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Toxicol In Vitro. 1997 Aug;11(4):329-35.

Toxicity and cytogenetic studies of ultrafine titanium dioxide in cultured rat liver epithelial cells.

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Finnish Institute of Occupational Health, Department of Industrial Hygiene and Toxicology, Topeliuksenkatu 41 aA, FIN-00250 Helsinki, Finland.


The in vitro cytotoxicity and the induction of micronuclei of two ultrafine titanium dioxide (TiO(2)) samples was assessed in a rat liver epithelial cell (RLE) assay. Pigmentary TiO(2) was used as a control particle, and mitomycin C, a potent inducer of chromosome damage, was used as a positive control agent in the micronucleus experiments. Since photoexcitation of TiO(2) particles has been reported to increase the cell-killing effect of the dust, a duplicate series of experiments was carried out by irradiating the TiO(2) exposed cells with near-UV light. Neither of the ultrafine TiO(2) samples was toxic to the cells at the concentration range of 5-200 mug/cm(2). The UV treatment had no significant effect on the results. The induction of micronuclei was tested in three concentrations (5, 10 and 20 mug/cm(2)). None of the TiO(2) samples, either ultrafine or pigmentary, increased the numbers of micronuclei in the RLE cells. By contrast, all three samples had a slight decreasing effect on the frequency of micronuclei at the lowest treatment concentration of 5 mug/cm(2), both in the absence and in the presence of UV irradiation. The results suggest that ultrafine particles, similar to pigmentary TiO(2), have no direct clastogenic potential.

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