Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, 110-799, Korea.
J Appl Toxicol. 2013 Oct;33(10):1089-96. doi: 10.1002/jat.2862. Epub 2013 Feb 13.
Zinc oxide (ZnO) nanoparticles (NPs) are used in diverse applications ranging from paints and cosmetics to biomedicine and food. Although micron-sized ZnO is a traditional food supplement, ZnO NPs are an unknown public health risk because of their unique physicochemical properties. Herein, we studied the 13-week subchronic toxicity of ZnO NPs administered via the oral route according to Organization for Economic Cooperation and Development (OECD) test guideline 408. Well-dispersed ZnO NPs were administered to Sprague-Dawley (SD) rats (11/sex/group) at doses of 67.1, 134.2, 268.4 or 536.8 mg kg(-1) per body weight over a 13-week period. The mean body weight gain in males given 536.8 mg kg(-1) ZnO NPs was significantly lower than that of control male rats, whereas no significant differences were observed between the other treatment groups and the controls. Male and female rats dosed at 536.8 mg kg(-1) ZnO NPs had significant changes in anemia-related hematologic parameters. Mild to moderate pancreatitis also developed in both sexes dosed at 536.8 mg kg(-1) , whereas no histological changes were observed in the other treatment groups. To evaluate the mechanism of toxicity, we performed a bio-persistence study and evaluated the effects of the ZnO NPs on cell proliferation. The treatment of a human gastric adenocarcinoma cell line with ZnO NPs resulted in a significant inhibition of cellular proliferation. The anti-proliferative effect of ZnO NPs or Zn(2+) was effectively blocked by treatment with chelators. These results indicate that the bio-persistence of ZnO NPs after ingestion is key to their toxicity; the no-observed-adverse effect level (NOAEL) of ZnO NPs was found to be 268.4 mg kg(-1) per day for both sexes.
氧化锌（ZnO）纳米粒子（NPs）广泛应用于从涂料和化妆品到生物医学和食品等领域。尽管微米级 ZnO 是传统的食品补充剂，但由于其独特的物理化学性质，ZnO NPs 是一种未知的公共健康风险。在此，我们根据经济合作与发展组织（OECD）测试指南 408 研究了经口给予 ZnO NPs 的 13 周亚慢性毒性。将分散良好的 ZnO NPs 以 67.1、134.2、268.4 或 536.8 mg/kg 体重的剂量给予 Sprague-Dawley（SD）大鼠（每组 11 只），为期 13 周。给予 536.8 mg/kg 体重 ZnO NPs 的雄性大鼠的平均体重增加明显低于对照组雄性大鼠，而其他处理组与对照组之间没有观察到显著差异。给予 536.8 mg/kg 体重 ZnO NPs 的雄性和雌性大鼠的贫血相关血液学参数发生显著变化。给予 536.8 mg/kg 体重 ZnO NPs 的两种性别的大鼠均出现轻度至中度胰腺炎，而其他处理组未见组织学变化。为了评估毒性机制，我们进行了生物持久性研究，并评估了 ZnO NPs 对细胞增殖的影响。用 ZnO NPs 处理人胃腺癌细胞系导致细胞增殖受到显著抑制。用螯合剂处理可有效阻断 ZnO NPs 或 Zn(2+) 的抗增殖作用。这些结果表明，摄入后 ZnO NPs 的生物持久性是其毒性的关键；发现 ZnO NPs 对雌雄两性的无观察不良效应水平（NOAEL）为 268.4 mg/kg 体重/天。
