Abstract
The objectiveof this study is whether or not intratracheal instillation study is useful for screening of harmful effect of nanoparticles before inhalation study. As a first step, we performed inhalation and intratracheal instillation studies using same sample of nanoparticles, and compared with pulmonary inflammation between both studies. Nickel oxide nanoparticles (NiO) and titanium dioxide nanoparticles (TiO2) were used as chemicals with high and low toxicities, respectively. In intratracheal instillation study, rats were exposed to 0.2mg or 1mg of NiO or TiO2. In inhalation study, rats were exposed to inhaled NiO or TiO2 (1.65-1.84 mg/m3) for 4 weeks (6hours/day, 5 days/week). Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at 3 days and 1month after end of exposure in both studies.
NiO induced total and neutrophil number in BALF and concentration of CINC-1 in both studies. Compared with inhalation studies, the tendency of persistent inflammationis observed in intratracheal instillation study. TiO2 transiently induced neutrophil number in BALF at acute phase (3days) in intratracheal instillation study, however did not induce pulmonary inflammation in inhalation study. Taken together difference in pulmonary response is observed at acute phase in both studies, and it suggested that the pulmonary inflammation is evaluated not only acute phase but also chronic phase.
This work is partially supported by “Development of innovative methodology for safety assessment of industrial nanomaterials" by Ministry of Economy, Trade and Industry (METI) of Japan.
- © 2014 ERS
