Physiological and histopathological alterations in male Swiss mice after exposure to titanium dioxide (anatase) and zinc oxide nanoparticles and their binary mixture

Existing studies have shown the systemic damage of titanium dioxide (TiO₂) or zinc oxide (ZnO) nanoparticles (NPs), but there is little or no existing knowledge on the potential adverse toxic effects of the mixture of the two. In order to investigate the <i>in vivo</i> toxic effect of the mixture of TiO₂ NPs and ZnO NPs, the acute toxicities of TiO₂ NPs, ZnO NPs by themselves, and their mixture (1:1) were determined. The systemic toxicities of the individual NPs and mixture were evaluated in mice using hematological indices, hepatic, renal, and lipid profile parameters, and histopathology as endpoints. NPs were intraperitoneally administered at doses of 9.38, 18.75, 37.50, 75.00, and 150.00 mg/kg bw each. Individual NPs and their mixture were administered daily for 5 and 10 d, respectively. The LD₅₀ of ZnO NPs was 299.9 mg/kg while TiO₂ NPs by themselves or TiO₂ NPs + ZnO NPs were indeterminate due to the absence of mortality of the male mice treated. TiO₂ NPs, ZnO NPs by themselves and TiO₂ NPs + ZnO NPs induced significant alterations in the hematological and biochemical parameters, with higher toxicity at 10 d. Histopathological lesions were observed in the liver, kidneys, spleen, heart, and brain of mice treated with the individual NPs and their mixture. TiO₂ NPs + ZnO NPs were able to induce a higher systemic toxicity than TiO₂ NPs or ZnO NPs individually. Our data suggest that more comprehensive risk assessments should be carried out on the mixture of NPs before utilization in consumer products.

现有研究已证实二氧化钛（titanium dioxide, TiO₂）或氧化锌（zinc oxide, ZnO）纳米颗粒（nanoparticles, NPs）会造成系统性损伤，但目前鲜有或几乎没有关于二者混合后潜在有害毒性效应的相关认知。为探究TiO₂ NPs与ZnO NPs混合物的体内（in vivo）毒性效应，本研究分别测定了单一TiO₂ NPs、单一ZnO NPs以及二者以1:1比例混合后的急性毒性。以血液学指标、肝肾功能与血脂谱参数及组织病理学作为检测终点，在小鼠体内评估单一纳米颗粒及其混合物的系统性毒性。纳米颗粒采用腹腔注射方式给药，剂量设置为9.38、18.75、37.50、75.00及150.00 mg/kg体重（bw为body weight的缩写）。单一纳米颗粒及其混合物分别每日给药，持续5天与10天。单一氧化锌纳米颗粒的半数致死剂量（LD₅₀）为299.9 mg/kg，而单一TiO₂ NPs以及TiO₂ NPs与ZnO NPs的混合物因给药后雄性小鼠未出现死亡，无法确定其LD₅₀。单一TiO₂ NPs、单一ZnO NPs以及二者的混合物均会显著改变血液学与生化参数，且给药10天时毒性更强。经单一纳米颗粒及其混合物处理的小鼠，其肝脏、肾脏、脾脏、心脏与大脑均观察到组织病理学损伤。TiO₂ NPs与ZnO NPs的混合物相较于单一的TiO₂ NPs或ZnO NPs，可诱发更强的系统性毒性。本研究数据表明，在将纳米颗粒混合物应用于消费品前，应开展更为全面的风险评估。