The toxicological impact of nanoparticlesTiO2 and ZnO nanoparticlesCarbon-based nanomaterialsAu nanoparticlesCytotoxicity of inhaled nanoparticlesConclusionsAcknowledgmentsReferencesISSN:1748 0132 © Elsevier Ltd 2008FEB-APR 2008 | VOLUME 3 | NUMBER 1-248The toxicological impact of nanoparticlesNanotechnology is a relatively new and vast field. The increased presence of nanomaterials in commercial products such as cosmetics and sunscreens, dental fillings, photovoltaic cells, and water filtration and catalytic systems has resulted in a growing public debate on the toxicological and environmental effects of direct and indirect exposure to these materials. At present, these effects are not completely elucidated.Roberta BraynerInterfaces, Traitements, Organisation et Dynamique des Systèmes (ITODYS), Université Paris Diderot, UMR-CNRS 7086, case 7090, 2 place Jussieu, 75251 Paris Cedex 05, FranceE-mail: [email protected] though nanotechnology is a fairly new field, nanomaterials are not. Au and Ag nanoparticles (NPs) were used in Persia in the 10th century BC to fabricate ceramic glazes to provide a lustrous or iridescent effect. This technique was then brought to Spain, where it was improved by the Moors during the 14th century, before finally spreading throughout much of Europe1. In addition, over 5000 years ago, the Egyptians ingested Au NPs for mental and bodily purification2. In all cases, the users did not know that they were NPs.The study of the toxicity of nanomaterials toxicity on living cells and within the context of environmental air pollution is a very large research field3. Here I show some relevant studies of the toxicological impact of (i) oxide NPs (TiO2 and ZnO), (ii) carbon-based nanomaterials, and (iii) Au NPs on living cells. Finally, at the end of this review, I discuss the toxicity of some kinds of inhaled NPs.TiO2 and ZnO nanoparticlesNowadays, NPs are frequently found commercially as cosmetics and sunscreens (TiO2, Fe3O4, and ZnO), fillers in dental fillings (SiO2), in water filtration and catalytic systems, and in photovoltaic cells (CdS, CdSe, ZnS), etc. Unfortunately, toxicological studies carried out in the last ten years have shown that ultrafine particles (d <100 nm) pose serious problems to the lungs4–6. It has been demonstrated that some NPs cause more inflammation than larger respirable particles made from the same material when delivered at the same mass dose. This behavior has been observed for a range of different materials of generally low toxicity such as carbon black (CB) and TiO27. For example, micronized or ultrafine (20–50 nm) TiO2, a so-called microreflector, (US Federal Register, 43FR38206, 25 August 1978) has been known to be a safe physical sunscreen because it reflects and scatters ultraviolet (UV) B and UVA in sunlight. However, TiO2 absorbs about 70% of incident UV and in aqueous environments this leads to the generation of hydroxyl radicals. The crystalline forms of TiO2, anatase and rutile, are semiconductors with gap energies of about 3.23 and 3.06 eV respectively8. Consequently, light at or below these wavelengths contains enough energy to promote electrons from the valence band (vb) to the conduction band (cb), generating single electrons (e-) and positively charged holes (h+) as carriers (Fig. 1).Electrons and holes often recombine quickly, but they can also migrate to the particle surface, where they react with adsorbed species:The toxicological impact of nanoparticles REVIEWFEB-APR 2008 | VOLUME 3 | NUMBER 1-249(i) electrons react with oxygen and (ii) holes with hydroxyl ions or water to form superoxide and hydroxyl radicals (Fig. 1).According to Dunford et al.8, such photo-oxidations may explain the toxicity of illuminated TiO2 and its possible effects on DNA. The authors studied commercial TiO2 samples (20–50 nm in diameter) with different anatase/rutile ratios (some samples also contained ZnO) following illumination of DNA in vivo using comet assays. The comet assay is a single-cell based technique that allows detection and quantification of DNA damage. The assay uses nuclei embedded in agarose and exposed to an electric field. In these assays, human cells (MRC-5 fibroblasts) were illuminated on ice with or without a TiO2-containing sunscreen. The study demonstrates that DNA in human cells is damaged by illumination in the presence of TiO2 (Fig. 2). In addition, suppression by the quencher dimethyl sulfoxide (DMSO) implies that the damage is caused by hydroxyl radicals8. According to the authors, these assays detect direct strand breaks and alkali-labile sites, and reveal the damage attributable to TiO2.The fate of these NPs, when applied to human skin, is not completely understood. Moreover, some autoradiographic studies using 65ZnO suggest that such particles can pass through rat and rabbit skin9,10. In these studies, 65Zn species from ZnCl2 aqueous solution and ZnO suspension have been applied to the intact skin of rats or rabbits. 65Zn species rapidly appear in the blood and other tissues. A total penetration of 65Zn species from a carrier-free 65Zn-ZnCl2 solution at pH 1 and from a 65Zn-ZnO suspension at pH 8 was detected. Autoradiography shows 65Zn activity in both dermis and panniculus carnosus, mostly concentrated on or near the epidermis and around hair follicles in the dermis. Some reports maintain that ZnO and TiO2 NPs, and even micronized TiO2 in sunscreens, can pass through human skin too11–14 although more systematic studies are necessary. It is important to note that only a minority of publications suggest the possibility of human dermal penetration and then only under certain conditions. On the other hand, there is a larger volume of work suggesting that NPs do not penetrate through healthy skin3.ZnO NPs are used as a sunscreen because it is a semiconductor with a bandgap of 3.3 eV, very close to the anatase gap energy of TiO215. Preliminary studies indicate that ZnO NPs (~15 nm) at concentrations of 3–10 mM cause 100% inhibition of Escherichia coli Fig. 1 Simplified semiconductor bandgap structure and schematic formation of superoxide and hydroxyl radicals.Fig. 2 Damage inflicted on human cells revealed by comet assays. Row (a): comets obtained using X-rays from a Gavitron RX30 source. The dose rate was 8.9 Gy min-1 and cells were exposed on ice for 0 s, 15 s, 30 s, and 60 s, giving comets falling into the five main standard classes shown: (1) class 0; (2)