Both human cells and animal cells react in vitro to silver particles depending on the dose applied. The cellular reactions, however, are different depending on the cell type. While studies using low doses did not reveal any changes in the appearance of the cells, different modifications, that is abnormal size followed by shrinkage, rounding, and, eventually, cell death, were observed after treatment with very high concentrations of silver particles within the framework of other studies. Another in vitro test performed on primary cells showed that the cells take up particles but are protected from oxidative damage by the cellular antioxidative mechanisms. Studies carried out using a skin model revealed that silver nanoparticles can penetrate the human skin in vitro (see also skin). These different approaches point out that, even though there is no consensus on the cytotoxicity of nanosilver particles, it is manifest that relatively high concentrations of silver particles impair the health of cells.

Literature:

1. Wijnhoven, S et al 2009, Nanotoxicology, 3:2,109-138
2. Arora, S et al 2008, Toxicology Letters 179(2): 93-100
3. Arora, S et al 2009, Toxicology and Applied Pharmacology, Volume 236, Issue 3
4. Larese, F et al 2009, Toxikology 255 (1-2), Pages 33-37
5. Hussain, SM et al 2005, Toxicol in vitro 19: 975 -983
6. Hussain, SM et al 2006, Toxocological Sciences 92(2): 456–463
7. Hardes, J et al 2007, Sarcoma Volume 2007

In addition to carrying out in vitro studies on cell cultures outside the body, one has performed experiments on laboratory animals over longer periods of time (28 to 90 days). Small quantities of the nanosilver particles inhaled by the test animals could be detected in the blood and in organs such as the liver, the kidneys, the lymph nodes, and the brain. No definite clinical or histopathological effects were found in rats exposed over 28 days. In the course of the 90-days study, the rodents showed a reduced lung function and inflammations of the lung. When silver particles were fed to the animals over a longer period of time, silver was detected in the blood and in different organs (in the liver, lung, kidneys, stomach, testicles, and in the brain), one gender-related difference consisting in the fact that double as many particles accumulated in the kidneys of the female rats than in the kidneys of the male ones. It remains to be investigated, however, whether ions or particles are taken up via the gastrointestinal tract to be transported to other areas in the body. Studies of the genotype revealed that damage had been caused neither in the male nor female test animals.
During studies performed in the 60s and 70s of the 20^th century, very large quantities of colloidal silver were injected directly into the bloodstreams of the test animals. With the mean lethal dose (LD50) amounting to at least 67 mg/kg weight, corresponding to 4.7 g for a person weighing 70 kg, the animals died of pulmonary oedemas . Brown stains ( argyria ) were found on the liver, spleen, and kidneys. For humans, however, the quantities injected then are unrealistically high.
Only extremely high doses were observed to cause significant adverse effects on health. Small doses of silver particles are toxic neither to humans nor to mammals. While a maximum daily quantity of 5 µg per kg body weight is recommended in the USA, the use of silver as a dietary supplement is not permitted in Europe. There, provided that it is declared on the respective labels of sweets, confectionery, and pastries, silver is allowed to be used as food coloring E174 for dyeing product surfaces.

Literature

1. Wijnhoven, S et al 2009, Nanotoxicology, 3:2,109-138
   
2. Kim, Y S et al 2008, Inhalation Toxicology, 20 (6): 575 — 583
   
3. Ji JH et al 2007,   Inhalation Toxicology 19 (10): 857-871
   
4. NanoTrust Dossier No10: Nanosilber: http://nanotrust.ac.at/dossiers.html
5. Möller M, et al 2009, Nanotechnologie im Bereich der Lebensmittel. ISBN 978-3-7281-3234-5
   

Independent of the size of particles, permanent exposure to silver may cause argyria (a disease causing irreversible staining of the skin and mucous membranes) or argyrosis (local accumulation of silver) when high doses are taken up and are deposited in the body. In Germany, (nano)silver is not permitted for use as a dietary supplement. It is considered as a pharmaceutical (colloidal silver) which is subject to the regulations of the German Medicines Law.
Dietary supplements containing nanoscale heavy metals such as silver, gold, platinum, palladium, and iridium, however, are already sold internationally on the internet and are, therefore, also available to German buyers.

Literature:

1. Wijnhoven, S et al 2009, Nanotoxicology, 3:2,109-138
   
2. Wikipedia: http://de.wikipedia.org/wiki/Argyrie /// ]
   
3. Law on the marketing of medicines: http://bundesrecht.juris.de/amg_1976/index.html
   
4. Möller M et al, 2009, Nanotechnologie im Bereich der Lebensmittel, ISBN 978-3-7281-3234-5

As with many other nanomaterials, the direct detection of particles in air, soil or water is very difficult, hence, simulations applying computer programs are used. A study on the contribution of nano silver derived from plastic and textiles, which is approximately 15% of the total input of silver, predicts no risk to freshwater ecosystems ^[1]. However, another study based its calculations on the entire production volumes of nano-silver. Here, the risk quotients have substantially higher values. First, the distribution in the environment was simulated and then environmental concentrations predicted (PEC value, predicted environmental concentration). Most of the nano-silver reaches either the inflow of sewage treatment plants and subsequently the ground or is disposed in landfills. When comparing the calculated environmental concentrations with concentrations not dangerous for environmental organisms (PNEC, predicted no observed effect concentration), it appears that one can expected risks to the environment from nanosilver, with especially high risks from the effluent of sewage treatment plants . The risks for surface water is generally was found to be lower, however existing, for the air no risk was calculated. How such a risk is calculated is explained in more detail in the table. For environmental areas with an estimated risk, future experimental studies have been to be carried out for confirmation ^[2]. 

The risk quotient is calculated by dividing the predicted environmental concentrations (PEC) by the predicted concentrations, which have no effects on environmental organisms (PNEC) was formed. If the risk quotient is smaller than 1, there is no risk to the environment, at levels above 1, there is a risk, and further investigations should be carried out (from ^[2]).

For example, silver nanoparticles are processed in textiles in order to prevent smell and to lengthen the washing intervals. However, presumed due to the solubility of silver, during each washing step a part of the silver coating leaches into the wash water. A very application-oriented study dealt with socks and stability of silver nanoparticles in the tissue during the washing process. It turned out that during each wash silver was released from the socks in the washing water ^[3,4]. Sometimes the entire silver was washed out after a few washes. Both particles of different sizes and silver ions could be detected in the washing water. A computer based modeling of the washing water treatment process showed that the majority of the silver remains in the sludge. This study is direct evidence that nanoparticles from a product can enter the environment and thus contribute to exposure of environmental organisms.
However, there are already first approaches to remove silver nanoparticles from wastewater. For this purpose, the washing water of textiles is treated with bacteria which are able to collect the silver. Thus it has been the one hand removed from the water and the other can be recycled ^[5].

Literature

1. Blaser, S. A. et al. (2008), Science of The Total Environment 390, 396-409.
2. Gottschalk, F. et al. (2009), Environ Sci & Technol 43, 9216-9222.
3. Benn, T. M.Westerhoff, P. (2008), Environ Sci & Technol 42, 4133.
4. Geranio, L. et al. (2009), Environ Sci Technol 43, 8113-8118.
5. Duran, N. et al. (2010), J Nanopart Res 12, 285-292.
Luoma, S.N. (2008) Silver nanotechnologies and the environment: old problems or new challenges. In Project on emerging nanotechnologies. PEN 15 . (ed. W.W.I.C.f. Scholars).