Titanium dioxide nanoparticles: A review of current toxicological data

Particle and Fibre Toxicology (Impact Factor: 7.11). 04/2013; 10(1):15. DOI: 10.1186/1743-8977-10-15
Source: PubMed


Titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide in large quantities for use in a wide range of applications. TiO2 NPs possess different physicochemical properties compared to their fine particle (FP) analogs, which might alter their bioactivity. Most of the literature cited here has focused on the respiratory system, showing the importance of inhalation as the primary route for TiO2 NP exposure in the workplace. TiO2 NPs may translocate to systemic organs from the lung and gastrointestinal tract (GIT) although the rate of translocation appears low. There have also been studies focusing on other potential routes of human exposure. Oral exposure mainly occurs through food products containing TiO2 NP-additives. Most dermal exposure studies, whether in vivo or in vitro, report that TiO2 NPs do not penetrate the stratum corneum (SC). In the field of nanomedicine, intravenous injection can deliver TiO2 nanoparticulate carriers directly into the human body. Upon intravenous exposure, TiO2 NPs can induce pathological lesions of the liver, spleen, kidneys, and brain. We have also shown here that most of these effects may be due to the use of very high doses of TiO2 NPs. There is also an enormous lack of epidemiological data regarding TiO2 NPs in spite of its increased production and use. However, long-term inhalation studies in rats have reported lung tumors. This review summarizes the current knowledge on the toxicology of TiO2 NPs and points out areas where further information is needed.

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Available from: Vincent Castranova
    • "Moreover, since we did not detect any micronuclei, it appears that these DNA strand breaks are efficiently repaired. Our results are in line with the generally accepted paradigm that oxidative mechanisms drive TiO 2 -NP toxicity, which is widely accepted for acute exposure mode (Johnston, 2009;Shi, 2013). It confirms the conclusion of the IARC Working Group, i.e. in vitro studies show that titanium dioxide particles, both fine and ultrafine, induce DNA damage that is " suggestive of the generation of reactive oxygen species " (IARC, 2010). "
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    ABSTRACT: Titanium dioxide nanoparticles (TiO2-NPs) are one of the most produced NPs in the world. Their toxicity has been studied for a decade using acute exposure scenarios, i.e. high exposure concentrations and short exposure times. In the present study, we evaluated their genotoxic impact using long-term and low concentration exposure conditions. A549 alveolar epithelial cells were continuously exposed to 1-50 µg/mL TiO2-NPs, 86% anatase/14% rutile, 24±6 nm average primary diameter, for up to two months. Their cytotoxicity, oxidative potential and intracellular accumulation were evaluated using MTT assay and reactive oxygen species measurement, transmission electron microscopy observation, micro-particle-induced X-ray emission and inductively-coupled plasma mass spectroscopy. Genotoxic impact was assessed using alkaline and Fpg-modified comet assay, immunostaining of 53BP1 foci and the cytokinesis-blocked micronucleus assay. Finally, we evaluated the impact of a subsequent exposure of these cells to the alkylating agent methyl methanesulfonate. We demonstrate that long-term exposure to TiO2-NPs does not affect cell viability but causes DNA damage, particularly oxidative damage to DNA and increased 53BP1 foci counts, correlated with increased intracellular accumulation of NPs. In addition, exposure over 2 months causes cellular responses suggestive of adaptation, characterized by decreased proliferation rate and stabilization of TiO2-NP intracellular accumulation, as well as sensitization to MMS. Taken together, these data underline the genotoxic impact and sensitization effect of long-term exposure of lung alveolar epithelial cells to low levels of TiO2-NPs.
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    • "From these, only the first two are important for industrial applications, ranging from white pigment, mostly in paints, varnishes, paper , to plastics and accounting for 80 % of the global TiO 2 consumption (Ceresana 2013). Ink, fibers, rubber, cosmetic products, and food additives (E171, red-colored candy) (Fries and Simkó 2012; Shi et al. 2013; Larue et al. 2014; Jamuna et al. 2014) account for another 8 % (Ceresana 2013) of the consumption. The predominant production process of TiO 2 is the chloride process, which primarily produces the rutile form TiO 2 , having the highest TiO 2 content (Fries and Simkó 2012). "
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    • "The profiles of generated aerosols (size and concentration) are expected to differ due to distinct agglomeration levels caused by varied surface properties. Moreover, titanium dioxides are widely used in industrial sectors and have raised a high concern for human hazard risks (Shi et al., 2013). "
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