# Does Nanosilver Have a Pronounced Toxic Effect on Humans?
## 4 Discussion  
Along with reports on the toxicity of AgNPs, there are contradicting studies in which toxic effects of NPs are (1) not disclosed, (2) not detected during the behavioral testing, and (3) not detected in certain types of behavioral tests. At the same time, it is known in medicine that the excessive use of silver preparations, even in the usual, non-nano-scale form, can lead to toxic effects and systemic diseases, for example, at doses of more than 70 mg of silver per kg of body weight, to argyria [64].  
Several aspects may be related to the occurrence of such discrepancies. Firstly, it has not yet been determined what exactly causes the supposed toxic effect of AgNPs. Some studies suggest that the observed toxicity (including the antibacterial effect) may be caused by Ag\({}^{+}\) present in the solution and not by NPs themselves [29; 65]. The assumption was made on the basis of the similarity and, at the same time, significantly greater severity of toxic effects provoked by animals' contact with a solution containing Ag\({}^{+}\) in comparison with NPs. However, silver practically does not dissociate in aqueous solutions; therefore, the content of Ag\({}^{+}\) in solutions of AgNPs is very low, hundreds of times lower than its concentrations used in experiments with Ag\({}^{+}\). Secondly, AgNP toxicity can be determined by the compounds used to cover nanoparticles, i.e., biopolymers that form a protein crown and polymers of stabilizing coating. The structure and interaction of NPs coated by the protein crown with cell structures are poorly studied in vivo, especially in terms of the toxic effect of NPs [66; 67]. There is evidence that toxic effects of AgNPs were expressed to varying degrees in experimental animals administrated with NPs with different coatings, and only in several studies, the effect of the coating substance on animals was assessed [12; 45; 68]. Precise mechanisms of how coating materials can impact toxicity remain unknown and need to be studied. However, for example, [PERSON] et al. [23] associated the low toxicity of citrate-coated AgNPs for microorganisms with their negative charge. Since functional groups on the cellular membrane of bacteria provide organisms with a negative charge, there is a high degree of repulsion between negative NPs and bacterial cells, which forms an electrostatic barrier that limits cell-particle interactions, thereby reducing toxicity. Thirdly, the age and state of experimental animals are also important factors--namely, healthy, mobile, sexually mature young animals in the first half of their life are more resistant to any adverse effects than aged animals or juveniles.  
If we discuss toxic effects observed in the experiments with animals through the prism of a possible analogy with humans, then it is noteworthy that in many experiments, the doses of AgNPs were so high in terms of the animal's body weight that it is difficult to imagine such a situation for a human being. For example, in our experiments simulating chronic occupational or household contact with NPs, the doses of silver received by an animal in terms of 1 kg of body weight significantly exceed the amount of silver that a person can actually receive if the individual does not consume silver forcibly. For instance, for a person weighing 70 kg to receive an amount of silver comparable to that given to a mouse in [55], the person needs to drink 12.6 L of a concentrated solution of silver NPs per day for 6-12 years. Apart from cases of the intentional consumption of AgNP solutions, it is difficult to imagine such a situation. However, even in this case, the revealed toxic effects of AgNPs are not fatal for the organism. An adult healthy individual is able to cope with such an impact with minimal damage. The question of the impact of AgNPs on children, the elderly, or people with any chronic diseases remains open. Few such experiments were carried out, but it is reasonable to suggest that the elderly and children are more sensitive to the effects of NPs.