Humans have been exposed to a multitude of naturally occurring nanosized particles (e.g., ultrafine particulates from volcanic activity or forest fires) throughout our evolution. Only over the past two decades have we had the capability to manipulate matter at the nanoscale level (1
). The beneficial applications of nanotechnology in numerous industrial, consumer, and medical applications are extremely promising. These applications include those that may lead to more efficient water purification, stronger and lighter building materials, increased computing power and speed, improved generation and conservation of energy, and new tools for the diagnosis and treatment of disease. However, the outlook for a future improved by nanotechnology should be tempered by the fact that relatively little is known about the adverse effects of nanomaterials on human health and the environment (2
). Rapid advances in nanotechnology have created a multitude of new structures, and we cannot precisely predict how these new nanomaterials will interact with biological systems.
The definition of a nanoparticle is generally considered to be a particle with at least one dimension of 100 nm or less. As a result of their small size and unique physicochemical properties, the toxicological profiles of nanoparticles may differ considerably from those of larger particles composed of the same materials (1
). Furthermore, nanoparticles of different materials (e.g., gold, silica, titanium, carbon nanotubes, quantum dots) may have their own unique mechanism of toxicity. Therefore, it seems unlikely that the toxic potential and/or mechanisms of nanoparticles can be predicted or explained by any single unifying concept.
The respiratory system represents a unique target for the potential toxicity of nanoparticles due to the fact that in addition to being the portal of entry for inhaled particles, it also receives the entire cardiac output. As such, there is potential for exposure of the lungs to nanoparticles that are introduced to the body via the act of breathing or by any other exposure route that may result in systemic distribution, including dermal and gastrointestinal absorption and direct injection. Interest in the respiratory system as a target for the potential effects, both beneficial and adverse, of nanoparticles is reflected by the steady increase in the number of scientific publications on these subjects during the past decade (3
). For the purposes of this article, only intentionally engineered nanoparticles are considered; unintentionally generated (e.g., via combustion engines, grilling, welding) and naturally occurring nanoparticles are not included in this discussion. Special emphasis will be given to carbon nanotubes, which are an emerging focus of occupational and environmental exposures.
There is the potential for the respiratory system to be exposed to a seemingly countless number of unique nanoparticles, essentially none of which has been sufficiently examined for potential toxicity at this time. A substantial number of nanoparticles are already present in the marketplace in consumer products such as sunscreens, cosmetics, and car wax, just to name a few. A comprehensive list is maintained and updated by the Project on Emerging Technologies at the Woodrow Wilson International Center for Scholars (www.wilsoncenter.org/nano
). While many nanoparticles may prove to have little or no toxicity, the fact that there is any potential for adverse effects from nanoparticle exposure suggests that prudence is warranted. Therefore, the potential of nanomaterials to cause disease after occupational or environmental exposures, as well as in drug delivery scenarios, should be carefully evaluated to determine specific outcomes, some of which are illustrated in .
Biologic endpoints that should be evaluated to determine the potential of nanomaterials to cause disease in mice after inhalation to mimic occupational or environmental exposures or by nebulization routes to mimic drug delivery scenarios.
The diversity of nanoparticles include those that are carbon-based (e.g., nanotubes, nanowires, fullerenes), metal-based (e.g., gold, silver, quantum dots, metal oxides such as titanium dioxide and zinc oxide), and those of a biological nature (e.g., liposomes and viruses designed for gene or drug delivery). To demonstrate the complexity of the situation, it is worthwhile to consider the case of carbon nanotubes as an example. Carbon nanotubes can be: (1
) produced and/or cleaned using one of several different methods; (2
) produced using one of several different metal catalysts; (3
) single- or multi-walled; (4
) of various lengths; and (5
) subjected to numerous surface modifications (3
). The result is a vast number of unique carbon nanotube derivatives, all of which fall under the category of “carbon nanotubes.”