Assessment of the complex processes of distribution and deposition as well as of the mechanisms of action of nanomaterials in the lung and other organs after inhalation requires performing inhalation studies in biological test systems (cell and tissue cultures or laboratory animals) (see also “in vivo”).
Testing animals within such inhalation studies it turned out that inhalation of 15 nm silver particles can cause silver to pass into the bloodstream. In a further study, it was shown that inhaled silver particles (12 – 16 nm particles) can be eventually detected in the livers and the brains of rats. However, no pathological changes of tissues due to inhalation of silver particles over a period of 28 days could be observed ^[1].
In the course of the 90-days inhalation studies of exposure to 18 nm-sized particles for 6 hours a day over a period of 90 days, the laboratory animals exhibited a dose-dependent reduced lung function and inflammations of the lung ^[3,4].
Health impacts are mainly dose and time-dependent.

Literatur: 

1. Ji JH et al 2007, Inhalation Toxicology 19: 857-871
2. Wijnhoven, S et al 2009, Nanotoxicology, 3:2,109-138
   
3. Sung JH et al 2008, Inhalation Toxicology 20: 567-574
   
4. Sung J H et al, 2009 Tox Sciences 108 (2), 452-461
   
5. ATSDR, Toxicological Profile for Silver, 1990

15 nm nanosilver particles can be observed to be absorbed from silver-coated dressings that are applied to the injured skin. Increased quantities of silver can be detected in the plasma and the urine of the patient after one week of local treatment. It remains to be investigated, however, whether ions or particles are transported in the body.
The European Parliament has recently reacted to the fear that very small particles may penetrate the skin and exert toxic effects by changing the EU Cosmetics Directive which stipulates that all nanoparticles contained in cosmetics be declared. An in vitro study using the so-called Franz diffusion cell proved that silver nanoparticles can penetrate the human skin. In the experiment, two chambers are separated by a human-skin membrane. The (coated) nanosilver particles in aqueous solution in the first chamber pass the membrane and get into the other chamber where they are detected.
Electron-microscopic studies have proved the presence of individual nanosilver particles in the deeper layers of the skin. A systemic toxicity, however, can only be developed by the part of silver that penetrates the skin and breaks the barrier. The relevant concentration was determined within the framework of in vitro and in vivo studies which agreed that the quantity of silver ions penetrating the stratum corneum is extremely small or not detectable at all. After application of creams and lotions with active-agent contents in the range of 0.1 to 1.5 percent, less than 0.1 percent of the respective quantities applied were found in the corneal layer without penetration of the skin being detectable. From a conservative risk assessment on the basis of these data it follows that 10 g cream with a microsilver content of 1 percent contain 100 mg silver with an estimated amount of silver ions in the range of 10 to 500 μg of which 1 percent, at most, penetrates the deeper layers of the skin. This corresponds to 0.1 to 5 μg silver ions, which means that 0.3 to 15 μg silver out of a generously estimated 30 g top-to-toe portion of cream is taken up via the skin.

Literature:

1. Larese F et al 2009, Toxikology 255 (1-2), Pages 33-37
2. Wijnhoven, S et al 2009, Nanotoxicology, 3:2,109-138
3. Daniels R et al 2009,  PZ Pharmazeutische Zeitung online
   
4. Silberprodukte: http://www.nanoproducts.de

Silver particles fed to animals during in vivo studies over a longer period of time were detected as silver in the blood and in different organs (liver, lung, kidney, stomach, testicles, and brain) ^[1]. It can be concluded that the silver was taken up via the gastrointestinal tract and was transported via the bloodstream into the respective organs. The uptake of silver particles into cells of the gastrointestinal tracts of fishes and humans was shown by means of in vitro studies ^[3].
Plastic packaging materials available in the USA and in Asia may contain silver particles which may get into the food and be taken up by the body. Significant adverse health effects, however, were observed only after administration of extremely high doses. Neither silver as a dietary supplement nor antimicrobial packaging materials that contain silver particles are permitted for use in Germany.
 

Literature:

1. Wijnhoven, S et al 2009, Nanotoxicology, 3:2,109-138
2. Reinhart A, 2008, Journal für Verbraucherschutz und Lebensmittelsicherheit, 3 (3), S. 294-301
3. Gaiser et al 2009, Environ Health. /// 21;8 Suppl 1:S2 

The toxic effect of silver against bacteria is used in many applications. Why many microorganisms react much more sensitive to silver than higher organisms, is still not clearly understood. The general mechanism of silver toxicity, however, is well known: silver ions bind to proteins and can thus interfere with their functions. This mechanism applies to higher organisms as well as to microorganisms. One explanation for the higher sensitivity of microorganisms to silver might be that certain proteins for the production of energy are not located inside the cell, but directly on the cell surface, where they are easily attacked by the silver.
At the same time this is the biggest problem for the environment, because released silver does not distinguish between "desirable" and "undesirable" bacteria. This leads to possible unintended effects, e.g. in the biological step of wastewater treatment plants, when the waste water is cleaned by the decomposition activity of bacteria, or in soils where bacteria play an important role in fertilization. It was shown that the activity of nitrogen converting bacteria is considerably reduced in the presence of silver. This effect was stronger, the smaller the particles were ^[1]. However, the toxic effect of silver was attenuated in the presence of organic materials contained in surface waters ^[2]. One study showed no reduction in bacterial diversity by silver nanoparticles in the marine environment. One reason could be that the silver ions bind fast to the chloride contained in the salt water and are therefore harmless.
However, there are certain silver-resistant bacterial and fungal species, as evidenced by the production of silver nanoparticles by these organisms ^[3]. Such bacteria are able to effectively incorporate and store metals. For these organisms silver is not toxic and they can even be used for cleaning silver-contaminated wastewater ^[3].
Even for green algae, which possess more complex cells compared to bacterial cells, silver is toxic. Silver nanoparticles inhibited the metabolism and thereby the growth of algae ^[4,5]. The inhibitory effect of silver nanoparticles, based on the concentration of dissolved silver ions was stronger than that of silver ions, which were from silver salts.
The early development of zebrafish embryos was affected by very small silver particles ^[5,6,7], the particles could be detected both within the egg membrane and within the embryos. The damage to the embryos was dose-dependent. Among others, damage to the heart and the spine were observed. In a cell line of medaka silver nanoparticles resulted in damage to the chromosomes (carriers of genetic information) and the death of the cells ^[8]. Also for water fleas silver nanoparticles are proven to be toxic, the particles were also clearly more toxic than the ions ^[5].
As the silver ions are considered as the effective or toxic component, for the assessment of silver toxicity the solubility by oxidation is an important aspect. In general, the solubility of silver ions from the particles will be low. Nevertheless, in many studies silver ions, which do not originate from particles are less toxic than silver ions dissolved out of nanoparticles ^[1,2,4,5]. This shows that for the biocidal effect, the presence of the particles, their shape or type of surface plays a role. So far it is unclear whether the specific amplification of the effect by the particle shape is due to a better solubility or availability of silver particles on contact with organisms or an increased reactivity.
In summary, silver is a known ecotoxic substance and present as nanoparticles it is more toxic compared to silver ions in a number of organisms studied.

Literature:
 

1.   Choi, O. et al. (2008), Environ Sci Technol 42, 4583-4588. 
2.   Fabrega, J. et al. (2009), Environ Sci Technol 43, 7285-7290. 
3.   Duran, N. et al. (2010), J Nanopart Res 12, 285-292. 
4.   Navarro, E. et al. (2008), Environ Sci Technol 42, 8959-8964.
5.   Grif fitt, R.J. et al. (2008), Environ Tox Chem 27, 1972-1978.
6.   Lee, K.J. et al. (2007), ACS Nano 1, 133-143.5.
7.   Ashrani, P.V. et al. (2008), Nanotechnology 19, 255102.
8.   Wise Sr., J.P. et al. (2010), Aqua Tox 97, 34-41.