Nanosilver: progress in the sphere of analysis, gaps in toxicology and exposure
According to industry and trade sources, nanoscale silver is the nanomaterial most often used in products intended for consumers. However, consumers are frequently not told which products actually contain nanosilver. In Europe, nanosilver is predominantly used as an antimicrobial substance in functional and clothing textiles, for biocidal surface coatings and in some spray products. Little research has to date been done on the health effects of nanoscale silver. From 8 to 9 February 2012, experts from Europe and the USA exchanged knowledge at the "Conference on Nanosilver" organised by the Federal Institute for Risk Assessment. Apart from toxicological aspects, the discussions covered the possible development of silver resistances in pathogenic germs as well as analytical procedures for the detection of nanosilver in various matrices such as foods, sprays and consumer products and its release from such matrices. "We still don't know enough about potential detrimental health effects of nanosilver. For this reason, we cannot currently evaluate scientifically the health risks it poses to consumers," says Professor Dr. Dr. Andreas Hensel, President of the Federal Institute for Risk Assessment. "The conference at the BfR was an important step on the road to better safety for consumers. It revealed where the risks of using nanosilver may currently be, in what areas we still know too little and, most importantly, where we have already made early progress," the President summarised the findings of conference. For nanoscale materials such as nanosilver, characterisation of both the used nanoparticles and its dosage was carried out to an insufficient degree for many years. One reason for this was that the required chemical analytical and physicochemical methods were not available and / or could not be used. As a result, only a handful of toxicological studies are currently available on dose response relationship of nanoscale forms of silver. Many older studies therefore are not sufficient for the assessment of potential health risks. The conference showed that in recent years, significant progress has been made in the area of analysis and physicochemical characterisation of nanomaterials. At the same time, the need for further improvements in terms of validation, standardisation and provision of reference materials was identified. Such improvements are essential, if the level of reliability currently achieved for conventional chemicals is to be attained in the assessment of nanosilver and other nanomaterials as well. Experience with the treatment of different products containing silver nanoparticles shows that the analytical methods must be adjusted to the relevant matrix particle combinations. Depending on the intended use, different forms of nanosilver with other physicochemical properties continue to be used. This is toxicologically significant, because the coating of individual particles, for example, influences the effect on cells and tissue to the same degree irrespective of whether silver is encountered as a metal, as salt, in large aggregates or even as a composite with other materials. It is to be assumed that the toxic properties vary depending on the structure of the particles. For toxicology, this means: insights into health effects which have been gained from studies with a specific nano form of silver are not directly transferrable to other materials. So far it is not fully known to what extent consumers actually come into contact with silver nanoparticles along the various paths. Thus studies conducted in Switzerland show that certain sprays, while containing nano silver, such particles were not present in the sprayed aerosol. However, other undeclared nanoparticles were detected in the examined nanosilver sprays. Whether consumers absorb significant amounts of silver nanoparticles through inhalation is not known at present. Dermal exposure is more likely. Oral exposure through packaging materials containing nanosilver is low according to the experts, since only little nanoscale silver is released into food from such materials. Generally speaking, silver is a cytotoxin which, however, appears to be more poisonous in nano from than it is at microscale level. This is evidenced by studies with cell cultures and water organisms. Nevertheless, little is known at this stage about the behaviour of nanosilver in the body of mammals. Studies conducted with rats show that after single oral administration, silver nanoparticles to a certain degree overcome the intestinal barrier, enter the blood stream and notably spread in the spleen, liver, kidneys, lungs as well as, to a lesser extent, in other organs. With regard to speed and extent of excretion, the available data are partially contradictory. Even after repeated oral and inhalation administration of low doses of nanoscale silver particles, no visible signs of any effects on the health of the test animals were observed. However, according to these studies, nanosilver particles in high doses appeared, just like conventional forms of silver, to have an adverse effect on the intestinal flora. Equally, pathological changes to the liver and kidneys as well as to the lungs have been described. If silver nanoparticles are repeatedly injected into the bloodstream, this results, according to a new study by the Dutch National Institute for Public Health and the Environment (RIVM), in high nanoparticle concentrations in certain liver cells and especially in the spleen. In those organs, they have a toxic effect on individual cell populations of the immune system. Of course, the data from these animal experiments cannot directly be transferred to humans but nevertheless show that nanosilver may have an immunotoxic potential. Silver is a potent weapon in the fight against pathogens in the treatment of large-area wounds (burn wound dressings), but also for combating germs, for example in tubes and catheters as well as medical implants. So far, no research has been done to determine whether uncontrolled large-scale and low-dosage use of silver and nanosilver in everyday products leads to a selection process which favours silver-resistant microorganisms. In fact, numerous resistant bacteria strains from very different environments - including clinics - were detected and characterised in detail. They include zoonotic pathogens such as Salmonella typhimurium, Pseudomonas aeruginosa and Enterobacter cloacae. Often resistance to silver is combined with resistance to antimicrobial substances. The reason for this is that resistance towards silver is in many cases encoded on a ring-shaped extrachromosomal DNA, referred to as a plasmid. The best studied example of these resistance plasmids, isolated from a Ag+ resistant Salmonella typhimurium, also confers resistance to several antibiotics. This finding reinforces the opinion of the BfR that silver as an antimicrobial substance should not be used in consumer products on a large scale, except of clinical applications, since conjugative plasmids could be transferred to other bacteria, resulting in spreading not only of silver resistance but also cotransmission of resistance towards antibiotics. Unfortunately, research is far from understanding the mechanisms underlying silver resistance. In addition, the currently available data on the prevalence of silver-resistant microorganisms in the environment, and our knowledge on how increased use of consumer products containing nanosilver influences the prevalence of silver resistance is very limited. Although first studies commissioned by manufacturers do not indicate any harmful effects, there is consensus that research has to be conducted in order to determine long-term effects nanosilver in textiles on the microbial skin flora. The scientific exchange at the BfR has shown where risk research and assessment currently stand with regard to the issue of nanosilver. This exchange thus constitutes an important step on the road to improved safety and health for consumers.