Toxicological assessment of nanostructured silica. IV. Immunological and allergological indices in animals sensitized with food allergen and final discussioin
This paper is the final in a series of publications on the assessment of subacute oral toxicity of nanostructured silica (SiO2). Preparation studied was a commercial nanopowder of SiO2, obtained by hydrolysis of tetrachlorosilane in the gaseous phase with the size of primary nanoparticles (NPs) of 5–30 nm. The experiment was conducted in 95 male Wistar rats weighing 150–180 g, divided into 6 groups numbering 25 (group 1), 26 (group 2), 11 (groups 3–6) of animals. The aqueous dispersion of SiO2 after sonication was administered to animals of groups 2, 4 and 6 for 28 days by intragastric gavage at a dose of 100 mg/kg of body weight per day. Animals of groups 1, 3, and 5 were treated with deionized water. On the 1st, 3d, 5th and 21st day of experiment the rats of groups 1, 2, 3 and 4 were sensitized intraperitoneally with hen’s egg ovalbumin (OVA) adsorbed to aluminum hydroxide. Intravenous administration of the challenge dose OVA to rats in groups 1 and 2 was carried out on the 29th day. In the same period animals of groups 3–6 were bled for analysis of cellular immunity. There were evaluated the severity of systemic anaphylaxis reaction, the level of specific IgG antibodies to OVA in sensitized animals, state of erythrocytes, platelets and leukocytes of peripheral blood using standard methods. Using flow cytometry there were measured contents of lymphocyte populations of B-lymphocytes (CD45RA+), total T-lymphocytes (CD3+), T-helper cells (CD4+), T-cytotoxic cells (CD8+), NKcells (CD161a+), phagocytic activity of polymorphonuclear leukocytes in respect of latex particles. Serum levels of TNFα and IL-10 cytokines were determined by ELISA. The result showed that NPs SiO2, at dose of 100 mg/kg body weight had no any marked effect on severity of active anaphylactic shock and level of specific antibodies. The changes in cellular immunity under the influence of nanomaterial had similar direction in sensitized and non-sensitized animals and were more pronounced in the latter. Based on the discussion of the results, together with data from previous publications it was concluded that oral maximum level without observable adverse effect (NOAEL) of nanostructured SiO2 is located below 100 mg/kg body weight.
Keywords:silica, nanoparticles, rats, subacute toxicity, NOAEL, systemic anaphylaxis, cellular immunity, cytokines, antibodies, phagocytosis