The FDA has not updated its general guidance on safety assessments since 2007. Within that time, there has been a significant increase in research on the confluence of toxicology, nanotechnology and human health. The EU updates its guidance regularly with new science available to offer proper safety assessments, with its most recent update published in 2021.

A  2023 study published in the journal Environmental Research, scientists examined the effect of titanium dioxide nanoparticles on important gut bacteria in mice. Their results showed “the growth inhibitory effects could be associated with cell membrane damage caused by titanium dioxide nanoparticles to the bacterial strains. Metabolomics analysis showed that TiO2 NPs caused alterations in multiple metabolic pathways of gut bacteria, such as tryptophan and arginine metabolism, which were demonstrated to play crucial roles in regulating gut and host health.” The researchers also found that four different neuroprotective metabolites “were significantly reduced” in urine and in vitro bacteria and vivo urine samples. The researchers concluded: “Increasing evidence implies that the gut microbiome plays a profound role in regulating host metabolism. Our results illustrated that TiO2 NPs hindered the growth of four beneficial gut bacterial strains.”

CSPI says it might reconsider its rating if specifications for food-grade titanium dioxide in the U.S. are updated to ensure nanoparticles are minimized, and new studies are conducted to assess its capacity to cause cancer or other health problems. 

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 Ti_nO_2n−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).