Comparison of Responses in Rat Lung Following Inhalation and Intratracheal Administration of Nanoparticles

Abstract

We compared the concentration of total protein in bronchoalveolar lavage fluid (BALF) exposed to four types of nanomaterials in an inhalation study and in an intratracheal instillation study in order to examine whether the ranking of the harmful effect of nanomaterials following intratracheal instillation accorded with the ranking following inhalation. We used nickel oxide (NiO) nanoparticles and cerium dioxide (CeO2) nanoparticles as high toxicity nanomaterials, and titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles as low toxicity nanomaterials. In the inhalation study, rats were exposed to approximately 2 mg/m3 of four nanomaterials for 4 weeks, and the total protein concentrations in the bronchoalveolar lavage fluid (BALF) were examined from 3 days to 3 months after the end of exposure as the endpoint of pulmonary toxicity. In the intratracheal instillation study, rats were exposed to 0.2 or 1 mg of four nanomaterials, and, with the same endpoint, the BALF was analyzed from 3 days to 6 months after the exposure. The inhalation of NiO and CeO2, the high toxicity nanomaterials, induced a significant amount of total protein in the BALF, while the inhalation of ZnO and TiO2, the low toxicity nanomaterials, did not. The intratracheal instillation of NiO and CeO2 resulted in a persistently elevated concentration of total protein in the BALF, while the same result with the intratracheal instillation of ZnO and TiO2 was transient. Taken together, a difference in concentration of total protein in BALF was observed between the high and low toxicity nanomaterials following intratracheal instillation as well as inhalation, suggesting that the ranking of the harmful effects of nanoparticles in intratracheal instillation studies may reflect the ranking in inhalation studies.