Good things come in small packages? A chat about nanotechnology and food safety

Photo: Titanium dioxide nanoparticles, photo courtesy of Dr. Prabir Dutta, The Ohio State University.

Show of hands: who would like to see computers that are smaller and more powerful? Or a cancer therapy that precisely targets only cancer cells? Or foods with better nutritional value? Or packaging that keeps food fresher and bacteria free for longer?

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Nanotechnology promises to do all this ? and more!

Already in hundreds, if not thousands, of consumer products, nanomaterials provide UV protection in sunscreens and durability in automobile paints and surface coatings. In foods, they improve color, flavor and texture as well as enhance nutritional value.

Yet the health and environmental impact of these tiny particles is largely unknown.

Which begs the question: Have we become so mesmerized by the shiny gleam of nanotechnology that we have ignored safety, especially in our food?

Are they safe?

Questions of toxicity and the long-term effects of accumulation in the human body abound ? especially when nanomaterials are introduced into the food we eat. Intentionally placed there or not, these tiny particles could have unexpected effects on our overall health as they pass through the digestive tract.

Take for example the food additive titanium dioxide (which is also used in sunscreens, cosmetics and toothpastes). In its non-nano form, this white substance has been approved for use in foods since 1966. It is what makes food such as cake icing ?white.? It is also approved as a food contact substance, meaning it is deemed safe to incorporate into food packaging. The nano form of titanium dioxide is colorless making it ideal to use in clear plastic food wraps for UV protection. And because titanium dioxide has already been approved for food packaging, the nano form will not need special approval for use in those plastic wraps.

But are titanium dioxide nanoparticles safe?

Several research groups have shown they may have an impact on health.

When titanium dioxide nanoparticles were fed to mice, the nanoparticles traveled out of the digestive tract and into places such as the liver and kidney where signs of tissue injury were observed. And at certain doses, titanium dioxide nanoparticles given to pregnant mice led to birth defects.

In one study of the long-term effects of exposure, titanium dioxide nanoparticles were shown to interfere with egg production and embryo survival in zebrafish.

Clearly these studies hint that the use of nanomaterials (such as titanium dioxide) may warrant caution.

Just how small are nanomaterials?

Photo: Fluorescent nanoparticles (green) taken up and compartmentalized within a cell, photo courtesy of Dr. W. James Waldman, The Ohio State University.

Although scientists, industry, and governmental agencies do not entirely agree on how to define the size of nanomaterials, it is generally accepted that a nanomaterial measures between 1 and 100 nanometers in at least one dimension. To put their size into perspective, it would take 1600 trillion of the 100-nanometer particles to fill a one-inch cube. Or stated another way, if you stacked them end to end, it would take nine million to span a yard stick.

Many viruses, including the common cold virus, fall into this size range.

If small enough, nanoparticles can easily enter a human cell and accumulate there. One research study found that 45-nanometer sized gold nanoparticles were readily taken up by and accumulated in cultured human cells but not the larger 70-nanometer size. While gold nanoparticles are not typically used in food products, they are often used in scientific studies because they are easily traceable. Though gold is considered an inert metal, one animal study found that injecting rats with gold nanoparticles resulted in liver injury.

A confounding problem is that nanoparticles have considerably more surface area than their larger (and better-characterized) counterparts called ?fine particles.? (Think glass marbles versus a basketball.) The increase in surface area of nanoparticles can have a remarkable effect on how they behave chemically and physically ? behavior that may have unexpected outcomes.

But size isn?t everything. The shape and chemical composition of a nanoparticle can also affect how they interact within the body. Nanomaterials are made in various shapes including spheres, rods, and tubes. They can be made of a single material or a mixture of several materials, and they can be of organic or inorganic composition. Each of these characteristics must be considered when evaluating their food safety.

Regulating their use

Governmental agencies are not just having a tough time defining what constitutes a ?nanomaterial? but also how to regulate it in consumer products like food.

In June 2011, the Food and Drug Administration began courting the issue of nanomaterials in FDA-regulated products by releasing a 5-page guidance document. This document strives to open a discourse between the FDA, industry and the public regarding when to say that nanotechnology is involved in an FDA-regulated product.

The European Food Safety Authority (the European counterpart to the United States? FDA) released a 37-page document in May 2011 specifically addressing nanotechnologies in food for both humans and animals. This document offers a rigorous discussion of how engineered nanomaterials should be tested and characterized before they are added to food. It is clear EFSA is taking nanomaterial safety seriously and this agency has drafted the most thorough guidance document thus far.

Last month, the U.S. National Nanotechnology Initiative released a 131-page research strategy document outlining where research on nanotechnology should focus. This hefty tome is somewhat reassuring in that it appears the government is taking nanotechnology safety seriously throughout the material?s life cycle (ranging from manufacture to consumer use to disposal in landfills) considering safety for workers, consumers and the environment. However, this document seems more a handshake with the issue than a defined course of action.

Other considerations

In the National Nanotechnology Initiative?s research strategy document, it is stated ?where nanomaterials are effectively embedded in the product matrix, such as computer circuit boards, the potential for exposure during routine use of the product is unlikely because the embedded nanomaterials are not available for exposure.? This may be oversimplified. When researchers embedded silver nanoparticles into an inert substrate to explore its antimicrobial properties, they were surprised to find that not all of the silver remained in place and that silver ions actually leached from the substrate. There was a ?silver lining? to the study: the ions were found to kill bacteria.

Another research team showed that silver nanoparticles can bind to DNA and interfere with its replication. While this study was conducted in a test tube, it implies the same effect could occur in cells, possibly impacting gene expression.

With this research in mind, silver nanomaterials (as well as other nanomaterials) used in various food packaging may require special consideration. Some types of nanomaterials may migrate out of the packaging material and into the very food it is designed to protect. This could potentially pose a health risk to the consumer.

Another consideration is that many of these nanomaterials will pass through the digestive tract with little harm to the consumer. However, these tiny particles will then pass into the sewage treatment system and the environment where they could have a significant impact.

Several studies have examined the ability of nanoparticles to move up in the food chain:

Titanium dioxide nanoparticles were found in the tissue of zebrafish that were fed a steady diet of nanoparticle-exposed zooplankton.

Gold nanoparticles were added to a laboratory-simulated aquatic ecosystem, and shown to accumulate in the bacteria and shellfish, suggesting the nanoparticles were passed up the food chain.

Gold nanoparticles were added to the water used to grow tobacco plants. The nanoparticles concentrated in the leaves. When tobacco hornworms were allowed to munch on those plants, the worms were found to have ten times the number of nanoparticles in their tissue than found in the plant tissue. This suggests not only can nanoparticles move up the food chain, but they may accumulate or concentrate as they do so.

As nanomaterials move up through the food chain, they may find their way back on our dinner plates, thus increasing our potential exposure to nanomaterials in our food ? this time unintentionally. And this time, those nanomaterials may have been altered chemically as they move through the ecosystem.

So, are all nanomaterials potentially dangerous?

At this point, scientists and government agencies simply do not have enough information to know what health and environmental impact nanomaterials will have ? especially over the long haul.

Many nanomaterials will have little or no observable impact while others may prove to have unforeseen consequences.

Clearly, more research is needed.

One thing is for certain: nanotechnology is here to stay. And it will continue to revolutionize the world as we know it.

It is a brave new world out there, folks! A small world ? a nanoworld.

For more reading on this topic:

Magnuson B.A., Jonaitis T.S., and Card J.W. (2011) ?A brief review of the occurrence, use, and safety of food-related nanomaterials,? Journal of Food Science 76: R126 ? R133.

Sozer N. and Kokini J.L. (2009) ?Nanotechnology and its applications in the food sector.? Trends in Biotechnology 27: 83 ? 89.

Currall S.C., King E.B., Lane N., Madera J., and Turner S. (2006) ?What drives public acceptance of nanotechnology?? Nature Nanotechnology 1: 153 ? 155.

McCall M.J. (2011) ?Nanoparticles in the real world.? Nature Nanotechnology 6: 613-614.

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