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Review

Pulmonary Toxicity of Nanomaterials: A Critical Comparison of Published In Vitro Assays and In Vivo Inhalation or Instillation Studies

, , , &
Pages 2557-2585 | Published online: 09 Dec 2014

References

  • Stone V , JohnstonH, SchinsRPF. Development of in vitro systems for nanotoxicology: methodological considerations. Crit. Rev. Toxicol.39 (7), 613–626 (2009).
  • Kroll A , DierkerC, RommelCet al. Cytotoxicity screening of 23 engineered nanomaterials using a test matrix of ten cell lines and three different assays. Part. Fibre Toxicol.8, 9 (2011).
  • Nel AE , XiaT, MengHet al. Nanomaterial toxicity testing in the 21st century: use of a predictive toxicological approach and high-throughput screening. Acc. Chem. Res.46 (3), 607–621 (2013).
  • Oberdörster G , FerinJ, LehnertBE. Correlation between particle size, in vivo particle persistence, and lung injury. Environ. Health Perspect.102 (Suppl. 5), 173–179 (1994).
  • Nel AE , NasserE, GodwinHet al. A multi-stakeholder perspective on the use of alternative test strategies for nanomaterial safety assessment. ACS Nano7 (8), 6422–6433 (2013).
  • Cho WS , DuffinR, BradleyMet al. Predictive value of in vitro assays depends on the mechanism of toxicity of metal oxide nanoparticles. Part. Fibre Toxicol.10 (1), 55 (2013).
  • Hirsch C , RoessleinM, KrugHF, WickP. Nanomaterial cell interactions: are current in vitro tests reliable?Nanomed.6 (5), 837–847 (2011).
  • Wohlleben W , KolleSN, HasenkampLCet al. Artifacts by marker enzyme adsorption on nanomaterials in cytotoxicity assays with tissue cultures. J. Phys. Conf. Series304, 012061 (2011).
  • Guadagnini R , Halamoda KenzaouiB, CartwrightLet al. Toxicity screenings of nanomaterials: challenges due to interference with assay processes and components of classic in vitro tests. Nanotoxicology doi: 10.3109/17435390.829590 (2013) ( Epub ahead of print).
  • Xia T , HamiltonRF, BonnerJCet al. Interlaboratory evaluation of in vitro cytotoxicity and inflammatory responses to engineered nanomaterials: the NIEHS Nano GO Consortium. Environ. Health Persp.121 (6), 683–690 (2013).
  • Han X , CorsonN, Wade-MercerPet al. Assessing the relevance of in vitro studies in nanotoxicology by examining correlations between in vitro and in vivo data. Toxicology297 (1–3), 1–9 (2012).
  • Sauer UG , VogelS, AumannAet al. Applicability of rat precision-cut lung slices in evaluating nanomaterial cytotoxicity, apoptosis, oxidative stress, and inflammation. Toxicol. Appl. Pharmacol.276 (1), 1–20 (2014).
  • Rushton EK , JiangJ, LeonardSSet al. Concept of assessing nanoparticle hazards considering nanoparticle dosemetric and chemical/biological response metrics. J. Toxicol. Environ. Health A73 (5), 445–461 (2010).
  • OECD . Nanosafety at the OECD: The first six years. www.oecd.org/science/nanosafety/.
  • Oesch F , LandsiedelR. Genotoxicity investigations on nanomaterials. Arch. Toxicol.86 (7), 985–994 (2012).
  • Russell W , BurchR. The Principles of Humane Experimental Technique.Methuen, York, UK (1959).
  • Hayes A , BakandS. Inhalation toxicology. EXS100, 461–488 (2010).
  • Landsiedel R , FabianE, Ma-HockLet al. Toxico-/biokinetics of nanomaterials. Arch. Toxicol.86 (7), 1021–1060 (2012).
  • Savolainen K , BackmanU, BrouwerDet al. Nanosafety in Europe 2015–20125: towards safe and sustainable nanomaterials and nanotechnology innovations. www.ttl.fi/en/publications/electronic_publications/pages/default.aspx.
  • ICRP (International Commission on Radiological Protection) . Human respiratory tract model for radiological protection. Ann. ICRP24 (1–3), 231 (1994).
  • Bräu M , Ma-HockL, HesseCet al. Nanostructured calcium silicate hydrate seeds accelerate concrete hardening, a combined assessment of benefits and risks. Arch. Toxicol.86 (7), 1077–1087 (2012).
  • Anttila S . Dissolution of stainless steel welding fumes in the rat lung: an x ray microanalytical study. Br. J. Ind. Med.43 (9), 592–596 (1986).
  • Morrow PE . Possible mechanisms to explain dust overloading of the lungs. Fund. Appl. Toxicol.10 (3), 369–384 (1988).
  • Donaldson K , TranL. Inflammation caused by particles and fibers. Inhal. Toxicol.14 (1), 5–27 (2002).
  • Monteiller C , TranL, MacNeeWet al. The pro-inflammatory effects of low-toxicity low-solubility particles, nanoparticles and fine particles, on epithelial cells in vitro: the role of surface area. Occup. Environ. Med.64 (9), 609–615 (2007).
  • Pauluhn J . Comparative pulmonary response to inhaled nanostructures: considerations on test design and endpoints. Inhal. Toxicol.21 (Suppl. 1), 40–54 (2009).
  • European Centre for Exotoxicology and Toxicology of Chemicals . Technical Report 122. Poorly soluble particles. Lung overload. www.ecetoc.org.
  • Oomen AG , BosPMJ, FernandesTFet al. Concern-driven integrated approaches to nanomaterial testing and assessment –Report of the NanoSafety Cluster Working Group 10. Nanotoxicology8 (3), 334–348 (2014).
  • Donaldson K , PolandCA. Nanotoxicity: challenging the myth of nano-specific toxicity. Curr. Opin. Biotechnol.24 (4), 724–734 (2013).
  • Cho WS , DuffinR, HowieSEet al. Progressive severe lung injury by zinc oxide nanoparticles; the role of Zn2+ dissolution inside lysosomes. Part. Fibre Toxicol.8, 27 (2011).
  • Cho WS , DuffinR, PolandCAet al. Differential pro-inflammatory effects of metal oxide nanoparticles and their soluble ions in vitro and in vivo; zinc and copper nanoparticles, but not their ions, recruit eosinophils to the lungs. Nanotoxicology6 (1), 22–35 (2012).
  • Nel AE , MädlerL, VelegolDet al. Understanding biophysicochemical interactions at the nano–bio interface. Nat. Mater.8 (7), 543–557 (2009).
  • Wang A , BergEL, PolokoffMet al. Ranking and profiling nanomaterial (NM) bioactivity by ToxCast high-throughput screening (HTS). Presented at : 52nd Annual Meeting of the Soc Toxicol (SOT) . San Antonio, TX, USA, 10–14March 2013.
  • Landsiedel R , WienchK, WohllebenW. Geeignete Methoden zur Prüfung der Sicherheit von Nanomaterialien. Chemie Ingenieur Technik80, 1641–1651 (2008).
  • Landsiedel R , Ma-HockL, KrollAet al. Testing metal-oxide nanomaterials for human safety. Adv. Mater.22 (24), 2601–2627 (2010).
  • Shvedova AA , YanamalaN, MurrayARet al. Oxidative stress, inflammatory biomarkers, and toxicity in mouse lung and liver after inhalation exposure to 100% biodiesel or petroleum diesel emissions. J. Toxicol. Environ. Health A76 (15), 907–921 (2013).
  • Shvedova AA , PietroiustiA, FadeelB, KaganVE. Mechanisms of carbon nanotube-induced toxicity: focus on oxidative stress. Toxicol. Appl. Pharmacol.261 (2), 121–133 (2012).
  • Yanamala N , KaganVE, ShvedovaAA. Molecluar modeling in structural nano-toxicology: interactions of nano-particles with nano-machinery of cells. Adv. Drug Deliv. Rev.65 (15), 2070–2077 (2013).
  • Kreyling WG , SemmlerM, ErbeFet al. Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low. J. Toxicol. Environ. Health A65 (20), 1513–1530 (2002).
  • Kreyling WG , Semmler-BehnkeM, SeitzJet al. Size dependence of the translocation of inhaled iridium and carbon nanoparticle aggregates from the lung of rats to the blood and secondary target organs. Inhal. Toxicol.21 (Suppl. 1), 55–60 (2009).
  • Maier M , HannebauerB, HolldorffH, AlbersP. Does lung surfactant promote disaggregation of nanostructured titanium dioxide?J. Occup. Environ. Med.48 (12), 1314–1320 (2006).
  • Demokritou P , GassS, PyrgiotakisGet al. An in vivo and in vitro toxicological characterisation of realistic nanoscale CeO2 inhalation exposures. Nanotoxicology7 (8), 1338–1350 (2013).
  • Cohen JM , TeeguardenJG, DemokritouP. An integrated approach for the in vitro dosimetry of engineered nanomaterials. Part. Fibre Toxicol.11, 20 (2014).
  • Lundqvist M , StiglerJ, CedervallTet al. The evolution of the protein corona around nanoparticles: a test study. ACS Nano5 (9), 7503–7509 (2011).
  • Monopoli MP , WalczykD, CampbellAet al. Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles. J. Am. Chem. Soc.133 (8), 2525–2534 (2011).
  • Monopoli MP , ÅbergC, SalvatiA, DawsonKA. Biomolecular coronas provide the biological identity of nanosized materials. Nat. Nanotechnol.7 (12), 779–786 (2012).
  • Wolfram J , YangY, ShenJet al. The nano–plasma interface: implications of the protein corona. Colloids Surf. B Biointerfaces doi https://doi.org/10.1016/j.colsurfb.2014.02.035 (2014) ( Epub ahead of print).
  • Bihari P , VippolaM, SchultesSet al. Optimized dispersion of nanoparticles for biological in vitro and in vivo studies. Part. Fibre Toxicol.5, 14 (2008).
  • Sauer UG , AumannA, Ma-HockL, LandsiedelR, WohllebenW. Influence of dispersive agent on nanomaterial agglomeration and implications for biological effects in vivo or in vitro. Toxicol. In Vitro29, 182–186 (2014).
  • Hu G , JiaoB, ShiX, ValleRP, FanQ, ZuoYY. Physicochemical properties of nanoparticles regulate translocation across pulmonary surfactant monolayer and formation of lipoprotein corona. ACS Nano7 (12), 10525–10533 (2013).
  • Choi HS , AshitateY, LeeJHet al. Rapid translocation of nanoparticles from the lung airspaces to the body. Nat. Biotechnol.28 (12), 1300–1303 (2010).
  • Landsiedel R , Ma-HockL, HaussmannHJ, van RavenzwaayB, KayserM, WienchK. Inhalation studies for the safety assessment of nanomaterials: status quo and the way forward. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol.4 (4), 399–413 (2012).
  • Pauluhn J . Common denominators of carbon nanotubes. In : Nanomaterials. Commission for the Investigation of Health Hazards of Chemical Compounds. Report.DeutscheForschungsgemeinschaft ( Ed.). Wiley-VCH Verlag GmbH, Weinheim, Germany, 68–83 (2013).
  • Schulze C , KrollA, LehrCet al. Not ready to use – overcoming pitfalls when dispersing nanoparticles in physiological media. Nanotoxicology2, 51–61 (2008).
  • Oberdörster G . Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology. J. Int. Med.267 (1), 89–105 (2009).
  • Heng BC , ZhaoX, XiongS, NgKW, BoeyFYC, LooJSC. Cytotoxicity of zinc oxide (ZnO) nanoparticles is influenced by cell density and culture format. Arch. Toxicol.85 (6), 695–704 (2011).
  • Braakhuis HM , ParkMV, GosensI, De JongWH, CasseeFR. Physicochemical characteristics of nanomaterials that affect pulmonary inflammation. Part. Fibre Toxicol.11, 18 (2014).
  • Duffin R , TranL, BrownD, StoneV, DonaldsonK. Proinflammogenic effects of low-toxicity and metal nanoparticles in vivo and in vitro: highlighting the role of particle surface area and surface reactivity. Inhal. Toxicol.19 (10), 849–856 (2007).
  • Tran CL , BuchananD, CullenRT, SearlA, JonesAD, DonaldsonK. Inhalation of poorly soluble particles. II. Influence of particle surface area on inflammation and clearance. Inhal. Toxicol.12 (12), 1113–1126 (2000).
  • Kuempel ED , CastranovaV, GeraciCL, SchultePA. Development of risk-based nanomaterial groups for occupational exposure control. J. Nanopart. Res.14, 1029 (2012).
  • Pauluhn J . Subchronic 13-week inhalation exposure of rats to multiwalled carbon nanotubes: toxic effects are determined by density of agglomerate structures, not fibrillar structures. Toxicol. Sci.113 (1), 226–242 (2010).
  • Wiemann M , BruchJ. Comparison of in vitro and in vivo findings. In : NanoCare. Health related Aspects of Nanomaterials. Final Scientific Report. KuhlbuschTKJ, NauK, KrugH ( Eds). Dechema, Frankfurt, Germany, 68–73 (2009).
  • Gosens I , PostJA, de la FonteyneLJJet al. Impact of agglomeration state of nano- and submicron sized gold particles on pulmonary inflammation. Part. Fibre Toxicol.7 (1), 37 (2010).
  • Donaldson K , BormPJ, OberdörsterG, PinkertonKE, StoneV, TranCL. Concordance between in vitro and in vivo dosimetry in the proinflammatory effects of low-toxicity, low-solubility particles: the key role of the proximal alveolar region. Inhal. Toxicol.20 (1), 53–62 (2008).
  • Teeguarden JG , HinderliterPM, OrrG, ThrallBD, PoundsJG. Particokinetics in vitro: dosimetry considerations for in vitro nanoparticle toxicity assessments. Toxicol. Sci.95 (2), 300–312 (2007).
  • Hinderliter PM , MinardKR, OrrGet al. ISDD: acomputational model of particle sedimentation, diffusion and target cell dosimetry for in vitro toxicity studies. Part. Fibre Toxicol.7 (1), 36 (2010).
  • Anjilvel S , AsgharianB. A multiple-path model of particle deposition in the rat lung. Fundam. Appl. Toxicol.28 (1), 41–50 (1995).
  • Schippritt D , LipinskiHG, WiemannM. Measurement of nanoparticle uptake by alveolar macrophages: a new approach based on quantitative image analysis. In : Nanomaterials Throughout their Lifecycles: Safety, Human Hazard and Exposure.WohllebenW, KuhlbuschT, SchnekenburgerJ, LehrC-M ( Eds). Taylor & Francis, FL, USA (2014).
  • Simko M , NosskeD, KreylingWG. Metrics, dose, and dose concept: the need for a proper dose concept in the risk assessment of nanoparticles. Int. J. Environ. Res. Public Health11 (4), 4026–4048 (2014).
  • Meng H , XiaT, GeorgeS, NelAE. A predictive toxicological paradigm for the safety assessment of nanomaterials. ACS Nano3 (7), 1620–1627 (2009).
  • Damoiseaux R , GeorgeS, LiMet al. No time to lose –high throughput screening to assess nanomaterial safety. Nanoscale3 (4), 1345–1360 (2011).
  • Yu KN , YoonTJ, Minai-TehraniAet al. Zinc oxide nanoparticle induced autophagic cell death and mitochondrial damage via reactive oxygen species generation. Toxicol. In Vitro27 (4), 1187–1195 (2013).
  • Johnston HJ , HutchisonGR, ChristensenFM, PetersS, HankinS, StoneV. A review of the in vivo and in vitro toxicity of silver and gold particulates: particle attributes and biological mechanisms responsible for the observed toxicity. Crit. Rev. Toxicol.40 (4), 328–346 (2010).
  • Kermanizadeh A , PojanaG, GaiserBKet al. In vitro assessment of engineered nanomaterials using a hepatocyte cell line: cytotoxicity, pro-inflammatory cytokines and functional markers. Nanotoxicology7 (3), 301–313 (2013).
  • Gojova A , GuoB, KotaRS, RutledgeJC, KennedyIM, BarakatAI. Induction of inflammation in vascular endothelial cells by metal oxide nanoparticles: effect of particle composition. Environ. Health Perspect.115 (3), 403–409 (2007).
  • Hackenberg S , ScherzedA, TechnauAet al. Cytotoxic, genotoxic and pro-inflammatory effects of zinc oxide nanoparticles in human nasal mucosa cells in vitro. Toxicol. In Vitro25 (3), 657–663 (2011).
  • Hsiao IL , HuangYJ. Effects of various physicochemical characteristics on the toxicities of ZnO and TiO2 nanoparticles toward human lung epithelial cells. Sci. Total Environ.409 (7), 1219–1228 (2011).
  • Palomäki J , KarisolaP, PylkkänenL, SavolainenK, AleniusH. Engineered nanomaterials cause cytotoxicity and activation on mouse antigen presenting cells. Toxicology267 (1–3), 125–131 (2010).
  • Roy R , TripathiA, DasM, DwivediPD. Cytotoxicity and uptake of zinc oxide nanoparticles leading to enhanced inflammatory cytokines levels in murine macrophages: comparison with bulk zinc oxide. J. Biomed. Nanotechnol.7 (1), 110–111 (2011).
  • Park EJ , YiJ, ChungKH, RyuDY, ChoiJ, ParkK. Oxidative stress and apoptosis induced by titanium dioxide nanoparticles in cultured BEAS-2B cells. Toxicol. Lett.180 (3), 222–229 (2008).
  • Feltis BN , O'KeefeSJ, HarfordAJ, PivaTJ, TurneyTW, WrightPFA. Independent cytotoxic and inflammatory responses to zinc oxide nanoparticles in human monocytes and macrophages. Nanotoxicology6 (7), 757–765 (2012).
  • Foldbjerg R , DangDA, AutrupH. Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549. Arch. Toxicol.85 (7), 743–750 (2011).
  • Heng BC , ZhaoX, TanECet al. Evaluation of the cytotoxic and inflammatory potential of differentially shaped zinc oxide nanoparticles. Arch. Toxicol.85 (12), 1517–1528 (2011).
  • Herzog F , CliftMJD, PiccapietraFet al. Exposure of silver-nanoparticles and silver ions to lung cells in vitro at the air liquid interface. Part. Fibre Toxicol.10, 11 (2013).
  • Kim HR , KimMJ, LeeSY, OhSM, ChungKH. Genotoxic effects of silver nanoparticles stimulated by oxidative stress in human normal bronchial epithelial (BEAS-2B) cells. Mutat. Res.726 (2), 129–135 (2011).
  • Roy R , ParasharV, ChauhanLKet al. Mechanism of uptake of ZnO nanoparticles and inflammatory responses in macrophages require PI3K mediated MAPKs signaling. Toxicol. In Vitro28, 457–467 (2013).
  • Sayes CM , ReedKL, WarheitDB. Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. Toxicol. Sci.97 (1), 163–180 (2007).
  • Landsiedel R , Ma-HockL, HofmannTet al. Application of short-term inhalation studies to assess the inhalation toxicity of nanomaterials. Part. Fibre Toxicol.11, 16 (2014).
  • Sung JH , JiJH, SongKSet al. Acute inhalation toxicity of silver nanoparticles. Toxicol. Ind. Health27 (2), 149–154 (2011).
  • Sung JH , JiJH, ParkJDet al. Subchronic inhalation toxicity of silver nanoparticles. Toxicol. Sci.108 (2), 452–461 (2009).
  • Song KS , SungJH, JiJHet al. Recovery from silver-nanoparticle-exposure-induced lung inflammation and lung function changes in Sprague Dawley rats. Nanotoxicology7 (2), 169–180 (2013).
  • Joint Research Centre. Institute for Health and Consumer Protection (IHCP) . List of materials in the JRC nanomaterials repository – Oct 2011. http://ihcp.jrc.ec.europa.eu/our_activities/nanotechnology/nanomaterials-repository/list_materials_JRC_rep_oct_2011.pdf/view.
  • Wilkinson LJ , WhiteRJ, ChipmanJK. Silver and nanoparticles of silver in wound dressings: a review of efficacy and safety. J. Wound Care20 (11), 543–549 (2011).
  • Kao YY , ChenYC, ChengTJ, ChiungYM, LiuPS. Zinc oxide nanoparticles interfere with zinc ion homeostasis to cause cytotoxicity. Toxicol. Sci.125 (2), 462–472 (2012).
  • Klein CL , WienchK, WiemannM, Ma-HockL, van RavenzwaayB, LandsiedelR. Hazard identification of inhaled nanomaterials: making use of short-term inhalation studies. Arch. Toxicol.86 (7), 1137–1151 (2012).
  • Guadagnini R , MoreauK, HussainS, MaranoF, BolandS. Toxicity evaluation of engineered nanoparticles for medical applications using pulmonary epithelial cells. Nanotoxicology doi: 10.3109/17435390.855830 (2013) ( Epub ahead of print).
  • Zhang XQ , YinLH, TangM, PuYP. ZnO, TiO2, SiO2, and Al2O3 nanoparticles-induced toxic effects on human fetal lung fibroblasts. Biomed. Environ. Sci.24 (6), 661–669 (2011).
  • Bermudez E , MangumJB, AsgharianBet al. Long-term pulmonary responses of three laboratory rodent species to subchronic inhalation of micron-scale titanium dioxide particles. Toxicol. Sci.70 (1), 86–97 (2002).
  • Bermudez E , MangumJB, WongBAet al. Pulmonary responses of mice, rats, and hamsters to subchronic inhalation of ultrafine titanium dioxide particles. Toxicol. Sci.77 (2), 347–357 (2004).
  • Heinrich U , FuhstR, RittinghausenSet al. Chronic inhalation exposure of Wistar rats and two different strains of mice to diesel engine exhaust, carbon black, and titanium dioxide. Inhal. Toxicol.7, 533–556 (1995).
  • Lee KP , TrochimowiczHJ, ReinhardtCF. Pulmonary response of rats exposed to titanium dioxide (TiO2) by inhalation for two years. Toxicol. Appl. Pharmacol.79 (2), 179–192 (1985).
  • Ma-Hock L , BurkhardtS, StraussVet al. Development of a short-term inhalation test in the rat using nano-titanium dioxide as a model substance. Inhal. Toxicol.21 (2), 102–118 (2009).
  • Pott F , RollerM. Carcinogenicity study with nineteen granular dusts in rats. Eur. J. Oncol.10, 249–281 (2005).
  • van Ravenzwaay B , LandsiedelR, FabianE, BurkhardtS, StraussV, Ma-HockL. Comparing fate and effects of three particles of different surface properties: nano-TiO2, pigmentary TiO2 and quartz. Toxicol. Lett.186 (3), 152–159 (2009).
  • Sayes CM , WahiR, KurianPAet al. Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. Toxicol. Sci.92 (1), 174–185 (2006).
  • Johnston HJ , HutchisonGR, ChristensenFM, PetersS, HankinS, StoneV. Identification of the mechanisms that drive the toxicity of TiO2 particulates: the contribution of physicochemical characteristics. Part. Fibre Toxicol.6, 33 (2009).
  • Ferin J , OberdörsterG, PenneyDP. Pulmonary retention of ultrafine and fine particles in rats. Am. J. Respir. Cell Mol. Biol.6 (5), 535–542 (1992).
  • Park EJ , ChoiJ, ParkYK, ParkK. Oxidative stress induced by cerium oxide nanoparticles in cultured BEAS-2B cells. Toxicology245 (1–2), 90–100 (2008).
  • Eom HJ , ChoiJ. Oxidative stress of CeO2 nanoparticles via p38-Nrf-2 signaling pathway in human bronchial epithelial cell, Beas-2B. Toxicol. Lett.187 (2), 77–83 (2009).
  • Kim IS , BaekM, ChoiSJ. Comparative cytotoxicity of Al2O3, CeO2, TiO2 and ZnO nanoparticles to human lung cells. J. Nanosci. Nanotechnol.10 (5), 3453–3458 (2010).
  • Shi J , KarlssonHL, JohanssonKet al. Microsomal glutathione transferase 1 protects against toxicity induced by silica nanoparticles but not by zinc oxide nanoparticles. ACS Nano6 (3), 1925–1938 (2012).
  • De Marzi L , MonacoA, De LapuenteJet al. Cytotoxicity and genotoxicity of ceria nanoparticles on different cell lines in vitro. Int. J. Mol. Sci.14 (2), 3065–3077 (2013).
  • Schubert D , DarguschR, RaitanoJ, ChanSW. Cerium and yttrium oxide nanoparticles are neuroprotective. Biochem. Biophys. Res. Commun.342 (1), 386 (2006).
  • Xia T , KovochichM, LiongMet al. Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. ACS Nano2 (10), 2121–2134 (2008).
  • Cho WS , DuffinR, PolandCAet al. Metal oxide nanoparticles induce unique inflammatory footprints in the lung: important implications for nanoparticle testing. Environ. Health Perspect.118 (12), 1699–1706 (2010).
  • Srinivas A , RaoPJ, SelvamG, MurthyPB, ReddyPN. Acute inhalation toxicity of cerium oxide nanoparticles in rats. Toxicol. Lett.205 (2), 105–115 (2011).
  • Arts JH , MuijserH, DuistermaatEet al. Five-day inhalation toxicity study of three types of synthetic amorphous silicas in Wistar rats and post-exposure evaluations for up to 3 months. Food Chem. Toxicol.45 (10), 1856–1867 (2007).
  • Napierska D , ThomassenLC, LisonD, MartensJA, HoetPH. The nanosilica hazard: another variable entity. Part. Fibre Toxicol.7 (1), 39 (2010).
  • Diedrich T , DybowskaA, SchottJ, Valsami-JonesE, OelkersEH. The dissolution rates of SiO2 nanoparticles as a function of particle size. Environ. Sci. Technol.46 (9), 4909–4915 (2012).
  • Horie M , NishioK, KatoHet al. Evaluation of cellular effects of silicon dioxide nanoparticles. Toxicol. Mech. Methods24 (3), 196–203 (2014).
  • Ha SW , SikorskiJA, WeitzmannMN, BeckGRJr. Bio-active engineered 50nm silica nanoparticles with bone anabolic activity: therapeutic index, effective concentration, and cytotoxicity profile in vitro. Toxicol. In Vitro28, 354–364 (2013).
  • Uboldi C , GiudettiG, BroggiF, GillilandD, PontiJ, RossiF. Amorphous silica nanoparticles do not induce cytotoxicity, cell transformation or genotoxicity in Balb/3T3 mouse fibroblasts. Mutat. Res.745 (1–2), 11–20 (2012).
  • Kasper J , HermannsMI, BantzCet al. Interactions of silica nanoparticles with lung epithelial cells and the association to flotillins. Arch. Toxicol.87 (6), 1053–1065 (2013).
  • Napierska D , ThomassenLC, RabolliVet al. Size-dependent cytotoxicity of monodisperse silica nanoparticles in human endothelial cells. Small5 (7), 846–853 (2009).
  • Coccini T , ManzoL, RodaE. Safety evaluation of engineered nanomaterials for health risk assessment: an experimental tiered testing approach using pristine and functionalized carbon nanotubes. ISRN Toxicol.2013, 825427 (2013).
  • Panas A , MarquardtC, NalcaciOet al. Screening of different metal oxide nanoparticles reveals selective toxicity and inflammatory potential of silica nanoparticles in lung epithelial cells and macrophages. Nanotoxicology7 (3), 259–273 (2013).
  • Wilhelmi V , FischerU, van BerloD, Schulze-OsthoffK, SchinsRPF, AlbrechtC. Evaluation of apoptosis induced by nanoparticles and fine particles in RAW 264.7 macrophages: facts and artefacts. Toxicol. In Vitro26 (2), 323–334 (2012).
  • Zhu M , NieG, MengH, XiaT, NelAE, ZhaoY. Physicochemical properties determine nanomaterial cellular uptake, transport and fate. Acc. Chem. Res.46 (3), 622–631 (2013).
  • Johnston CJ , DriscollKE, FinkelsteinJNet al. Pulmonary chemokine and mutagenic responses in rats after subchronic inhalation of amorphous and crystalline silica. Toxicol. Sci.56 (2), 405–413 (2000).
  • Reuzel PG , BruijntjesJP, FeronVJ, WoutersenRA. Subchronic inhalation toxicity of amorphous silicas and quartz dust in rats. Food Chem. Toxicol.29 (5), 341–354 (1991).
  • Chusuei CC , WuCH, MallavarapuSet al. Cytotoxicity in the age of nano: the role of fourth period transition metal oxide nanoparticle physicochemical properties. Chem. Biol. Interact.206 (2), 319–326 (2013).
  • Burello E , WorthAP. A theoretical framework for predicting the oxidative stress potential of oxide nanoparticles. Nanotoxicology5 (2), 228–235 (2011).
  • Johnston HJ , HutchisonGR, ChristensenFMet al. A critical review of the biological mechanisms underlying the in vivo and in vitro toxicity of carbon nanotubes: the contribution of physico-chemical characteristics. Nanotoxicology4 (2), 207–246 (2010).
  • Schinwald A , DonaldsonK. Use of back-scatter electron signals to visualize cell/nanowires interactions in vitro and in vivo; frustrated phagocytosis of long fibres in macrophages and compartmentalisation in mesothelial cells in vivo. Part. Fibre Toxicol.9, 34 (2012).
  • Rodriguez-Yanez Y , MunozB, AlboresA. Mechanisms of toxicity by carbon nanotubes. Toxicol. Mech. Meth.23 (3), 178–195 (2013).
  • Donaldson K , MurphyFA, DuffinR, PolandCA. Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma. Part. Fibre Toxicol.22, 5 (2010).
  • Schinwald A , MurphyFA, Prina-MelloAet al. The threshold length for fiber-induced acute pleural inflammation: shedding light on the early events in asbestos-induced mesothelioma. Toxicol. Sci.128 (2), 461–470 (2012).
  • Schinwald A , ChernovaT, DonaldsonK. Use of silver nanowires to determine thresholds for fibre length-dependent pulmonary inflammation and inhibition of macrophage migration in vitro. Part. Fibre Toxicol.9, 47 (2012).
  • Murphy FA , SchinwaldA, PolandCA, DonaldsonK. The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells. Part. Fibre Toxicol.9, 8 (2012).
  • Chen B , LiuY, SongWM, HayashiY, DingXC, LiWH. In vitro evaluation of cytotoxicity and oxidative stress induced by multiwalled carbon nanotubes in murine RAW 264.7 macrophages and human A549 lung cells. Biomed. Environ. Sci.24 (6), 593–601 (2011).
  • Cavallo D , FanizzaC, UrsiniCLet al. Multi-walled carbon nanotubes induce cytotoxicity and genotoxicity in human lung epithelial cells. J. Appl. Toxicol.32 (6), 454–464 (2012).
  • Haniu H , SaitoN, MatsudaYet al. Effect of dispersants of multi-walled carbon nanotubes on cellular uptake and biological responses. Int. J. Nanomed.6, 3295–3307 (2011).
  • Aldieri E , FenoglioI, CesanoFet al. The role of iron impurities in the toxic effects exerted by short multiwalled carbon nanotubes (MWCNT) in murine alveolar macrophages. J. Toxicol. Env. Health Part A76 (18), 1056–1071 (2013).
  • Ursini CL , CavalloD, FresegnaAMet al. Comparative cyto-genotoxicity assessment of functionalized and pristine multiwalled carbon nanotubes on human lung epithelial cells. Toxicol. In Vitro26 (6), 831–840 (2012).
  • Ma-Hock L , StraussV, TreumannSet al. Comparative inhalation toxicity of multi-wall carbon nanotubes, graphene, graphite nanoplatelets and low surface carbon black. Part. Fibre Toxicol.10, 23 (2013).
  • Ma-Hock L , TreumannS, StraussVet al. Inhalation toxicity of multiwall carbon nanotubes in rats exposed for 3 months. Toxicol. Sci.112 (2), 468–481 (2009).
  • Ge C , LiY, YinJJet al. The contributions of metal impurities and tube structure to the toxicity of carbon nanotube materials. NPG Asia Materials4, e32 (2012).
  • Sargent LM , PorterDW, StaskaLMet al. Promotion of lung adenocarcinoma following inhalation exposure to multi-walled carbon nanotubes. Part. Fibre Toxicol.11, 3 (2014).
  • Shvedova AA , TkachAV, KisinERet al. Carbon nanotubes enhance metastatic growth of lung carcinoma via up-regulation of myeloid-derived suppressor cells. Small9 (9–10), 1691–1695 (2013).
  • Muller J , DelosM, PaninN, RabolliV, HuauxF, LisonD. Absence of carcinogenic response to multiwall carbon nanotubes in a 2-year bioassay in the peritoneal cavity of the rat. Toxicol Sci.110 (2), 442–448 (2009).
  • Joris F , ManshianBB, PeynshaertK, De SmedtSC, BraeckmansK, SoenenSJ. Assessing nanoparticle toxicity in cell-based assays: influence of cell culture parameters and optimized models for bridging the in vitro–in vivo gap. Chem. Soc. Rev.42 (21), 8339–8359 (2013).
  • Balls M , FentemJ. The use of basal cytotoxicity and target organ tests in hazard identification and risk assessment. ATLA20, 368–388 (1992).
  • European Chemicals Agency . Guidance on information requirements and chemical safety assessment. Appendix R7–1 Recommendations for nanomaterials applicable to Chapter R7a Endpoint specific guidance (2012). http://echa.europa.eu/documents/10162/13632/appendix_r7a_nanomaterials_en.pdf.
  • European Chemicals Agency . Assessing human health and environmental hazards of nanomaterials – best practice for REACH registrants. 2nd GAARN meeting. European Chemicals Agency, Helsinki, 21–22 January 2013. http://echa.europa.eu/documents/10162/5399565/best_practices_human_health_environment_nano_en.pdf.
  • Sauer UG . Conference Report. Session Nanotoxicology. 16th Congress on Alternatives to Animal Testing. Linz 2010. ALTEX27, 318–322 (2010).
  • Patel T , TelescaD, Low-KamCet al. Relating nanoparticle properties to biological outcomes in exposure escalation experiments. Environmetrics25 (1), 57–68 (2014).
  • Lai DY . Toward toxicity testing of nanomaterials in the 21st century: a paradigm for moving forward. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol.4 (1), 1–15 (2012).

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