TECHBriefs www.burnsmcd.com A quarterly publication by Burns & McDonnell 2009 No. 1

Small Concerns: Nanoscale MaterialsResearch Suggests Tiny Particles May Present HazardBy Jeffrey J. Keller, PE Manufacturers are designing, testing and selling products built with nanoscale materials, from electronics to pharmaceuticals to high-strength composites. The industry is projected to grow from $42 billion in 2005 to $1 trillion or more by 2015.

As larger volumes of these nano materials are released into the environment, preliminary research suggests that these materials may be the next class of compounds of emerging concern (CECs). The toxicity of nanoscale materials is difficult to quantify because of their unique physical properties. New approaches to toxicity studies and material classification schemes may be required to properly assess the impact of this new class of compoundson human health and the environment.

Nano-DefinedThe prefix nano- is rapidly being commandeered by marketers to suggest a product on the cutting edge. It really refersto a scale of roughly 1 to 1 trillion. Specifically, nanoscale materials are those with at least one dimension of approximately 0.1 to 100 nanometers. For comparison, a typical human hair measures about 80,000 nanometers in width, a single circuit element on today’s family of microprocessors measures 50 to 100 nanometers in width, and a water molecule has a mean diameter of one-fifth of a nanometer.

The water and wastewater field utilizes the nanoscale in a number of ways. In membrane technology, pore size in reverse osmosis membranes are typically in the range of 0.5 to 1.5 nanometers in diameter. In current research of CECs, concentrations of many potential contaminants not typically considered nanomaterials (particularly pharmaceuticals) sometimes lie within the nanogram-per-liter (ng/l) range. So, for water and wastewater professionals, the concept of nanoscale materials is not completely new.

Nanoscale materials typically consist of compounds or elemental materials that are manufactured and/or isolated and used to capitalize on the unique physical, chemical or electrical properties of the material. Fullerenes are possibly the most celebrated group of nanomaterials. These geometrically simple structures of carbon atoms, measuring as small as 0.4 nanometers in diameter, are proven to exhibit a variety of interesting properties. Tubular fullerenes can act as conductors, semiconductors or insulators, depending on the specific “twist” in their three-dimensional framework (Perkins, 1998) (see Figure 1). Another configuration of fullerenes has exhibited strength-to-weight ratios many times greater than that of steel (Universities Space Research Association, 2001). Nanomaterials are not purely synthetic or manufactured items. Current research has also considered nanoscale cellular materials that may have a detrimental impact on wastewater treatment processes. Known as biogenic organic nanomaterials, this material mainly consists of

Properties of Carbon at Nanoscale Dimension

Figure 1: Tubular fullerenes as small as 0.4 nanometers in diameter exhibit differentproperties depending on structural variations in their three-dimensional framework.

Conductor Insulator Semiconductor

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organic-nitrogen enriched cellular debris that may be a byproduct of biological treatment.

Use Limited by CostThe widespread dissemination of commercial and industrial nanotechnology-based products is limited due to the relative high cost of manufacturing nanoscale materials. However, as demand grows, economics of scale and pressure to develop more cost-effective manufacturing processes should drive down material costs dramatically. In the late 1990s, single-walled carbon nanotubes, one form of fullerenes, were available at prices reaching $2,000 per gram and higher (Amato, 2001). By 2006, that price had dropped to just a few hundred dollars per gram due to refined manufacturing methods and competitive pressures (Rawstern, 2006).

While the market for pure nanomaterials and specialized technologies will certainly grow rapidly over the next five to 10 years, the number of industries and products that make use of nanomaterials within more mundane applications will grow even faster. Nanotechnology has the potential to impact nearly every industry in existence, with aggressive forecasts predicting a market size of over $2 trillion before 2020 (Lux Research, 2006).

Risks and ResearchCurrent research focuses on the potential toxicity of such compounds in the natural environment and/or within the human body (Kulinowski, 2004). Because of their miniscule size, nanomaterials exhibit higher surface areas, making them excellent catalysts (Karakoti, 2006). Their small size also makes them more able to pass through pores, ducts, membranes and organs (Kimbrell, 2006). Finally, their size may compound the problems of detection.Reaching detection levels of ng/l or less is challenging, requiring precise measurement and advanced methods to remove material and signal contamination in the analysis.

Consider the potential routes of exposure to nanomaterials (see Figure 2). The most obvious route for nanoscale materials is that many current or developing applications for

nanomaterials are for application onto or into the body. The cosmetic and personal care product industries utilize nanoscale versions of titanium dioxide and zinc oxide in sunblock, as well as other nanoscale polymers in makeup (http://www.chem.info, 2006). Wound dressings using silver nanoparticles exhibiting rapid antimicrobial activity are used worldwide (Lyndon B. Johnson Space Center, 2006). Food storage containers embedded with silver nanoparticles claim to retard spoilage (Nano Science and Technology Institute, 2006). And most dramatically, studies are under way demonstrating the possibility of treating cancer using a nanoscale compound of silica and gold “nanoshells” that find their way onto and into cancer cells. These nanoshells absorb applied infrared light and transform it into heat, something at which macroscale gold and silica are not nearly as proficient. As a therapy, the heat from the nanoshells would kill the cancer cells, leaving most healthy tissue undamaged (National Science and Technology Council, 2004).

Are Nano-Materials Dangerous?Given numerous routes of exposure and the possibility of exposure routes not normally considered, it is valuable to consider a more fundamental question: Are nanoscale materials dangerous? For nanomaterials, the ancient mantra by Paracelsus “the dose makes the poison” could be revised to “the size makes the poison.” In the case of nanomaterials, although

Because of the widespread use of nanomaterials, there are many potential exposure routes to consider:

• Ingestion of nanoparticles used in pharmaceuticals.• Inhalation or adsorption of nanoparticles during exposure to nanoproduct manufacturing processes.• Adsorption of nanoparticles onto the skin or membranes as a consequence of wearing materials partially composed of nanoscale materials.• Ingestion of nanoparticles through accidental release into the aquatic environment. This route could be facilitated by a number of scenarios including a release into a waterway or the poorly managed use of nanotechnology at a wastewater treatment plant.

Figure 2: Potential routes of exposure to nanomaterials will guide future research.

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many of the materials have already been investigated for toxicity at the macro scale, the size of the materials requires a completely new toxicologic approach.

Consider the toxicity of carbon. At the macro scale, carbon in all its forms is relatively innocuous, and ingestion of carbon is often used in hospitals as a treatment for poisoning or overdose. However, when used at the nanoscale, carbon has been shown to be toxic. Early tests in the 1990s, focused on the destruction of HIV in rats using fullerene-derived particles, were successful in deactivating the virus at certain doses, but at slightly higher doses, the rats quickly died. There is also concern that carbon-based molecules might absorb other toxic materials in the environment and allow greater migration and exposure (Amato, 2004). Although fullerenes have shown a tendency to settle in clean water, fullerenes in water with natural organic matter tend to stay in suspension for long periods of time. This behavior suggests that some nanoparticles in natural waters could be easily distributed (Hyung, 2007).

Other Effects of NanomaterialsStudies with nanoscale forms of titanium dioxide have shown that mouse microglia cells exposed to these nanoparticles exhibit a strong defensive response that include the generation of reactive oxygen species that can damage cells through oxidative stress. In brain tissues, this type of defensive response can lead to neuronal damage similar to proposed destructive pathways for Parkinson’s and Alzheimer’s diseases (Thrall, 2006).

Teflon®, that ubiquitous non-stick material, has been observed to present toxic properties when manufactured in nanoscale sizes. A study at the University of Rochester exposed laboratory rats to nanoscale particles of Teflon® at concentrations of 60 micrograms per cubic meter. The rats experienced bleeding of the lungs and many died within 30 minutes of exposure (Winters, 2006).

Lab studies have also suggested that many types of nanoscale particles can reach deeper into

organs and tissues than can larger particles. A study at the University of Bern in Switzerland found that clusters of nanoparticles were able to pass into red blood cells. This research also suggests that nanomaterials may be able to penetrate the blood-brain barrier and other regions that traditional contaminants cannot (Rothen-Rutishauser et al., 2006).

These results suggest a number of potentially troubling characteristics of nanoscale materials in general: an ability to translocate and accumulate into various tissues and organs, a potential to exhibit toxic properties at very low concentrations and, most striking, the ability to produce a toxic response from exposure to materials not known to be toxic at the macro scale (Lubick, 2006). The toxicity at low concentrations may be related to the fact that manufactured nanomaterials tend to be produced in a tight particle size distribution compared to macroscale toxic materials. It would therefore be reasonable to think that if toxicity was only exhibited in a narrow size range, materials commonly manufactured in a tight size range would elicit a rapid toxic response. An analogy to this is imagining exposure to a broad-spectrum beam of light versus a laser beam.

Some Nanoscale Materials Considered SafeHowever, the results of some studies may not be completely applicable to real-world contact with nanoparticles. Laboratory tests, even on biological systems, do not always translate perfectly into the human experience. For example, even though some nanoparticles have exhibited an ability to enter red blood cells, these studies were performed on isolated red cells only, possibly ignoring the response of the immune system (Rothen-Rutishauser et al., 2006).

Add to this the fact that the Food and Drug Administration (FDA) has previously ruled that the type of nanoparticles used in sunscreens and cosmetics, such as titanium dioxide and zinc oxide, are safe to use in personal care products. Nanoscale zinc oxide has, in fact, been approved for use as a color additive in food as well in drugs, contact lenses and as part of a

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product to treat injured skin (www.chem.info, 2006, Lyndon B. Johnson Space Center, 2006).

Materials such as nanoscale gold have been shown to exhibit no cytotoxic effects on human cells (Connor, 2005).

And while nanomaterials may be relatively new to most of the public, researchers have been working directly with nanoscale materials for nearly two decades without a single known publicized injury specifically due to exposure. Research laboratories and manufacturing plants utilize potentially toxic materials every day, and it is certainly possible that lessons learned from previous sets of materials can be applied here to minimize the risk of workplace exposure or accidental release into the environment.

The problem of maintaining public safety when nanomaterials or nanotechnology products are intentionally released into the public may be more difficult. How would a manufacturer sell a nano-based product while also providing protection from toxic exposure? An analogy might be drawn from the use of mercury switches in thermostats. The solution was,for a time, to seal the mercury adequately to reduce the risk of exposure to an acceptable level. Can nanotechnology be “sealed” within a product to eliminate the risk of public exposure? Recent research has suggested that some nanomaterials could be redesigned or modified at the molecular level to significantly reduce their toxicity while not affecting their desired properties.

More Study NeededBecause studies have only recently begun on these materials, it is important that resultsfrom toxicological studies are recognized bythe public and media as preliminary in nature. More thorough studies, representative of real-life exposure situations, are needed. New studies will be critical to properly understanding the interactions between nanoscale materials,the environment and human health.

Practical MeasuresA key point in developing an approach to these studies is the need to avoid the use

of existing data on macroscale materials,such as in the apparent case of Teflon® (see Figure 3). Another key point should be that some material characteristics that traditionally have little bearing on toxicology may become key factors in studying nanoscale materials. Water and wastewater engineers are familiar with the concepts of maximum contaminant levels, LC50 (50% lethal contamination) and other measures of potential toxicity relevant to macroscale materials, but the traditional mass-based exposure metric may not always be applicable when considering the nanoscale. Parameters such as specific surface area (surface area per unit volume or mass), zeta potential (a common measure in colldoial chemistry) and particle size distribution may turn out to be key parameters in evaluating the toxicity of nanomaterials (Karakoti, 2006).

An additional hurdle that may also need to be overcome is the matter of dosage. Since many of these preliminary studies have suggested impacts at very low dosages, affordable methodologies for reliably measuring nanomaterials in both the solid and liquid phase at concentrations much lower than we typically see with macroscale materials must be found. Measurement of materials in the ng/l range is becoming more common as water and wastewater professionals investigate other CECs in the environment. This should help to prepare the laboratory industry for future investigations of potential contamination of water, soils and tissues.

Approaches to managing the contamination issue could include a stronger focus on waste

Toxicity ResearchResults of carbon and Teflon® nanoparticle exposure in laboratory rats:

• Strong oxidative response to nanoparticles in the brain• Penetration of blood and other cells• Possible access through blood/brain barrier

Nanoparticles also show a tendency to persistent suspension in water.

Figure 3: Research suggests that some materials considered safe at the macro level may be hazardous as nanoparticles.

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minimization and pretreatment. Capture of nanoparticles in a wastewater stream couldbe attained in many instances through theuse of reverse osmosis (RO) membranesand an enhanced coagulation step (Huang et al., 2004; Den and Huang, 2005). Methods for water or gas media include capture of metallic nanoparticles through an induced magnetic field (Christen, 2007). Inorganics in exhaust gas could potentially be removed through a type of electrostatic precipitation. Organic nanoscale materials could possibly be destroyed by an aggressive oxidation method.

Federal InvolvementIn 2001, the National Nanotechnology Initiative was established. This initiative was designed to coordinate the research and development of nanoscale science, engineering and technology across the various branches of the federal government (see Figure 4).

There is a silver lining to the cloud of nanotechnology as a new CEC: A number of applications of nanotechnology in the environmental industry could provide significant benefits. Available information reports include:

• In-situ sensors capable generating nearly real-time data on the presence of specific

microbes in a system or the presence of specific contaminants in treated water (Popovtzer, 2005, and Fu, 2007)• Removal of virus-sized pathogens using nano ceramic fiber filters (Lyndon B. Johnson Space Center, May 2005)• Disinfection using solar power and a powerful photocatalytic material manufactured with nanoscale materials (www.azonano.com)• Wastewater treatment systems that treat high-nitrogen industrial wastewater using air bubbles with diameters in the nanometer range, resulting in a much higher oxygen transfer efficiency (Sharp, 2006)• Carbon and silicon-nitride membranes with pores only 1-2 nm in diameter. Because the pores are so smooth compared to normal membrane pores, they allow water to pass at rates up to 100 times that provided by an RO membrane using a similar energy input (Trimbath, 2006).

Considering the other potential uses for nanotechnology, this list of applications for wastewater might be only the tip of the iceberg. Ironically, the potential risks of nanoscale materials in the aqueous environment might be most effectively addressed by the proper application of nanotechnology in both industrial and municipal wastewater facilities.

Jeffrey J. Keller, P.E.,is the manager of the Burns & McDonnell wastewater department in Kansas City. He received his bachelor’s and master’s degrees in civil engineering at Kansas State University and studied nanoscale materials in the doctoral program at Rice University. He specializes in industrial and civil wastewater treatment.

For more information, please e-mail: jkeller@burnsmcd.com.

Agencies and departments involved today include:

Other participating organizations include the FDA, the Consumer Product Safety Commission, and the U.S. Patent and Trademark Office (National Science and Technology Council, 2004).

• Department of Agriculture• Department of Defense• Department of Energy• Department of Homeland Security• Department of Justice• Environmental Protection Agency• National Aeronautics and Space Administration

• National Institute of Standards and Technology• National Institute of Occupational Safety and Health• National Institutes of Health• National Science Foundation

Figure 4: The National Nanotechnology Institute helps coordinate research across federal agencies.