In May 2008, the International Center for Technology Assessment (ICTA) submitted a petition to EPA requesting that it regulate nano-silver used in products as a pesticide under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).  The petition calls on EPA to take the following specific actions:

1. Classify nano-silver as a pesticide.
2. Determine that nano-silver is a new pesticide and require its registration as such.
3. Analyze the potential risks of nano-silver to human health and the environment.
4. Take enforcement actions against nano-silver-containing products being sold illegally without EPA approval under FIFRA.

EDF supports this petition.  The rapid increase in the largely unregulated use of nano-silver in consumer products is alarming, especially given the lack of systematic evaluation of their possible harm to human health and the environment. 

As I have explained in past posts, bulk forms of silver, while having generally low direct human toxicity, have potent anti-bacterial properties and are quite toxic to many freshwater organisms.  In a recent report on nano-silver prepared for the Project on Emerging Nanotechnologies, Dr. Samuel Luoma characterized bulk-scale silver and silver ions as environmental hazards because they are toxic, persistent and bioaccumulative under at least some circumstances.  He also concluded that insufficient information is available to predict whether nano-scale silver's hazards will be comparable to or greater than those of bulk-scale silver and silver ions.   Baker and colleagues have described how silver nanoparticles appear to have greater antibacterial potency than larger-sized particles due to their larger surface area-to-volume ratio. 

Product manufacturers are seeking to capitalize on nano-silver's antimicrobial properties by adding it to dozens of products.  Many are already on the market, including nano-silver-impregnated socks and nano-silver-containing cosmetics.  That means both human contact and the release of nano-silver into the environment are already occurring, yet we are unable to predict the consequences.

So it is essential for EPA to exert its authority under FIFRA to require each manufacturer using nano-silver in a product to demonstrate that the addition of nano-silver is effective in achieving any claimed benefits, that labeling is accurate and that its use is safe for both humans and the environment. 

In a November 19, 2008 Federal Register Notice, EPA has solicited comments on this petition, with the comment period recently extended to March 20, 2009.   See that notice for details on how you can voice your opinion on this important issue.

In 2004, Gunter Oberdorster and colleagues demonstrated that upon inhalation, ultrafine particles, the dimensions of which are measured in nanometers, can move from the nasal passages of rodents to the brain via a specialized nerve called the olfactory bulb.  The evolutionary purpose of the olfactory bulb is to relay information about odors directly and rapidly from the nose to the brain. 

The extent to which rapid transit via the olfactory bulb is a significant potential route of exposure to engineered nanomaterials is still an open question.  But two new papers add support for the relevance of this intriguing exposure pathway, raising important questions regarding the safety of inhaled nanoparticles. 

The first paper, by Jiangxue Wang and colleagues, followed the movement of nanoscale titanium dioxide (TiO₂) particles placed directly in the nasal passages of mice to the brain via the olfactory bulb.  When they looked to see where in the brain the TiO₂ went, they found it went pretty much everywhere, although after 30 days the highest concentrations were found in the olfactory bulb and hippocampus.  Moreover, the brain tissue of the exposed mice exhibited changes in structure and biochemistry consistent with damage from reactive oxygen compounds.

Nanoscale silver was the subject of the second paper by Jae Hyuck Sung and colleagues.  Instead of a single exposure, rats were exposed to nanosilver in the air for 13 weeks.  Like an earlier 28-day inhalation study, this one also found widespread distribution of nanosilver in the rats. 

This study also sought to determine if there were any health effects associated with longer-term exposures.  And they did find effects:  inflammation in the lungs, and subtle cellular changes in the livers that are sometimes indicative of pre-cancerous conditions. 

Nanosilver was detected in both the olfactory bulb and the brain but unfortunately the paper did not report on any effects that might have been associated with the presence of nanosilver.  It is not clear from the description provided if the extent of examination of the brain would have been able to identify subtle effects if they were present.

So what should the next steps be?  Elucidating the possible impacts of nanoscale materials on the brain is tricky, in part because the effects could be very diverse, requiring lots of different types of tests to capture them.  While damage to brain cells may be relatively easy to discern, other effects, such as those altering brain development or biochemistry, may require more sophisticated testing. 

While it is often assumed that inhalation exposure to nanomaterials will be limited primarily to workplaces, such materials are also being used in consumer products that can be widely dispersed.  This is particularly true of nanosilver, which can be found in sprays that release nanosilver into the air.  This is why we have repeatedly advocated that such dispersive uses be avoided until more is known about the potential adverse effects that could come with these kinds of exposures. 

A recent article posted on scienceline includes a claim that bacteria cannot develop resistance to silver, which is widely used as an antimicrobial.  That assertion is not only false, but also dangerous.

Resistance of bacteria to antimicrobials is a serious and growing problem, so it is imperative that antimicrobials be used only where shown to be essential and effective.  The cavalier use of antimicrobials, including their routine use as feed additives for growth promotion and prophylaxis in animal agriculture, increases the likelihood of the development of resistance in dangerous human pathogenic bacteria (Refs. 1-3, below).

The unqualified claim in this post that “bacteria cannot build up a resistance to silver nanoparticles as they can to antibiotics, because of the way the silver nanoparticle attacks – destroying the structure of the cells and killing them…” is wrong and reckless.  First, bacteria have developed numerous strategies to overcome the activity of antimicrobials, including those that destroy cells (4).

Second, silver is a potent antimicrobial (5,6), but numerous studies have documented resistance to it in several different types of bacterial (7-14).  Resistance can arise through multiple mechanisms, some of which also impart resistance to other antimicrobial agents.  Two important reviews summarize the broader concerns over bacterial resistance to silver, cautioning that the current lack of oversight on its expanding use could have serious consequences (15,16).

Nanosilver is the new kid on the block, generating a new wave of antimicrobial products, from odor-resistant socks to purportedly self-sterilizing computer mice. (For a list of consumer products containing nanosilver, search for “silver” in the Woodrow Wilson Center’s Project on Emerging Nanotechnology online inventory.)  As with other nanomaterials, nanosilver’s use in consumer products is happening without sufficient regulatory oversight, although EPA may actually be starting to pay some attention to this use. 

The widespread and indiscriminate use and release of such nanosilver materials could negatively impact both beneficial microbial communities in the ecosystem, and our capacity to combat dangerous microbes that threaten human health.  Until we have a better understanding of the ramifications of the use of nanosilver in consumer products, strict regulation against overuse is warranted.  There is also an urgent need for additional research before nanosilver is allowed to become ubiquitous in consumer products and our environment.

References:

1. Alliance for the Prudent Use of Antibiotics.  2002.  Report on the Facts about Antibiotics in Animals and the Impact on Resistance (FAAIR) Project.  Clinical Infectious Disease.  34(S3):S71-S144. Available at: http://www.tufts.edu/med/apua/Ecology/faair.html

2. General Accounting Office.  2004.  Antibiotic Resistance: Federal Agencies Need to Better Focus Efforts to Address Risk to Humans from Antibiotic Use in Animals.  GAO-04-490.  April 2004.  Available at: http://www.gao.gov/docsearch/abstract.php?rptno=GAO-04-490

3. Silbergeld EK, Graham J, Price LB.  2008.  Industrial Food Animal Production, Antimicrobial Resistance, and Human Health.  Ann Rev Public Health.  29:151–169.  http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.publhealth.29.020907.090904

4. Tenover FC.  2006.  Mechanisms of antimicrobial resistance in bacteria. Am J Infect Control.  34(S1):S3-S10. http://www.ajicjournal.org/article/S0196-6553(06)00836-4/abstract

5. Edward-Jones V.  2006.  Antimicrobial and barrier effects of silver against methicillin-resistant Staphylococcus aureus.  J Wound Care.  15(7):285-290.  http://www.journalofwoundcare.com/cgi-bin/go.pl/library/abstract.html?uid=26951

6. EPA (U.S. Environmental Protection Agency). 1993. R.E.D. Facts: Silver. Office of Prevention, Pesticides and Toxic Substances. EPA-738-F-93-005. June. Available online: http://www.epa.gov/oppsrrd1/REDs/factsheets/4082fact.pdf

7. McHugh GL, Moellering RC, Hopkins CC et al. 1975. Salmonella typhimurium resistant to silver nitrate, chloramphenicol, and ampicillin. Lancet. 1: 235–40.

8. Hendry AT, Stewart IO. 1979. Silver-resistant Enterobacteriaceae from hospital patients. Can J Microbiol. 25:915–21.  http://rparticle.web-p.cisti.nrc.ca/rparticle/AbstractTemplateServlet?calyLang=eng&journal=cjm&volume=25&year=0&issue=8&msno=m79-136

9. Bridges K, Kidson A, Lowbury EJ et al. 1979. Gentamicin- and silver-resistant Pseudomonas in a burns unit. Br Med J. 1:446–9. 

10. Deshpande LM, Chopade BA. 1994. Plasmid mediated silver resistance in Acinetobacter baumannii. Biometals  7:49–56.  http://www.springerlink.com/content/j56050×270861k14/?p=83dca07d9d6b44afa60e6f401a32d06a&pi=7

11. Li X-Z, Nikaido H, Williams KE. 1997. Silver-resistant mutants of Escherichia coli display active efflux of Ag+ and are deficient in porins. J Bacteriol. 179(19):6127–6132.  http://jb.asm.org/cgi/content/abstract/179/19/6127

12. Gupta A, Matsui K, Lo F, Silver S. 1999. Molecular basis for resistance of silver cations in Salmonella. Nature Medicine. 5(2):183–188.  http://www.nature.com/nm/journal/v5/n2/abs/nm0299_183.html

13. Gupta A, Maynes M, Silver S. 1998. Effects of halides on plasmid-mediated silver resistance in Escherichia coli. Appl Env Microbiol. 12:5042–5045.  http://aem.asm.org/cgi/content/abstract/64/12/5042

14. Silver S, Phung le T, Silver G.  2006.  Silver as biocides in burn and wound dressings and bacterial resistance to silver compounds. J. Ind Microbiol Biotechnol.  33(7):627-34.  http://www.springerlink.com/content/e66l0g6125655482/?p=a5939d6f624545d5a1da96dbd01c3a56&pi=19

15. Gupta A, Silver S. 1998.  Silver as a biocide: will resistance become a problem? Nature Biotechnology. 16:888. 

16. Chopra I.  2007.  The increasing use of silver-based products as antimicrobial agents: a useful development or a cause for concern?  Journal of Antimicrobial Chemotherapy. 59:587–590  http://jac.oxfordjournals.org/cgi/content/full/59/4/587