Pulmonary toxicity of tungsten trioxide nanoparticles in an inhalation study and an intratracheal instillation study

OBJECTIVES: We conducted inhalation and intratracheal instillation studies in order to examine the effects of tungsten trioxide (WO(3)) nanoparticles on the lung, and evaluated whether or not the nanoparticles would cause persistent lung inflammation. METHODS: In the inhalation study, male 10‐week‐old Fischer 334 rats were classified into 3 groups. The control, low‐dose, and high‐dose groups inhaled clean air, 2, and 10 mg/m(3) WO(3) nanoparticles, respectively, for 6 h each day for 4 weeks. The rats were dissected at 3 days, 1 month, and 3 months after the inhalation, and the bronchoalveolar lavage fluid (BALF) and lung tissue were examined. In the intratracheal instillation study, male 12‐week‐old Fischer 334 rats were divided into 3 subgroups. The control, low‐dose, and high‐dose groups were intratracheally instilled 0.4 ml distilled water, 0.2, and 1.0 mg WO(3) nanoparticles, respectively, dissolved in 0.4 ml distilled water. The rats were sacrificed at 3 days, 1 week, and 1 month after the intratracheal instillation, and the BALF and lung tissue were analyzed as in the inhalation study. RESULTS: The inhalation and instillation of WO(3) nanoparticles caused transient increases in the number and rate of neutrophils, cytokine‐induced neutrophil chemoattractant (CINC)‐1, and CINC‐2 in BALF, but no histopathological changes or upregulation of heme oxygenase (HO)‐1 in the lung tissue. CONCLUSION: Our results suggest that WO(3) nanoparticles have low toxicity to the lung. According to the results of the inhalation study, we also propose that the no observed adverse effect level (NOAEL) of WO(3) nanoparticles is 2 mg/m(3).