Courtesy of Vicki Colvin
The cytotoxicity of three fullerene derivatives in cell culture (human dermal fibroblasts, 48-hour exposures). As the derivatization of the fullerene surface changes from a sparingly soluble version (black) to a fully hydroxylated material (blue), the dose that kills half the cells changes over many orders of magnitude. This result highlights the importance of surface coatings and derivatizations to biological activity.
When materials and devices are fabricated with tiny dimensions, their properties and applications expand enormously. Small size, which for nanotechnology means less than 100 nm, confers on devices and materials enhanced flexibility and improved performance. We've begun exploiting such properties in a multitude of emerging areas ranging from computing to translational medicine. Yet, just as the promise of nanotechnology becomes more defined, skeptics raise questions about the unforeseen risks this new technology may present for the environment and our health.12
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More than 500 years ago one of the first toxicologists, Paracelsus, said, "The dose makes the poison." Clearly, the exposure of an organism to a substance is at least as important as its biological effects when measuring overall risk. A discussion of engineered nanomaterial risk must then begin by examining exposure issues.
Currently the average person faces virtually no exposure to nanoparticles and thus little risk. While there are many manufacturing plants under construction, commercial technologies for most nanoparticles are several years away. High cost precludes widespread application in bulk consumer products, and I estimate that for engineered nanoparticles such as fullerenes, quantum dots, and metal nanocrystals, the total global production is less than one ton. (The term engineered nanoparticle as yet lacks a formal definition. Some colloidal particles, such as carbon black, fused silica, or pigments in cosmetics and sunscreens, may have dimensions of less than 100 nm. For the purposes of this article, I am limiting my discussion to more modern materials with tunable properties and high molecular control). These substances thus currently pose little risk to public health. Nevertheless, the substantial investment research and manufacturing by governments and industry alike suggests a budding industry poised to expand over the next 10 years. Accurately identifying environmental and health risks arms this new industry with the information needed to ensure good stewardship and product sustainability.
Initial information concerning nanoparticle exposure issues suggests that environmental processes such as bioaccumulation, biodegradation, fate, and transport will have significant effects on the local concentration and form of engineered nanomaterials. On one hand, nanoparticles may be less mobile in groundwater systems than larger particles. The high surface areas of these materials maximize chemical interactions with porous media so that even relatively noninteracting particles experience slow transport through pores. On the other hand, the high surface areas of engineered nanoparticles can lead to significant adsorption of molecular contaminants. In one case, hydrophobic contaminants irreversibly interacted with fullerene aggregates in water, and these species showed a high capacity for concentrating a model polyaromatic hydrocarbon.4 Thus, while engineered nanoparticles may be less mobile than larger particles, their higher surface areas could concentrate hydrophobic molecules.
In considering nanoparticles' effects on organisms, the most compelling feature is physical size. With dimensions of less than 100 nm and more typically less than 10 nm, these materials have in principle wide access to biological systems. In practice, however, engineered nanoparticles are prone to aggregation in biological systems, producing much larger particles that lack the solubility and mobility of isolated materials. Such aggregation problems confounded pulmonary toxicology studies designed to evaluate the effects of single-walled carbon nanotubes on rodents.5 Indeed, great effort must be expended in designing appropriate surfaces to resist aggregation. Still, with appropriate derivatization, engineered nanoparticles access even the smallest biological compartments within human cells.
Courtesy of Rice University
Another consequence of their small size is that for a constant weight, a sample will contain many more nanoparticles than an equivalent micron-sized material. In pulmonary toxicology, this property has been suggested to result in macrophage overload, in which cells responsible for clearing foreign particles become overloaded by the sheer number of particles requiring clearance.6 This can result in enhanced inflammation and in some cases translocation of aerosolized nanoparticles to the central nervous system and the olfactory bulb.
Whether engineered nanoparticles can be aerosolized from routine handling of powders and liquids is not yet known. One study found no respirable levels of small nanoparticles in a variety of workplaces that processed the materials. Rapid and irreversible aggregation of engineered nanoparticles in air may increase their mean size significantly and thus limit the inhalation exposure of organisms to isolated nanoparticles.
For those engineered nanoparticles that retain their small size in biological systems and are resistant to aggregation, it is likely they will be widely distributed in most organisms. Many engineered nanomaterials are designed to be chemically active, and in those cases exposures will result in unique and in some cases unwanted biological properties.8 However, it is typically straightforward to render nanostructures chemically inert; in the case of C60 such a treatment can change its cytotoxicity many orders of magnitude (Figure 1).910 These data illustrate that for nanomaterials, the core composition of a material may be only a small component in defining its toxicity. Far more critical will be how the surface chemistry controls aggregation, bioavailability, and the subsequent reactivity of the nanoparticles.
Because the industry is in its infancy, limited exposures to people and the environment of engineered nanomaterials mean that this area is not of immediate importance to public health. Still, rapid growth coupled with the existing data concerning ultrafine particles does make the question immediately relevant. Significant strides are being made in answering this question, and over the next few years an explosion of technical data will appear in this area, which will equip nanotechnologists for the future.
While these data are certain to transform nanotechnology, the greater impact may be on the general process of technology assessment. Traditionally, risk assessment begins when the source of a contaminant and its exposure pathways are well known. From this starting point a multitude of possible outcomes and their risks can be calculated. Clearly for nanotechnology this process must expand to include a wider range of "what-if" scenarios for possible products, nanomaterials, and exposure routes. All these factors will lead to more general risk assessments with less accurate risk projections. If the nanotechnology industry can benefit from these more general and less quantitative models, then future technologies may approach risk assessment in a new way.
Nanotechnology also provides a new model for how scientists and engineers should manage the technical issues associated with technology's risks. In the past, technologies experienced their environmental and health considerations as downstream hurdles for nearly mature products. Now, toxicologists and environmental engineers are integrated into the nanomaterials engineering process; rather than being gatekeepers, they enable chemists like myself to design biocompatible nanostructures and manufacturing processes with minimal environmental impact.
Safety and sustainability are no longer problems that concern only end-users well after the field is commercialized. Instead, they are flexible parameters in a new, and I think wiser, technology-design process.
Vicki L. Colvin is a professor of chemistry and chemical engineering at Rice University and also director of the NSF-funded Center for Biological and Environmental Nanotechnology, which addresses nanotech's health and environmental impact. Her research focuses on developing and applying new nanomaterials to solve problems in environmental and biomedical technologies. She has received numerous awards including an Alfred P. Sloan Research Fellowship and the Camille Dreyfus teacher-scholar prize.
Her e-mail is