠在本研究中分析的所有参数中都表现出更高的敏感性。