On the other hand, the U.S. Food and Drug Administration (FDA) in their Final Administrative Order on Sunscreen Drug Products posted in September 2021 still accepts titanium dioxide up to 25% in the list of Generally Recognized As Safe and Effective (GRASE) in the main document, without further clarification on what kind or size of particles [9]. However, on page 24 (Sunscreen containing nanomaterials) FDA clearly “distinguish nanomaterials from other forms of these ingredients'' (zinc oxide and titanium dioxide) and ask for comments on “any particular nanomaterials that you believe should not be permitted for use in OTC sunscreen products”. To the best of our knowledge, this Agency did not ban the use of nanoparticulate titanium dioxide in any form, even though it is mentioned on page 34 that the anatase form is the more photoactive one, due to the lack of evidence with real sunscreens OTC (over the counter) in vivo. Moreover, other regulations in Latin America (MERCOSUR agreement, 2006) do not state clearly their position on the use of nanoparticulate TiO2NPs [10].
For a review published in 2023 in the journal Environmental Pollution, researchers examined E171 as a possible factor promoting obesity-related metabolic disorders. Because gut microbiota play an important role in immune function maintenance and development, and because titanium dioxide as a food additive has been shown to alter gut microbiota, researchers wanted to review “the dysregulations along the gut microbiota-immune system axis after oral TiO2 exposure compared to those reported in obese or diabetic patients, and to highlight potential mechanisms by which foodborne TiO2 nanoparticles may increase the susceptibility to develop obesity-related metabolic disorders.” The study authors discovered recurrent changes in the gut microbiota composition when exposed to titanium dioxide nanoparticles, with an imbalance of intestinal symbiotic microbiota. These changes and imbalances were also reported and played a role in the development of obesity, the authors wrote. This highlights “foodborne TiO2 nanoparticles as an endocrine disruptor-like chemical promoting obesity-related disorders,” the authors concluded.
The basic scenario of resistive switching in TiO2 (Jameson et al., 2007) assumes the formation and electromigration of oxygen vacancies between the electrodes (Baiatu et al., 1990), so that the distribution of concomitant n-type conductivity (Janotti et al., 2010) across the volume can eventually be controlled by an external electric bias, as schematically shown in Figure 1B. Direct observations with transmission electron microscopy (TEM) revealed more complex electroforming processes in TiO2 thin films. In one of the studies, a continuous Pt filament between the electrodes was observed in a planar Pt/TiO2/Pt memristor (Jang et al., 2016). As illustrated in Figure 1C, the corresponding switching mechanism was suggested as the formation of a conductive nanofilament with a high concentration of ionized oxygen vacancies and correspondingly reduced Ti3+ ions. These ions induce detachment and migration of Pt atoms from the electrode via strong metal–support interactions (Tauster, 1987). Another TEM investigation of a conductive TiO2 nanofilament revealed it to be a Magnéli phase TinO2n−1 (Kwon et al., 2010). Supposedly, its formation results from an increase in the concentrations of oxygen vacancies within a local nanoregion above their thermodynamically stable limit. This scenario is schematically shown in Figure 1D. Other hypothesized point defect mechanisms involve a contribution of cation and anion interstitials, although their behavior has been studied more in tantalum oxide (Wedig et al., 2015; Kumar et al., 2016). The plausible origins and mechanisms of memristive switching have been comprehensively reviewed in topical publications devoted to metal oxide memristors (Yang et al., 2008; Waser et al., 2009; Ielmini, 2016) as well as TiO2 (Jeong et al., 2011; Szot et al., 2011; Acharyya et al., 2014). The resistive switching mechanisms in memristive materials are regularly revisited and updated in the themed review publications (Sun et al., 2019; Wang et al., 2020).
