Risk Assessment could Benefit from Nanoparticle Categorization Framework

On some days you see articles in the media that slam certain nanomaterials, and nanotechnology in general, as inherently risky because of a new scientific paper that reports alarming levels of toxicity of a particular nanoparticle. On other days you find research papers that report no apparent risk whatsoever with the same nanomaterials. This has become quite a familiar pattern for regular readers of nanoscience and nanotechnology literature. The cosmetics industry, for instance, claims its products and the nanoparticles in them are perfectly safe; environmental groups contend that nanomaterials are inherently risky and that rigorous testing is needed before large-scale commercialization of nano-products can happen; some even call for a complete moratorium on nanoma-terial production. The result is a situation that is confusing not only for lay people but also for industry, researchers, and the journalists who cover the field.

The fact is that every new technology is inherently risky. Plenty of people are being injured or killed every year by electricity, cars, or chemicals, just to name a few. In order to reap the benefits of a new technology and make it acceptable to society there has to be a general perception that the risks are fully understood, can be managed, and it is clear who is responsible for what. All of that is currently missing in nanotechnology. Although the speed and scope of nano-technology risk research, and the emerging field of nanotoxicology, is picking up, a lot of this work is stand-alone research that is not being coordinated within a larger framework.

As an emerging science, nanotoxicology is expanding the boundaries of traditional toxicology from a testing and auxiliary science to a new discipline where toxicological knowledge of nanomaterials can be put to constructive use in therapeutics as well as the development of new and better biocompatible materials. Until now, though, no one has been able to pinpoint which properties determine or influence the inherent hazards of nanoparticles.

A group of Danish scientists proposes a categorization framework that enables scientists and regulators to systematically identify the various categories of nanomaterials.

''We believe that, in order to reap the many benefits offered by nano-technology, it is necessary that environmental and human health risks are considered at an early stage in product development," says Steffen Foss Hansen. ''However, before this can be done, there is a need for clarification of terminology. The current literature addressing the potential hazards of nano-materials shows a strong tendency to use the terms 'nanotechnology' and 'nanomaterials' as synonyms for 'nanoparticles'. The hazards related to nanotechnology/nanomaterials have so far predominantly been documented for specific nanoparticles, mainly titanium dioxide and carbon-based nano-particles. However, the physical, chemical, and biological properties of various nanomaterials differ quite substantially from those of specific nanoparticles, as do the expected routes of exposure, making it necessary to differentiate nanomaterials in order to identify the potential hazards and risks they pose.''

Hansen, a researcher in the Department of Environmental Engineering at Technical University of Denmark (DTU), together with colleagues, has developed a framework that can be applied to a proposed hazard identification approach and is aimed at identifying causality between inherent physical and chemical properties and observed adverse effects reported in the literature.

The DTU scientists tested the workability of their proposed procedure using nanoparticles as an illustrative case study. ''We generated a database noting the reported inherent physical and chemical properties of the nanoparticles tested and the main effects observed,'' Hansen explains. ''428 studies were noted in the database, reporting on a total of 965 nanoparticles. We found that, although a limited number of studies have been reported on ecotoxicity, more than 120 have been reported on mammalian toxicity and 270 on cytotoxicity. In general there was a lack of characterization of the nanoparticles studied and it was not possible to link specific properties of nanoparticles to the observed effects. Our study shows that future research strategies must have a strong focus on characterization of the nanoparticles tested.''

Hansen and his colleagues suggest that nanomaterials should be categorized depending on the location of the nanoscale structure in the system. This leads to a division of nanomaterials into three main categories, which then can be further divided into subcategories: (1) materials that are nanostructured in the bulk; (2) materials that have nanostructure on the surface; and (3) materials that contain nanostructured particles.

Hansen points out that it is possible for a system to consist of nanostructured elements belonging to different categories in this framework. He gives the example of catalysts used to remove nitrogen oxide from car exhaust: ''The chemical reaction that removes nitrogen oxide is catalyzed by platinum and ruthenium nanoparticles 2-3 nm in size. These nanoparticles are bound to the surface of a support material. At the same time, the support material is a nanoporous material consisting mostly of G-Al2O3 (70-85%) and other oxides such as cerium oxide or lanthanum oxide. A similar analysis would apply to fuel cells, for example.''

A major benefit of the proposed categorization framework is that it provides a tool for dividing nanosystems into identifiable parts and thereby facilitates evaluations of relevant exposure routes or analysis of effect.

Other aspects that need to be considered in assessing the toxicity of nano-materials are their physical and chemical properties. Today, which properties determine or influence the inherent hazards of nanoparticles is still an open question.

''After an initial literature review, and considering the information needed in order to describe a nanomaterial from a physical and chemical perspective when estimating the hazard of nanomaterials, we propose the following nine properties as being important,'' says Hansen: ''(1) chemical composition, (2) size, (3) shape, (4) crystal structure, (5) surface area, (6) surface chemistry, (7) surface charge, (8) solubility, and (9) adhesion, defined as the force by which the nanoparticle and its components are held together.''

The Danish researchers then went ahead and combined their categorization framework with this list of properties to construct a hazard identification scheme.

''Clearly, not all the properties apply to all the different categories," says Hansen. ''We distinguish three cases: (1) the property is relevant in determining the hazard; (2) the property does not apply to the category; and (3) the property can be determined, but it is not relevant in order to determine the hazard of the nanomaterial of that category, because it is unlikely that the surface charge of nanoparticles suspended in a solid plays any role in the overall toxicity given the limited exposure potential.''

Having constructed their model, the researchers then went on to test its workability by reviewing the literature on the potential hazards of nanoma-terials belonging to two of the proposed categories: nanoparticles suspended in liquids and airborne nanoparticles. Altogether, they identified 428 relevant studies which, in total, reported the observed adverse effects of 965 tested nanoparticles of various compositions. Hansen and his colleagues then analyzed each of the 428 studies in order to identify which inherent physical and chemical properties were reported and the main effects observed. Then they filled the information into their hazard identification scheme.

''In general, there is a lack of characterization of the nanoparticles tested in the identified studies and this hampers the potential for identifying causality between observed hazards and specific physical and chemical properties,'' explains Hansen. ''Furthermore, it is evident from our work that the information provided is all over the map, making it impossible to analyze the studies systematically for properties of the nanoparticles that are important for the observed effects.''

Although the lack of characterization is troublesome, it is hardly surprising, as nanotoxicology is a very new field. Hansen points out that a true understanding of the hazardous properties that materials begin to exhibit at the nanoscale requires a level of interdisciplinary research that has not yet been achieved.

''In order to conduct and interpret scientific studies on the hazardous properties of nanomaterials that are relevant for future risk assessment of nanotechnology-based compounds and products, we need strong interdisciplinary collaborations between (eco)toxicologists, and nanoscientists such as physicists, chemists, and material engineers.''

Featured scientist: Steffen Foss Hansen

Organization: DTU Environment, Technical University of Denmark,

Lyngby (Denmark) Relevant publication: Steffen Foss Hansen, Britt H. Larsen, Stig I. Olsen, Anders Baun: Categorization framework to aid hazard identification of nanomaterials, Nanotoxicology, 1, 243-250.

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