Time-dependent translocation and potential impairment on central nervous system by intranasally instilled TiO₂ nanoparticles

Nanoparticles can be administered via nasal, oral, intraocular, intratracheal (pulmonary toxicity), tail vein and other routes. Here, we focus on the time-dependent translocation and potential damage of TiO₂ nanoparticles on central nervous system (CNS) through intranasal instillation. Size and structural properties are important to assess biological effects of TiO₂ nanoparticles. In present study, female mice were intranasally instilled with two types of well-characterized TiO₂ nanoparticles (i.e. 80 nm, rutile and 155 nm, anatase; purity > 99%) every other day. Pure water instilled mice were served as controls. The brain tissues were collected and evaluated for accumulation and distribution of TiO₂, histopathology, oxidative stress, and inflammatory markers at post-instillation time points of 2, 10, 20 and 30 days. The titanium contents in the sub-brain regions including olfactory bulb, cerebral cortex, hippocampus, and cerebellum were determined by inductively coupled plasma mass spectrometry (ICP-MS). Results indicated that the instilled TiO₂ directly entered the brain through olfactory bulb in the whole exposure period, especially deposited in the hippocampus region. After exposure for 30 days, the pathological changes were observed in the hippocampus and olfactory bulb using Nissl staining and transmission electron microscope. The oxidative damage expressed as lipid peroxidation increased significantly, in particular in the exposed group of anatase TiO₂ particles at 30 days postexposure. Exposure to anatase TiO₂ particles also produced higher inflammation responses, in association with the significantly increased tumor necrosis factor alpha (TNF-α) and interleukin (IL-1β) levels. We conclude that subtle differences in responses to anatase TiO₂ particles versus the rutile ones could be related to crystal structure. Thus, based on these results, rutile ultrafine-TiO₂ particles are expected to have a little lower risk potential for producing adverse effects on central nervous system. Although understanding the mechanisms requires further investigation, the present results suggest that we should pay attention to potential risk of occupational exposure for large-scaled production of TiO₂ nanoparticles.