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.