Studies with various consumer products show a possible release of nano-silver depending on the application and processing of the silver nanoparticles in the product. Studies show that silver nanoparticles administered in low doses do not cause any health effects, although silver can be detected in organs regardless of the respective uptake route.
Regardless of the particle size permanent exposure to silver can cause diseases, where high doses of silver are taken in and deposited in the body. Symptoms of the so-called argyria include irreversible staining of the skin and mucous membranes, whereas in case of argyrosis the silver deposits are locally confined. In Germany the occupational limit values for the handling of powdered substances are also applicable for silver nanoparticles and should not exceed a value of 0.01 mg/m³ for inhalable silver compounds .
Looking at many consumer products it is not always clear whether silver is actually added in the nano form for functional or for promotional purposes only. To create more transparency for the consumers the EU has put into place mandatory labelling for nano-containing products in the cosmetics and biocides sector since July 2013 and for food since December 2014. The normal calculated dietary intake of silver is approximately 70-90 mg per day .
Can textiles release nanoparticles? © Used with permission from Von Goetz, N et al. (2013). Migration of Ag- and TiO2-(Nano)particles from textiles into artificial sweat under physical stress: experiments and exposure modelling. Environ Sci Technol, 47(17): 9979-9987. Copyright © 2013 American Chemical Society.
In Germany nano silver is not approved for use as a food supplement and considered a pharmaceutical product (colloidal silver) subjected to the regulations of the German Medicinal Products Act. 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.
Commercially available products with integrated silver nanoparticles, such as performance sportswear, food packaging and various children's products have been shown to release silver ions and silver nanoparticles. Studies in which the wearing of silver nanoparticles containing sportswear was simulated in the laboratory have shown that both silver ions and silver nanoparticles are being released into artificial sweat. This would correspond to a worst case scenario of a non-negligible maximum exposure of the skin with 8.2 - 17.1 micrograms of silver per kg of body weight .
The same is also true for food packaging materials, but in this case the amounts found were far below the natural silver-load of humans. Nevertheless, in March 2014 the US Environmental Protection Agency (EPA) has banned the sale of the plastic containers investigated in this study .
Analysis of (nano) silver containing consumer products for children. © Used with permission from Quadros M.E., Pierson R.T., Tulve N.S., Willis R., Rogers K., Thomas T.A., Marr L.C. (2013). Environ Sci Technol, 47(15): 8894-8901. Copyright © 2013 American Chemical Society
In another study, various children's products including toys, clothes and wipes were tested on a possible release of nano silver or silver ions. Here the silver nanoparticles were firmly embedded in the product, so that only very small amounts of silver ions could be detected in artificial sweat or urine .
Investigations of spray products that, according to the product description, contain silver nanoparticles only detected the silver in the form of silver chloride and silver agglomerates, but not in the nano form. However, the calculated exposure levels with silver for a worst case scenario were still below the WHO (World Health Organization) defined daily limit of 5 micrograms of silver per kg body weight .
First human studies with commercially available silver nanoparticle products, e.g. in textiles, sprays or nano silver suspensions for oral intake, showed no negative health effects of the studied subjects. Nevertheless examining the products for longer periods as well as a possible chronic exposure to silver nanoparticles are necessary steps for a comprehensive assessment of consumer products containing silver nanoparticles .
Taken together, it is not possible to make a general statement on the potential dangers of silver nanoparticle containing consumer products. Important clues are provided from the processing and integration of silver nanoparticles into the respective product.
Studies on Living Organisms – in vivo
Possible entry routes of silver nanoparticles into the human body. © Used with permission from Eckhardt S., Brunetto P.S., Gagnon J., Priebe M., Giese B., Fromm K.M. (2013). Chem Rev, 113(7): 4708-4754. Copyright © 2013 American Chemical Society
To examine the possible entry routes of silver nanoparticles in the body experiments with laboratory animals were performed over longer periods of time (28-90 days). After administering silver nanoparticles to test animals via inhalation, small amounts of silver were detected in the blood and various organs such as liver, kidney, lymph nodes and brain. No definite clinical or histopathological effects were found in rats exposed to nano silver over 28 days. In the course of long-term studies over 90 days the rodents displayed decreased lung function and inflammation in the lungs .
Feeding the laboratory animals with a nano silver supplemented diet over a longer period of time also resulted in silver being detectable in the blood and different organs such as liver, lung, kidneys, stomach, testicles and in the brain. Related to this exposure scenario there occurred gender-related differences in distribution and retention of silver nanoparticles in the body. Twice as much nano silver was found in the kidneys of female rats compared to their male counterparts, whereas the male test animals showed a persistent accumulation of silver in the brain and testes. However, it is still unclear whether either silver ions or (nano) particles are absorbed via the gastrointestinal tract and transported to other areas in the body.
As silver ions are very reactive they usually agglomerate immediately upon release or interact with and bind to other chemical compounds making them more bioavailable for the body. Analyses of the genetic material revealed no DNA-damage to either male or female test animals. Repeated doses of silver nanoparticles in the diet were not toxic to the animal and had no effect on fertility of the rats .
Silver nanoparticles used in wound dressing material protect damaged skin (e.g. from skin burns) against excessive bacterial colonisation by the release of silver ions. Studies in rats have shown that the silver nanoparticles can penetrate deep into the damaged skin of rats where they work effectively against microorganisms and promote healing. Another study confirmed that the dermal application of silver nanoparticles only triggered a slight irritation of the skin but no acute toxicity .
First studies with volunteers using commercially available nano silver containing products (T-shirt, spray, silver nanoparticle solution) showed no adverse health effects on the human body. Taken together small and thus realistic amounts of silver nanoparticles are not toxic for humans and mammals based on the current scientific knowledge .
Studies Outside the Body – in vitro
Typically in the lab different cell lines are used as representative models for the respective routes of exposure under investigation (lung, skin, gastrointestinal tract) or as models for various target organs. These in vitro studies showed a dose-dependent effect of silver nanoparticles similar to the results obtained in animal experiments (in vivo studies). Besides cellular shrinkage and cell death (apoptosis) the generation of inflammation markers and the formation of reactive oxygen species (ROS) (oxidative stress) could be detected as well as further activation of stress signalling pathways within the cells .
Cellular reaction and response to silver nanoparticle exposure. © Used with permission of Verano-Braga T., Miethling-Graff R., Wojdyla K., Rogowska-Wrzesinska A., Brewer J.R., Erdmann H., Kjeldsen F. (2014). ACS Nano, 8(3): 2161-2175. Copyright © 2014 American Chemical Society
It is still an open question whether it is the silver nanoparticles or rather the released silver ions or even both which are responsible for the aforementioned effects. In an aqueous environment (e.g. in in vitro experiments or in the body) you will always find dissolved silver ions together with surface-bound ionic silver in addition to the silver nanoparticles. As silver ions are very reactive and would favour the formation of ROS, they will equally interact with, and bind rapidly to, other groups (ions, sulphur groups, proteins) thus being converted into "neutral" complexes. The desired amount of released silver ions can be easily altered by specifically adapting the size and surface properties (Coatings for Nanomaterials) of the silver nanoparticles .
The majority of the in vitro studies support the "Trojan Horse" hypothesis, in which the release of silver ions only happens after intracellular uptake of the silver nanoparticles subsequently triggering the effects described (stress responses, cell death). The acidic environment within the cellular vesicles favours the dissolution of the nanoparticles. Therefore, researchers advocate to not only analyse the silver nanoparticle suspensions in in vitro experiments but also the nanoparticle-free supernatant in order to correlate the observed effects more accurately .
Depending on the type of silver nanoparticles used, some studies were able to directly link ROS formation and toxicity, whilst in other investigations ROS production and cell damage were only detectable after cellular uptake. In another analysis the silver nanoparticles activated cellular anti-oxidative protection mechanisms upon uptake thereby protecting the cell from oxidative damage. Oxidative DNA damage occurred only at very high doses which in turn further strengthened the "Trojan Horse" hypothesis .
"Trojan Horse" hypothesis for the mode of action of silver nanoparticles in cells. Adapted from Quadros et al. 2011
By releasing ions, silver nanoparticles are very effective against microorganisms and therefore are often used in medicine, e.g. in wound dressings or for spray disinfectants. However, comparative studies have shown that only a relatively small therapeutic window exists for the use of silver nanoparticles in wound dressing materials, in which the nanoparticles effectively kill the undesirable pathogens and act not toxic to the cells .
The various studies have shown that relatively high concentrations of nano silver act negatively towards cellular health. As the size and surface coating of the silver nanoparticles generally have a strong influence on the nanoparticles' dissolution rate, bioavailability and distribution in the body, these properties can be altered specifically for the intended application and also to avoid undesirable side effects.
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