Inhaled silica-coated TiO₂ nanoparticles induced airway irritation, airflow limitation and inflammation in mice

Abstract

The wide use of nanotechnology is here to stay. However, the knowledge on the health effects of different engineered nanomaterials (ENMs) is lacking. In this study, irritation and inflammation potential of commercially available silica-coated TiO₂ ENMs (10 × 40 nm, rutile) were studied. Single exposure (30 min) at mass concentrations 5, 10, 20 and 30 mg/m³, and repeated exposure (altogether 16 h, 1 h/day, 4 days/week for 4 weeks) at mass concentration of 30 mg/m³ to silica-coated TiO₂ induced first phase of pulmonary irritation (P1), which was seen as rapid, shallow breathing. During repeated exposures, P1 effect was partly evolved into more intense pulmonary irritation. Also sensory irritation was observed at the beginning of both single and repeated exposure periods, and the effect intensified during repeated exposures. Airflow limitation started to develop during repeated exposures. Repeated exposure to silica-coated TiO₂ ENMs induced also pulmonary inflammation: inflammatory cells infiltrated in peribronchial and perivascular areas of the lungs, neutrophils were found in BAL fluids, and the number of CD3 and CD4 positive T cells increased significantly. In line with these results, pulmonary mRNA expression of chemokines CXCL1, CXCL5 and CXCL9 was enhanced. Also expression of mRNA levels of proinflammatory cytokines TNF-α and IL-6 was elevated after repeated exposures. Taken together, these results indicated that silica-coated TiO₂ ENMs induce pulmonary and sensory irritation after single and repeated exposure, and airflow limitation and pulmonary inflammation after repeated exposure.

• Engineered nanomaterials
• inflammation
• inhalation
• pulmonary irritation
• titanium dioxide

Acknowledgements

The personnel of the National Laboratory Animal Centre, especially senior laboratory technician Auli Nissinen, is acknowledged for technical help. The authors thank emeritus professor Yves Alarie from Pittsburgh University for his advice on the breathing pattern analysis.

Declaration of interest

The authors acknowledge the financial support from the Academy of Finland, FinNano program (grant 117924). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Supplementary material available online

Supplementary Tables S1–S3 and Figures S1–S5