Pulmonary toxicity study in rats with three forms of ultrafine-TiO

DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE 19714-0050, USA.
Toxicology (Impact Factor: 3.62). 02/2007; 230(1):90-104. DOI: 10.1016/j.tox.2006.11.002
Source: PubMed


Surface properties are critical to assess effects of ultrafine-TiO(2) particles. The aim of this study was to assess lung toxicity in rats of newly developed, well characterized, ultrafine-TiO(2) particles and compare them to TiO(2) samples in two different size ranges and surface modifications. Groups of rats were intratracheally instilled with doses of 1 or 5mg/kg of either two ultrafine rutile TiO(2) particles (uf-1 or uf-2); rutile R-100 fine-TiO(2) (F-1); 80/20 anatase/rutile P25 ultrafine-TiO(2) (uf-3); or alpha-quartz particles. Phosphate-buffered saline (PBS) solution instilled rats served as vehicle controls. Following exposures, the lungs of PBS and particle-exposed rats were evaluated for bronchoalveolar lavage (BAL) fluid inflammatory markers, cell proliferation, and by histopathology at post-instillation time points of 24h, 1 week, 1 and 3 months. The ranking of lung inflammation/cytotoxicity/cell proliferation and histopathological responses was quartz>uf-3>F-1=uf-1=uf-2. Exposures to quartz and to a lesser degree, uf-3 anatase/rutile TiO(2) particles produced pulmonary inflammation, cytotoxicity and adverse lung tissue effects. In contrast, exposures to F-1 fine-TiO(2) particles or to uf-1/uf-2 ultrafine-TiO(2) particle-types produced transient inflammation. We conclude that differences in responses to anatase/rutile uf-3 TiO(2) particles versus the rutile uf-1 and uf-2 TiO(2) particles could be related to crystal structure, inherent pH of the particles, or surface chemical reactivity. Thus, based on these results, inhaled rutile ultrafine-TiO(2) particles are expected to have a low risk potential for producing adverse pulmonary health effects. Finally, the results demonstrate that exposures to ultrafine-TiO(2) particle-types can produce differential pulmonary effects, based upon their composition, and crystal structure. Thus, the lung toxicity of anatase/rutile uf-3 should not be viewed as representative for all ultrafine-TiO(2) particle-types.

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    • "One can only speculate about the reason why TiO 2 anatase but not TiO 2 rutile nanoparticles accelerated thrombus formation. There is good evidence that the toxicity of TiO 2 nanoparticles depends on their crystallite structure in that TiO 2 anatase nanoparticles are supposed to be more toxic than TiO 2 rutile nanoparticles or mixtures of both (Jiang et al., 2008; Petkovic et al., 2011; Sayes et al., 2006; Warheit et al., 2007). Another aspect could be the mechanism underlying the initiation of platelet aggregation. "
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    ABSTRACT: Abstract It has been suggested that engineered nanomaterials (ENM), once arrived in the circulation, may affect the cardiovascular system. The aim of this in vivo study was to screen major cardiovascular effects of acute systemic administration of a panel of five nanomaterials, TiO2 anatase (NM-101), TiO2 rutile (NM-104), ZnO (NM-110), SiO2 (NM-200) and Ag (NM-300). Mice were anesthetized and the ENM were injected at a dose of 1 mg/kg via a catheter placed in the left femoral artery. Hemodynamic parameters were determined by invasive measurement of blood pressure and non-invasive measurement of heart rate. Ten minutes after injection of the ENM, the formation of light/dye-induced thrombi was assessed in the cremasteric microcirculation by intravital microscopy. In addition, the numbers of rolling, firmly adherent and transmigrated leukocytes were recorded in postcapillary cremasteric venules over a time period of 120 min after injection of ENM by intravital microscopy. The systemic administration of a single dose of the ENM tested did not dramatically alter hemodynamic parameters or affect early steps of leukocyte recruitment. However, the presence of circulating TiO2 anatase, but not of TiO2 rutile, SiO2, ZnO or Ag nanoparticles, significantly accelerated thrombus formation in the murine microcirculation. Moreover, TiO2 anatase but not TiO2 rutile nanoparticles increased murine platelet aggregation in vitro. Taken together, only one of the five systemically administered ENM, TiO2 anatase, affected hemostasis, whereas none of the ENM tested in this screening study dramatically modulated hemodynamic parameters or early steps of leukocyte recruitment.
    Nanotoxicology 02/2015; 11(8):1-9. DOI:10.3109/17435390.2014.992815 · 6.41 Impact Factor
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    • "and are distributed to important organ systems, including the lymph, brain, lung, liver, and kidney (Bermudez et al. 2004; Wang et al. 2007). Other studies have shown that it produced pulmonary inflammation, cytotoxicity, and histopathological changes by intratracheally instillation (Warheit et al. 2007), intraperitoneal injection, or oral administration. Many studies have unequivocally showed that exposure to TiO 2 NPs could be translocated into the central nervous system (CNS) via the olfactory pathway and damaged brain neurocyte and tissue in vitro and in vivo (Hu et al. 2010). "
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    ABSTRACT: Titanium dioxide nanoparticles (TiO2 NPs) have a wide range of applications in many fields (paint, industry, medicine, additives in food colorants, and nutritional products). Over the past decade research, TiO2 NPs have been focused on the potential toxic effects of these useful materials. In the present study, we investigated the effects of subacute exposure to TiO2 NPs on emotional behavior in adult Wistar rats, the biochemical parameters, and the histology of organs. Animals were injected intraperitoneally (ip) with TiO2 NPs (20 mg/kg body weight) every 2 days for 20 days. The elevated plus-maze test showed that subacute TiO2 NPs treatment increased significantly the anxious index (AI) compared to control group. The toxicological parameters were assessed 24 h and 14 days after the last injection of TiO2 NPs. Subacute exposure to nanoparticles increased the AST/ALT enzyme ratio and LDH activity. However, the blood cell count remained unchanged, except the platelet count increase. Histological examination showed a little inflammation overall. Moreover, our results provide strong evidence that the TiO2 NPs can induce the liver pathological changes of rats. The intraperitoneal injection of TiO2 NPs increased the accumulation of titanium in the liver, lung, and the brain. The results suggest that TiO2 NPs could alter the neurobehavioral performance of adult Wistar rats and promotes alterations in hepatic tissues.
    Environmental Science and Pollution Research 01/2015; 22(11). DOI:10.1007/s11356-014-4002-5 · 2.83 Impact Factor
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    • "The calculated values are considered very small amounts to cause inflammation or cancer compared to the amounts used in animal studies to investigate TiO 2 nanoparticles health effects ( Ramanakumar 2008 and Warheit 2007 ) . "
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    ABSTRACT: Titanium dioxide (TiO 2) is recognized for its safe use as an additive (E171) in food and drugs. However, TiO 2 was the subject of recent studies regarding its toxicity and carcinogenicity. The new studies targeted TiO 2 nanoparticles that may exist in the pigment grade in small amounts. These recent investigations initiated a local survey in the Jordanian market to determine the TiO 2 content in the different types of foodstuffs to ensure that limits did not exceed the 1% by weight (as established by the Food and Drug Administration). Myers' spectrophotometric procedure for faecal samples was optimized and validated for TiO 2 analysis. In this study, TiO 2 was evaluated in 25 traditional foodstuffs in the Middle East (Tahini, Halawa, Jameed, Humus, gums and juice powders). Food grade TiO 2 supplied in the local market for the food industry was tested for TiO 2 nanoparticles by SEM. The data obtained in this study indicated the absence of TiO 2 from Tahini, Halawa, canned humus, and Jameed (for all tested brands); in accordance with the information provided in the labels. For the tested gums and juice powders, TiO 2 content also did not exceed 1%.
    International Food Research Journal 12/2014; 22(3):1024-1029.
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