This study was undertaken to investigate the potential toxicity and establish the no observed adverse effect level (NOAEL) and target organ(s) of negatively charged colloidal silica particles of different sizes, ie, SiO₂^EN,20(-) (20 nm) or SiO₂^EN,100(-) (100 nm), administered by gavage in Sprague-Dawley rats. After verification of the physicochemical properties of the SiO₂ particles to be tested, a preliminary dose range-finding study and 90-day repeated dose study were conducted according to the Organisation for Economic Cooperation and Development test guideline. Based on the results of the 14-day dose range-finding study, a high dose was determined to be 2,000 mg/kg, and middle and low doses were set at 1,000 and 500 mg/kg, respectively. In the 90-day toxicity study, there were no animal deaths in relation to administration of SiO₂ particles of either size. In addition, no treatment-related clinical changes or histopathological findings were observed in any of the experimental groups. Moreover, no difference in toxic effects from chronic exposure to SiO₂^EN,20(-) (20 nm) or SiO₂^EN,100(-) (100 nm) was observed. The results of this study indicate that the NOAEL for SiO₂^EN,20(-) and SiO₂^EN,100(-) would most likely be 2,000 mg/kg, and no target organ was identified in rats of either sex.

Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnO^AE100[-]) or positively (ZnO^AE100[+]) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnO^AE100(-) and ZnO^AE100(+) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg.

Nanoparticles (NPs) are currently used in chemical, cosmetic, pharmaceutical, and electronic products. Nevertheless, limited safety information is available for many NPs, especially in terms of their interactions with various binding proteins, leading to potential toxic effects. Zinc oxide (ZnO) NPs are included in the formulation of new products, such as adhesives, batteries, ceramics, cosmetics, cement, glass, ointments, paints, pigments, and supplementary foods, resulting in increased human exposures to ZnO. Hence, we investigated the potential ZnO nanotoxic pathways by analyzing the adsorbed proteins, called protein corona, from blood and brain from four ZnO NPs, ZnO^SM20(-), ZnO^SM20(+), ZnOAE100(-), and ZnO^AE100(+), in order to understand their potential mechanisms in vivo. Through this study, liquid chromatography–mass spectroscopy/mass spectroscopy technology was employed to identify all bound proteins. Totals of 52 and 58 plasma proteins were identified as being bound to ZnO^SM20(-) and ZnO^SM20(+), respectively. For ZnO^AE100(-) and ZnO^AE100(+), 58 and 44 proteins were bound, respectively. Similar numbers of proteins were adsorbed onto ZnO irrespective of size or surface charge of the nanoparticle. These proteins were further analyzed with ClueGO, a Cytoscape plugin, which provided gene ontology and the biological interaction processes of identified proteins. Interactions between diverse proteins and ZnO nanoparticles could result in an alteration of their functions, conformation, and clearance, eventually affecting many biological processes.