Peroral Toxicological Assessment of Two-Dimensional Forms of Nickel Nanoparticles Sized between 20 and 120 nm.

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.

Detrimental effects of 6 months exposure to very low doses of a mixture of six pesticides associated with chronic vitamin deficiency on rats.

This study aimed to evaluate the long-term low-dose effects of exposure to a mixture of 6 pesticide active substances (diquat, imazamox, imazethapyr, tepraloxydin, bentazone, acifluorfen) and to elucidate if chronic vitamin deficiency can influence their toxicity. Two hundred Wistar rats were divided in 4 groups: a vitamin-sufficiency control group, a vitamin-deficiency control group, a vitamin sufficiency test group and a vitamin-deficiency test group. The test groups were treated with the aforementioned pesticides at doses 100 times lower than the corresponding NOAEL. After 6 months, ten rats from each group were sacrificed and a complete evaluation of blood and urine biochemistry, biomarkers of oxidative stress, xenobiotic detoxification enzymes and lysosomal enzymes and organ histopathology was performed. The pesticides mixture and vitamin deficiency determined an increase in alkaline phosphatase levels and urinary calcium levels, abnormal serum lipid profile, and a decrease of total blood proteins levels, red blood cells, haematocrit and haemoglobin. The combination of the two stressors up-regulated CYP1A1, CYP1A2, CYP2B1 and GST levels. This study provides a new proof for the need to move forward from single chemical testing to a more complex approach to account for the multitude of stressors that can challenge the setting of real safety levels.

Toxicity Evaluation of Nanostructured Silica Orally Administered to Rats: Influence on Immune System Function.

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.