Engineered nanomaterials (ENMs) have great potential to benefit animal and human health. But there are uncertainties surrounding the long-term effects of applying ENMs to food and pharmaceutical products consumed by humans and animals. Therefore, in a previous article, I suggested that more regulations should be applied to ENMs in our food system. I believe that a precautionary approach to nanotechnology is a suitable balancing measure to manage the rapid commercialization of ENMs. This argument is built on the premise that at least some ENMs pose health risks to human, animal, and environmental health. Readers have asked for evidence to demonstrate such risks; hence, this article reviews various studies that reveal harmful effects of ENMs on living organisms. These negative impacts justify a call for a precautionary approach, one which should enable us to enjoy the benefits of nanotechnology while preventing serious and unforeseen harm. Nanomaterial Toxicity The toxicity of ENMs can be significantly different from that of conventional materials, even when the two materials have the same chemical composition. There are two reasons for this. First, chemical reactions generally occur only on the surfaces of particles. Since the surface area of a nanoparticle is much larger than that of a conventional particle of the same weight, nanoparticles are likely to be far more reactive. For a compound that has any level of toxicity, “more reactive” almost always means more toxic. The findings of Duffin et al. demonstrate that the pulmonary inflammatory response to various particles correlated to the total surface area of the dosage received, but not at all to the weight of the dosage (1). The second reason that the toxicity of ENMs can differ from that of conventional materials is that ENMs have unique surface geometries at the molecular scale, which make them effective for their intended industrial purpose. Different molecular surface geometries, however, can change the reactivity of a material in significant and unpredictable ways. As the FDA’s Nanotechnology Task Force noted, “at this scale, properties of a material relevant to the safety and effectiveness of FDA-regulated products might change repeatedly as size enters into or varies within the nanoscale range” (2). Nanotoxicology researchers are only in the early stages of developing models that predict whether or not a specific nanomaterial will be toxic. According to Maysinger et al., the toxicity of a particular nanomaterial depends upon its makeup, particle size, surface charge, possible ligand attachments, and concentration (3). Another study by Jia examined fullerenes or “buckyballs”– spherical nanostructures made exclusively of carbon, finding that variances in geometry alone led to large differences in toxicity (4). Xia et al. are also making progress in their research which suggests a possible way of predicting the toxicity of certain types of ENMs by assessing the relative ability of different fullerenes to generate reactive oxygen species (ROS) such as hydrogen peroxide. ROS cause oxidative stress in living systems and the amount of ROS that a particle generates may be a good indicator of its toxicity (5). These studies offer a deeper understanding of the toxic effect of some nanoparticles and of the wide variability in the reactions of living organisms when exposed to ENMs. Are Engineered Nanomaterials like Asbestos? Carbon nanotubes (CNT), both single- and multi-walled, are good examples of ENMs known to have significant potential for toxicity. CNTs are very thin yet strong tube-shaped carbon polymers used in cancer treatments (6), and some commercial salad dressings contain CNTs in the form of nanoscale oil droplets, intended to slow the separation of ingredients (7). Many researchers are investigating CNTs because they are similar in size, shape and insolubility to asbestos fibres. Inhaling CNTs may also be as dangerous as inhaling asbestos, which causes fibrosis- the formation of excess fibrous connective tissue, and mesothelioma- a rare form of cancer that develops in the lungs (8). A study by Poland et al. found that exposing the lining of the body cavities of mice (a surrogate for the lining of the human chest cavity) to CNTs resulted in inflammation and lesion formations known as granulomas (9). Subsequently, Ryman-Rasmussen et al. discovered that inhaled CNTs were able to move from the alveoli to the sub-pleural membrane of mice (10); this movement is part of the process in which asbestos fibres cause tumours. In a different study, Schinwald et al. found that the ability of nanofibres to damage the pleura (membrane surrounding the lungs) depends highly on the length of the fibres; fibres shorter than 4 micrometres do not cause damage (11). Other variables affecting the responses to ENMs include the type of nanoparticles used, duration of exposure, concentration of ENMs, and the conditions under which interactions to nanoparticles take place. Cells may either tolerate interactions with nanoparticles or succumb to their invasion (12). Additionally, the reaction of cells exposed to nanoparticles will depend on the tissue of origin, type of cell, cell density, and the presence of serum (13). The above reasons show that the impacts of ENMs on animal and human health are highly unpredictable. Impacts of Nanotechnology on Animal Health Several studies demonstrate that certain ENMs can be toxic to animals. Zhu et al. experimented with different fish species and fullerenes, nanocapsulates made entirely of carbon used in dietary supplements and pharmaceutical drugs to administer medicine to targeted areas. The study found that chemically stabilized fullerenes were much more toxic to fathead minnows than water-soluble fullerenes (14). All of the fish in the experiment died after six to eighteen hours of exposure to the chemically stabilized fullerenes. Similarly, Zhu et al. tested fullerenes and fullerols – used in pharmaceuticals for the human eye – on zebrafish embryos. The tests found that fullerenes caused significantly greater mortality and failure to hatch, while fullerols had no effects (15). Another study showed that the gills and livers of juvenile carp produced antioxidants in response to exposure to fullerene aggregates, and that the fish suffered weight and length decreases (16). Nanotoxicology researchers are beginning to develop models that can simulate the release and diffusion of ENMs to forecast impacts on living systems in certain situations. Gottschalk et al. compared ecotoxicological data to predict that aquatic organisms living in sewage waste in the US, Europe and Switzerland may be at risk from nanoscale metals (17). Nanoscale silver in particular is widely utilized in consumer products, such as toothpaste, for its antibacterial properties (18). Approximately 2.5 million kilograms of silver are lost to the environment in the US every year; 27 percent of that amount is released to water and 77 percent to land (19). Studies show that nanoscale silver poses greater health risks than other metals: It is toxic to mammalian liver and brain cells, and contributes to abnormalities in mammalian cell functions (20). Moreover, nanoscale silver has been found to cause embryonic contamination in zebrafish (21). Thus far, it is proven that some types of human cells react adversely to specific types of ENMs under certain circumstances. Therefore, continuous research is required to determine whether a particular nanoparticle is safe or harmful, because biological impacts of ENMs vary significantly. Some studies display toxic effects in animal testing, but the factors that cause toxicity are not fully understood. Given the above variables and the lack of conclusive data on nanotechnology, it is not yet possible to confirm the risks associated with most ENMs, unless each material is specifically tested. These factors justify implementation of a precautionary approach in managing nanotechology. Legislation Does Not Restrict Innovation Nanotechnology has great potential to improve food, medicine and other health products. I have argued that precautionary regulations are appropriate to monitor the application of nanotechnology. However, opponents of market regulations argue that government should avoid interfering in the nanotechnology market to allow this promising field to come to full fruition. Some believe that individuals’ free choice should not be fettered, and that the government should not demand legal approval before a product containing ENMs can be introduced to the consumer market (22). But implementation of labeling laws and mandatory containment of ENMs to prevent contamination of environmental, animal, and human health does not have to interfere with development or restrict consumer choice. In fact, true freedom of choice lies in whether or not consumers will purchase goods containing nanomaterials, fully aware of their potential risks. Conclusion Many scientific studies have shown that nanomaterials pose health risks and uncertain impacts to natural living systems. Continuous research and risk assessment are required to investigate the long-term effects of nanotechnology, in order to better understand any unpredictable consequences. Current FDA procedures allow many ENMs to enter our food system without requirements on risk assessment, reporting of potential risks, or mandatory labeling on foods that contain nanoparticles (23). Insufficient food safety procedures have already allowed genetically-engineered organisms, which were not fully tested for long-term risks, into our food system (24). Now, human, animal and environmental health is again placed at risk due to a lack of precautionary regulations on nanotechnology. Hence, it is pertinent for government to implement stricter regulations on ENMs. Note to readers: Comments on my last article on nanomaterials noted that proposals on food safety standards were not discussed. I am grateful to these readers and I will discuss such proposals in an upcoming article. — (1) Duffin R, Clouter A, Brown DM, C. L. Tran, MacNee W, Stone V, and Donaldson K., (2002) ‘The importance of surface area and specific reactivity in the acute pulmonary inflammatory response to particles’ Ann Occup.Hyg 46 Suppl 1:242-245. (2) FDA Nanotechnology Task Force, Nanotechnology: A Report of the U.S. Food and Drug Administration Nanotechnology Task Force 33 (FDA, 2007), 13. (3) D. Maysinger et al., ‘Death by Nanoparticles’ (2006) 1 NanoPharmaceuticals Online Journal 9 <http://nanopharmaceuticals.org/files/Death_by_Nanoparticles_nanopharmaceuticals2.org_OCT_2006.pdf>. (4) G. Jia et al., ‘Cytotoxicity of carbon nanomaterials: single-wall nanotube, multi-wall nanotube, and fullerene’ (2005) 39 Environmental Science & Technology 5, 1378–83. (5) Tian Xia, Michael Kovochich, Jonathan Brant, Matt Hotze, Joan Sempf, Terry Oberley, Constantinos Sioutas, Joanne I. Yeh, Mark R. Wiesner, and Andre E. 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