IRB members soon will see — if they haven’t already — protocols involving medical therapies with materials that are so tiny that a human hair is 80,000 times their width.
“There are lots of studies now where people are exposed to nanomaterials,” says David B. Resnik, JD, PhD, bioethicist and IRB chair at the National Institute of Environmental Health Sciences (NIEHS) — part of the National Institutes of Health (NIH) — in Research Triangle Park, NC.
Nanotechnology involves designing materials that are 100 millionths of a millimeter, called 100 nanometres. Nanomaterials have been used in drug delivery, diagnostics, and regenerative medicine. (For more information, visit: http://bit.ly/2VbYDDR.)
Resnik recently authored a paper addressing ways in which engineered nanomaterials should be regulated. He concluded that existing legal frameworks sufficiently minimize and manage risks of engineered nanomaterials.1
Policymakers should regulate nanomaterials through existing laws and support research on risks posed by nanotechnology, he wrote.1
Seven years earlier, more than two dozen researchers in a multidisciplinary, NIH-funded project group addressed the nanomedicine research field and potential for additional oversight. The project group recommended a coordinated approach to federal and institutional oversight of nanomedicine human subjects research. They called for a focus on strengthening existing oversight and avoiding new requirements unless they were found to be necessary.2
So far, nanomaterials research has not set off alarms. “As far as I know, right now, the nanomaterials they are using in research are not very risky,” Resnik says. “It might be, in the future, that there are things that are riskier that we need to be aware of.”
For example, one of the most promising uses of nanomaterials is in drug delivery, he explains.
“There are cancer treatments now that use a nanoshell to deliver chemotherapy, and the shell attaches to the cancer cell and delivers chemo to the cancer cell but doesn’t deliver it to the rest of the body,” Resnik says.
The NIEHS IRB, which Resnik chairs, has reviewed a study that uses inhaled nanosilver to look at lung function.
“They wanted to know how nanosilver would affect the microbiota in the lung, the lung’s bacteria,” he says. “Silver is used as an antibacterial agent, and nanosilver is widely used in wound dressings.”
The research examined the risks of inhaling nanosilver. The IRB wanted to know about prior nanosilver research and studies, Resnik says.
“We also wanted to know something about the manufacturers and their quality control and how they’re making the material,” he adds. “Since people were already using nanosilver, and there were no reports of adverse events coming out of it, we assumed it was relatively safe — especially given the small amount we’d ask people to inhale, and the duration.”
When the IRB reviewed the study, members were unaware of any safety warnings by the FDA, but there still could be risks, he notes.
“Safety issues often take time to emerge; you don’t find out about things until something has been on the market for years,” Resnik says.
A chief risk of nanosilver is that it might interfere with the body’s microbiota, which studies show is important to human health.
“When you use an antibiotic, you cause an imbalance in microbiota, and people can get sick because their flora in their body is out of balance — you kill off the good bacteria you need,” Resnik says.
One of the outcomes being addressed in the nanosilver study was whether the product killed off some of the bacteria in the lungs and interfered with lung function, he adds.
The European Commission also examined safety, health, and environmental effects of nanosilver, concluding that more research data are needed. (More information is available at: http://bit.ly/2GVEKqx.)
When IRBs review nanomedicine protocols, they should assess the risk of introducing nanomaterials into the body, and they should approach this with a degree of skepticism, Resnik says.
“Researchers probably owe IRBs some proof of safety of the materials, based on prior animal studies or laboratory studies,” he adds.
For instance, IRBs might view nanomaterials research in the same way they approach review of a Phase I study that tests a new chemical in a human or a new gene therapy procedure, he suggests.
“You have to do a proper risk assessment before you use this new therapy in humans,” Resnik says.
Some nanotechnology might pose risk to people who work with the material, such as carbon nanotubes, which are nanocarrier systems used in engineering and science. In 2010, the U.S. Department of Health and Human Services (HHS) published a 284-page paper about the occupational health and other risks of carbon nanotubes and carbon nanofibers. The paper described rodent studies that showed adverse lung effects from the nanomaterials, and HHS recommended exposure limits. (For more information, visit: http://bit.ly/2Y2ElcW.)
“They’ve done studies in animals where when they inhale carbon nanotubes, the lung produces an immune response to it, which is not surprising and can interfere with lung function,” Resnik says. “So there are definitely concerns about nanotubes and immune response.”
The risk of inhaled carbon nanotubes has to do with manufacturing the material — not research, he notes.
“The studies we’ve looked at have been in animals, and no one I know of is asking people to inhale carbon nanotubes,” he adds. “So it’s more of a risk for people manufacturing carbon nanotubes, where they can get loose in the environment or in dust.”
When carbon nanotubes are inhaled into the lungs, they act like asbestos, Resnik says.
1. Resnik DB. How should engineered nanomaterials be regulated for public and environmental health? AMA J Ethics. 2019;21(4):E363-369.
2. Fatehi L, Wolf SM, McCullough J, et al. Recommendations for nanomedicine human subjects research oversight: an evolutionary approach for an emerging field. J Law Med Ethics. 2012;40(4):716-750.