Environmental Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Toxicology and Environmental Health, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
J Occup Health. 2024 Jan 4;66(1). doi: 10.1093/joccuh/uiae019.
We aimed to analyze the subchronic toxicity and tissue distribution of indium after the intratracheal administration of indium-tin oxide nanoparticles (ITO NPs) to the lungs of rats.
Male Wistar rats were administered a single intratracheal dose of 10 or 20 mg In/kg body weight (BW) of ITO NPs. The control rats received only an intratracheal dose of distilled water. A subset of rats was periodically euthanized throughout the study from 1 to 20 weeks after administration. Indium concentrations in the serum, lungs, mediastinal lymph nodes, kidneys, liver, and spleen as well as pathological changes in the lungs and kidneys were determined. Additionally, the distribution of ionic indium and indium NPs in the kidneys was analyzed using laser ablation-inductively coupled plasma mass spectrometry.
Indium concentrations in the lungs of the 2 ITO NP groups gradually decreased over the 20-week observation period. Conversely, the indium concentrations in the mediastinal lymph nodes of the 2 ITO groups increased and were several hundred times higher than those in the kidneys, spleen, and liver. Pulmonary and renal toxicities were observed histopathologically in both the ITO groups. Both indium NPs and ionic indium were detected in the kidneys, and their distributions were similar to the strong indium signals detected at the sites of inflammatory cell infiltration and tubular epithelial cells.
Our results demonstrate that intratracheal administration of 10 or 20 mg In/kg BW of ITO NPs in male rats produces pulmonary and renal toxicities.
本研究旨在分析经气管给予氧化铟锡纳米粒子(ITO NPs)后,大鼠肺部铟的亚慢性毒性和组织分布。
雄性 Wistar 大鼠经气管单次给予 10 或 20 mg In/kg 体重(BW)的 ITO NPs。对照组大鼠仅经气管给予蒸馏水。在给药后 1 至 20 周的整个研究期间,定期从部分大鼠处死并检测血清、肺、纵隔淋巴结、肾脏、肝脏和脾脏中的铟浓度以及肺和肾脏的病理变化。此外,还使用激光烧蚀-电感耦合等离子体质谱法分析了肾脏中离子态铟和 ITO NPs 的分布。
2 个 ITO NP 组大鼠肺中的铟浓度在 20 周的观察期内逐渐下降。相反,2 个 ITO 组大鼠纵隔淋巴结中的铟浓度增加,比肾脏、脾脏和肝脏中的铟浓度高数百倍。在这两个 ITO 组中均观察到肺部和肾脏的组织病理学毒性。肾脏中均检测到 ITO NPs 和离子态铟,其分布与炎症细胞浸润和肾小管上皮细胞部位检测到的强铟信号相似。
本研究结果表明,雄性大鼠经气管给予 10 或 20 mg In/kg BW 的 ITO NPs 可引起肺部和肾脏毒性。