The regulation of engineered nanoparticles requires a widely agreed definition of such particles. Nanoparticles are routinely defined as particles with sizes between about 1 and 100 nm that show properties that are not found in bulk samples of the same material. Here we argue that evidence for novel size-dependent properties alone, rather than particle size, should be the primary criterion in any definition of nanoparticles when making decisions about their regulation for environmental, health and safety reasons. We review the size-dependent properties of a variety of inorganic nanoparticles and find that particles larger than about 30 nm do not in general show properties that would require regulatory scrutiny beyond that required for their bulk counterparts.
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Académie des Sciences, Académie des Technologies. Nanosciences - Nanotechnologies. Science and Technology Report No. 18 (French Academy of Sciences, 2004); summary of recommendations (in English) available at <http://www.tinyurl.com/nqwdda>.
The Royal Society and The Royal Academy of Engineering. Nanoscience and Nanotechnology: Opportunities and Uncertainties (The Royal Society, 2004); available at <http://www.nanotec.org.uk>.
Hansen, S. F., Larsen, B. H., Olsen, S. I. & Baun, A. Categorization framework to aid hazard identification of nanomaterials. Nanotoxicology 1, 243–250 (2007).
Nanoscale Science Engineering and Technology Subcommittee. The National Nanotechnology Initiative: Strategic Plan (US National Science and Technology Council, 2004); available at <http://www.nano.gov/NNI_Strategic_Plan_2004.pdf>.
Donaldson, K., Stone, V., Tran, C. L., Kreyling, W. & Born, P. J. A. Nanotoxicology. Occup. Environ. Med. 61, 727–728 (2004).
Oberdörster, G., Oberdörster, E. & Oberdörster, J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect. 113, 823–839 (2005).
Auffan, M. et al. CeO2 nanoparticles induce DNA damage towards human dermal fibroblasts in vitro. Nanotoxicology 3, 161–171 (2009).
Carlson, C. et al. Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species. J. Phys. Chem. B 112, 13608–13619 (2008).
Xia, T. et al. Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Lett. 6, 1794–1807 (2006).
Murdock, R. C., Braydich-Stolle, L., Schrand, A. M., Schlager, J. J. & Hussain, S. M. Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique. Toxicol. Sci. 101, 239–253 (2008).
Billinge, S. J. L. & Levin, I. The problem with determining atomic structure at the nanoscale. Science 316, 561–565 (2007).
Bottero, J. Y., Rose, J. & Wiesner, M. R. Nanotechnologies: tools for sustainability in a new wave of water treatment processes. Integr. Environ. Assess. Manag. 2, 391–395 (2006).
Emerich, D. F. & Thanos, C. G. The pinpoint promise of nanoparticle-based drug delivery and molecular diagnosis. Biomol. Eng. 23, 171–184 (2006).
Gupta, A. K. & Gupta, M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 26, 3995–4021 (2005).
Pereira de Abreu, D. A., Paseiro Losada, P., Angulo, I. & Cruz, J. M. Development of new polyolefin films with nanoclays for application in food packaging. Eur. Polym. J. 43, 2229–2243 (2007).
Zhang, W. Nanoscale iron particles for environmental remediation: an overview. J. Nanopart. Res. 5, 323–332 (2003).
Sahoo, S. K. & Labhasetwar, V. Nanotech approaches to drug delivery and imaging. Drug Discov. Today 8, 1112–1120 (2003).
Kim, C. K. et al. Entrapment of hydrophobic drugs in nanoparticle monolayers with efficient release into cancer cells. J. Am. Chem. Soc. 131, 1360–1361 (2009).
Xia, Y. Nanomaterials at work in biomedical research. Nature Mater. 7, 758–760 (2008).
Nel, A., Xia, T., Madler, L. & Li, N. Toxic potential of materials at the nanolevel. Science 311, 622–627 (2006).
Wiesner, M. R., Lowry, G. V. & Alvarez, P. J. J. Assessing the risks of manufactured nanomaterials. Environ. Sci. Technol. 40, 4336–4345 (2006).
Lanone, S. & Boczkowski, J. Biomedical applications and potential health risks of nanomaterials: molecular mechanisms. Curr. Mol. Med. 6, 651–663 (2006).
Moore, M. N. Do nanoparticles present ecotoxicological risks for the health of the aquatic environment? Environ. Int. 32, 967–976 (2006).
Fortner, J. D. et al. C60 in water: nanocrystal formation and microbial response. Environ. Sci. Technol. 39, 4307–4316 (2005).
Oberdörster, E. Manufactured nanomaterials (fullerene, C60) induce oxidative stress in the brain of juvenile largemouth bass. Environ. Health Perspect. 112, 1058–1062 (2004).
Auffan, M. et al. Relation between the redox state of iron-based nanoparticles and their cytotoxicity towards Escherichia Coli. Environ. Sci. Technol. 42, 6730–6735 (2008).
Auffan, M. et al. In vitro interactions between DMSA-coated maghemite nanoparticles and human fibroblasts: a physicochemical and cyto-genotoxical study. Environ. Sci. Technol. 40, 4367–4373 (2006).
Thill, A. et al. Cytotoxicity of CeO2 nanoparticles for Escherichia coli. Physico-chemical insight of the cytotoxicity mechanism. Environ. Sci. Technol. 40, 6151–6156 (2006).
Scheufele, D. A., Corley, E. A., Shih, T.-J., Dalrymple, K. E. & Ho, S. S. Religious beliefs and public attitudes toward nanotechnology in Europe and the United States. Nature Nanotech. 4, 91–94 (2009).
Lin, K.-F., Cheng, H.-M., Hsu, H.-C., Lin, L.-J. & Hsieh, W.-F. Band gap variation of size-controlled ZnO quantum dots synthesized by sol–gel method. Chem. Phys. Lett. 409, 208–211 (2005).
Moreels, I. et al. Composition and size-dependent extinction coefficient of colloidal PbSe quantum dots. Chem. Mater. 19, 6101–6106 (2007).
Norris, D. J. & Bawendi, M. G. Measurement and assignment of the size-dependent optical spectrum in CdSe quantum dots. Phys. Rev. B 53, 16338–16346 (1996).
Wang, Y. & Herron, N. Quantum size effects on the exciton energy of CdS clusters. Phys. Rev. B 42, 7253–7255 (1990).
Lai, S. L., Guo, J. Y., Petrova, V., Ramanath, G. & Allen, L. H. Size-dependent melting properties of small tin particles: nanocalorimetric measurements. Phys. Rev. Lett. 77, 99–102 (1996).
Tang, Z. X., Sorensen, C. M., Klabunde, K. J. & Hadjipanayis, G. C. Size-dependent Curie temperature in nanoscale MnFe2O4 particles. Phys. Rev. Lett. 67, 3602–3605 (1991).
Jolivet, J. P. et al. Size tailoring of oxide nanoparticles by precipitation in aqueous medium. A semi-quantitative modelling. J. Mater. Chem. 14, 3281–3288 (2004).
Lamber, R., Wetjen, S. & Jaeger, N. I. Size dependence of the lattice parameter of small palladium particles. Phys. Rev. B 51, 10968–10971 (1995).
Ayyub, P., Palkar, V. R., Chattopadhyay, S. & Multani, M. Effect of crystal size reduction on lattice symmetry and cooperative properties. Phys. Rev. B 51, 6135–6138 (1995).
Banfield, J. F. & Navrotsky, A. (eds) Nanoparticles and the Environment (Mineralogical Society of America, 2001).
Brice-Profeta, S. et al. Magnetic order in γFe2O3 nanoparticles: a XMCD study. J. Magn. Magn. Mater. 288, 354–365 (2005).
Baudrin, E. et al. Structural evolution during the reaction of Li with nano-sized rutile type TiO2 at room temperature. Electrochem. Commun. 9, 337–342 (2007).
Hwang, Y.-N., Park, S.-H. & Kim, D. Size-dependent surface phonon mode of CdSe quantum dots. Phys. Rev. B 59, 7285–7288 (1999).
Alivisatos, A. P. Semiconductor clusters, nanocrystals and quantum dots. Science 271, 933–937 (1996).
Kelly, K. L., Coronado, E., Zhao, L. L. & Schatz, G. C. The optical properties of metal nanoparticles: The influence of size, shape and dielectric environment. J. Phys. Chem. B 107, 668–677 (2003).
Pottier, A. S. et al. Size tailoring of TiO2 anatase nanoparticles in aqueous medium and synthesis of nanocomposites. Characterization by Raman spectroscopy. J. Mater. Chem. 13, 877–882 (2003).
Chernyshev, A. P. Effect of nanoparticle size on the onset temperature of surface melting. Mater. Lett. 63, 1525–1527 (2009).
Zhang, M. et al. Size-dependent melting point depression of nanostructures: Nanocalorimetric measurements. Phys. Rev. B 62, 10548–10557 (2000).
Sun, J. & Simon, S. L. The melting behavior of aluminium nanoparticles. Thermochim. Acta 463, 32–40 (2007).
Dormann, J. L., Fiorani, D. & Tronc, E. Magnetic relaxation in fine-particle systems. Adv. Chem. Phys. 98, 283–494 (1997).
Gangopadhyay, S. et al. Magnetic properties of ultrafine iron particles. Phys. Rev. B 45, 9778–9787 (1992).
Pastor, G. M., Dorantesdavila, J. & Bennemann, K. H. Size and structural dependence of the magnetic properties of small 3d-transition-metal clusters. Phys. Rev. B 40, 7642–7654 (1989).
Chen, Q. & Zhang, Z. J. Size-dependent superparamagnetic properties of MgFe2O4 spinel ferrite nanocrystallites. Appl. Phys. Lett. 73, 3156–3158 (1998).
Selbach, S. M., Tybell, T., Einarsrud, M. A. & Grande, T. Size-dependent properties of multiferroic BiFeO3 manoparticles. Chem. Mater. 19, 6478–6484 (2007).
Shetty, S., Palkar, V. R. & Pinto, R. Size effect study in magnetoelectric BiFeO3 system. Pramana 58, 1027–1030 (2002).
Chattopadhyay, S., Ayyub, P., Palkar, V. R. & Multani, M. Size-induced diffuse phase transition in the nanocrystalline ferroelectric PbTiO3 . Phys. Rev. B 52, 13177–13183 (1995).
Shih, W. Y., Shih, W.-H. & Aksay, I. A. Size dependence of the ferroelectric transition of small BaTiO3 particles: effect of depolarization. Phys. Rev. B 50, 15575–15585 (1994).
Rusanov, A. I. Surface thermodynamics revisited. Surf. Sci. Rep. 58, 111–239 (2005).
Borm, P. et al. Research strategies for safety evaluation of nanomaterials, Part V: role of dissolution in biological fate and effects of nanoscale particles. Toxicol. Sci. 90, 23–32 (2006).
Fan, C., Chen, J., Chen, Y., Ji, J. & Teng, H. H. Relationship between solubility and solubility product: the roles of crystal sizes and crystallographic directions. Geochim. Cosmochim. Acta 70, 3820–3829 (2006).
Talapin, D. V., Rogach, A. L., Haase, M. & Weller, H. Evolution of an ensemble of nanoparticles in a colloidal solution: theoretical study. J. Phys. Chem. B 105, 12278–12285 (2001).
Rogach, A. L. et al. Organization of matter on different size scales: monodisperse nanocrystals and their superstructures. Adv. Funct. Mater. 12, 653–664 (2002).
McHale, J. M., Auroux, A., Perrotta, A. J. & Navrotsky, A. Surface energies and thermodynamic phase stability in nanocrystalline aluminas. Science 277, 788–791 (1997).
Zhang, H. & Banfield, J. F. Understanding polymorphic phase transformation behavior during growth of nanocrystalline aggregates: insights from TiO2 . J. Phys. Chem. B 104, 3481–3487 (2000).
Ranade, M. R. et al. Energetics of nanocrystalline TiO2 . Proc. Natl Acad. Sci. USA 99, 6476–6481 (2002).
Gratton, S. E. et al. The effect of particle design on cellular internalization pathways. Proc. Natl Acad. Sci. USA 105, 11613–11618 (2008).
Jiang, W., Kim, B. Y. S., Rutka, J. T. & Chan, W. C. W. Nanoparticle-mediated cellular response is size-dependent. Nature Nanotech. 3, 145–150 (2008).
Tao, F. et al. Reaction-driven restructuring of Rh–Pd and Pt–Pd core-shell nanoparticles. Science 322, 932–934 (2008).
Auffan, M. et al. Enhanced adsorption of arsenic onto nano-maghemites: As(III) as a probe of the surface structure and heterogeneity. Langmuir 24, 3215–3222 (2008).
Hoyer, P. & Weller, H. Size-dependent redox potentials of quantized zinc oxide measured with an optically transparent thin layer electrode. Chem. Phys. Lett. 221, 379–384 (1994).
Yokoyama, A., Komiyama, H., Inoue, H., Masumoto, T. & Kimura, H. M. Hydrogenation of carbon monoxide by amorphous ribbons. J. Catalys. 68, 355–361 (1981).
Liu, Y., Choi, H., Dionysiou, D. & Lowry, G. V. Trichloroethene hydrodechlorination in water by highly disordered monometallic nanoiron. Chem. Mater. 17, 5315–5322 (2005).
Nurmi, J. T. et al. Characterization and properties of metallic iron nanoparticles: spectroscopy, electrochemistry and kinetics. Environ. Sci. Technol. 39, 1221–1230 (2005).
Liu, Y., Majetich, S. A., Tilton, R. D., Sholl, D. S. & Lowry, G. V. TCE dechlorination rates, pathways, and efficiency of nanoscale iron particles with different properties. Environ. Sci. Technol. 39, 1338–1345 (2005).
Jolivet, J. P. & Barron, A. R. in Environmental Nanotechnology — Applications and Impacts of Nano-materials (eds Wiesner, M. R. & Bottero, J. Y.) 29–103 (McGraw Hill, 2007).
Banus, E. D., Milt, V. G., Miro, E. E. & Ulla, M. A. Structured catalyst for the catalytic combustion of soot: Co, Ba, K/ZrO2 supported on Al2O3 foam. Appl. Catalys. A 362, 129–138 (2009).
Martinez, A., Prieto, G. & Rollan, J. Nanofibrous γ-Al2O3 as support for Co-based Fischer-Tropsch catalysts: Pondering the relevance of diffusional and dispersion effects on catalytic performance. J. Catalys. 263, 292–305 (2009).
Euzen, P. et al. in Handbook of Porous Materials (eds Schuth, F., Sing, K. S. W. & Weitkamp, J.) 1591–1677 (Wiley-VCH, 2002).
Maira, A. J., Yeung, K. L., Lee, C. Y., Yue, P. L. & Chan, C. K. Size effects in gas-phase photo-oxidation of trichloroethylene using nanometer-sized TiO2 catalysts. J. Catalys. 192, 185–196 (2000).
Wang, C. C., Zhang, Z. & Ying, J. Y. Photocatalytic decomposition of halogenated organics over nanocrystalline titania. Nanostruct. Mater. 9, 583–586 (1997).
Almquist, C. B. & Biswas, P. Role of synthesis method and particle size of nanostructured TiO2 on its photoactivity. J. Catalys. 212, 145–156 (2002).
Santra, A. K. & Goodman, D. W. Oxide-supported metal clusters: models for heterogeneous catalysts. J. Phys. Condens. Matter 15, R31–R62 (2003).
Daniel, M. C. & Astruc, D. Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties and applications toward biology, catalysis and nanotechnology. Chem. Rev. 104, 293–346 (2004).
Haruta, M. Size- and support-dependency in the catalysis of gold. Catalys. Today 36, 153–166 (1997).
Sau, T. K., Pal, A. & Pal, T. Size regime dependent catalysis by gold nanoparticles for the reduction of eosin. J. Phys. Chem. B 105, 9266–9272 (2001).
Cortie, M. B. & Van der Lingen, E. Catalytic gold nanoparticles. Mater. Forum 26, 1–14 (2002).
Turner, M. et al. Selective oxidation with dioxygen by gold nanoparticle catalysts derived from 55-atom clusters. Nature 454, 981–983 (2008).
Miller, J. T. et al. The effect of gold particle size on Au–Au bond length and reactivity toward oxygen in supported catalysts. J. Catalys. 240, 222–234 (2006).
Madden, A. S., Hochella, M. F. & Luxton, T. P. Insights for size-dependent reactivity of hematite nanomineral surfaces through Cu2 sorption. Geochim. Cosmochim. Acta 70, 4095–4104 (2006).
Villiéras, F. et al. Surface heterogeneity of minerals. C. R. Geosci. 334, 597–609 (2002).
Yean, S. et al. Effect of magnetic particle size on adsorption and desorption of arsenite and arsenate. J. Mater. Res. 20, 3255–3264 (2005).
Stumm, W. & Morgan, J. J. Aquatic Chemistry: An Introduction Emphasizing Chemical Equilibria in Natural Waters 2nd edn (Wiley-Interscience, 1981).
Sigg, L., Behra, P. & Stumm, G. N. Chimie des Milieux Aquatiques, Chimie des Eaux Naturelles et des Interfaces dans l'Environnement (Dunod, 2000).
Navrotsky, A., Mazeina, L. & Majzlan, J. Size-driven structural and thermodynamic complexity in iron oxides. Science 319, 1635–1638 (2008).
Jolivet, J. P. & Tronc, E. Interfacial electron transfer in colloidal spinel iron oxide. Conversion of Fe3O4-γ-Fe2O3 particles in aqueous medium. J. Colloid Interface Sci. 125, 688–701 (1988).
Gurr, J.-R., Wang, A. S. S., Chen, C.-H. & Jan, K.-Y. Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicology 213, 66–73 (2005).
Warheit, D. B., Webb, T. R., Sayes, C. M., Colvin, V. L. & Reed, K. L. Pulmonary instillation studies with nanoscale TiO2 rods and dots in rats: Toxicity is not dependent upon particle size and surface area. Toxicol. Sci. 91, 227–236 (2006).
Hirakawa, K., Mori, M., Yoshida, M., Oikawa, S. & Kawanishi, S. Photo-irradiated titanium dioxide catalyzes site specific DNA damage via generation of hydrogen peroxide. Free Radic. Res. 38, 439–447 (2004).
Sato, T. & Taya, M. Enhancement of phage inactivation using photocatalytic titanium dioxide particles with different crystalline structures. Biochem. Eng. J. 28, 303–308 (2006).
Jang, H. D., Kim, S.-K. & Kim, S.-J. Effect of particle size and phase composition of titanium dioxide nanoparticles on the photocatalytic properties. J. Nanopart. Res. 3, 141–147 (2001).
Braydich-Stolle, L. et al. Crystal structure mediates mode of cell death in TiO2 nanotoxicity. J. Nanopart. Res. 11, 1361–1374 (2009).
Auffan, M., Rose, J., Wiesner, M. R. & Bottero, J. Y. Chemical stability of metallic nanoparticles: a parameter controlling their potential toxicity in vitro. Environ. Pollut. 157, 1127–1133 (2009).
Brunner, T. J. et al. In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility. Environ. Sci. Technol. 40, 4374–4381 (2006).
Pourbaix, M. Atlas of Electrochemical Equilibria in Aqueous Solutions (US National Association of Corrosion Engineers, 1974).
Franklin, N. M. et al. Comparative toxicity of nanoparticulate ZnO, bulk ZnO, and ZnCl2 to a freshwater microalga (Pseudokirchneriella subcapitata): the importance of particle solubility. Environ. Sci. Technol. 41, 8484–8490 (2007).
Derfus, A. M., Chan, W. C. W. & Bhatia, S. N. Probing the cytotoxicity of semiconductor quantum dots. Nano Lett. 4, 11–18 (2004).
Morones, J. R. et al. The bactericidal effect of silver nanoparticles. Nanotechnology 16, 2346–2353 (2005).
Wang, S. et al. Challenge in understanding size and shape dependent toxicity of gold nanomaterials in human skin keratinocytes. Chem. Phys. Lett. 463, 145–149 (2008).
Park, E. J., Choi, J., Park, Y. K. & Park, K. Oxidative stress induced by cerium oxide nanoparticles in cultured BEAS-2B cells. Toxicology 245, 90–100 (2008).
This material is based on work supported by the US National Science Foundation (NSF) and Environmental Protection Agency (EPA) under an NSF Cooperative Agreement (EF-0830093, Center for Environmental Implications of NanoTechnology). The French Atomic Energy Commission (CEA) and National Center for Scientific Research (CNRS) are acknowledged for their support and funding of the international Consortium for the Environmental Implications of Nanotechnology. This work has also been funded by the French National Program ANR and ACI-FNS ECCO supported by the French National Institute for Earth Sciences and Astronomy.
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Auffan, M., Rose, J., Bottero, JY. et al. Towards a definition of inorganic nanoparticles from an environmental, health and safety perspective. Nature Nanotech 4, 634–641 (2009). https://doi.org/10.1038/nnano.2009.242
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