Nanotechnology is indispensable to many different applications. Although nanoparticles have been widely used in, for example, cosmetics, sunscreen, food packaging, and medications, they may pose human safety risks associated with nanotoxicity. Thus, toxicity testing of nanoparticles is essential to assess the relative health risks associated with consumer exposure. In this study, we identified the NOAEL (no observed adverse effect level) of the agglomerated/aggregated TiO2 P25 (approximately 180 nm) administered at repeated doses to Sprague-Dawley (SD) rats for 28 and 90 days. Ten of the 15 animals were necropsied for toxicity evaluation after the repeated-dose 90-day study, and the remaining five animals were allowed to recover for 28 days. The agglomerated/aggregated TiO2 P25 dose levels used included 250 mg kg− 1 d− 1 (low), 500 mg kg− 1 d− 1 (medium), and 1000 mg kg− 1 d− 1 (high), and their effects were compared with those of the vehicle control. During the treatment period, the animals were observed for mortality, clinical signs (detailed daily and weekly clinical observations), functional observation battery, weekly body weight, and food and water consumption and were also subjected to ophthalmological examination and urinalysis. After termination of the repeated-dose 28-day, 90-day, and recovery studies, clinical pathology (hematology, blood coagulation time, and serum biochemistry), necropsy (organ weights and gross findings), and histopathological examinations were performed. No systemic toxicological effects were associated with the agglomerated/aggregated TiO2 P25 during the repeated-dose 28-day, 90-day, and recovery studies in SD rats. Therefore, the NOAEL of the agglomerated/aggregated TiO2 P25 was identified as 1000 mg kg− 1 d− 1, and the substance was not detected in the target organs. Subacute and subchronic oral administration of the agglomerated/aggregated TiO2 P25 was unlikely to cause side effects or toxic reactions in rats.

中文翻译：

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28天和90天重复剂量对大鼠的二氧化钛P25的口服毒性。

纳米技术对于许多不同的应用都是必不可少的。尽管纳米粒子已广泛用于例如化妆品，防晒霜，食品包装和药物中，但它们可能会带来与纳米毒性相关的人类安全风险。因此，纳米颗粒的毒性测试对于评估与消费者接触相关的相对健康风险至关重要。在这项研究中，我们确定了对Sprague-Dawley（SD）大鼠重复给药28天和90天的团聚/聚集TiO2 P25（约180 nm）的NOAEL（未观察到不利影响水平）。在重复剂量的90天研究后，对15只动物中的10只进行了尸检，以进行毒性评估，其余5只动物恢复了28天。所使用的团聚/聚集TiO2 P25剂量水平包括250 mg kg-1 d-1（低），将500 mg kg-1 d-1（中）和1000 mg kg-1 d-1（高）进行比较，并将其效果与车辆对照进行比较。在治疗期间，观察动物的死亡率，临床体征（每天和每周进行详细的临床观察），功能性观察，每周体重以及食物和水的消耗，并对它们进行眼科检查和尿液分析。在重复剂量的28天，90天和恢复研究终止后，进行了临床病理学（血液学，凝血时间和血清生化），尸检（器官重量和总体发现）以及组织病理学检查。在SD大鼠中，重复剂量28天，90天和恢复研究期间，聚集/聚集的TiO2 P25没有系统的毒理作用。因此，团聚/聚集的TiO2 P25的NOAEL被确定为1000 mg kg-1 d-1，并且在目标器官中未检测到该物质。聚集/聚集的TiO2 P25的亚急性和亚慢性口服不太可能在大鼠中引起副作用或毒性反应。