Biopersistence of NiO and TiO₂ Nanoparticles Following Intratracheal Instillation and Inhalation.

Takako Oyabu,Takami Okada,Taisuke Tomonaga,Manabu Shimada,Yukiko Yoshiura,Masaru Kubo,Yasuo Morimoto,Kenji Kawaguchi,Toshihiko Myojo,Kazuhiro Yamamoto,Takeshi Sasaki,Hiroto Izumi,Kazuaki Kawai,Byeong-Woo Lee,Yun-Shan Li

doi:10.3390/ijms18122757

Abstract

The hazards of various types of nanoparticles with high functionality have not been fully assessed. We investigated the usefulness of biopersistence as a hazard indicator of nanoparticles by performing inhalation and intratracheal instillation studies and comparing the biopersistence of two nanoparticles with different toxicities: NiO and TiO2 nanoparticles with high and low toxicity among nanoparticles, respectively. In the 4-week inhalation studies, the average exposure concentrations were 0.32 and 1.65 mg/m3 for NiO, and 0.50 and 1.84 mg/m3 for TiO2. In the instillation studies, 0.2 and 1.0 mg of NiO nanoparticles and 0.2, 0.36, and 1.0 mg of TiO2 were dispersed in 0.4 mL water and instilled to rats. After the exposure, the lung burden in each of five rats was determined by Inductively Coupled Plasma-Atomic Emission Spectrometer (ICP-AES) from 3 days to 3 months for inhalation studies and to 6 months for instillation studies. In both the inhalation and instillation studies, NiO nanoparticles persisted for longer in the lung compared with TiO2 nanoparticles, and the calculated biological half times (BHTs) of the NiO nanoparticles was longer than that of the TiO2 nanoparticles. Biopersistence also correlated with histopathological changes, inflammatory response, and other biomarkers in bronchoalveolar lavage fluid (BALF) after the exposure to nanoparticles. These results suggested that the biopersistence is a good indicator of the hazards of nanoparticles.

Highlights

Thanks to their various functions and extreme usefulness as industrial products, nanomaterials (TiO2, silica, carbon black, and carbon nanotubes, etc.) are being developed and manufactured in a wide variety of fields, including plastics, colorants, coating, cosmetics, semiconductors, and drug delivery systems
In the histopathological observation shown in the Supplementary File, NiO exposure leads to infiltration of neutrophils and macrophages into the alveoli or interstitial tissue at 3 days after inhalation, but in the TiO2 inhalation group, pigment-like particles were observed in the alveoli
This indicates that the biological half times (BHTs) of inhaled NiO nanoparticles with high toxicity were longer than those of the TiO2 nanoparticles with low toxicity, and the longer BHT correlated with the toxicity of the particles

Summary

Introduction

Thanks to their various functions and extreme usefulness as industrial products, nanomaterials (TiO2, silica, carbon black, and carbon nanotubes, etc.) are being developed and manufactured in a wide variety of fields, including plastics, colorants, coating, cosmetics, semiconductors, and drug delivery systems. There are reports of their higher toxicity compared with micron-size particles and the possibility of the translocation of inhaled nanoparticles from the lung to the brain [1,2,3,4,5,6], there are differing results [7]. As for the hazard indicator, several toxicity biomarkers, including pulmonary inflammation, polymorphonuclear neutrophils in bronchoalveolar lavage fluid (BALF), cytokine release, oxidative stress, and the biopersistence of particles in the lung, have been examined in inhalation exposure tests using animal models [8,9,10]. The biopersistence of inhaled particles in the lung is reported to be a useful toxicity index [11,12,13]. Slower or faster pulmonary clearance indicates higher or lower toxicity, respectively

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