US EPA

88436 

Journal Article 

Pulmonary instillation studies with nanoscale TiO2 rods and dots in rats: Toxicity is not dependent upon particle size and surface area 

Warheit, DB; Webb, TR; Sayes, CM; Colvin, VL; Reed, KL 

2006 

1 

Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929 

91 

1 

227-236 

English 

16495353 

10.1093/toxsci/kfj140 

WOS:000236808200026 

Pulmonary toxicology studies in rats demonstrate that nanoparticles administered to the lung are more toxic than larger, fine-sized particles of similar chemistry at identical mass concentrations. The aim of this study was to evaluate the acute lung toxicity in rats of intratracheally instilled pigment-grade TiO(2) particles (rutile-type particle size = approximately 300 nm) versus nanoscale TiO(2) rods (anatase = 200 nm x 35 nm) or nanoscale TiO(2) dots (anatase = approximately 10 nm) compared with a positive control particle type, quartz. Groups of rats were instilled with doses of 1 or 5 mg/kg of the various particle types in phosphate-buffered saline (PBS). Subsequently, the lungs of PBS- and particle-exposed rats were assessed using bronchoalveolar lavage fluid biomarkers, cell proliferation methods, and by the histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postinstillation exposure. Exposures to nanoscale TiO(2) rods or nanoscale TiO(2) dots produced transient inflammatory and cell injury effects at 24 h postexposure (pe) and were not different from the pulmonary effects of larger sized TiO(2) particle exposures. In contrast, pulmonary exposures to quartz particles in rats produced a dose-dependent lung inflammatory response characterized by neutrophils and foamy lipid-containing alveolar macrophage accumulation as well as evidence of early lung tissue thickening consistent with the development of pulmonary fibrosis. The results described herein provide the first example of nanoscale particle types which are not more cytotoxic or inflammogenic to the lung compared to larger sized particles of similar composition. Furthermore, these findings run counter to the postulation that surface area is a major factor associated with the pulmonary toxicity of nanoscale particle types. 

titanium dioxide particles; pulmonary toxicity; nanoscale TiO2 rods and dots, particle size; particle surface area