Human exposure to nanoparticles from natural and anthropogenic sources has occurred since ancient times. Following the invention of combustion engines and the development of industry, however, significant levels of nanoparticle pollution have arisen in most major cities and even across large regions of our planet, with climatic and environmental effects that are generally unknown.

There is heightened concern today that the development of nanotechnology will negatively impact public health, and it is indisputable that engineered nanomaterials are a source of nanoparticle pollution when not safely manufactured, handled, and disposed of or recycled. A large body of research exists regarding nanoparticle toxicity, comprising epidemiological, animal, human, and cell culture studies. Compelling evidence that relates levels of particulate pollution to respiratory, cardiovascular disease, and mortality has shifted attention to particles with smaller and smaller sizes (nanometer scale). Research on humans and animals indicates that some nanoparticles are able to enter the body, and rapidly migrate to the organs via the circulatory and lymphatic systems. Subjects with preexisting diseases (such as asthma and diabetes, among others) may be more prone to the toxic effects of nanoparticles. Genetic factors may also play an important role in the response of an organism to nanoparticle exposure.

As shown in this review, it is clear that workers in nanotechnology related industries may be potentially exposed to uniquely engineered nanomaterials with new sizes, shapes, and physicochemical properties. Exposure monitoring and control strategies are necessary. Indeed, there is a need for a new discipline—nanotoxicology—that would evaluate the health threats posed by nanoparticles and would enable safe development of the emerging nanotechnology industry.¹⁹ We emphasize that this field of study should include not only newly engineered nanomaterials, but also those generated by nature and pollution.

The ability of nanoparticles to enter cells and affect their biochemical function makes them important tools at the molecular level. The toxic properties of nanoparticles can, in some instances, be harnessed to improve human health through targeting cancer cells or harmful bacteria and viruses. These very properties that might be exploited as beneficial may also have secondary negative effects on health and the environment. For example, nanoparticles used to destroy cancer cells may cause harmful effects elsewhere in the body, or nanoparticles used for soil remediation may have an adverse impact upon entering the food chain via microorganisms, such as bacteria and protozoa.

In the following, we highlight important questions and research directions that should be addressed in the near future by the scientific community involved in the study of nanoparticle sciences and by government agencies responsible for regulations and funding.

Advanced analysis of the physical and chemical characteristics of nanoparticles will continue to be essential in revealing the relationship between their size, composition, crystallinity, and morphology and their electromagnetic response properties, reactivity, aggregation, and kinetics. It is important to note that fundamental properties of nanoparticles are still being discovered, such as magnetism in nanoparticles made of materials that are nonmagnetic in bulk form. A systematic scientific approach to the study of nanoparticle toxicity requires correlation of the physical and chemical characteristics of nanoparticles with their toxicity. Existing research on nanotoxicity has concentrated on empirical evaluation of the toxicity of various nanoparticles, with less regard given to the relationship between nanoparticle properties (such as exact composition, crystallinity, size, size dispersion, aggregation, and aging) and toxicity. This approach gives very limited information, and should not be considered adequate for developing predictions of toxicity of seemingly similar nanoparticle materials.

Further studies on kinetics and biochemical interactions of nanoparticles within organisms are imperative. These studies must include, at least, research on nanoparticle translocation pathways, accumulation, short- and long-term toxicity, their interactions with cells, the receptors and signaling pathways involved, cytotoxicity, and their surface functionalization for an effective phagocytosis. Existent knowledge on the effects of nanoparticle exposure on the lymphatic and immune systems, as well as various organs, is sparse. For example, it is known that nanoparticle exposure is able to modulate the response of the immune system to different diseases, however much research is needed in order to better understand to what extent this occurs and the full implications of risk groups (age and genotype). In order to clarify the possible role of nanoparticles in diseases recently associated with them (such as Crohn's disease, neurodegenerative diseases, autoimmune diseases, and cancer), nanoscale characterization techniques should be used to a larger extent to identify nanoparticles at disease sites in affected organs or tissues, and to establish pertinent interaction mechanisms.

Other important research topics to be pursued include nanoparticle aging, surface modifications, and change in aggregation state after interaction with bystander substances in the environment and with biomolecules and other chemicals within the organisms. How do these interactions modify the toxicity of nanoparticles? Do they render toxic nanoparticles less toxic? Or can they render benign nanoparticles more toxic? What about the beneficial properties of some nanoparticles? Do they change in the short and long term after undergoing chemical interactions? Research should also be directed toward finding ways to reduce nanoparticle toxicity (such as antioxidants provided by dietary sources and supplements, metals chelators, and anti-inflammatory agents).

Understanding and rationally dealing with the potentially toxic effects of nanoparticles require a multidisciplinary approach, necessitating a dialogue between those involved in the disparate aspects of nanoparticle fabrication and their effects, including but not limited to nanomaterial fabrication scientists, chemists, toxicologists, epidemiologists, environmental scientists, industry, and policy makers. In order to achieve an interdisciplinary dialogue, systematic summaries should be prepared, discussing current knowledge in the various nano fields and using a common vocabulary. This will help bring together scientists in different fields as well as policy makers and society at large. These summaries should include periodic written reviews, conferences, and accessible databases that contain the collected knowledge of nanoparticle synthesis, characterization, properties, and toxicity in a format easily comprehensible to a wide audience of scientists. A database initiative has already begun, led by the National Institute for Occupational Safety and Health, as the “Nanoparticles Information Library.”

We also suggest several directions for minimizing human exposure to nanoparticles, and thereby reducing associated adverse health effects. National governments and international organizations should enact stringent air quality policies with standardized testing methods and low exposure limits. With such compelling existing evidence of the correlation between particle pollution levels, mortality, and a wide range of diseases (comprising cardiovascular, respiratory diseases, and malignant tumors), the primary source of atmospheric nanoparticles in urban areas—combustion-based vehicles—should be mandated to have lower nanoparticle emission levels. In the light of their potential toxicity, the commercialization of dietary and cosmetic nanoparticles, as well as other consumer products incorporating nanoparticles, must be strictly regulated. In particular, they must be regulated as distinct materials from their bulk constituents. Before using these nanoparticles, several questions should be answered: Are they biocompatible? Do they translocate and accumulate in the body (including skin)? What are the long-term effects of uptake and accumulation? In general, consumer products containing nanomaterials should be recycled. A model initiative began in 2001 in Japan for electrical appliances, where the retailers, manufacturers, and importers are now responsible for recycling the goods they produce or sell.

There is limited existing research regarding ecological and environmental implications of natural and anthropogenic nanoparticle pollution, though the role of nanoparticles in some forms of environmental degradation is well known, e.g., atmospheric nanoparticles play a central role in ozone depletion. Nanoparticulate pollution is likely to play an important role in global climate balance, despite the fact that current anthropogenic climate changes are attributed solely to greenhouse gases. This is dangerous as it encourages the misconception that wood burning does not contribute to pollution and/or climate change. In a simple calculation of carbon liberation and fixation, it appears that wood burning, as a so-called renewable source of energy, is benign to the environment. A proper accounting of nanoparticle pollution in addition to CO₂ reveals the naivety of this analysis.

Advances in nanotechnology are driven by rapid commercialization of products containing nanostructures and nanoparticles with remarkable properties. This is reflected in the enormous number of publications on nanotechnology. In comparison, the number of publications on nanoparticle toxicity is much smaller, as the funding available for toxicity studies are mostly government related. One way of increasing funding for nanotoxicity research might be via international regulations requiring that a fraction of the revenues of each company involved in their production and commercialization be dedicated to this field of research. Without this level of commitment, it is likely that a current or future industrial nanoparticle product, with nonobvious or delayed toxicity, will cause significant human suffering and/or environmental damage. The field of nanotechnology has yet to have a significant public health hazard, but it is a real possibility that can and should be prevented.

We conclude that the development of nanotechnology and the study of nanotoxicology have increased our awareness of environmental particulate pollution generated from natural and anthropogenic sources, and hope that this new awareness will lead to significant reductions in human exposure to these potentially toxic materials. With increased knowledge, and ongoing study, we are more likely to find cures for diseases associated with nanoparticle exposure, as we will understand their causes and mechanisms. We foresee a future with better-informed and, hopefully, more cautious manipulation of engineered nanomaterials as well as the development of laws and policies for safely managing all aspects of nanomaterial manufacturing, industrial and commercial use, and recycling.