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Nanoscale titanium dioxide (TiO(2)) is massively produced and widely used in living environment, which hence make the potential risk to human health. Central nervous system (CNS) is the potential susceptible target of inhaled nanoparticles, but the studies on this aspect are limited so far. We report the accumulation and toxicity results in vivo of two crystalline phases of TiO(2) nanoparticles (80nm, rutile and 155nm, anatase; purity >99%). The female mice were intranasally instilled with 500microg of TiO(2) nanoparticles suspension every other day for 30 days. Synchrotron radiation X-ray fluorescence analysis (SRXRF) and inductively coupled plasma mass spectrometry (ICP-MS) were used to determine the contents of titanium in murine brain. Then, the pathological examination of brain tissue, oxidative stress-mediated responses, and levels of neurochemicals in the brain of exposed mice were also analyzed. The obvious morphological changes of hippocampal neurons and increased GFAP-positive astrocytes in the CA4 region were observed, which were in good agreements with higher Ti contents in the hippocampus region. Oxidative stress occurred obviously in whole brain of exposed mice such as lipid peroxidation, protein oxidation and increased activities of catalase, as well as the excessive release of glutamic acid and nitric oxide. These findings indicate anatase TiO(2) nanoparticles exhibited higher concern on some tested biological effects. To summarize, results provided the preliminary evidence that nasal instilled TiO(2) nanoparticles could be translocated into the central nervous system and cause potential lesion of brain, and the hippocampus would be the main target within brain.

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 TiO(2) nanoparticles on central nervous system (CNS) through intranasal instillation. Size and structural properties are important to assess biological effects of TiO(2) nanoparticles. In present study, female mice were intranasally instilled with two types of well-characterized TiO(2) 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 TiO(2), 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 TiO(2) 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 TiO(2) particles at 30 days postexposure. Exposure to anatase TiO(2) particles also produced higher inflammation responses, in association with the significantly increased tumor necrosis factor alpha (TNF-alpha) and interleukin (IL-1 beta) levels. We conclude that subtle differences in responses to anatase TiO(2) particles versus the rutile ones could be related to crystal structure. Thus, based on these results, rutile ultrafine-TiO(2) 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 TiO(2) nanoparticles.

Hair is a well-established and widely used matrix for measuring mercury exposure of an individual. Although a variety of washing procedures to remove external mercury contamination have been proposed, no standardized procedures are available yet. In this study, different washing reagents like l-cysteine (Cys), 2-mercaptoethanol (ME), and disodium diaminoethanetetra acetate (EDTA) were used to find out if it is possible to remove mercury contamination from human scalp hair spiked with HgCl2 solutions at different concentrations. It was found that the external mercury contamination could not be fully washed off even using reagents with high affinity to mercury like l-cysteine and ME. However, for the well-pulverized CRM hair samples some of the endogenous mercury was washed off. It suggests that hair is not a suitable biomarker for evaluation of total mercury exposure especially in people like mercury miners or gold miners/burners associated with serious external Hg exposure. However, hair still can be used as an indicator for methyl mercury exposure because, generally, there is almost no exogenous contamination of methyl mercury in hair.

In order to evaluate the toxicity of TiO(2) particles, the acute toxicity of nano-sized TiO(2) particles (25 and 80nm) on adult mice was investigated compared with fine TiO(2) particles (155nm). Due to the low toxicity, a fixed large dose of 5g/kg body weight of TiO(2) suspensions was administrated by a single oral gavage according to the OECD procedure. In 2 weeks, TiO(2) particles showed no obvious acute toxicity. However, the female mice showed high coefficients of liver in the nano-sized (25 and 80nm) groups. The changes of serum biochemical parameters (ALT/AST, LDH) and pathology (hydropic degeneration around the central vein and the spotty necrosis of hepatocytes) of liver indicated that the hepatic injury was induced after exposure to mass different-sized TiO(2) particles. In addition, the nephrotoxicity like increased BUN level and pathology change of kidneys was also observed in the experimental groups. The significant change of serum LDH and alpha-HBDH in 25 and 80nm groups showed the myocardial damage compared with the control group. However, there are no abnormal pathology changes in the heart, lung, testicle (ovary), and spleen tissues. Biodistribution experiment showed that TiO(2) mainly retained in the liver, spleen, kidneys, and lung tissues, which indicated that TiO(2) particles could be transported to other tissues and organs after uptake by gastrointestinal tract.