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Graphene Toxicity - The Interview
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A Realistic Assessment of Graphene Toxicity:
An Interview with Andrew Maynard


The hot-button issue during the last ten years of nanotechology’s development has been determining how toxic and dangerous nanomaterials are to our health and environment.


As this issue started to gain momentum in both the mainstream media and the research community, the Royal Society in the UK released its landmark piece in 2004 entitled “Nanoscience and Nanotechnologies: Opportunities and Uncertainties”. In this carefully researched piece, there were some pretty basic recommendations. First, more research was needed to determine the toxicity of nanomaterials. But perhaps more importantly, it explained that the dangers of nanomaterials before they were incorporated into a final product mainly put the people who were working with the materials at risk, not the users of the final product. Once the nanomaterials were placed into a material matrix, such as a polymer for a tennis racquet, the risk of exposure to the nanomaterial was highly restricted.


Of course, this really came as no surprise to anyone involved in making products, like the computer you are now using. There are a host of hazardous chemicals used to make your computer that by themselves could be toxic but when added to a final product present no risk to you.


This important distinction between the toxicity and risk of freeborn nanomaterials versus their risks after they have been incorporated into another material has remained oddly absent from both the mainstream media and to an extent the research community, and most definitely from the non-governmental organizations (NGOs) who want to ban all nanotechnology research.


We are now at the point where graphene is getting its fair share of toxicological studies and the ratcheting up of the fear quotient in the stories covering this work is still as high as it’s ever been. 


Last year, researchers at Brown University reported in the journal Proceedings of the National Academy of Sciences that indicated that edges of graphene platelets were capable of cutting, or piercing, human lung tissue. In the research, the Brown team placed the graphene next to lung, skin and immune cells in a petri dish.


In one of the latest pieces of graphene toxicity research, a team at the University of California Riverside developed a method by which to measure the level of exposure to groundwater if there was a sudden spill of graphene oxide (GO) at a manufacturing facility. While the work did not establish the toxicity of GO (other research has established  GO is toxic in the range of 50 to 300 mg/L. To give you some context, arsenic is considered toxic at 0.01 mg/L), the headlines didn’t report that a tool had been found to measure whether GO is getting into our water supplies, but instead reported: “Graphene Not All Good”.


There is always a disconnect between science and the coverage of it since alarmism is always more appealing that circumspection, but is it reaching a critical tipping point in the area of nanomaterials, and, specifically, graphene?


To help us address this question and those that rise up when discussing nanomaterials and toxicity, we have a Q&A with Dr. Andrew Maynard, who is the National Science Foundation’s International Chair of Environmental Health Sciences as well as the Director for the University of Michigan’s Risk Science Center. 


Dr. Maynard has offered his balanced perspective on the risks of nanomaterials on his blog, 2020 Science, which he no longer maintains. Despite the fact that new articles won’t be forthcoming, the blog’s archives still offer us  a rich context to understand the risks and opportunities in nanomaterials.


Recently, Dr. Maynard penned a piece for Slate that offers us a way to understand the risks presented by nanomaterials, and suggests we shouldn’t be overly concerned.


Here is our interview:


Q: In your recent article for Slate, you make the implied distinction between nanomaterials in their free form (before they have been incorporated into a final product) and those same nanomaterials after they have become part of a larger material matrix belonging to the product. This is an important distinction that was made as far back as the Royal Society’s 2004 report “Nanoscience and nanotechnologies: Opportunities and Uncertainties”. Why has the important distinction remained often absent in most discussions on the risk of nanomaterials, especially in the mainstream press? And, is there a way to counteract that omission?


A: To be honest, I’m not entirely sure why poor differentiation between the materials that go into a product, and the potential risks associated with that product, continue to exist, although I can certainly hazard a professional opinion.  


Simplistically, risk researchers, regulators and consumers are used to thinking in terms of molecularly distinct chemicals that can both go into a product and come out of it – leading to questions around risk that are focused on the chemical rather than the product.  If you think of substances from DDT and BPA to formaldehyde and dioxin, it’s the chemical we tend to concentrate on, as these are the precisely describable substances that can potentially cause harm.


When interest began to grow over the intentional use of engineered nanomaterials, these materials were initially treated in the same way – a precisely definable substance that can be put into a product and that can in principle be released from it, and that may be harmful if release and exposure occur.  Unfortunately, materials are more dynamic and less easily defined than molecules, and as a result, this tendency to treat them as molecular entities has led to considerable confusion.  Many engineered nanomaterials – unlike some of the more harmful molecular entities that are in use – are modified by how they are used and what they are combined with: as a result, what is released from a product may have little in common with what went into it from a risk and impact perspective.  


Understanding the potential relevance to risk of this mutability of engineered nanoparticles is much more complex than addressing the precursor nanomaterials that go into products, which is perhaps why it hasn’t received as much attention as those pristine nanomaterials.  Fortunately, research is now beginning to focus more on released materials and exposures.  But there is still a long way to go before uses of nanomaterials are assessed by what comes out of a product, rather than what goes into it.


Q: You reference the some 6000 research papers that have been published about studies into the toxicity of nanomaterials. Do you have any sense of how many of those, or still others, have looked into the toxicity of the products that contain the nanomaterials in their material matrix?


The vast majority of research papers on nanomaterial toxicity have focused on precursor materials, and not materials released from a matrix.  This is appropriate on one level – to understand the hazardous nature of a material, you need to be able to get a handle on how its properties mediate its behavior within a biological system, and developing this level of scientific knowledge means starting with well-defined pristine materials.  Where I think the research community is still struggling though is in designing experiments that offer insight into what happens when these materials are incorporated into a product, and then complex, heterogeneous materials are released from the product into the environment.


We are making progress though.  Research into how engineered nanomaterials interact with biological systems – and how this in turn modulates their behavior – is becoming more sophisticated, especially with progress in areas like high throughput screening.  And an increasing number of exposure studies are characterizing what is released as nanomaterial-based products are used and disposed of.  But researchers still need to close the gap between potential real-world exposures and understanding how these may impact human health or the environment.


Q: Whenever the mainstream press covers these research papers, the stories are without exception told as though the nanomaterial is toxic, sometimes when questions of dosage and exposure seem pretty undetermined. Why is there is this headlong rush to find a boogeyman in nanomaterials by the media when the science is pretty inconclusive in some cases?


Here I think there are multiple factors at play.  Some are driven by a media looking for a story (“material x shown to be boringly safe” doesn’t make a great story), and some are driven by a research community on a quest to find possible risks.  If you go back 15 years to when nanotechnology was being hyped as the next industrial revolution, there was a prevalent narrative that engineered nanomaterials were fundamentally different in nature and behavior to existing materials.  As a result, the default assumption for many toxicology studies was and continues to be that the materials they are researching must have some potential to cause harm in unexpected ways.  In other words, the hype around nanotechnology has led to a working hypothesis that engineered nanoparticles are dangerous until shown otherwise.  Under this hypothesis, every negative result indicates that the researchers just didn’t do enough to find the risk that is assumed to exist.


Of course, most researchers aren’t this naïve, but if you are a toxicology researcher, your aim is often to find evidence of harm, not safety.  This plays right into a media that often equates evidence of hazard – the potential to cause harm – with risk – the probability of harm occurring.  And to be fair, if a press release on a toxicology study emphasizes what could occur, albeit under extreme circumstances, the human-interest narrative in the media is inevitably one of the worst that could happen rather than one of “there’s nothing to see here”.


Because of this, there is a responsibility on the expert community to contextualize research for a public audience in ways that at least takes the edge off the unfettered scare stories.


Q: Despite the media’s willingness to hype the dangers of nanomaterials, some have noted that nanomaterials enjoy a “White Hat” status with the public: All the bad publicity doesn’t seem to concern them. Do you see this reaction as apathy or is the general public more circumspect than they are given credit for?


I think this is more a case of business as usual.  We tend to notice the big issues that grab the attention of the media, but these tend to be the exception rather than the rule – and even then, it’s always surprising to observe the disparity between how many people we often think are riled up by an issue, and how many are even aware of it.  With nanotechnology, surveys that probe public awareness indicate that nanotechnology isn’t particularly higher or lower on people’s attention than many other issues.  On top of this, nanotechnology is a heterogeneous and eclectic collection of technologies and products, meaning that there’s not much for people to focus on – especially regarding risks.  Certainly, it’s easier to get excited about a general trend in engineering and design capabilities such as those that nanotechnology represents, rather than elusive risks which, to many, are little more than a hinted-at ghost in the machine.  And beyond the occasional piece of media hype, I think that members of the general public are smarter and more savvy than is often realized when it comes to assessing what a new technology might mean to them personally. 


Q: Graphene is beginning to get the toxicological scrutiny that other nanomaterials have been experiencing for the last decade. In important research performed last year at Brown University on the toxicity of graphene, one of the researchers even went so far as to say in a press release from the university that “These materials can be inhaled unintentionally, or they may be intentionally injected or implanted as components of new biomedical technologies.” What do you suppose he imagined would be the scenario in which we unintentionally inhaled graphene? Could this happen outside of a manufacturing facility in which graphene was used to make a product?


There’s always a chance that poor exposure control during the production or use of a material like graphene could lead to inhalation.  For instance, if a slurry or suspension of graphene platelets was aerosolized, droplets containing platelets could be inhaled.  Or even if a graphene-based powder was being handled, there’s a chance that large aggregates could become airborne and inhaled – delivering the platelets to the lungs.  Outside manufacturing facilities, it’s much harder to imagine exposure scenarios leading to significant inhalation exposure.  Graphene embedded in a polymer matrix would most likely become irreversibly bound to the polymer for instance.  But it’s possible that ill-conceived uses might lead to small clusters of platelets entering the lungs.


If this could occur – and it’s a worthwhile scenario to consider in helping understand and mitigate potential risks – the resulting harm would depend on a number of factors, including the precise physicochemical nature of the graphene, the amount inhaled and the behavior of the graphene in a complex biological system rather than a cell culture.  The research from Brown University is important in that it helps researchers focus on plausible hypotheses that may be useful in preventing harm and enabling safe uses of graphene.  But there is a long and tortuous path between these studies and understanding the safety or otherwise of graphene-based materials in real world settings.


Q: Is there anything in the research that you have seen thus far that would indicate that graphene is intrinsically any more toxic that any other nanomaterial, like carbon nanotubes?


It’s potentially misleading to compare the toxicity of nanomaterials like graphene and carbon nanotubes, as the mechanisms by which they interact with biological systems appear to be somewhat different.  Certainly, there are mechanisms of interaction associated with some forms of carbon nanotubes that indicate that they can cause harm by virtue of their length and shape – two aspects that differentiate them from graphene platelets.  On this front, I would expect different mechanisms of action and different health outcomes to be associated with the two materials.  There are some indications that graphene platelets could be hazardous – i.e. have the potential to cause harm – under some conditions, but it is not at all clear how serious any resultant risk might be yet – or even whether there is a substantial risk.  One important similarity though – if you can grace it with that term – is that graphene, like carbon nanotubes, cannot be treated as a single entity from a risk perspective.  If biological interactions are mediated by factors like how many graphene sheets make up platelets, the size and physical form of these platelets, whether they are oxidized or functionalized, how aggregated they are, and what else they are attached to, questions around risk and safety will need to be anchored to specific graphene materials, and not graphene more generally.


Q: What is the way forward at this point to ensure that nanomaterials like graphene can provide technological improvements to new products and do so safely for the environment and for our health? 


As with any chemical or material, the rules of safe design and use need to be developed if materials like graphene are to be utilized effectively.  Increasingly, commercial success will depend on innovating responsibly – taking account of the environmental and societal benefits and impacts of a product as well as its technological and economical viability.  This will require relevant research on exposure, hazard and risk.  But it will also depend on bounding that research and how it is applied by considering plausible use and exposure scenarios as well as plausible risks.  One of the greatest challenges to developing and using new materials is that it is impossible to prove a negative – to show through research that something is completely safe.  Because of this, there needs to be reasonable boundaries placed on what is considered safe enough, and what is a reasonable research questions.  Without these, there’s a danger that relatively safe materials will suck up precious research time and funding, while potentially dangerous new materials slip under the radar of scientific scrutiny.

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