Toxicological properties of mixtures of binary silver-copper, silver-zinc, and copper nanoparticles on cell culture model and laboratory animals

Abstract

The development, testing, and implementation of antimicrobial agents necessitates the determination of their toxicological characteristics. The objective of our research was to ascertain the direction and magnitude of the impact of experimental samples of disinfectants based on binary silver-copper, silver-zinc, and copper nanoparticles on biological entities of disparate levels of organization (cell culture, laboratory animals). The culture of calf coronary vessel cells (CVCs), 220 mature white laboratory rats, and 45 Chinchilla rabbits were used for the study. Mixtures of binary nanoparticles D1: MeNPs content – 5.4 mmol/L; D2: MeNPs content – 4.9 mmol/L were used as antimicrobial compounds. Toxic effects on cell culture were determined by the percentage of monolayer integrity, and biological effects in animals were determined by determining acute and subacute toxicity by clinical and biochemical parameters. The results of the culture studies demonstrated that the CC50 value of D2 was 6.2 times lower than that of D1, indicating a higher degree of cytotoxicity. No animal deaths were observed in the acute toxicity test (single intragastric administration to white rats at a dose of 30000 mg/kg body weight), which permitted the classification of the test samples as Class VI toxicity (relatively harmless) and Class IV hazardous (low-hazardous). When applied topically to rabbits' skin and mucous membranes, the experimental samples did not exhibit a pronounced irritant effect. A 30-day dermal application of the drugs to rats at doses of 0.5 and 5.0 mL/kg was conducted to determine the impact on hematological and biochemical parameters of a tenfold dose. Following the cessation of the administration of the aforementioned experimental disinfectant samples, the levels of all indicators were observed to return to the control levels within 14 days. The higher toxicity of the D2 drug for biological systems of different levels of organization, compared to the D1 drug, may be attributed to two factors: the higher concentration of AgNPs (2.4 times) and the potentiation of the toxic effect of two binary compounds (Ag-Zn and Ag-Cu) in its composition. Further research is needed to determine the biological impact of experimental samples of disinfectants based on silver, copper, and zinc metal nanoparticles on other functional systems of laboratory animals and the clinical and biochemical status of productive agricultural animals in production conditions.