Pulmonary toxicity study in rats with three forms of ultrafine-TiO2 particles: Evidence for differential responses

DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE 19714-0050, USA.
Toxicology (Impact Factor: 3.75). 02/2007; 230(1):90-104. DOI: 10.1016/j.tox.2006.11.002
Source: PubMed

ABSTRACT 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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    • "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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    • "The pulmonary clearance rate constants estimated using a classical 2-compartment model were compared over a range of doses. AEROSIL 1 P25 TiO 2 nanoparticles, which have often been employed for toxicity testing of TiO 2 nanoparticles and have been shown to induce lung inflammation (Rehn et al., 2003; Sager et al., 2008; Warheit et al., 2007) were used in the present study. "
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