Due to this reason, they have been traditionally used as a “negative control” in many in vitro and in vivo particle toxicological studies. Traditionally, TiO 2 FPs have been considered as poorly soluble, low toxicity particles. Since surface properties, such as energy level, electronic structure, and reactivity are quite different from interior states, the bioactivity of NPs will likely differ from that of the fine size analogue. The smaller size of NPs ensures that a large portion of atoms will be on the particle surface. NPs generally possess dramatically different physicochemical properties compared to fine particles (FPs) of the same composition. Others have defined NPs as objects with at least one of their three dimensions in the range of 1–100 nm. In October 2011 the European Union defined nanomaterials as a natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or agglomerate where 50% or more of the particles exhibited, one or more external dimensions in the size range 1–100 nm. With the development of nanotechnology, there has been a tremendous growth in the application of NPs for drug delivery systems, antibacterial materials, cosmetics, sunscreens, and electronics. This review summarizes the current knowledge on the toxicology of TiO 2 NPs and points out areas where further information is needed. However, long-term inhalation studies in rats have reported lung tumors. There is also an enormous lack of epidemiological data regarding TiO 2 NPs in spite of its increased production and use. We have also shown here that most of these effects may be due to the use of very high doses of TiO 2 NPs. Upon intravenous exposure, TiO 2 NPs can induce pathological lesions of the liver, spleen, kidneys, and brain. In the field of nanomedicine, intravenous injection can deliver TiO 2 nanoparticulate carriers directly into the human body. Most dermal exposure studies, whether in vivo or in vitro, report that TiO 2 NPs do not penetrate the stratum corneum (SC). Oral exposure mainly occurs through food products containing TiO 2 NP-additives. There have also been studies focusing on other potential routes of human exposure.
TiO 2 NPs may translocate to systemic organs from the lung and gastrointestinal tract (GIT) although the rate of translocation appears low. Most of the literature cited here has focused on the respiratory system, showing the importance of inhalation as the primary route for TiO 2 NP exposure in the workplace.
TiO 2 NPs possess different physicochemical properties compared to their fine particle (FP) analogs, which might alter their bioactivity. Titanium dioxide (TiO 2) nanoparticles (NPs) are manufactured worldwide in large quantities for use in a wide range of applications.
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