Pulmonary toxicity study in rats with three forms of ultrafine-TiO₂ particles: Differential responses related to surface properties

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• 作者：David B. Warheit ; Thomas R. Webb ; Kenneth L. Reed ; Scott Frerichs ; Christie M. Sayes
• 关键词：Titanium dioxide particles ; Ultrafine particles ; Titanium dioxide nanocrystals ; Pulmonary toxicity ; Rutile crystal structure ; Particle surface treatments ; Nanomaterials
• 刊名：Toxicology
• 出版年：2007
• 期刊代码：47_0300483x
• 类别：pha
• 出版时间：25 January 2007
• 卷：230
• 期：1
• 页码：90-104
• 文件大小：1231 K

摘要

Surface properties are critical to assess effects of ultrafine-TiO₂ particles. The aim of this study was to assess lung toxicity in rats of newly developed, well characterized, ultrafine-TiO₂ particles and compare them to TiO₂ samples in two different size ranges and surface modifications. Groups of rats were intratracheally instilled with doses of 1 or 5 mg/kg of either two ultrafine rutile TiO₂ particles (uf-1 or uf-2); rutile R-100 fine-TiO₂ (F-1); 80/20 anatase/rutile P25 ultrafine-TiO₂ (uf-3); or α-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 24 h, 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 TiO₂ particles produced pulmonary inflammation, cytotoxicity and adverse lung tissue effects. In contrast, exposures to F-1 fine-TiO₂ particles or to uf-1/uf-2 ultrafine-TiO₂ particle-types produced transient inflammation. We conclude that differences in responses to anatase/rutile uf-3 TiO₂ particles versus the rutile uf-1 and uf-2 TiO₂ particles could be related to crystal structure, inherent pH of the particles, or surface chemical reactivity. Thus, based on these results, inhaled rutile ultrafine-TiO₂ particles are expected to have a low risk potential for producing adverse pulmonary health effects. Finally, the results demonstrate that exposures to ultrafine-TiO₂ 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-TiO₂ particle-types.