Nanoscale materials are a broadly defined set of substances that have at least one critical dimension less than 100 nanometers and possess unique optical, magnetic, or electrical properties. Ultrafine particulate matter is a well-known example of nanoscale particles found in the environment. The NTP's research program focuses on engineered nanoscale materials of current or projected commercial importance. Theoretically, nanoscale materials can be engineered from nearly any chemical substance; semiconductor nanocrystals, organic dendrimers, and carbon fullerenes and carbon nanotubes are a few of the many examples.
Nanoscale materials are already appearing in commerce as additives or modifications to industrial and consumer products and as novel drug delivery formulations. Commercial applications that result in human exposure may differ substantially for nanoscale versus "bulk" manufactured base materials.
Currently, there is very little research focused on the potential toxicity of manufactured nanoscale materials. Published studies on the inhalation of ultrafine particles suggest that particle size can impact toxicity equally, if not more so, than chemical composition and hints at the complexity of the topic. The unique and diverse physico-chemical properties of nanoscale materials suggest that toxicological properties vary for materials of similar composition but differing size. There are indications in the literature that manufactured nanoscale materials may distribute in the body in unpredictable ways. Certain nanoscale materials have been observed to accumulate preferentially in particular cellular organelles. In 2003, the Rice University Center for Biological and Environmental Nanotechnology (CBEN) nominated nanoscale materials to the NTP toxicology testing program. The NTP initiated a research program evaluating nanoscale materials because of the intense current and anticipated future research and development focus on nanotechnology and the CBEN nomination.. The complexity of the issue requires the NTP to utilize both existing and new toxicological testing methods to adequately assess potential human health effects. Specific details on the nomination and study recommendations can be found at "Nominations to the Testing Program" for 2003.
NTP is an interagency program headquartered at the National Institute of Environmental Health Sciences of the National Institutes of Health (NIEHS/NIH). Three agencies, NIEHS/NIH, the National Institute for Occupational Safety and Health of the Centers for Disease Control and Prevention (NIOSH/CDC), and the National Center for Toxicological Research of the Food and Drug Administration (NCTR/FDA), form the core of the NTP. The Director of the NIEHS/NIH also serves as the NTP Director.
NIEHS staff serve as principle coordinators of the NTP's nanotechnology safety initiative and work together with NCTR/FDA and NIOSH/CDC staff from a variety of scientific disciplines. At this stage, NTP research on nanoscale materials is being conducted primarily through government contracts with outside research organizations, by FDA staff at the NTP's Phototoxicology Center based at NCTR in Jefferson, AK and the Center for Food Safety and Applied Nutrition (CFSAN) in Washington, DC, and through collaborations with staff at the Center for Biological and Environmental Nanotechnology (CBEN) at Rice University.
The NTP intends to conduct studies that test hypotheses focused on the relationship of key physicochemical parameters of selected manufactured nanomaterials to their potential toxicity. Initial parameters of greatest concern are size, shape, surface chemistry, and composition. This strategy will be accomplished by developing a suite of analytical approaches to evaluate and characterize the physiochemical properties of nanoscale materials in their raw form and as formulated when given to animals or exposed to cells in culture. In addition, we will conduct animal toxicity studies of varying durations with specific nanomaterials using routes of administration that mimic possible human exposure. These studies will include evaluations of the absorption and handling of the materials by rodents. We also intend to develop a battery of in vitro models to evaluate the biological and toxicological effects of nanoscale materials. These models would be used to assess whether in vitro methods can predict which nanoscale materials might be a hazard for animals or people.
Based on these findings, the NTP will develop mathematical models (physiologically based pharmacokinetic models) to predict the absorption, distribution, metabolism, and elimination of nanoscale materials in humans. These models would be used to predict how modification of a given nanomaterial's physicochemical properties might reduce its absorption or increase its elimination, thereby reducing the probability that a toxic response would occur.
The NTP's nanotechnology safety initiative is focusing on 3 areas of research with respect to specific types or groups of nanoscale materials:
Ongoing research activities are focusing initially on 4 classes of nanoscale materials: (1) metal oxides, (2) fluorescent crystalline semiconductors (quantum dots), (3) fullerenes, (4)carbon nanotubes.
We anticipate the results from our studies being available in the next 1-5 years, depending on the type of study. Results from longer-term rodent studies will likely take several years.
The NTP is coordinating and communicating its activities on nanotoxicology with other groups to aid the identification of areas where research is needed and avoid duplicative efforts.
Prioritizing and obtaining materials to evaluate are major challenges for the NTP. Specific nanomaterials with the highest exposure potentials are not well known, making it difficult to identify the most important materials to study. Obtaining materials is also an impediment. In many cases, information about the nanoscale material is proprietary. Consequently, the NTP may be unable to study those materials that pose the highest potential exposure to humans. In other cases, the material may be available, but not in sufficient quantities to allow an adequate hazard evaluation, particularly regarding long-term, repeated exposure studies.
Characterization of nanomaterials has proven to be more difficult than anticipated for several reasons. First, a standard nomenclature has not been developed. Second, biologists, physicists, and materials scientists working in this area often do not communicate effectively. In addition, an analytical infrastructure to allow characterization is not consistently available or well-located. The high degree of variability in size and surface chemistry of nanoscale materials and in the coatings, crystal structure, shape, and composition used in preparing these materials increase both their complexity and the multiple permutations that must be considered in their evaluation. Adequate methods to detect nanomaterials in cells and tissues also need further development.
Some of these impediments can be addressed by ensuring the availability of dedicated staff and resources. For example, development of a repository of well characterized model nanomaterials for use in both toxicological and biomedical research would significantly enhance the quality research investigating the heath effects of nanoscale materials. In addition, increased personnel, resources, and analytical capabilities could potentially enable the NTP nanotechnology safety assessment to move forward at a faster pace and/or broaden its scope.