Titanium dioxide nanoparticles: a review of current toxicological data

Abstract

Titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide in large quantities for use in a wide range of applications. TiO2 NPs possess different physicochemical properties compared to their fine particle (FP) analogs, which might alter their bioactivity. Most of the literature cited here has focused on the respiratory system, showing the importance of inhalation as the primary route for TiO2 NP exposure in the workplace. TiO2 NPs may translocate to systemic organs from the lung and gastrointestinal tract (GIT) although the rate of translocation appears low. There have also been studies focusing on other potential routes of human exposure. Oral exposure mainly occurs through food products containing TiO2 NP-additives. Most dermal exposure studies, whether in vivo or in vitro, report that TiO2 NPs do not penetrate the stratum corneum (SC). In the field of nanomedicine, intravenous injection can deliver TiO2 nanoparticulate carriers directly into the human body. Upon intravenous exposure, TiO2 NPs can induce pathological lesions of the liver, spleen, kidneys, and brain. We have also shown here that most of these effects may be due to the use of very high doses of TiO2 NPs. There is also an enormous lack of epidemiological data regarding TiO2 NPs in spite of its increased production and use. However, long-term inhalation studies in rats have reported lung tumors. This review summarizes the current knowledge on the toxicology of TiO2 NPs and points out areas where further information is needed.

Figure 1

Particulate distribution of TiO₂ particles by size through different regions of the respiratory tract. This diagram was derived from an explanation of particulate distribution after inhalation given by Simko and Mattsson [75]. Arrows represent downward movement of particles through the respiratory tract. Most particles in the size range of 1–5 nm are distributed throughout the three regions. 1 nm and 20 nm particles are mostly distributed in the nasopharyngeal region and alveolar regions respectively. 0.5-10 μm particles remain on the epithelial surface of the airways and alveoli.

Figure 2

Toxicokinetics and accumulation sites of TiO₂ NPs. The arrows in dotted lines represent uncertainties.