Probing Hazards Of Nanomaterials

NANOTECHNOLOGY has been called a new industrial revolution. Nanomaterials, which contain tiny bits such as metal oxides and carbon nanotubes, could have promising applications ranging from stain-resistant clothing and faster electronics to cancer medicines and solutions to the energy crisis. Market analysts estimate that those materials could add up to a multi-trillion-dollar industry in less than a decade. Although little is known about how nanosized particles will fare in the human body or in the environment, researchers are well aware that damaging pollution emerged from previous industrial revolutions. Efforts to design safe materials now may prevent environmental or human health tragedy later.

The National Science Foundation and the Environmental Protection Agency are taking the issue seriously and announced on Sept. 17 that they will grant $38 million over five years to establish two new research centers to study the environmental implications of nanotechnology. EPA's $5 million contribution is the largest award for nanotechnology research in the agency's history. Duke University and the University of California, Los Angeles, will lead the centers.

The rationale behind the investment, the agencies say, is that once researchers understand how nanosized particles, which are defined as less than 100 nm in any one dimension, interact with the environment, they can translate that information into improved risk assessment, which in turn will better inform policy-making and commercial development of nanotechnology. Currently, nanomaterials are produced industrially, but no regulations specifically address these materials in relation to the environment (C&EN, Aug. 11, page 35).

Scientists at the two new centers have outlined plans to conduct research on the possible environmental health impacts of nanomaterials. The plans include new approaches, such as creating a predictive toxicology model based on cell assays and building ecosystems to track nanoparticles.

The University of California Center for Environmental Implications of Nanotechnology (UC CEIN) will be based in the California NanoSystems Institute at UCLA. With $24 million in funding, the center will focus on developing a scientific model that can forecast how different types of nanomaterials could affect environmental health.

Because there are so many nanomaterials to test, preliminary toxicity studies must largely shift from see-what-happens-in-an-animal to high-throughput cell assays, says André Nel, chief of UCLA's division of nanomedicine and UC CEIN's director. The center will still use animals for more in-depth studies, he adds.

MEANWHILE, at Duke, the Center for Environmental Implications of Nanotechnology (CEINT, pronounced "saint") will focus on the fate and transport of natural and manufactured nanomaterials in ecosystems. Plans for the center include building a unique system of experimental ecosystems in a forest next to Duke's campus and studying nanosized mineral particles that contain metal, such as those found at former open-pit mines.

Mark R. Wiesner, an environmental engineering professor at Duke who will direct the center with $14 million in funding, says that designing nanotechnology to be environmentally sustainable "is a real challenge." No one knows how much of a nanomaterial will be produced, its concentrations, or its form in nature, let alone how it will be used or disposed of.

In total, five principal investigators and three additional research group leaders are involved in CEINT, and UC CEIN has five principal investigators and seven additional research group leaders. Experts in disciplines such as materials science, biology, geochemistry, and environmental science from more than 20 academic and government facilities around the world are named in research proposals for the two centers.

Industrial collaboration is welcome, Wiesner says, noting that industry is on the front lines of large-scale production of nanomaterials, so knowing about their processes and problems is important. "We want to understand where industry is headed while informing them about the results of our research so that they can better manage any potential environmental or human health liabilities that might come down the line," he says. To maintain objectivity in the research, CEINT and UC CEIN will not depend on commercial funding, the center directors say.

UC CEIN and CEINT are the latest additions to the research portfolio of the National Nanotechnology Initiative, the consortium of 25 U.S. federal agencies that study and regulate nanotechnology (C&EN, June 23, page 26). "The new centers are aimed at strengthening our nation's commitment to research on the environmental, health, and safety implications of nanomaterials," Arden J. Bement Jr., NSF's director, said in a statement.

George Gray, EPA assistant administrator for research and development, said in a statement, "This comprehensive research model promises to augment the knowledge we need to be good stewards of the environment."

The new centers are not the first to address the effects of nanotechnology in the environment. In 2001, NSF funded the Center for Biological & Environmental Nanotechnology (CBEN) at Rice University, a collaboration that Wiesner cofounded. CBEN was the first institution to look at the potential risks of nanomaterials to human health and the environment. Its mission, to discover and develop nanomaterials that enable new medical and environmental technologies, is broader than the fundamental work proposed by UC CEIN and CEINT. CBEN researchers are working on several products, including nanoshells that are in clinical trials for treating head and neck cancers and a "nanorust" material that will be field-tested soon for cleaning contaminated groundwater. CBEN is funded through 2011.

Kristen Kulinowski, a chemist and CBEN's director of external affairs, is glad to see that studying the potential impacts of nanotechnology on the environment has garnered solid research support. Establishing UC CEIN and CEINT is "great news" because the huge data gaps can't be filled by just existing researchers, she adds.

Alan J. Tessier, project director for the new centers at NSF, says that in the end, the funding agencies decided that the data gaps couldn't even be filled by one additional center, which is why the two new centers were funded. "Looking at this emerging interdisciplinary field overall, it was really hard to cover the full breadth with funding only one of them." He adds that the centers were awarded independently, but they end up complementing each other.

The funding announcement for the new centers came a week after the unveiling of a separate but related international effort to address the environmental, health, and safety (EHS) impacts of nanomaterials. Materials scientists and toxicologists from the U.S., Europe, and Japan put forth funding from their own labs to form the International Alliance for NanoEHS Harmonization (IANH) to develop standard protocols for laboratory tests (C&EN, Sept. 15, page 5).

IANH researchers plan to do round-robin testing—the same experiments on the same materials in different labs—to see whether they get the same results. Then the researchers will try to reach consensus on protocols ranging from sample preparation to cell culturing.

Both Nel and Wiesner belong to IANH. Wiesner says the centers will be developing protocols that go beyond toxicology and into ecosystem-level effects, but some protocols developed at the centers will be given to IANH researchers so they can do round-robin tests.

Aside from testing related to IANH, researchers at the centers have some similar interests that they will explore in different ways. For example, each center plans to start by characterizing biological and physicochemical properties of nanomaterials that are likely to be produced in high volume and used in many different consumer products. Examples include metals such as silver, gold, and iron; metal oxides including TiO₂, Fe_xO_y, SiO₂, CeO₂, and ZnO; and carbon materials such as nanotubes and fullerenes.

EACH CENTER also plans to fabricate nanomaterials for study. The researchers are looking to strike a balance between studying materials of immediate concern, such as silver, and looking at ones that vary in size and functionality. The aim is to build a foundation for predictive science so they can begin to understand materials that have not yet been conceived.

Nel explains that UC CEIN will, for example, take a single material with interesting biological effects or toxicity and make multiple derivatives with different shapes, sizes, and surface characteristics through a controlled, high-throughput synthesis developed at the Molecular Foundry at the Lawrence Berkeley National Laboratory.

UC CEIN researchers will examine the effects of these derivatives on three levels of terrestrial, freshwater, and marine animals, ranging from protozoa to spiny lobsters. Nel adds that such biological testing will help demonstrate which materials are most dangerous. It will also establish qualitative structure-activity relationships that will help build a computer model to predict toxicity in organisms ranging from bacteria to mammals.

At CEINT, researchers will also vary structure and surface characteristics and compare how synthetic and natural nanoscale particles with the same chemical composition may behave differently in the environment, Wiesner explains. Results from bioavailability and toxicity testing in the laboratory will be vital to building a database for calibrating and validating models that relate nanomaterial properties to their environmental effects, he adds.

To see how lab results translate to responses by aquatic and terrestrial ecosystems, CEINT researchers will conduct experiments on varying time scales in 32 new mesocosms—what Wiesner describes as "giant aquarium-terrariums"—to be built in the Duke Forest. Wiesner says the physical plans for the mesocosms are not yet complete, but the idea is to mimic aspects of real ecosystems to see whether, for example, plants take up nanoparticles or whether soil bacteria mineralize them. He notes that the mesocosms will allow his team to do mass balances while avoiding the release of synthetic nanoparticles into the environment at large. The mesocosms will contain organisms ranging from bacteria to plants and from invertebrates to fish.

In terms of risk assessment, CEINT will build on traditional environmental risk analysis—for example, modeling interactions among nanoparticles, soil, water, vegetation, and simple organisms. The computer model of predictive toxicology that UC CEIN is developing, however, is based on previous work Nel did to forecast cell injury in animals from particles in air pollution.

Nel explains that his previous model is based on characteristics such as particle source, size, and chemical composition. The model can determine whether the particles will cause oxidative stress or injury to cells and tissues via oxygen radicals in, for example, a mouse that is exposed to small pollutant particles near an urban freeway. "I propose the same type of predictive model should be possible for screening engineered nanomaterials in bacteria, plants, animals, and other organisms in the environment," he says.

To advance predictive toxicology and the study of environmental implications of nanotechnology, each center hopes to attract scientists-in-training, from undergraduate interns through postdoctoral fellows, who will learn how to anticipate and mitigate potential environmental risk. Researchers at the centers plan to disseminate information about the work to the public through NSF partners such as the Center for Nanotechnology in Society at Arizona State University.

ALTHOUGH the two centers were not created solely to address the public's misunderstanding of risk associated with nanomaterials, the public's comprehension is critical to acceptance of new technology, says Günter Oberdörster, a professor of environmental medicine at the University of Rochester who studies respiratory effects of nanoparticles in humans. "Most people mix up hazard and risk," he says. Hazard is a danger, such as a shark in the ocean, he explains. But risk requires both hazard and exposure. Sharks aren't a risk to people on land, but they are a risk to people swimming in the ocean. Following that line of reasoning, high doses of nanoparticles may cause oxidative stress in cells in a dish, but those particles will not harm humans who are not exposed to them, he says.

As scientists in the new centers continue to learn about hazard and strive to predict risk, advances in nanotechnology surge onward. Getting a handle now on how simple particles could affect human and environmental health is important because more complex particles, from composite materials to "smart" particles with multiple functions, are already in development, says Andrew D. Maynard, chief science adviser for the Project on Emerging Nanotechnologies at the Woodrow Wilson International Center for Scholars.