Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Rome, Italy.
Experimental Animal Welfare Sector, Istituto Superiore di Sanità, Rome, Italy.
Toxicol Ind Health. 2021 Jun;37(6):328-335. doi: 10.1177/07482337211010579. Epub 2021 Apr 29.
Synthetic amorphous silica (SAS) nanomaterial - consisting of aggregates and agglomerates of primary silicon dioxide (SiO) particles in the nanorange (<100 nm) - is commonly used as excipient in pharmaceuticals, in cosmetics and as food additive (E551). The available data suggest that SAS nanoparticles (NP) after intravenous (IV) exposure persist in liver and spleen; however, insufficient data exist to verify whether SAS may also induce adverse effects. The aim of the present study was to verify the potential long-term effects of SAS NP (NM-203) on spleen and liver as target organs following short-term exposure. Adult male and female Sprague-Dawley rats were treated by IV injection in the tail vein with a single (1-day) dose (SD) and repeated (5-day) doses (RD) of 20 mg/kg bw per day of SAS dispersed in sterile saline solution as vehicle. Histopathological examinations of target organs were performed after 90 days. Tissue biodistribution and full characterization of NM-203, primary particle size 13-45 nm, was performed within the framework of the Nanogenotox project. No mortality or general toxicity occurred; histopathological analysis showed splenomegaly in the RD group accompanied by inflammatory granulomas in both sexes. Granulomas were also present in liver parenchyma in the RD (both sexes) and SD groups (male only). The histopathological results indicated that SAS NP have the potential to persist and induce sex-specific chronic inflammatory lesions in spleen and liver upon short-term treatment. Overall, the data showed that the widespread use of silica in drugs might elicit chronic reactions in spleen and liver prompting to the need of further investigations on the safety of SAS NP.[Formula: see text].
合成无定形二氧化硅（SAS）纳米材料-由初级二氧化硅（SiO）颗粒的聚集体和团聚体组成，处于纳米范围内（<100nm）-通常用作药物中的赋形剂，在化妆品中和食品添加剂（E551）中使用。现有数据表明，静脉内（IV）暴露后SAS 纳米颗粒（NP）在肝脏和脾脏中持续存在；然而，目前尚缺乏数据来验证 SAS 是否也会引起不良反应。本研究旨在验证 SAS NP（NM-203）在短期暴露后作为靶器官对肝脏和脾脏的潜在长期影响。成年雄性和雌性 Sprague-Dawley 大鼠通过尾静脉 IV 注射，以无菌生理盐水作为载体，每天每公斤体重 20mg/kg 单次（1 天）剂量（SD）和重复（5 天）剂量（RD）给予 SAS。90 天后对靶器官进行组织病理学检查。在 Nanogenotox 项目框架内，对 NM-203（初级粒径为 13-45nm）进行了组织分布和全面表征。未发生死亡或一般毒性；组织病理学分析显示 RD 组脾肿大，两性均伴有炎症性肉芽肿。RD（两性）和 SD 组（仅雄性）肝实质中也存在肉芽肿。组织病理学结果表明，SAS NP 在短期治疗后具有持续存在并在脾脏和肝脏中诱导性别特异性慢性炎症性病变的潜力。总的来说，这些数据表明，硅酸钠在药物中的广泛应用可能会在脾脏和肝脏中引发慢性反应，这促使人们需要进一步研究 SAS NP 的安全性。
