What we know at this point is merely suggestive, but in some cases worrisome. One study of cells in culture, for instance, showed that when human lung tissue is exposed to carbon nanotubes, the lung cells see these not as foreign agents but as a biological substrate on which to build other tissue. Rather than mounting an immune response to attack the nanotubes as invaders, the lung cells start building layers of collagen around them. No one can say how likely it is in real life for carbon nanotubes to be inhaled; for most current uses, such as lightweight bicycle parts or tennis rackets, they are fixed in a matrix. But there is a chance that they might be inhaled during manufacture or as the product degrades, either through normal wear and tear or after it's disposed of. If they get into people's lungs, will carbon nanotubes act in vivo the way they do in cell culture, and become a scaffolding for new layers of collagen that could block the airways?
Similar questions about the safety of nanoparticles arise from animal models showing that they can get into the bloodstream through the skin and then travel to vital organs, including the brain. As with airborne exposure, the likelihood of skin expsure to carbon nanotubes is still an unknown, but once again early research indicates that there could be some health effects. Toxicologist Günter Oberdörster of the University of Rochester, working with rodents, found that carbon nanoparticles were small enough to enter the brain by way of the olfactory nerve, circumventing the blood-brain barrier, the usually impermeable membrane that protects the brain from foreign agents.
The main thing that is known about the toxicology of nanoparticles is how much remains to be discovered. Nanoparticles, says Maynard, "can penetrate into cells in ways that larger particles cannot, or migrate to places in the body large particles cannot get to."
Another worrisome finding is a possible link between nanoparticles and the more rapid formation of protein fibrils, a material found in neurons that, when it accumulates, can lead to the buildup of a brain toxin called amyloid. Chemists from several European universties, led by Sara Linse of University College Dublin, exposed a laboratory preparation of purified protein to four types of nanoparticle, including carbon nanotubes and so-called quantum dots (crystals just 5 or 10 nanometers in diameter that are used in the semiconductor industry to measure electric current down to the level of the electron). All four types of nanoparticle accelerated the abnormal development of the protein into amyloid fibrils. The reason for the concern is that amyloid has been implicated in a variety of neurological diseases, including Alzheimer's and Parkinson's.
As with most studies in nanotoxicology, the Linse study is preliminary; it was conducted in vitro, not in an animal or a human, and it remains to be seen whether the findings will be replicated in vivo. But it does point out the complexity of the emerging field of nanotoxicology.
"One of the most important messages of this work for chemists," wrote Vicki Colvin and Kristen Kulinowski of Rice University in last May's Proceedings of the National Academy of Sciences, "is that when NP's [nanoparticles] enter the biological world they become very different materials." According to Colvin and Kulinowski, "The small sizes of NP's convey the potential to access many biological compartments, where they are met with a smorgasbord of possible binding partners from the coplex and concentrated soup of biomolecules."
In terms of environmental consequences, if nanosilver is anything like ordinary silver, we might be in for some trouble. As with the potential human health risks, the environmental dangers can only be guessed at by analogy -- in this case, to the known impact of normal-scale silver on aquatic organisms. According to Samuel Luoma, a senior research scientist at the U.S. Geological Survey in Menlo Park, California, silver is a powerful environmental toxin, second only to mercury in the damage to invertebrates that even trace amounts can do. It kills microorganisms indiscriminately and can wipe out the beneficial ones as well as the pathogenic ones. In addition, it has a direct effect on the reproductive capabilities of certain aquatic invertebrates, and possibly fish as well.
Through most of the 1980s, says Luoma, silver pollution from a photo-processing plant led to widespread sterility among the Macoma balthica clams in South San Francisco Bay near Palo Alto. Clams are an important part of the bay-bottom food web, he says, and the population recovered only when new regulations limited the amount of silver in the bay. The photo-processing plant was eventually closed.
The lesson learned was a crucial one: It took a very low concentration of silver, less than one part per billion, to destroy the reproductive organs of virtually all adult M. balthica living within a certain distance of the silver source, and to spread silver contamination throughout the South Bay.
"No one outfall [the sewage pipe that carries wastewater from a treatment plant] could have effects everywhere in San Francisco Bay," Luoma says. "The risk with nanosilver from consumer products is that it would come from all outfalls that serve urban customers. What we need to know is how much silver would be released from many households. Would it be comparable to the mass from photo processing?"
Silver might have been especially toxic in San Francisco Bay because the bay is salt water. Unlike many other environmental toxins, silver seems to be more dangerous in salt water than in fresh. In freshwater, silver combines with chloride and forms a solid that sinks to the bottom, becoming less bioavailable (that is, less capable of absorption by the body). But in salt water, with a preponderance of chloride atoms, more silver chloride remains in solution, binding to particulate matter. This puts more of it into the food chain and therefore makes it more likely to do damage to marine organisms.
No other metal has this property of behaving one way in freshwater and another way in salt water. This presents a regulatory problem that's unique to silver, especially at the nano scale. According to Luoma, most toxicity testing is done in freshwater. "But a silver nanoparticle could look innocuous in freshwater and be extremely toxic in sea water," he says. How significant is this? Nobody really knows -- but Luoma is concerned. It's reasonable, he says, to expect that nanosilver will shed from treated fabrics and from the linings of washing machines and food containers and make its way into rivers and streams, eventually ending up in the ocean.
There is also some evidence that excessive use of silver as an antimicrobial can lead to silver resistance in bacteria, in much the same way that excessive use of antibiotics can lead to the development of antibiotic-resistant organisms. If E. coli could do it, could other, potentially more dangerous microbes do the same thing? And if it happened with normal-scale silver, would it be more or less likely to happen with nanosilver? At the very least, nanosilver complicates the picture, since it allows silver to be used in so many more products. "If we use it too widely," Maynard says, "we may be giving away our best weapon."
Are we foolish to forge ahead in developing nanosilver products without full toxicology information? Perhaps. Luoma, who lives in Silicon Valley, says that the frenzy surrounding nanotechnology, the rush to be first at any cost, reminds him of the heedless gold-rush mentality of the dot-com era. A lot of nano-promises might fail to materialize, as happened with so many brilliant Internet startup ideas. The crucial difference is that the dot-com boom did no harm to the environment or to human health while the Darwinian struggle for survival played itself out. Nanotechnology might.
Here's how one product made from nanosilver, a set of kitchen utensils available in the United States, is being promoted by its manufacturer, Nano Care Technology of Hong Kong: "People always use traditional ways such as sterilizer to kill bacteria and germs but the result is not satisfied [sic], because many bacteria and viruses survive or relive [sic] very quickly." But the company's nanosilver kitchen utensils may do the job permanently, its Web site continues, and "can prevent people from the following diseases: duodenitis caused by spirillums, virosis hepatitis, dysentery caused by salmonella and food poisoning caused by golden staphylococcus."
The Korean appliance manufacturer Daewoo makes similar claims for its products treated with nanosilver (currently distributed only in Europe), which include a washing machine, refrigerator, and vacuum cleaner. It's clear from the Daewoo Web site that the company is using nanosilver for its antimicrobial properties: "After splitting the particles of silver known to have superior deodorant and antibiotic power by 1/1,000,000 mm, we have applied it to major parts of [the] refrigerator in order to restrain the growth and increase of a wide variety of bacteria and eliminate odor particles." Not only is nanosilver a disinfectant and deodorant, the company writes, in an English-language translation so elliptical as to make the true meaning unclear. It also "maintains balance of hormone [sic] within our body and intercepts electromagnetic waves significantly."
At the moment, claims like Nano Care's and Daewoo's exist in a regulatory limbo. No single agency has jurisdiction over nanomaterials (the same applies to many materials of conventional size); it depends largely on how a product is used or where it is in its life cycle. During its manufacture, a nanoparticle might fall under the jurisdiction of the Occupational Safety and Health Administration, which deals with workplace exposure. After that, if it is to be ingested or used in a drug or a medical device, it might be regulated by the Food and Drug Administration. Once it's discarded, it might fall under the purview of the Environmental Protection Agency (EPA), charged with minimizing air- and water-borne toxins.