The experimental data on the oral toxicity of nanostructured amorphous silica (SiO₂), widely used in food supplements, pharmaceuticals, and cosmetics, in terms of its in vivo effect on the immune system, are contradictory. Therefore, this study aimed to assess the rat’s immune function after SiO₂ oral administration. In the first experiment, SiO₂ was daily orally administered to Wistar rats for 92 days in doses of 0.1, 1.0, 10, and 100 mg/kg of body weight (bw). In the second 28-day experiment, SiO₂ in a dose of 100 mg/kg bw was daily orally administered to rats parenterally immunized with the food allergen ovalbumin (OVA) for the reproduction of systemic anaphylaxis reaction. Together with integral indices, we assessed intestinal permeability to protein macromolecules; hematology; CD45RA+, CD3+, CD4+, CD8+, and CD161a+ cells; cytokines TNF-α, IL-6, and IL-10; and IgG to OVA. The results obtained showed that SiO₂ has no effect on the severity of the anaphylactic reaction, but is capable inducing a toxic effect on the T-cell immune systems of rats. Estimated no observed adverse effect level NOAEL for SiO₂ ranges up to 100 mg/kg bw in terms of its daily consumption for 1–3 months. Using SiO₂ as a food additive should be the subject of regulation.

Nickel (Ni) nanoparticles (NPs) are used as technological aids–catalysts in the oil and fat industry, in pharmaceuticals, and in the production of cosmetics and pesticides. The acute and subchronic oral toxicity of metallic Ni in the nanoform is not well understood. The study aimed to investigate the acute and subchronic oral toxicity of Ni NPs to rats. We used two NP preparations (Ni NP1 and Ni NP2) with spherical particles and an average diameter of 53.7 and 70.9 nm according to the electron microscopy data. In the study of acute toxicity, both kinds of Ni NPs were administered to male and female Wistar rats aged 8 weeks as a single dose of 2000 mg/kg b.w. through a gastric gavage. In the subchronic experiment, male Wistar rats initially aged 7 weeks received for 92 days Ni NP1 and Ni NP2 as well as the “traditional” soluble salt form of Ni (Ni basic carbonate) at doses of 0.1, 1, and 10 mg/kg body weight (mg/kg b.w.) in terms of Ni content as a part of the diet consumed. As a result, in an acute study, the oral LD₅₀ for Ni NP2 in male and female rats was about 1600 mg/kg b.w. (IV hazard class). The oral dose of Ni NP1 equal to 2000 mg/kg b.w. exceeded LD₁₀₀ for males and corresponded to LD₉₀ for females. In the subchronic study, the bioaccumulation of both Ni NPs as well as Ni salt was observed in the kidney but not in the liver and spleen. Ni NP1 decreased body weight only at a dose of 1 mg/kg b.w.; affected the relative weight of the spleen at 0.1 mg/kg, the brain at 1.0 mg/kg, and the thymus at 10 mg/kg; and decreased locomotor activity at 0.1 and 10 mg/kg. Thus, for Ni NP1, in such cases where a monotonic dose–response relationship could be traced, LOEL could be stated at 10 mg/kg b.w./day for 92 days of oral intake. However, for some endpoints where such a monotonic relationship could be absent, significant toxic effects were observed even at a dose 0.1 mg/kg. In the case of Ni NP2, changes in the relative weight of the liver, thymus, and brain were recorded starting from 0.1 mg/kg b.w.; locomotor activity decreased starting from 0.1 mg/kg. Other effects, including basophiles count and platelet system indexes, were observed at a dose of 1 mg/kg or higher. Thus, the LOEL value for Ni NP2 can be fixed at 0.1 mg/kg. The critical organs affected by both Ni NPs were the brain and immune system. Most of the toxic effects exhibited by metallic Ni NPs were absent or had an opposite orientation upon administration of equivalent doses of Ni in the salt form which indicates the signs of “nanotoxicity” in metallic Ni NPs. In conclusion, the data obtained show that there may be some additional health risks caused by the intake of Ni in a nanoform compared to soluble ionized forms of this element at equivalent doses.

Bacterial nanocellulose (BNC) is considered a promising alternative to microcrystalline cellulose, as well as an ingredient in low-calorie dietary products. However, the risks of BNC when consumed with food are not well characterized. The aim of this study is to investigate the impact of BNC on immune function, the intestinal microbiome, intestinal barrier integrity, and allergic sensitization in subacute experiments on rats. Male Wistar rats received BNC with a diet for eight weeks in a dose range of 1–100 mg/kg of body weight. The measurements of serum levels of cytokines, adipokines, iFABP2, indicators of cellular immunity, composition of the intestinal microbiome, and a histological study of the ileal mucosa were performed. In a separate four-week experiment on a model of systemic anaphylaxis to food antigen, BNC at a dose of 100 mg/kg of body weight did not increase the severity of the reaction or change the response of IgG antibodies. Based on dose–response effects on immune function, the non-observed adverse effect level for BNC was less than 100 mg/kg of body weight per day. The effects of BNC on the gut microbiome and the intestinal mucosal barrier were not dose-dependent. Data on the possible presence of prebiotic effects in BNC have been obtained.

Carbon nanomaterials (CNMs), such as single-walled (SWCNTs) carbon nanotubes, multi-walled carbon nanotubes (MWCNTs), and fullerene derivatives, are considered promising agents for the delivery of pharmacological drugs to target organs, including antitumor chemotherapy and theranostics. However, the question arises about CNMs’ possible effects on the general toxic and immunotoxic effects of cytostatic preparations when they are administered mutually. This work aimed to study the combined effects of cyclophosphamide (CP) intoxication and oral CNM administration in male Wistar rats. In two experiments lasting 16 and 35 days, MWCNTs, SWCNTs, or polyhydroxylated fullerenol (PHF60) were administered to control or treat CP rats, at a dose of 0.1 mg/kg of body weight daily prepared as dispersions in drinking water. The lethality and integral parameters of the rats were assessed; the content of erythrocytes and leukocytes, biochemical indicators, levels of cytokines, chemokines, and growth factors was measured. In the first experiment lasting 16 days, the consumption of both MWCNTs and SWCNTs led to an almost two-fold decrease in mortality caused by the administration of CP. In the second experiment lasting 35 days, a similar decrease in mortality was noted for SWCNTs; the capability of MWCNTs and PHF60 to increase the survival of animals was also pronounced. The administration of MWCNTs, SWCNTs, and PHF60 to the animals reduced the immunotoxic effects of CP, resulting in increased lymphocyte counts and a correction of the imbalance between cytokines and chemokines/growth factors, including IL-4, IL-13, IL-17A, IFN-g, IL-18, GM -CSF, GRO-KC, IL-12p70, IL-1b, IL-7, TNF-a, and VEGF. Thus, various CNMs, when administered together with CP, caused a partial abolition of their general toxic and immunotoxic action, which can be explained by the available literature data on the ability of CNMs to enhance the mobilization, migration, and adhesion of blood cells and trigger immune responses.