Titanium Detected in Liver, Kidney, Spleen, and Intestine Is Not Related to Dose, Time, or Route of Exposure to Titanium Dioxide: A Systematic Review.

Titanium dioxide (TiO2), used as a food additive (labeled E171 in Europe), was withdrawn from the European market in 2022. The E171 toxicity mechanism involves its uptake, oxidative stress, DNA damage, and inflammation. It has been hypothesized that the TiO2 accumulation nanoparticles (NPs) or E171 triggers tissue damage, and some studies have quantified titanium (Ti) concentration in several organs. Still, the accumulation pattern and toxicokinetics remain unknown. We aimed to systematically review the Ti accumulation in the liver, kidney, spleen, intestine, and colon as these tissues have been reported to accumulate the highest Ti levels. We defined the search terms, and the literature search yielded 418 records. After the inclusion and exclusion criteria, only 58 records that quantified Ti after exposure to TiO2 NPs or E171 by five variants of inductively coupled plasma methods were considered for the analysis. A comparison of the sex of the animal model, the doses, type of titanium dioxide tested, and the administration route was performed. Based on this systematic review, we conclude that Ti accumulation in the tissues analyzed is unrelated to dose, administration route, exposure time, or animal model. Additionally, we found that the sample collection and digestion processes for biological samples analyzed varied among the studies, and the impact of these variations on Ti detection is unknown.