Food grade titanium dioxide (E171) interferes with monocyte-macrophage cell differentiation and their phagocytic capacity

• Published in: Food and chemical toxicology 2024-10, Vol.192, p.114912, Article 114912
• Main Authors: Zagal-Salinas, Alejandro A., Ispanixtlahuatl-Meráz, Octavio, Olguín-Hernández, Jonadab E., Rodríguez-Sosa, Miriam, García Cuéllar, Claudia M., Sánchez-Pérez, Yesennia, Chirino, Yolanda I.
• Format: Article
• Language: English
• Subjects: Cell differentiation; Cell Differentiation - drug effects; Cell Survival - drug effects; Cytokines - metabolism; Food-grade titanium dioxide; Humans; Macrophages; Macrophages - drug effects; Monocytes; Monocytes - drug effects; Phagocytosis - drug effects; THP-1 Cells; Titanium - chemistry; Titanium - toxicity; Uptake
• ISSN: 0278-6915; 1873-6351; 1873-6351
• DOI: 10.1016/j.fct.2024.114912

Food grade titanium dioxide E171 has been used in products such as confectionery, doughs and flours to enhance organoleptic properties. The European Union has warned about adverse effects on humans due to oral consumption. After oral exposure, E171 reaches the bloodstream which raises the concern about effects on blood cells such as monocytes. One of the main functions of these cells is the differentiation of macrophages leading to the phagocytosis of foreign particles. The aim of this study was to evaluate the effect of E171 exposure on the phagocytic capacity and differentiation process of monocytes (THP-1) into macrophages. Physicochemical E171 properties were evaluated, and THP-1 monocytes were exposed to 4, 40 and 200 μg/ml. Cell viability, uptake capacity, cytokine release, the differentiation process, cytoskeletal arrangement and E171 internalization were assayed. Results showed that E171 particles had an amorphous shape with a mean of hydrodynamic size of ∼46 nm in cell culture media. Cell viability decreased until the 9th day of exposure, while the uptake capacity decreased up to 62% in a concentration dependent manner in monocytes. Additionally, the E171 exposure increased the proinflammatory cytokines release and decreased the cell differentiation by a 61% in macrophages. E171 induced changes in cytoskeletal arrangement and some of the E171 particles were located inside the nuclei. We conclude that E171 exposure in THP-1 monocytes induced an inflammatory response, impaired the phagocytic capacity, and interfered with cell differentiation from monocytes to macrophages. [Display omitted] •THP-1 monocytes and derived macrophages internalize E171 agglomerates.•E171 particles reduce the phagocytic capacity of THP-1 monocytes and macrophages.•The THP-1 derived macrophages differentiation is decreased by E171 exposure.•Decreased THP-1 differentiation does not exacerbate phagocytic capacity reduction.