Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Sublethal pulmonary toxicity screening of silica nanoparticles in rats after direct intratracheal instillation

  • Han, Hyoung-Yun (Department of Predictive Toxicology, Korea Institute of Toxicology)
  • Received : 2022.01.28
  • Accepted : 2022.04.05
  • Published : 2022.10.15
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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 ㎍/mL; high dose, 400 ㎍/mL) and 50 nm (low dose, 200 ㎍/mL; high dose, 400 ㎍/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 ㎍/mL and 400 ㎍/mL SiO2 50 nm exhibited a decreased mean corpuscular volume, while those treated with 400 ㎍/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 ㎍/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 ㎍/mL, and the approximate lethal dose of this test substance exceeded 400 ㎍/mL in male Sprague Dawley rats under the present experimental conditions.

Keywords

Acknowledgement

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).

References

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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 https://doi.org/10.3967/bes2017.036
  7. 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
  8. 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
  9. 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
  10. 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.biomateria ls.2011.07.078
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. Ortiz-Munoz G, Looney MR (2015) Non-invasive intratracheal instillation in mice. Bio Protoc 5:1504. https://doi.org/10.21769/bioprotoc.1504
  21. Derelanko MJ, Auletta CS (2014) Handbook of Toxicology. CRC Press, Boca Raton. https://doi.org/10.1201/b16632
  22. 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
  23. 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
  24. 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
  25. 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