Oral Excretion Kinetics of Food-Additive Silicon Dioxides and Their Effect on In Vivo Macrophage Activation

A food additive, silicon dioxide (SiO₂) is commonly used in the food industry as an anti-caking agent. The presence of nanoparticles (NPs) in commercial food-grade SiO₂ has raised concerns regarding their potential toxicity related to nano size. While recent studies have demonstrated the oral absorption and tissue distribution of food-additive SiO₂ particles, limited information is available about their excretion behaviors and potential impact on macrophage activation. In this study, the excretion kinetics of two differently manufactured (fumed and precipitated) SiO₂ particles were evaluated following repeated oral administration to rats for 28 d. The excretion fate of their intact particles, decomposed forms, or ionic forms was investigated in feces and urine, respectively. Monocyte uptake, Kupffer cell activation, and cytokine release were assessed after the oral administration of SiO₂ particles. Additionally, their intracellular fates were determined in Raw 264.7 cells. The results revealed that the majority of SiO₂ particles were not absorbed but directly excreted via feces in intact particle forms. Only a small portion of SiO₂ was eliminated via urine, predominantly in the form of bioconverted silicic acid and slightly decomposed ionic forms. SiO₂ particles were mainly present in particle forms inside cells, followed by ionic and silicic acid forms, indicating their slow conversion into silicic acid after cellular uptake. No effects of the manufacturing method were observed on excretion and fates. Moreover, no in vivo monocyte uptake, Kupffer cell polarization, or cytokine release were induced by orally administered SiO₂ particles. These finding contribute to understanding the oral toxicokinetics of food-additive SiO₂ and provide valuable insights into its potential toxicity.