Nervous system References Crystal phase composition (particle size in nm) Type of exposure Type and number of animals Results Wang et al., 2007 [91 ] TiO2 (25, 80, 155) Intranasal instillation : 50 mg/kg TiO2 BW every other day for 20 days.Female CD mice Ti brain content: increased. Neurotransmitters : NE and 5-HT increased; DA, DOPAC, HVA, and 5-HIAA decreased. Wang et al., 2008 [31 ] Rutile TiO2 (80) 2 (155) Intranasal instillation: 500 μ g TiO2 every other day for 15 times.15 female CD-1(ICR) mice Ti brain distribution: mainly in olfactory bulb and hippocampus. Oxidative stress: CAT, MDA, Pr. Carb. increased, SOD decreased. Neurotransmitters: AchE, Glu and NO increased. Wang et al., 2008 [92 ] See Wang et al., 2008 [31 ] Intranasal instillation : 500 μ g TiO2 every other day for 15 times.10 female CD-1(ICR) mice Ti brain distribution: mainly in hippocampus. Oxidative stress: GSH-Px, GST, SOD, GSH, and MDA increased. Histology: irregular neuronal arrangement, condensated chromatin. Inflammatory action: increased TNF-α and IL-1β levels. Shimizu et al., 2009 [102 ] Anatase TiO2 (25–70) Subcutaneous injections : 100 μ L of TiO2 at 1 μ g/μ L on gestational days 6, 9, 12, and 15.15 pregnant ICR mice, 21 male fetuses and pups Gene expression : up-regulated cell death, apoptosis, brain development, oxidative stress, apoptosis, neurotransmitter genes. Takeda et al., 2009 [101 ] Anatase TiO2 (25–70) Subcutaneous injections : 100 μ L of TiO2 at 1 mg/mL at 3, 7, 10 and 14 days post-coitum.6 pregnant Slc:ICR mice per group
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offspring brain distribution: cortex and olfactory bulb. Apoptosis: presence of markers and features in olfactory cells. Takahashi et al., 2010 [103 ] Anatase TiO2 (25–70) Subcutaneous injections : 100 μ L of TiO2 at 1 mg/mL at gestational days 6, 9, 12, 15, 18.Pregnant Slc:ICR mice per group Monoamine levels: DA, DOPAc, HVA, 3-MT increased in the prefrontal cortex and neostriatum. Ma et al., 2010 [93 ] Anatase TiO2 (5) 2 (10–15 nm.) Intra-abdominal injections: 5–150 mg/kg nano-TiO2 and 150 mg/kg bulk TiO2 every day for 14 days, respectively.10 female CD-1(ICR) mice per group Ti brain content : higher increase with nano TiO2 . Oxidative stress :
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, H2 O2 , MDA, NOS, iNOS, NO increased; antioxidative enzymes, GLU, AchE decreased. Histology : filamentous-shaped neurons and inflammatory cells. Shin et al., 2010 [99 ] Rutile TiO2 (1 μ m) 2 (21) Intraperitoneal injections: 40 mg/kg TiO2 30 min after vehicle or 5 mg/kg LPS.3–6 male C57BL/6 mice per group Inflammatory action: after LPS, TiO2 NPs increased IL-1β , TNF-α and iNOS and induced microglial activation. Oxidative stress: after LPS TiO2 NPs enhanced ROS. Hu et al., 2010 [94 ] Anatase TiO2 (5) Intragastric administration : 5–50 mg/kg TiO2 suspension every day for 60 days.20 female mice per group Neurotransmitters: ACh, Glu, and NO increased; NE, DA, DOPAC,5-HT, and 5-HIAA decreased. Enzyme activity: decreased Na+ /K+ , Ca2+ , Ca2+ /Mg2+ ATPase; promoted AchE, and iNOS. Li et al., 2010 [73 ] Anatase TiO2 (3) Intratracheal instillation: 3.3 mg/kg TiO2 once a wk for 4 wks.13 male Kunming mice per group Ti brain content : increased Oxidative stress:
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, OH− , H2 O2 , MDA increased in brain. Histology: exudates, inflammatory infiltration and necrosis. Yamashita et al., 2011 [100 ] TiO2 (35) Intravenous injection: 0.8 mg TiO2 for 2 consecutive gestational days.Pregnant mice Ti distribution: TiO2 detected in fetal brainJeon et al., 2011 [95 ] TiO2 N.A N.A. Proteomic analysis: altered protein expression. Oxidative stress: antioxidant and AchE activities reduced.
