Nanomaterial Characterization

THE NUMBER of peer-reviewed papers showing health or environmental effects of engineered nanoscale materials has grown exponentially during the past few years, but their quality in terms of the characterization of starting materials varies dramatically. The situation has left government agencies scrambling to determine which studies are relevant for regulatory purposes.

When it comes to studying the environmental, health, and safety (EHS) aspects of nanomaterials, it is critical for researchers to know what material they are working with, experts say. Formal characterization standards are in the works, but such processes are slow and tend to be ignored by academic researchers. In the interim, a grassroots effort has emerged to fill the gap.

"There is a great need for improved characterization of the nanomaterials used in toxicity studies. Everyone recognizes that the materials used in many of the earlier studies were not adequately characterized, and some of the conclusions should not have been drawn," says E. Clayton Teague, director of the National Nanotechnology Coordination Office, which coordinates federal nanotechnology R&D activities.

Studies with good characterization are important because the stakes of nanotech EHS research are so high. "These are the early-stage research papers that help craft a consensus opinion about the field and ultimately inform policy," says Vicki L. Colvin, a professor of chemistry and chemical engineering and director of the Center for Biological & Environmental Nanotechnology at Rice University.

A paper that makes false conclusions because of poor characterization could damage the entire field, industry experts warn. "If a study were to come out today saying that a certain nanoparticle causes cancer, it would be picked up by the nongovernment organizations or the press," says Shaun F. Clancy, director of product regulatory services at Evonik, a manufacturer of nanomaterials. If it is a bad paper, it would take a lot of time for somebody to refute it, he emphasizes.

To address the lack of physicochemical characterization of nanomaterials used in toxicology studies, a group of more than 40 concerned stakeholders—representing government, industry, and academia—participated in a two-day workshop hosted by the nonprofit Project on Emerging Nanotechnologies (PEN) at the Woodrow Wilson International Center for Scholars, in Washington, D.C., in late October.

The goal of the workshop was to develop a minimal list of recommended characterization parameters for nanotoxicology studies. Shortly after the workshop, the group, which calls itself the Minimum Information for Nanomaterial Characterization Initiative (MINChar Initiative), launched a community website—characterizationmatters.org—that it hopes will attract more supporters to the effort.

The recommended parameters, listed on the group's website, address three major questions: What does the material look like? What is it made of? What factors affect how it interacts with its surroundings? The parameters are intended to serve as guidance to the community and to encourage more robust physicochemical characterization of nanomaterials in toxicology studies.

"This is a grassroots effort by practitioners in the field trying to do something to raise the bar of the science," says Andrew D. Maynard, chief science adviser at PEN. "As the number of publications increases, there is much greater awareness that we need to make sure that the quality of these data are as good as possible." Maynard is one of the lead organizers of the MINChar Initiative and a member of C&EN's editorial advisory board.

THE MINCHAR INITIATIVE comes just months after a similar grassroots effort was launched to develop standard protocols for determining how nanomaterials interact with biological systems (C&EN, Sept. 15, page 5). That effort, called the International Alliance for NanoEHS Harmonization (IANH), focuses on biological characterization. It involves the use of round-robin studies, with scientists around the world performing the same experiments with the same materials to develop more reproducible methods.

In contrast, the MINChar Initiative aims "to make sure that if somebody publishes peer-reviewed data, their physicochemical characterization data sets are as complete as they can be," explains Colvin, who is involved in both the MINChar Initiative and IANH.

Both efforts are international in scope and complement other standard-setting activities, such as those of the International Organization for Standardization (ISO), the Organization for Economic Cooperation & Development, and ASTM International. But formal standards can take years to develop, and the community is asking for something now. "ISO is slow. It would be nice if we could get something out faster," Maynard says.

Even when official standards do get finalized, "most academic and government research scientists are unaware of those activities. The standards really impact trade and industry folks," says Angela R. Hight Walker, a physicist who works on nanotechnology at the National Institute of Standards & Technology (NIST).

EFFORTS TO RAISE the quality of nanomaterial characterization go back several years. In 2004, after a workshop at the University of Florida, researchers from the National Toxicology Program sent a letter to several editors of high-impact journals stressing the need for good characterization in nanotoxicology studies.

Those letters, however, did little to change the situation. "Very clearly, the timing wasn't right. There wasn't that feeling of urgency within the publishing community at the time," Maynard says. The issue bubbled up again at a nanotech meeting held at NIST in 2007. "There was a sense that it might be worth trying to tackle this issue again because it really hadn't been resolved," Maynard notes.

After that NIST meeting, a small group of people brainstormed how they could engage influential nanotoxicology researchers to improve the quality of characterization. The result was the October workshop that led to the MINChar Initiative.

At the October workshop it became clear that academic researchers do not want to be told how to conduct their experiments, Maynard notes. "If anything is going to happen, it's really got to come from the academic community. You can't take a top-down approach and tell academics what to do. They've got to realize that this is important and take action themselves," he emphasizes.

"I don't think we know enough to know what to mandate of people. But in this guidance we are trying to help people understand what is important," adds Clancy, who is also one of the lead organizers of the MINChar Initiative.

The group intends to reach out to journal editors and funding agencies to change the behavior of researchers so that they will be embarrassed to publish papers with poor characterization.

Editors of high-impact journals say that in general the characterization of nanomaterials in toxicology studies is improving, but it still varies considerably. "At a bare minimum, people typically characterize the particle size or size distribution," says Pedro J. J. Alvarez, an associate editor of the interdisciplinary journal Environmental Science & Technology, published by the American Chemical Society, which also publishes C&EN. "What we don't see, and need to see increasingly, is surface composition, particularly the impurities," he notes.

Impurities are important because "a lot of times the main driver of toxicity is not the nanomaterials but impurities like transition metals that accumulate at the surface," Alvarez explains. "We need to raise awareness that nanomaterials are not like typical hazardous materials," he emphasizes. The properties of nanomaterials are system specific. They depend on everything from manufacturing history to storage conditions, he says.

In some cases, however, the impurities may decrease the toxicity of nanomaterials. "People often neglect the role of natural organic matter or other coatings that nanomaterials may acquire in the environment or in the lab that significantly mitigate toxicity," Alvarez notes. His research group in the department of civil and environmental engineering at Rice University has found that low concentrations of natural organic matter dissolved in water can completely eliminate the toxicity of C₆₀ (Environ. Toxicol. Chem. 2008, 27, 1888).

"The bottom line is that the characterization of nanomaterials should be done pretty much at the time of exposure in the medium or in the organism or model cell component being exposed to the material. That is not often done," Alvarez emphasizes.

Stephen J. Klaine, a professor in the department of biological sciences at Clemson University and an editor of the journal Environmental Toxicology & Chemistry, also agrees that better characterization of nanomaterials in toxicology studies is needed. Klaine is one of the organizers of the MINChar Initiative and has proposed to modify ET&C's instructions to authors to include a clear statement of what should be considered in terms of nanomaterial characterization.

Getting funding agencies to require good nanomaterial characterization is a bit more complicated, but Klaine and others predict that eventually, requests for proposals for nanotoxicology research will include some mention of material characterization beyond particle size.

Efforts like the MINChar Initiative could go a long way toward increasing the quality of nanotoxicology research. "The more there is efficient communication among the researchers, the more likely that better characterization will happen. I think it is going to come from a lot of different directions. The more directions it comes from, the more likely it will be to happen," Teague says.

Kristen M. Kulinowski, director of the International Council on Nanotechnology at Rice University, agrees. "All of these allied efforts, each doing something a little bit different, will someday advance the quality of nanotechnology-risk-relevant research and help decision-making at the policy level," she says.

Many people hope that efforts like the MINChar Initiative will speed up the process. "We feel a sense of urgency that better characterization has to be done because we think there are numerous benefits of nanotechnology," says Mark D. Hoover, a senior scientist at the National Institute for Occupational Safety & Health and one of the organizers of the MINChar Initiative. "The asbestos and genetically modified food situations taught us a lot about what can happen if the right things are not done in a timely manner. If we can put the tools in place to create a useful knowledge base for nanomaterials, we will able to develop and implement the hazard evaluations, exposure assessments, and control measures needed to support safe nanotechnology."