The potential risks of nanomaterials: a review carried out for ECETOC

Particle and Fibre Toxicology The potential risks of nanomaterials: a review carried out for ECETOC Paul JA Borm 3 David Robbins 1 Stephan Haubold 0 Thomas Kuhlbusch 7 Heinz Fissan 7 Ken Donaldson 6 Roel Schins 5 Vicki Stone 4 Wolfgang Kreyling 9 Jurgen Lademann 8 Jean Krutmann 5 David Warheit 2 Eva Oberdorster 10 0 Nanogate Coating Systems , Saarbrucken , Germany 1 Cenamps , Newcastle upon Tyne , UK 2 Haskell Labs, Dupont de Nemours , Wilmington , USA 3 Centre of Expertise in Life Sciences, Zuyd University , Heerlen , The Netherlands 4 Dept of Biological Sciences, Napier University , Edinburgh, Scotland , UK 5 IUF at the University of Dusseldorf , Dusseldorf , Germany 6 ELEGI, University of Edinburgh , Edinburgh, Scotland , UK 7 IUTA , Duisburg , Germany 8 Dermatology Clinic , Charite, Berlin , Germany 9 GSF-Research Centre for Environment & Health, Institute of Inhalation Biology , Neuherberg , Germany 10 Department of Biology, Southern Methodist University , Dallas , USA During the last few years, research on toxicologically relevant properties of engineered nanoparticles has increased tremendously. A number of international research projects and additional activities are ongoing in the EU and the US, nourishing the expectation that more relevant technical and toxicological data will be published. Their widespread use allows for potential exposure to engineered nanoparticles during the whole lifecycle of a variety of products. When looking at possible exposure routes for manufactured Nanoparticles, inhalation, dermal and oral exposure are the most obvious, depending on the type of product in which Nanoparticles are used. This review shows that (1) Nanoparticles can deposit in the respiratory tract after inhalation. For a number of nanoparticles, oxidative stress-related inflammatory reactions have been observed. Tumour-related effects have only been observed in rats, and might be related to overload conditions. There are also a few reports that indicate uptake of nanoparticles in the brain via the olfactory epithelium. Nanoparticle translocation into the systemic circulation may occur after inhalation but conflicting evidence is present on the extent of translocation. These findings urge the need for additional studies to further elucidate these findings and to characterize the physiological impact. (2) There is currently little evidence from skin penetration studies that dermal applications of metal oxide nanoparticles used in sunscreens lead to systemic exposure. However, the question has been raised whether the usual testing with healthy, intact skin will be sufficient. (3) Uptake of nanoparticles in the gastrointestinal tract after oral uptake is a known phenomenon, of which use is intentionally made in the design of food and pharmacological components. Finally, this review indicates that only few specific nanoparticles have been investigated in a limited number of test systems and extrapolation of this data to other materials is not possible. Air pollution studies have generated indirect evidence for the role of combustion derived nanoparticles (CDNP) in driving adverse health effects in susceptible groups. Experimental studies with some bulk nanoparticles (carbon black, titanium dioxide, iron oxides) that have been used for decades suggest various adverse effects. However, engineered nanomaterials with new chemical and physical properties are being produced constantly and the toxicity of these is unknown. Therefore, despite - the existing database on nanoparticles, no blanket statements about human toxicity can be given at this time. In addition, limited ecotoxicological data for nanomaterials precludes a systematic assessment of the impact of Nanoparticles on ecosystems. 1) Background 1.1 Definitions Nanotechnology is considered by many as the next logical step in science, integrating engineering with biology, chemistry and physics [1]. It derives from the ongoing trend for miniaturisation in technology as described by Moore's Law and combination with other disciplines. Miniaturisation however has its limits and new approaches in manufacturing (bottom-up fabrication) have to be developed to reach anticipated milestones. Nanotechnology can be considered as the application of science that "steps across the limit" of miniaturisation, where" new rules" become valid [2] More specifically, when the dimensions of a piece of solid material become very small, its physical and chemical properties can become very different from those of the same material in larger bulk form. This is one of the hallmarks of Nanotechnology, which can be described as a research area in which this limit of new properties is reached and strategies are developed to exploit the regime of size-controlled properties. In the last couple of years, the term Nanotechnology has been inflated and has almost become synonymous for things that are innovative and highly promising. On the other hand it is also the subject of co (...truncated)