Agradecimentos: This study was supported by Fundação Araucária, CAPES (PhD scholarship), PPSUS (Programa Pesquisa para o Sistema Único de Saúde: Gestão Compartilhada em Saúde - PPSUS grant number 20/2017) Fundação Araucária-PR / SESA-PR/ CNPq/ MS-Decit. B.D. received a fellowship from CNPq, T.L.R. from CAPES and A.C.P.C. from Fundação Araucária. The authors thank the Program for Technological Development in Tools for Health-RPT-FIOCRUZ for the use of the flow cytometry and microscopy facilities at Carlos Chagas Institute – Fiocruz/PR and especially the biologist Tabata D'Maiella Freitas Klimeck for the electron microscopy sample preparation. M.B.C. and I.R.R. acknowledge the financial support of the São Paulo Research Foundation – FAPESP (processes 2015/25406-5 and 2017/21318-0). M.B.C. acknowledges CNPq for a productivity fellowship Ver menos

In recent years, much attention has been given to nanoparticles (NPs) due to their many possible applications, and as research has progressed, these NPs have become valuable tools for medical purposes. Among many different types of NPs, silica nanoparticles (SiO2NPs) have been specifically evaluated for medical purposes and have also been used in many different types of products. Although SiO2NPs have already been applied and are believed to be nontoxic, there is still a concern regarding possible adverse effects that may be triggered after SiO2NP exposure. Therefore, in the present study, we employed a recommended cell line (BALB/c 3T3) for the toxicity evaluation to investigate the cytotoxic effects of SiO2NPs produced by chemical synthesis at a laboratory scale. First, we employed OECD guideline 129 in order to evaluate cytotoxicity effects and also estimate the starting doses for acute oral systemic toxicity tests. We evaluated the cytotoxic effects of two types of SiO2NPs (nonfluorescent and fluorescent) and found that they were not significantly different (IC50 = 1986.39 ± 237 μg/mL and IC50 = 1861.13 ± 186.72 μg/mL, respectively). Then, we used the predicted LD50 of both types of SiO2NPs to suggest that they could be categorized as GHS category 4 substances. By ultrastructural evaluation, we found that SiO2NPs are internalized by 3 T3 cells and are located in vacuole-like structures with no other significant changes in cell structure. We also found that SiO2NPs lead to cell necrosis in a dose-dependent manner Ver menos