Toxicity Evaluation for Safe Use of Nanomaterials: Recent Achievements and Technical Challenges

Recent developments in the field of nanotechnology involving the synthesis of novel nanomaterials (NM) have attracted the attention of numerous scientists owing to the possibility of degradative perturbations in human health. This Review evaluates previous investigations related to NM toxicity studies using biological models and describes the limitations that often prevent toxicologists from identifying whether NM pose a real hazard to human health. One major limitation to assess toxicity is the characterization of the NM prior to and after exposure to living cells or animals. The most relevant physicochemical characteristics of NM are: size, surface chemistry, crystallinity, morphology, solubility, aggregation tendency, homogeneity of dispersions, and turbidity. All of these properties need to be assessed in order to determine their contribution to toxicity. Due to the lack of appropriate methods to determine the physicochemical nature of nanoparticles in biological systems, the exact nature of NM toxicity is not fully described or understood at this time. This Review emphasizes the need for state-of-the-art physicochemical characterization, the determination of appropriate exposure protocols and reliable methods for assessing NM internalization and their kinetics in living organisms. Once these issues are addressed, optimal experimental conditions could be established in order to identify if NM pose a threat to human health. Multidisciplinary research between materials scientists and life scientists should overcome these limitations in identifying the true hazards of NM.

[1]  M. Terrones,et al.  Viability studies of pure carbon- and nitrogen-doped nanotubes with Entamoeba histolytica: from amoebicidal to biocompatible structures. , 2007, Small.

[2]  Aaron Wold,et al.  Photocatalytic properties of titanium dioxide (TiO2) , 1993 .

[3]  G. Tosi,et al.  Peptide-derivatized biodegradable nanoparticles able to cross the blood-brain barrier. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[4]  M. Prato,et al.  Biomedical applications of functionalised carbon nanotubes. , 2005, Chemical communications.

[5]  E. Oberdörster Manufactured Nanomaterials (Fullerenes, C60) Induce Oxidative Stress in the Brain of Juvenile Largemouth Bass , 2004, Environmental health perspectives.

[6]  R. L. Jones,et al.  Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species. , 2008, The journal of physical chemistry. B.

[7]  David B Warheit,et al.  Pulmonary bioassay studies with nanoscale and fine-quartz particles in rats: toxicity is not dependent upon particle size but on surface characteristics. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[8]  Andrea Zappe,et al.  Dynamics of diamond nanoparticles in solution and cells. , 2007, Nano letters.

[9]  A Atilla Hincal,et al.  Sterile, injectable cyclodextrin nanoparticles: effects of gamma irradiation and autoclaving. , 2006, International journal of pharmaceutics.

[10]  K. Jan,et al.  Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. , 2005, Toxicology.

[11]  V. Colvin The potential environmental impact of engineered nanomaterials , 2003, Nature Biotechnology.

[12]  M. Prato,et al.  Translocation of bioactive peptides across cell membranes by carbon nanotubes. , 2004, Chemical communications.

[13]  M. Terrones,et al.  Biocompatibility and toxicological studies of carbon nanotubes doped with nitrogen. , 2006, Nano letters.

[14]  L. Dai,et al.  Can silver nanoparticles be useful as potential biological labels? , 2008, Nanotechnology.

[15]  W. Kreyling,et al.  Translocation of Inhaled Ultrafine Particles to the Brain , 2004, Inhalation toxicology.

[16]  Z. Gu,et al.  Biodistribution of carbon single-wall carbon nanotubes in mice. , 2004, Journal of nanoscience and nanotechnology.

[17]  Wolfgang Kreyling,et al.  Toxicological hazards of inhaled nanoparticles--potential implications for drug delivery. , 2004, Journal of nanoscience and nanotechnology.

[18]  J. Schlager,et al.  In vitro cytotoxicity of nanoparticles in mammalian germline stem cells. , 2005, Toxicological sciences : an official journal of the Society of Toxicology.

[19]  Craig A. Poland,et al.  Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. , 2008, Nature nanotechnology.

[20]  D D Allen,et al.  Nanoparticle Technology for Drug Delivery Across the Blood-Brain Barrier , 2002, Drug development and industrial pharmacy.

[21]  Jürgen Seitz,et al.  Efficient Elimination of Inhaled Nanoparticles from the Alveolar Region: Evidence for Interstitial Uptake and Subsequent Reentrainment onto Airways Epithelium , 2007, Environmental health perspectives.

[22]  Sanjiv S Gambhir,et al.  A pilot toxicology study of single-walled carbon nanotubes in a small sample of mice. , 2008, Nature nanotechnology.

[23]  H. Dai,et al.  Nanotube molecular transporters: internalization of carbon nanotube-protein conjugates into Mammalian cells. , 2004, Journal of the American Chemical Society.

[24]  Sabine Neuss,et al.  Size-dependent cytotoxicity of gold nanoparticles. , 2007, Small.

[25]  T. Webb,et al.  Pulmonary toxicity study in rats with three forms of ultrafine-TiO2 particles: differential responses related to surface properties. , 2007, Toxicology.

[26]  Gerhard Scheuch,et al.  Clearance of Particles Deposited in the Lungs , 2000 .

[27]  Saber M Hussain,et al.  Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[28]  C. Raston,et al.  Ni(II) N4-macrocycle grafted crown ether: caesium cobalt(III) bis(dicarbollide) coordination polymer. , 2002, Chemical communications.

[29]  Robert Gelein,et al.  Role of the alveolar macrophage in lung injury: studies with ultrafine particles. , 1992 .

[30]  Sungho Jin,et al.  Nanotoxicity of iron oxide nanoparticle internalization in growing neurons. , 2007, Biomaterials.

[31]  J. Gearhart,et al.  In vitro toxicity of nanoparticles in BRL 3A rat liver cells. , 2005, Toxicology in vitro : an international journal published in association with BIBRA.

[32]  K. Donaldson,et al.  Increased inflammation and altered macrophage chemotactic responses caused by two ultrafine particle types , 2004, Occupational and Environmental Medicine.

[33]  T. Tsuchiya,et al.  Novel harmful effects of [60]fullerene on mouse embryos in vitro and in vivo , 1996, FEBS letters.

[34]  John J. Schlager,et al.  Differential biocompatibility of carbon nanotubes and nanodiamonds , 2007 .

[35]  K. Lafdi,et al.  Effect of particle dimension on biocompatibility of carbon nanomaterials , 2007 .

[36]  Saber M Hussain,et al.  Are diamond nanoparticles cytotoxic? , 2007, The journal of physical chemistry. B.

[37]  B. Lehnert,et al.  Correlation Between Particle Size, in Vivo Particle Persistence, and Lung Injury , 1994 .

[38]  Saber M Hussain,et al.  The interaction of manganese nanoparticles with PC-12 cells induces dopamine depletion. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[39]  David B Warheit,et al.  Pulmonary instillation studies with nanoscale TiO2 rods and dots in rats: toxicity is not dependent upon particle size and surface area. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[40]  Y. Hirasawa,et al.  Distribution of synaptosomal-associated protein 25 in nerve growth cones and reduction of neurite outgrowth by botulinum neurotoxin A without altering growth cone morphology in dorsal root ganglion neurons and PC-12 cells , 1999, Neuroscience.

[41]  Güunter Oberdürster Toxicology of ultrafine particles: in vivo studies , 2000, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[42]  J. Mauderly,et al.  Lung Tissue Responses and Sites of Particle Retention Differ between Rats and Cynomolgus Monkeys Exposed Chronically to Diesel Exhaust and Coal Dust , 1997 .

[43]  Saber M Hussain,et al.  Cellular interaction of different forms of aluminum nanoparticles in rat alveolar macrophages. , 2007, The journal of physical chemistry. B.

[44]  M. U. Nollert,et al.  Chemical modification of SWNT alters in vitro cell-SWNT interactions. , 2006, Journal of biomedical materials research. Part A.

[45]  G. Oberdörster,et al.  Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles , 2005, Environmental health perspectives.

[46]  Liming Dai,et al.  DNA damage induced by multiwalled carbon nanotubes in mouse embryonic stem cells. , 2007, Nano letters.

[47]  Tae-Jong Yoon,et al.  Toxicity and tissue distribution of magnetic nanoparticles in mice. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.