Abstract
The present aimed to characterize the toxicity of silica nanoparticles in Sprague Dawley rats and determine the dose levels for a repeated-dose toxicity study. Silica nanoparticles (SiO2, 20 nm and 50 nm) were administered as a single intratracheal instillation of standardized SiO2 20 nm (low dose, 200 µg/mL; high dose, 400 µg/mL) and 50 nm (low dose, 200 µg/mL; high dose, 400 µg/mL). Each group consisted of five male rats. We documented the mortality rate, clinical signs, body weight, bronchoalveolar lavage fluid analysis, hematological values, serum chemistry values, organ weight, gross findings at necropsy, and histopathological assessments. Rats treated with 200 µg/mL and 400 µg/mL SiO2 50 nm exhibited a decreased mean corpuscular volume, while those treated with 400 µg/mL of SiO2 50 nm showed increases in absolute monocyte and absolute lymphocyte count as well as prothrombin time. In addition, rats treated with 400 µg/mL SiO2 20 nm and 50 nm presented reduced creatinine, alanine aminotransferase, and sodium levels. Therefore, a single intratracheal instillation of SiO2 20 nm and 50 nm elicited no toxicity up to a dose of 400 µg/mL, and the approximate lethal dose of this test substance exceeded 400 µg/mL in male Sprague Dawley rats under the present experimental conditions.
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References
Cho WS, Choi M, Han BS, Cho M, Oh J, Park K, Kim SJ, Kim SH, Jeong J (2007) Inflammatory mediators induced by intratracheal instillation of ultrafine amorphous silica particles. Toxicol Lett 175:24–33. https://doi.org/10.1016/j.toxlet.2007.09.008
Murugadoss S, Lison D, Godderis L, Van Den Brule S, Mast J, Brassinne F, Sebaihi N, Hoet PH (2017) Toxicology of silica nanoparticles: an update. Arch Toxicol 91:2967–3010. https://doi.org/10.1007/s00204-017-1993-y
Brinch A, Hansen S, Hartmann N, Baun A (2016) EU regulation of nanobiocides: challenges in implementing the biocidal product regulation (BPR). Nanomaterials 6:33. https://doi.org/10.3390/nano6020033
Kasaai MR (2015) Nanosized particles of silica and its derivatives for applications in various branches of food and nutrition sectors. J Nanotechnol 2015:1–6. https://doi.org/10.1155/2015/852394
Napierska D, Rabolli V, Thomassen LC, Dinsdale D, Princen C, Gonzalez L, Poels KL, Kirsch-Volders M, Lison D, Martens JA, Hoet PH (2012) Oxidative stress induced by pure and iron-doped amorphous silica nanoparticles in subtoxic conditions. Chem Res Toxicol 25:828–883. https://doi.org/10.1021/tx200361v
Yang H, Wu QY, Li MY, Lao CS, Zhang YJ (2017) Pulmonary toxicity in rats caused by exposure to intratracheal instillation of SiO2 nanoparticles. Biomed Environ Sci 30(4):264–279. https://doi.org/10.3967/bes2017.036
Chen Y, Chen J, Dong J, Jin Y (2004) Comparing study of the effect of nanosized silicon dioxide and microsized silicon dioxide on fibrogenesis in rats. Toxicol Ind Health 20:21–27. https://doi.org/10.1191/0748233704th190oa
Lin Z, MaZhu-Ge LX, Zhang H, Lin B (2013) A comparative study of lung toxicity in rats induced by three types of Nanomaterials. Nanoscale Res Lett 8:521. https://doi.org/10.1186/1556-276X-8-521
Kim YH, Boykin E, Stevens T, Lavrich K, Gilmour MI (2014) Comparative lung toxicity of engineered nanomaterials utilizing in vitro, ex vivo and in vivo approaches. J Nanobiotechnol 12:47. https://doi.org/10.1186/s12951-014-0047-3
Bauer AT, Strozyk EA, Gorzelanny C, Westerhausen C, Desch A, Schneider MF, Schneider SW (2011) Cytotoxicity of silica nanoparticles through exocytosis of von Willebrand factor and necrotic cell death in primary human endothelial cells. Biomaterials 32:8385–8393. https://doi.org/10.1016/j.biomaterials.2011.07.078
Irfan A, Cauchi M, Edmands W, Gooderham NJ, Njuguna J, Zhu H (2014) Assessment of temporal dose-toxicity relationship of fumed silica nanoparticle in human lung A549 cells by conventional cytotoxicity and 1H-NMR-based extracellular metabonomic assays. Toxicol Sci 138:354–364. https://doi.org/10.1093/toxsci/kfu009
Napierska D, Thomassen LC, Lison D, Martens JA, Hoet PH (2010) The nanosilica hazard: another variable entity. Part Fibre Toxicol 7:39. https://doi.org/10.1186/1743-8977-7-39
Zhu X, Cao W, Chang B, Zhang L, Qiao P, Li X, Si L, Niu Y, Song Y (2016) Polyacrylate/nanosilica causes pleural and pericardial effusion, and pulmonary fibrosis and granuloma in rats similar to those observed in exposed workers. Int J Nanomed 11:1593–1605. https://doi.org/10.2147/IJN.S102020
Niu YM, Zhu XL, Chang B, Tong ZH, Cao W, Qiao PH, Zhang LY, Zhao J, Song YG (2016) Nanosilica and polyacrylate/nanosilica: a comparative study of acute toxicity. Biomed Res Int 2016:9353275. https://doi.org/10.1155/2016/9353275
Akhtar MJ, Ahamed M, Kumar S, Siddiqui H, Patil G, Ashquin M, Ahmad I (2010) Nanotoxicity of pure silica mediated through oxidant generation rather than glutathione depletion in human lung epithelial cells. Toxicology 276:95–102. https://doi.org/10.1016/j.tox.2010.07.010
Sukhanova A, Bozrova S, Sokolov P, Berestovoy M, Karaulov A, Nabiev I (2018) Dependence of nanoparticle toxicity on their physical and chemical properties. Nanoscale Res Lett 13:44. https://doi.org/10.1186/s11671-018-2457-x
Nielsen E, Ostergaard G, Larsen JC (2008) Toxicological risk assessment of chemicals: a practical guide. CRC Press, Boca Raton. https://doi.org/10.1201/9781420006940
Najahi-Missaoui W, Arnold RD, Cummings BS (2020) Safe nanoparticles: are we there yet. Int J Mol Sci 22:385. https://doi.org/10.3390/ijms22010385
Ispas C, Andreescu D, Patel A, Goia DV, Andreescu S, Wallace KN (2009) Toxicity and developmental defects of different sizes and shape nickel nanoparticles in zebrafish. Environ Sci Technol 43:6349–6356. https://doi.org/10.1021/es9010543
Ortiz-Muñoz G, Looney MR (2015) Non-invasive intratracheal instillation in mice. Bio Protoc 5:1504. https://doi.org/10.21769/bioprotoc.1504
Derelanko MJ, Auletta CS (2014) Handbook of Toxicology. CRC Press, Boca Raton. https://doi.org/10.1201/b16632
Han ZZ, Xu HD, Kim KH, Bae JS, Lee JY, Gil KH, Lee JY, Woo SJ, Yoo HJ, Lee HK, Kim KH, Park CK, Zhang HS, Song SW (2010) Reference data of the main physiological parameters in control Sprague-Dawley rats from pre-clinical toxicity studies. Lab Anim Res 26:153–164. https://doi.org/10.5625/lar.2010.26.2.153
Wallig MA, Bolon B, Haschek W, Rousseaux C (2017) Fundamentals of Toxicologic pathology. Academic Press, Cambridge. https://doi.org/10.1016/C2015-0-02486-8
Chen YT, Lue PY, Chen PW, Chueh PJ, Tsai FJ, Liao JW (2021) Comparison of genotoxicity and pulmonary toxicity study of modified SiO2 nanomaterials. Appl Sci 11:11990. https://doi.org/10.3390/app112411990
Napierska D, Thomassen LC, Rabolli V, Lison D, Gonzalez L, Kirsch-Volders M, Martens JA, Hoet PH (2009) Size-dependent cytotoxicity of monodisperse silica nanoparticles in human endothelial cells. Small 5:846–853. https://doi.org/10.1002/smll.200800461
Acknowledgements
This work was supported by a grant from the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (NRF-2020R1F1A1054226, NRF-NRF‑2015M3A7B6027948 and NRF-2016M3A9C4953144), a grant from the Ministry of Food and Drug Safety in 2021 (21162MFDS045) and the Korea Institute of Toxicology (KIT) Research Program (No. 1711159817).
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This study was funded by the Department of Predictive Toxicology at the Korea Institute of Toxicology.
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Han, HY. Sublethal pulmonary toxicity screening of silica nanoparticles in rats after direct intratracheal instillation. Toxicol Res. 38, 523–530 (2022). https://doi.org/10.1007/s43188-022-00135-3
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DOI: https://doi.org/10.1007/s43188-022-00135-3