# Does Nanosilver Have a Pronounced Toxic Effect on Humans?
## 3 Experimental Research Conducted by the Authors of the Review
### First Results with Uncated AgNPs  
The study of the impact of AgNPs on animals began with the use of uncoated AgNPs in order to exclude the possible effect of the coating substance on the results. A colloidal solution \"Silver Shield\" (LLC \"Fractal-M\", Russia) with an average nanoparticle size of 15 nm was used. In the first experiments performed in 2009-2010, the task was to determine the maximum allowable dose of AgNPs, for example, LD10 for groups of mice, to explore it in further experiments. According to the design of the experiments on the effect of AgNPs on cognitive functions, mice should have received a strong toxic effect from AgNPs but not died from the general intoxication of the body. Therefore, it was necessary to select such a dose experimentally. For that purpose, two similar experiments were carried out on mice of different ages at the beginning of NP administration: young (3-4 weeks) in the first experiment and old (1.5 years) in the second one [52; 53]. The duration of NP intake was one month, and their concentrations in solutions were 25, 50, or 100 mg/L. A concentration of 100 mg/L is the maximum possible for a colloidal solution of uncoated AgNPs, at which NPs are suspended in the solution throughout the experiment. At concentrations above 100 mg/L, they conglomerate (aggregate) and settle to the bottom. \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Age** & **Study Goal** & **Coating** & **Dose of AgNPs** & **Amount of Silver in the Brain** & **Effect** & **Reference** \\ \hline \multirow{4}{*}{3–4 weeks} & Influence on & & & & Signs of \\  & health and & & 1.8, 3.7 or & & oxidative stress \\  & behavior, blood & & 7.1 mg/kg for & Not measured & in blood \\  & composition, & & 1 month & & composition \\  & and & & & & Signs of \\  & reproduction & & & & oxidative stress \\  & Influence on & & 1 month & & in blood \\  & health and & & & & composition \\  & behavior, blood & & & & Spatial \\  & composition & & & & \\  & cognitive & & 4.5 and & 319 \(\pm\) 155 ng & orientation, \\  & abilities in & & 5 mg/kg for & after 2 months; & memory, and \\  & adults, & & & females for 2 or & 870 \(\pm\) 200 ng & retrieval are \\  & accumulation in & & 4 months & after 4 months & undisturbed in \\  & the brain & & & & adults. \\  & Influence on & & & & \\  & cognitive & & & & \\  & abilities in & & & & \\  & offspring, & & & & \\  & estimation of & & 5 mg/kg for & mothers; & memory \\  & accumulation in & & 2 months & 385 \(\pm\) 57 ng in & formation in \\  & accumulation in & & & offspring & offspring \\  & the brain & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Summary of the experiments on the impact of AgNPs on mice: purpose and experimental conditions. Even according to the obtained results, small biochemical disturbances occurred in the blood of the mice, indicating the development of oxidative stress and, possibly, renal disorders [52; 53], which were more pronounced in adult mice than in young ones; all experimental animals to all appearances and behaviors in all groups did not differ from the control group. There were no deaths of mice in the groups. At average daily doses of the consumption of AgNPs per mouse 1.8; 3.7 or 7.1 mg/kg of body weight, the condition of internal organs in all experimental mice also did not differ in appearance from that of control animals. Analyzing histological preparations of the heart, liver, kidneys, and spleen, no obvious pathological changes were noted in any group of mice. In the first experiment, at the end of the intake of AgNPs, the birth rate in young females was also assessed. According to the obtained results, it did not differ from the other groups of animals used in the experiment. In general, both experimental and control individuals gave birth to 7-8 healthy infants [52]. Thus, no obvious toxic effects of AgNPs without coating were revealed, even at a concentration of AgNPs in a drinking solution of 100 mg/L.