Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation.

Yasuo Morimoto,Etsushi Kuroda,Takeshi Sasaki,Masaru Kubo,Toshihiko Myojo,Kazuhiro Yamamoto,Taisuke Tomonaga,Kazuhiro Yatera,Hiroto Izumi,Shinichi Kitajima,Kazuaki Kawai,Manabu Shimada,Kenji Kawaguchi,Takako Oyabu,Yukiko Yoshiura

doi:10.3390/ijms17081241

Abstract

We conducted inhalation and intratracheal instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m3) for four weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the intratracheal instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity.

Highlights

Various applications of nanomaterials, including metal oxide nanoparticles, have been enabled by new characteristics that have resulted from the progress of nanotechnology
Copper oxide nanoparticles, which are considered to have high solubility, were reported to induce inflammation in the lung through dissolution [14]. These pulmonary responses were based on acute responses, and if the inflammogenic potential of nanoparticles is considered to lead to instillation was biphasic, and that both rapid initial and slower terminal half times of Zinc oxide (ZnO) nanoparticles were less than two days
We examined the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2, representative chemokines for neutrophils, in the bronchoalveolar lavage fluid (BALF) exposed to ZnO nanoparticles

Summary

Introduction

Various applications of nanomaterials, including metal oxide nanoparticles, have been enabled by new characteristics that have resulted from the progress of nanotechnology. Many in vitro studies [1,2,3] and in vivo studies [4,5,6] have concluded that ZnO nanoparticles have a strong potential of toxicity, but these results are insufficient and controversial because the endpoints of toxicity in many such studies reflect acute responses, such as cytotoxicity and acute inflammation. Most of the reports on ZnO nanoparticles show acute pulmonary inflammation in vivo and cytotoxicity in vitro, suggesting that ZnO nanoparticles may have harmful effects on humans [1,2,3,4,6,7]. Considering the pulmonary toxicity of nanomaterials, it is important to evaluate the endpoints, such as inflammation and fibrosis, in the acute and in the chronic phase. We performed intratracheal instillation and inhalation studies of ZnO nanoparticles with more than three months of observation periods and examined pulmonary inflammation and fibrosis as the endpoints of toxicity in order to examine the pulmonary toxicity of ZnO nanoparticles

Methods

Results

Discussion

Conclusion