SOME PECULIARITIES OF THE ORGANISM’S RESPONSES TO A LONG-TERM INHALATION OF SILICA-CONTAINING SUBMICRON (PREDOMINANTLY, NANOSCALE) PARTICLES IN A REAL INDUSTRIAL AEROSOL

Female white rats were exposed in a «nose only» inhalation device to an aerosol containing predominantly submicron (nanoscale included) particles of amorphous silica in a total concentration of 2.6±0.6 or 10.6±2.1 mg/m3, 4 h/day, 5 times a week, during up to 6 months. In an auxiliary experiment with a single-shot intratracheal instillation of these particles, it was shown that they induced a pulmonary cell response comparable with that when administrated a highly cytotoxic and fibrogenic standard quartz dust DQ12. However in a long-term inhalation test, the aerosol investigated proved to be of a very low systemic toxicity and fibrogenicity. This paradox may be explained by a low retention of SiO2 in lungs and other organs due to a relatively high in vivo solubility of those nanoparticles. Nevertheless their genotoxic action and transnasal penetration into the brain urge caution when assessing occupational or environmental hazard of that aerosol.

Кeywords: nano-silica-containing industrial aerosol, long-term inhalation exposure, toxicity, fibrogenicity, toxicokinetics

1. Кацнельсон Б.А., Привалова Л.И., Сутункова М.П., Гурвич В.Б., Минигалиева И.А., Логинова Н.В. и др. Основные результаты токсикологических экспериментов «ин виво» с некоторыми металлическими и металло-оксидными наночастицами. Токсикологический Вестник. 2015; 3: 26-39.

2. Katsnelson B.A., Privalova L.I., Sutunkova M.P., Gurvich V.B., Minigalieva I.A., Loginova N.V. et al. Some inferences from in vivo experiments with metal and metal oxide nanoparticles: the pulmonary phagocytosis response subchronic systemic toxicity and genotoxicity, regulatory proposals, searchin for bioprotectors (a self-overview). International J. Nanomedicine. 2015;10: 3013–3029.

3. Минигалиева И.А. Некоторые закономерности комбинированной токсичности металлооксидных наночастиц. Токсикологический Вестник. 2016; 6:18-24.

4. Сутункова М.П. Экспериментальные данные и методические соображения к обоснованию предельно допустимой концентрации железооксидных наночастиц в воздухе рабочей зоны. Токсикологический Вестник. 2016; (6):11-17.

5. Privalova L.I., Gurvich V.B., Konysheva L.K., Shur V.Ya. et al. On the contribution of the phagocytosis and the solubilization to the iron oxide nanoparticles retention in and elimination from lungs under long-term inhalation exposure. Toxicology. 2016;363-364: 19-

6. Величковский Б.Т., Кацнельсон Б.А. Этиология и патогенез силикоза. М., Медицина; 1964.

7. Vance M.E, Kuiken T, Vejerano E.P., McGinnis S. P., Hochella Jr M. F., Rejeski D. et al. Nanotechnology in the real world: Redeveloping the nanomaterial consumer products inventory. Beilstein J. Nanotechnology. 2015; 6:1769–178

8. Eom H.J., Choi J. Oxidative stress of silica nanoparticles in human bronchial epithelial cell, Beas-2B. Toxicology in Vitro. 2009; 23(7):1326–1332.

9. Kim Y.J., Yu M., Park H.O., Yang S.I. Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by silica nanomaterials in human neuronal cell line. Molecular and Cellular Toxicology. 2010;6(4):336–343.

10. Sergent J.A., Paget V., Chevillard S. Toxicity and genotoxicity of nano-SiO2 on human epithelial intestinal HT-29 cell line. Annals Occupational Hygiene. 2012; 56(5):622–630

11. Du Z.J., Zhao D.L., Jing L.,Cui G., Jin M., Li Y.et al. Cardiovascular toxicity of different sizes amorphous silica nanoparticles in rats after intratracheal instillation. Cardiovascular Toxicology. 2013; 13(3): 194–207.

12. Petrick L., Rosenblat M., Paland N., Aviram M. Silicon dioxide nanoparticles increase macrophage atherogenicity: stimulation of cellular cytotoxicity, oxidative stress, and triglycerides accumulation. Environmental Toxicology. 2016;31(6):713–7

13. Guo C., Xia Y., Niu P., Jiang L., Duan J., Yu Y. et al. Silica nanoparticles induce oxidative stress, inflammation, and endothelial dysfunction in vitro via activation of the MAPK/Nrf2 pathway and nuclear factor-κB signaling. International J. Nanomedicine.2015;10:1463-1477

14. Guo C., Yang M., Jing l., Wang J., Yu Y., Li Y. et al. Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling. International J Nanomedicine. 2016; 11: 5257—5276

15. Privalova L.I., Katsnelson B.A., Osipenko A.B., Yushkov B.H., Babushkina L.G. Response of a phagocyte cell system to products of macrophage breakdown as a probable mechanism of alveolar phagocytosis adaptation to deposition of particles of different cytotoxicity. Environmental Health Perspectives. 1980;35: 205–218.

16. Кацнельсон Б.А., Алексеева О.Г., Привалова Л.И, Ползик Е.В.

17. Пневмокониозы. Патогенез и биологическая профилактика, Екатеринбург,У-рО РАН 1995.

18. Bellmann B., Muhle H., Creutzenberg O., Dasenbrock C., Kilpper R., MacKenzie J.C. et al. Lung clearance and retention of toner utilizing a tracer technique, during chronic inhalation exposure in rats. Fundamental and Applied Toxicology. 1991; 17: 300–313

19. Elder A., Gelein R., Silva V., Feikert T., Opanashuk L., Carter J. et al.. Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. Environ Health Perspect. 2006; 114 (8):1172–1178.

20. Kao Y.-Y., Cheng T.-J., Yang D.-M., Liu P.- Sh. Demonstration of an olfactory bulb–brain translocation pathway for ZnO nanoparticles in rodent ells in vitro and in vivo. J. Molecular Neuroscience. 2012; 48 (2): 464–471.

21. Oberdörster G., Sharp Z., Atudore V., Elder A., Gelein R., Kreylin W.Translocation of inhaled ultrafine particle to the brainI. Inhalation Toxicology. 2004; 16 (6/7),437–445

22. REFERENCES:

23. Katsnelson B.A., Privalova L.I., Sutunkova M.P., Gurvich V.B., Minigalieva I.A., Loginova N.V. et al. Main results of toxicological experiments in vivo with some metal and metal oxides nanoparticles. Toksikologicheskij Vestnik. 2015; 3: 26-39 (in Russian).

24. Katsnelson B.A., Privalova L.I., Sutunkova M.P., Gurvich V.B., Minigalieva I.A., Loginova N.V. et al. Some inferences from in vivo experiments with metal and metal oxide nanoparticles: the pulmonary phagocytosis response subchronic systemic toxicity and genotoxicity, regulatory proposals, searchin for bioprotectors (a selfoverview). International J. Nanomedicine. 2015;10: 3013–3029.

25. Minigalieva I.A. Some regularities of metal oxide nps combined toxicity. Toksicol Vestnik. 2016; 6:18-24 (in Russian).

26. Sutunkova M.P. Еxperimental data and methodological considersations for

27. justification of iron oxide nanoparticles maximum allowable

28. concentration in occupsational air. Toksicol Vestnik. 2016; 6:11-17 (in Russian).

29. Sutunkova M.P., Katsnelson B.A., Privalova L.I., Gurvich V.B., Konysheva L.K., Shur V.Ya. et al. On the contribution of the phagocytosis and the solubilization to the iron oxide nanoparticles retention in and elimination from lungs under long-term inhalation exposure. Toxicology. 2016;363-364: 19-

30. Velichkovsky B.T., Katsnelson B.A. Aetiology and Pathogenesis of Silicosis. Moscow: “Meditsina@ Publishing House.1964, (in Russian).

31. Vance M.E, Kuiken T, Vejerano E.P., McGinnis S. P., Hochella Jr M. F., Rejeski D. et al. Nanotechnology in the real world: Redeveloping the nanomaterial consumer products inventory. Beilstein J. Nanotechnology. 2015; 6:1769–178

32. Eom H.J., Choi J. Oxidative stress of silica nanoparticles in human bronchial epithelial cell, Beas-2B. Toxicology in Vitro.2009; 23(7):1326–1332.

33. Kim Y.J., Yu M., Park H.O., Yang S.I. Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by silica nanomaterials in human neuronal cell line. Molecular and Cellular Toxicology. 2010;6(4):336–343.

34. Sergent J.A., Paget V., Chevillard S. Toxicity and genotoxicity of nano-SiO2 on human epithelial intestinal HT-29 cell line. Annals Occupational Hygiene. 2012; 56(5):622–630

35. Du Z.J., Zhao D.L., Jing L.,Cui G., Jin M., Li Y.et al. Cardiovascular toxicity of different sizes amorphous silica nanoparticles in rats after intratracheal instillation. Cardiovascular Toxicology. 2013;13(3): 194–207.

36. Petrick L., Rosenblat M., Paland N., Aviram M. Silicon dioxide nanoparticles increase macrophage atherogenicity: stimulation of cellular cytotoxicity, oxidative stress, and triglycerides accumulation. Environmental Toxicology. 2016;31(6):713–7

37. Guo C., Xia Y., Niu P., Jiang L., Duan J., Yu Y. et al. Silica nanoparticles induce oxidative stress, inflammation, and endothelial dysfunction in vitro via activation of the MAPK/Nrf2 pathway and nuclear factor-κB signaling. International J. Nanomedicine.2015;10:1463-1477

38. Guo C., Yang M., Jing l., Wang J., Yu Y., Li Y. et al. Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling. International J Nanomedicine. 2016; 11: 5257—5276.

39. Privalova L.I., Katsnelson B.A., Osipenko A.B., Yushkov B.H., Babushkina L.G. Response of a phagocyte cell system to products of macrophage breakdown as a probable mechanism of alveolar phagocytosis adaptation to deposition of particles of different cytotoxicity. Environmental Health Perspectives. 1980;35: 205–218.

40. Katsnelson B.A., Alekseeva О.G., Privalova L.I, Polzik E. V.

41. "Pneumoconiosis. The pathogenesis and biological prophylaxis", Ekaterinburg, UrB RAS,

42. (in Russian).

43. Bellmann B., Muhle H., Creutzenberg O., Dasenbrock C., Kilpper R., MacKenzie J.C. et al. Lung clearance and retention of toner utilizing a tracer technique, during chronic inhalation exposure in rats. Fundamental and Applied Toxicology. 1991; 17: 300–3

44. Elder A., Gelein R., Silva V., Feikert T., Opanashuk L., Carter J. et al.. Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. Environ Health Perspect. 2006; 114 (8):1172–1178.

45. Kao Y.-Y., Cheng T.-J., Yang D.-M., Liu P.- Sh. Demonstration of an olfactory bulb–brain translocation pathway for ZnO nanoparticles in rodent ells in vitro and in vivo. J. Molecular Neuroscience. 2012; 48 (2): 464–471.

46. Oberdörster G., Sharp Z., Atudore V., Elder A., Gelein R., Kreylin W.Translocation of inhaled ultrafine particle to the brainI. Inhalation Toxicology. 2004; 16 (6/7),437–445.