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Manufactured nanomaterials: categorization and approaches to hazard assessment

Archives of Toxicology volume 88, pages 2191–2211 (2014)Cite this article

Abstract

Nanotechnology offers enormous potential for technological progress. Fortunately, early and intensive efforts have been invested in investigating toxicology and safety aspects of this new technology. However, despite there being more than 6,000 publications on nanotoxicology, some key questions still have to be answered and paradigms need to be challenged. Here, we present a view on the field of nanotoxicology to stimulate the discussion on major knowledge gaps and the critical appraisal of concepts or dogma. First, in the ongoing debate as to whether nanoparticles may harbour a specific toxicity due to their size, we support the view that there is at present no evidence of ‘nanospecific’ mechanisms of action; no step-change in hazard was observed so far for particles below 100 nm in one dimension. Therefore, it seems unjustified to consider all consumer products containing nanoparticles a priori as hazardous. Second, there is no evidence so far that fundamentally different biokinetics of nanoparticles would trigger toxicity. However, data are sparse whether nanoparticles may accumulate to an extent high enough to cause chronic adverse effects. To facilitate hazard assessment, we propose to group nanomaterials into three categories according to the route of exposure and mode of action, respectively: Category 1 comprises nanomaterials for which toxicity is mediated by the specific chemical properties of its components, such as released ions or functional groups on the surface. Nanomaterials belonging to this category have to be evaluated on a case-by-case basis, depending on their chemical identity. Category 2 focuses on rigid biopersistent respirable fibrous nanomaterials with a specific geometry and high aspect ratio (so-called WHO fibres). For these fibres, hazard assessment can be based on the experiences with asbestos. Category 3 focuses on respirable granular biodurable particles (GBP) which, after inhalation, may cause inflammation and secondary mutagenicity that may finally lead to lung cancer. After intravenous, oral or dermal exposure, nanoscaled GBPs investigated apparently did not show ‘nanospecific’ effects so far. Hazard assessment of GBPs may be based on the knowledge available for granular particles. In conclusion, we believe the proposed categorization system will facilitate future hazard assessments.

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References

  • AGS (2011) Wissensstand bezüglich möglicher Wirkprinzipien und Gesundheitsgefahren durch Exposition mit arbeitsplatzrelevanten Nanomaterialien. http://www.baua.de/de/Themen-von-A-Z/Gefahrstoffe/AGS/AGS-zu-Nanomaterialien.html

  • Almeida JP, Chen AL, Foster A, Drezek R (2011) In vivo biodistribution of nanoparticles. Nanomedicine (Lond) 6:815–835

    CAS  Google Scholar 

  • Al-Rawi M, Diabaté S, Weiss C (2011) Uptake and intracellular localization of submicron and nano-sized SiO2 particles in HeLa cells. Arch Toxicol 85:813–826

    CAS  PubMed  Google Scholar 

  • Arbeitsmedizin (BAuA, research project no. F2246). http://www.baua.de/de/Publikationen/Fachbeitraege/F2246.html

  • Astruc D, Lu F, Aranzaes JR (2005) Nanoparticles as recyclable catalysts: the frontier between homogeneous and heterogeneous catalysis. Angew Chem (Int Ed Engl) 44:7852–7872

    CAS  Google Scholar 

  • Baan RA (2007) Carcinogenic hazards from inhaled carbon black, titanium dioxide, and talc not containing asbestos or asbestiform fibres: recent evaluations by an IARC Monographs Working Group. Inhal Toxicol 19(Suppl 1):213–228

    CAS  PubMed  Google Scholar 

  • Baek M, Chung HE, Yu J, Lee JA, Kim TH, Oh JM, Lee WJ, Paek SM, Lee JK, Jeong J, Choy JH, Choi SJ (2012) Pharmacokinetics, tissue distribution, and excretion of zinc oxide nanoparticles. Int J Nanomed 7:3081–3097

    Google Scholar 

  • Balasubramanyam A, Sailaja N, Mahboob M, Rahman MF, Hussain SM, Grover P (2009) In vivo genotoxicity assessment of aluminium oxide nanomaterials in rat peripheral blood cells using the comet assay and micronucleus test. Mutagenesis 24:245–251

    CAS  PubMed  Google Scholar 

  • Beyersmann D, Hartwig A (2008) Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms. ArchToxicol 82:493–512

    CAS  Google Scholar 

  • Boisen AM, Shipley T, Jackson P, Hougaard KS, Wallin H, Yauk CL, Vogel U (2012) NanoTiO2 (UV-Titan) does not induce ESTR mutations in the germline of prenatally exposed female mice. Part FibreToxicol 9:19

    CAS  Google Scholar 

  • Bolt HM, Marchan R, Hengstler JG (2013) Recent developments in nanotoxicology (editorial). Arch Toxicol 87:927–928

    CAS  PubMed  Google Scholar 

  • Bordea C, Latifaj B, Jaffe W (2009) Delayed presentation of tattoo lymphadenopathy mimicking malignant melanoma lymphadenopathy. J Plast Reconstr Aesthet Surg 62:e283–e285

    CAS  PubMed  Google Scholar 

  • Bourdon JA, Saber AT, Jacobsen NR, Jensen KA, Madsen AM, Lamson JS, Wallin H, Møller P, Loft S, Yauk CL, Vogel UB (2012) Carbon black nanoparticle instillation induces sustained inflammation and genotoxicity in mouse lung and liver. Part Fibre Toxicol 9:5

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cangul H, Broday L, Salnikow K, Sutherland J, Peng W, Zhang Q, Poltaratsky V, Yee H, Zoroddu MA, Costa M (2002) Molecular mechanisms of nickel carcinogenesis. Toxicol Lett 127:69–75

    CAS  PubMed  Google Scholar 

  • Cedervall T, Lynch I, Lindman S, Berggård T, Thulin E, Nilsson H, Dawson KA, Linse S (2007) Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Proc Natl Acad Sci USA 104(7):2050–2055

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chen N, He Y, Su Y, Li X, Huang Q, Wang H, Zhang X, Tai R, Fan C (2012) The cytotoxicity of cadmium-based quantum dots. Biomaterials 33:1238–1244

    CAS  PubMed  Google Scholar 

  • Chithrani BD, Chan WC (2007) Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. Nano Lett 7:1542–1550

    CAS  PubMed  Google Scholar 

  • Chithrani BD, Ghazani AA, Chan WC (2006) Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 2006(6):662–668

    Google Scholar 

  • Cho WS, Kang BC, Lee JK, Jeong J, Che JH, Seok SH (2013) Comparative absorption, distribution, and excretion of titanium dioxide and zinc oxide nanoparticles after repeated oral administration. Part Fibre Toxicol 10:9

    CAS  PubMed Central  PubMed  Google Scholar 

  • Choi HS, Ashitate Y, Lee JH, Kim SH, Matsui A, Insin N, Bawendi MG, Semmler-Behnke M, Frangioni JV, Tsuda A (2010) Rapid translocation of nanoparticles from the lung airspaces to the body. Nat Biotechnol 28:1300–1303

    CAS  PubMed Central  PubMed  Google Scholar 

  • Corma A, Garcia H (2008) Supported gold nanoparticles as catalysts for organic reactions. Chem Soc Rev 37:2096–2126

    CAS  PubMed  Google Scholar 

  • Costa M, Sutherland JE, Peng W, Salnikow K, Broday L, Kluz T (2001) Molecular biology of nickel carcinogenesis. Mol Cell Biochem 222:205–211

    CAS  PubMed  Google Scholar 

  • Creutzenberg O (2013) Toxic effects of various modifications of a nanoparticle following inhalation. Bundesanstalt für Arbeitsschutz und, Dortmund

    Google Scholar 

  • Creutzenberg O, Bellmann B, Korolewitz R, Koch W, Mangelsdorf I, Tillmann T, Schaudien D (2012) Change in agglomeration status and toxicokinetic fate of various nanoparticles in vivo following lung exposure in rats. Inhal Toxicol 24(12):821–830

    CAS  PubMed  Google Scholar 

  • Dandekar P, Dhumal R, Jain R, Tiwari D, Vanage G, Patravale V (2010) Toxicological evaluation of pH-sensitive nanoparticles of curcumin: acute, sub-acute and genotoxicity studies. Food Chem Toxicol 48:2073–2089

    CAS  PubMed  Google Scholar 

  • Danielsen PH, Loft S, Jacobsen NR, Jensen KA, Autrup H, Ravanat JL, Wallin H, Møller P (2010) Oxidative stress, inflammation, and DNA damage in rats after intratracheal instillation or oral exposure to ambient air and wood smoke particulate matter. Toxicol Sci 118:574–585

    CAS  PubMed  Google Scholar 

  • Dankovic D, Kuempel E, Wheeler M (2007) An approach to risk assessment for TiO2. Inhal Toxicol 19(Suppl 1):205–212

    CAS  PubMed  Google Scholar 

  • De Jong WH, Hagens WI, Krystek P, Burger MC, Sips AJAM, Geertsma RE (2008) Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. Biomaterials 29:1912–1919

    PubMed  Google Scholar 

  • Demokritou P, Gass S, Pyrgiotakis G, Cohen JM, Goldsmith W, McKinney W, Frazer D, Ma J, Schwegler-Berry D, Brain J, Castranova V (2013) An in vivo and in vitro toxicological characterisation of realistic nanoscale CeO2 inhalation exposures. Nanotoxicology 7:1338–1350

    CAS  PubMed  Google Scholar 

  • Deng ZJ, Liang M, Monteiro M, Toth I, Minchin RF (2011) Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and Inflammation. Nat Nanotechnol 6:39–44

    CAS  PubMed  Google Scholar 

  • do Hwang W, Lee DS, Kim S (2012) Gene expression profiles for genotoxic effects of silica-free and silica-coated cobalt ferrite nanoparticles. J Nucl Med 53:106–112

    CAS  Google Scholar 

  • Doak SH, Manshian B, Jenkins GJS, Singh N (2012) In vitro genotoxicity testing strategy for nanomaterials and the adaptation of current OECD guidelines. Mutat Res 745:104–111

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dobrzyńska MM, Gajowik A, Radzikowska J, Lankoff A, Dušinská M, Kruszewski M (2014) Genotoxicity of silver and titanium dioxide nanoparticles in bone marrow cells of rats in vivo. Toxicology 315:86–91

    PubMed  Google Scholar 

  • Donaldson K, Poland CA (2013) Nanotoxicity: challenging the myth of nano-specific toxicity. Curr Opin Biotechnol 24:724–734

    CAS  PubMed  Google Scholar 

  • Donaldson K, Murphy FA, Duffin R, Poland CA (2010) 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 7:5

    PubMed Central  PubMed  Google Scholar 

  • Donaldson K, Poland CA, Murphy FA, MacFarlane M, Chernova T, Schinwald A (2013) Pulmonary toxicity of carbon nanotubes and asbestos—similarities and differences. Adv Drug Deliv Rev 65:2078–2086

    CAS  PubMed  Google Scholar 

  • Driscoll KE, Carter JM, Howard BW, Hassenbein DG, Pepelko W, Baggs RB, Oberdörster G (1996) Pulmonary inflammatory, chemokine, and mutagenic responses in rats after subchronic inhalation of carbon black. Toxicol Appl Pharmacol 136:372–380

    CAS  PubMed  Google Scholar 

  • Driscoll KE, Deyo LC, Carter JM, Howard BW, Hassenbein DG, Bertram TA (1997) Effects of particle exposure and particle-elicited inflammatory cells on mutation in rat alveolar epithelial cells. Carcinogenesis 18:423–430

    CAS  PubMed  Google Scholar 

  • Duan X, Li Y (2012) Physicochemical characteristics of nanoparticles affect circulation, biodistribution, cellular internalization, and trafficking. Small 9:1521–1532

    PubMed  Google Scholar 

  • Elder A, Gelein R, Finkelstein JN, Driscoll KE, Harkema J, Oberdörster G (2005) Effects of subchronically inhaled carbon black in three species. I. Retention kinetics, lung inflammation, and histopathology. Toxicol Sci 88:614–629

    CAS  PubMed  Google Scholar 

  • Elvevold K, Smedsrød B, Martinez I (2008) The liver sinusoidal endothelial cell: a cell type of controversial and confusing identity. Am J Physiol Gastrointest Liver Physiol 294:G391–G400

    CAS  PubMed  Google Scholar 

  • Ema M, Tanaka J, Kobayashi N, Naya M, Endoh S, Maru J, Hosoi M, Nagai M, Nakajima M, Hayashi M, Nakanishi J (2012) Genotoxicity evaluation of fullerene C60 nanoparticles in a comet assay using lung cells of intratracheally instilled rats. Regul Toxicol Pharmacol 62:419–424

    CAS  PubMed  Google Scholar 

  • Engel E, Vasold R, Santarelli F, Maisch T, Gopee NV, Howard PC, Landthaler M, Bäumler W (2010) Tattooing of skin results in transportation and light-induced decomposition of tattoo pigments—a first quantification in vivo using a mouse model. Exp Dermatol 19:54–60

    CAS  PubMed  Google Scholar 

  • Estevanato L, Cintra D, Baldini N, Portilho F, Barbosa L, Martins O, Lacava B, Miranda-Vilela AL, Tedesco AC, Báo S, Morais PC, Lacava ZG (2011) Preliminary biocompatibility investigation of magnetic albumin nanosphere designed as a potential versatile drug delivery system. Int J Nanomed 6:1709–1717

    CAS  Google Scholar 

  • European Commission (2011a) Regulation (EU) No 1169/2011 of the European Parliament and of the Council of 25 October 2011 on the provision of food information to consumers, amending regulations (EC) No 1924/2006 and (EC) No 1925/2006 of the European Parliament and of the Council, and repealing Commission Directive 87/250/EEC, Council Directive 90/496/EEC, Commission Directive 1999/10/EC, Directive 2000/13/EC of the European Parliament and of the Council, Commission Directives 2002/67/EC and 2008/5/EC and Commission Regulation (EC) No 608/2004. Off J Eur Union L 304/18, 22.11.2011

  • European Commission (2011b) Commission recommendation of 18 October 2011 on the definition of nanomaterial. Off J Eur Union L 275/38, 20.10.2011, http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2011:275:0038:0040:EN:PDF)

  • Ferin J, Oberdörster G, Penney DP (1992) Pulmonary retention of ultrafine and fine particles in rats. Am J Respir Cell Mol Biol 6:535–542

    CAS  PubMed  Google Scholar 

  • Filipe P, Silva JP, Silva R, Cirne de Castro JL, Marques Gomes M, Alves LC, Santus R, Pinheiro T (2009) Stratum corneum is an effective barrier to TiO2 and ZnO nanoparticle percutaneous absorption. Skin Pharmacol Physiol 22:266–275

    CAS  PubMed  Google Scholar 

  • Folkmann JK, Risom L, Jacobsen NR, Wallin H, Loft S, Moller P (2009) Oxidatively damaged DNA in rats exposed by oral gavage to C60 fullerenes and single-walled carbon nanotubes. Environ Health Perspect 117:703–708

    CAS  PubMed Central  PubMed  Google Scholar 

  • Freitas MLL, Silva LP, Azevedo RB, Garcia VAP, Lacava LM, Grisólia CK, Lucci CM, Morais PC, Da Silva MF, Buske N, Curi R, Lacava ZGM (2002) A double-coated magnetite-based magnetic fluid evaluation by cytometry and genetic tests. J Magn Magn Mater 252:396–398

    CAS  Google Scholar 

  • Fubini B (1997) Surface reactivity in the pathogenic response to particulates. Environ Health Perspect 105(Suppl 5):1013–1020

    PubMed Central  PubMed  Google Scholar 

  • Fubini B, Bolis V, Cavenago A, Volante M (1995) Physicochemical properties of crystalline silica dusts and their possible implication in various biological responses. Scand J Work Environ Health 21(Suppl 2):9–14

    CAS  PubMed  Google Scholar 

  • Fubini B, Ghiazza M, Fenoglio I (2010) Physico-chemical features of engineered nanoparticles relevant to their toxicity. Nanotoxicology 4:347–363

    CAS  PubMed  Google Scholar 

  • Gallagher J, Sams R 2nd, Inmon J, Gelein R, Elder A, Oberdörster G, Prahalad AK (2003) Formation of 8-oxo-7,8-dihydro-2′-deoxyguanosine in rat lung DNA following subchronic inhalation of carbon black. Toxicol Appl Pharmacol 190:224–231

    CAS  PubMed  Google Scholar 

  • Gebel T (2012) Small difference in carcinogenic potency between GBP nanomaterials and GBP micromaterials. ArchToxicol 86:995–1007

    CAS  Google Scholar 

  • Gebel T (2013) Health hazards of nanomaterials: anxiety versus science. In: Luther W, Zweck A (eds) Aspects of engineered nanomaterials. Pan Stanford Publ, Singapore, pp 219–233

    Google Scholar 

  • Gebel T, Landsiedel R (2013) Inhalte der Sicherheitsforschung: Langzeitwirkungen biobeständiger Nanostäube. Gefahrstoffe Reinhalt Luft 10:414

    Google Scholar 

  • Gehrke H, Fruhmesser A, Pelka J, Esselen M, Hecht LL, Blank H, Schuchmann HP, Gerthsen D, Marquardt C, Diabaté S, Weiss C, Marko D (2013) In vitro toxicity of amorphous silica nanoparticles in human colon carcinoma cells. Nanotoxicology 7:274–293

    CAS  PubMed  Google Scholar 

  • Ghosh MJM, Sinha S, Chakraborty A, Mallick SK, Bandyopadhyay M, Mukherjee A (2012) In vitro and in vivo genotoxicity of silver nanoparticles. Mutat Res 749:60–69

    CAS  PubMed  Google Scholar 

  • Goodman CM, McCusker CD, Yilmaz T, Rotello VM (2004) Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. Bioconjug Chem 15:897–900

    CAS  PubMed  Google Scholar 

  • Gopee NV, Cui Y, Olson G, Warbritton AR, Miller BJ, Couch LH, Wamer WG, Howard PC (2005) Response of mouse skin to tattooing: use of SKH-1 mice as a surrogate model for human tattooing. Toxicol Appl Pharmacol 209:145–158

    CAS  PubMed  Google Scholar 

  • Grassian VH, Adamcakova-Dodd A, Pettibone JM, O’Shaughnessy PI, Thorne PS (2007) Inflammatory response of mice to manufactured titanium dioxide nanoparticles: comparison of size effects through different exposure routes. Nanotoxicology 1:211–226

    CAS  Google Scholar 

  • Hadrup N, Loeschner K, Mortensen A, Sharma AK, Qvortrup K, Larsen EH, Lam HR (2012) The similar neurotoxic effects of nanoparticulate and ionic silver in vivo and in vitro. NeuroToxicol 33:416–423

    CAS  Google Scholar 

  • Høgsberg T, Saunte DM, Frimodt-Møller N, Serup J (2013) Microbial status and product labelling of 58 original tattoo inks. J Eur Acad Dermatol Venereol 27:73–80

    PubMed  Google Scholar 

  • Hwang YJ, Jeung YS, Seo MH, Yoon JY, Kim DY, Park JW, Han JH, Jeong SH (2010) Asian dust and titanium dioxide particles-induced inflammation and oxidative DNA damage in C57BL/6 mice. Inhal Toxicol 22:1127–1133

    CAS  PubMed  Google Scholar 

  • Jackson P, Hougaard KS, Boisen AM, Jacobsen NR, Jensen KA, Møller P, Brunborg G, Gutzkow KB, Andersen O, Loft S, Vogel U, Wallin H (2012) Pulmonary exposure to carbon black by inhalation or instillation in pregnant mice: effects on liver DNA strand breaks in dams and offspring. Nanotoxicology 6:486–500

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jacobsen NR, Møller P, Jensen KA, Vogel U, Ladefoged O, Loft S, Wallin H (2009) Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE −/− mice. Part FibreToxicol 6:2

    Google Scholar 

  • Katsnelson BA, Privalova LI, Gurvich VB, Makeyev OH, Shur VY, Beikin YB, Sutunkova MP, Kireyeva EP, Minigalieva IA, Loginova NV, Vasilyeva MS, Korotkov AV, Shuman EA, Vlasova LA, Shishkina EV, Tyurnina AE, Kozin RV, Valamina IE, Pichugova SV, Tulakina LG (2013) Comparative in vivo assessment of some adverse bioeffects of equidimensional gold and silver nanoparticles and the attenuation of nanosilver’s effects with a complex of innocuous bioprotectors. Int J Mol Sci 14:2449–2483

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kettler K, Veltman K, van de Meent D, van Wezel A, Hendriks AJ (2014) Cellular uptake of nanoparticles as determined by particle properties, experimental conditions, and cell type. Environ Toxicol Chem 33:481–492

    CAS  PubMed  Google Scholar 

  • Khalil WK, Girgis E, Emam AN, Mohamed MB, Rao KV (2011) Genotoxicity evaluation of nanomaterials: DNA damage, micronuclei, and 8-hydroxy-2-deoxyguanosine induced by magnetic doped CdSe quantum dots in male mice. Chem Res Toxicol 24:640–650

    CAS  PubMed  Google Scholar 

  • Khlebtsov N, Dykman L (2011) Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies. Chem Soc Rev 40:1647–1671

    CAS  PubMed  Google Scholar 

  • Kim YS, Kim JS, Cho HS, Rha DS, Kim JM, Park JD, Choi BS, Lim R, Chang HK, Chung YH, Kwon IH, Jeong J, Han BS, Yu IJ (2008) Twenty-eight-day oral toxicity, genotoxicity, and gender-related tissue distribution of silver nanoparticles in Sprague–Dawley rats. Inhal Toxicol 20:575–583

    CAS  PubMed  Google Scholar 

  • Kim JS, Sung JH, Ji JH, Song KS, Lee JH, Kang CS, Yu IJ (2011) In vivo genotoxicity of silver nanoparticles after 90-day silver nanoparticle inhalation exposure. Saf Health Work 2(1):34–38

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kirkland D, Pfuhler S, Tweats D, Aardema M, Corvi R, Darroudi F, Elhajouji A, Glatt H, Hastwell P, Hayashi M, Kasper P, Kirchner S, Lynch A, Marzin D, Maurici D, Meunier JR, Müller L, Nohynek G, Parry J, Parry E, Thybaud V, Tice R, van Benthem J, Vanparys P, White P (2007) How to reduce false positive results when undertaking in vitro genotoxicity testing and thus avoid unnecessary follow-up animal tests: report of an ECVAM workshop. Mutat Res 628:31–55

    CAS  PubMed  Google Scholar 

  • Krug HF, Wick P (2011) Nanotoxicology: an interdisciplinary challenge. Angew Chem (Int Ed Engl) 50:1260–1278

    CAS  Google Scholar 

  • Kuempel ED, Castranova V, Geraci CL, Schulte PA (2012) Development of risk-based nanomaterial groups for occupational exposure control. J Nanopart Res 14:1029

    Google Scholar 

  • Kumar A, Dhawan A (2013) Genotoxic and carcinogenic potential of engineered nanoparticles: an update. ArchToxicol 87:1883–1900

    CAS  Google Scholar 

  • Kunzmann A, Andersson B, Thurnherr T, Krug H, Scheynius A, Fadeel B (2011) Toxicology of engineered nanomaterials: focus on biocompatibility, biodistribution and biodegradation. Biochim Biophys Acta 1810:361–373

    CAS  PubMed  Google Scholar 

  • Landsiedel R, Ma-Hock L, Van Ravenzwaay B, Schulz M, Wiench K, Champ S, Schulte S, Wohlleben W, Oesch F (2010) Gene toxicity studies on titanium dioxide and zinc oxide nanomaterials used for UV-protection in cosmetic formulations. Nanotoxicology 4:364–381

    CAS  PubMed  Google Scholar 

  • Landsiedel R, Ma-Hock L, Haussmann HJ, van Ravenzwaay B, Kayser M, Wiench K (2012a) Inhalation studies for the safety assessment of nanomaterials: status quo and the way forward. Wiley Interdiscip Rev Nanomed Nanobiotechnol 4:399–413

    CAS  PubMed  Google Scholar 

  • Landsiedel R, Fabian E, Ma-Hock L, Wohlleben W, Wiench K, Oesch F, van Ravenzwaay B (2012b) Toxico-/biokinetics of nanomaterials. Arch Toxicol 86:1021–1060

    CAS  PubMed  Google Scholar 

  • LeFevre ME, Green FH, Joel DD, Laqueur W (1982) Frequency of black pigment in livers and spleens of coal workers: correlation with pulmonary pathology and occupational information. Hum Pathol 13:1121–1126

    CAS  PubMed  Google Scholar 

  • Lewinski N, Colvin V, Drezek R (2008) Cytotoxicity of nanoparticles. Small 4:26–49

    CAS  PubMed  Google Scholar 

  • Li X, Lenhart JJ, Walker HW (2012a) Aggregation kinetics and dissolution of coated silver nanoparticles. Langmuir 28:1095–1104

    CAS  PubMed  Google Scholar 

  • Li CH, Shen CC, Cheng YW, Huang SH, Wu CC, Kao CC, Liao JW, Kang JJ (2012b) Organ biodistribution, clearance, and genotoxicity of orally administered zinc oxide nanoparticles in mice. Nanotoxicology 6:746–756

    CAS  PubMed  Google Scholar 

  • Li Y, Bhalli JA, Ding W, Yan J, Pearce MG, Sadiq R, Cunningham CK, Jones MY, Monroe WA, Howard PC, Zhou T, Chen T (2014) Cytotoxicity and genotoxicity assessment of silver nanoparticles in mouse. Nanotoxicology 8(Suppl 1):36–45

  • Lindberg HK, Falck GC, Catalán J, Koivisto AJ, Suhonen S, Järventaus H, Rossi EM, Nykäsenoja H, Peltonen Y, Moreno C, Alenius H, Tuomi T, Savolainen KM, Norppa H (2012) Genotoxicity of inhaled nanosized TiO2 in mice. Mutat Res 745:58–64

    CAS  PubMed  Google Scholar 

  • Magdolenova Z, Collins A, Kumar A, Dhawan A, Stone V, Dusinska M (2014) Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles. Nanotoxicology 8:233–278

    CAS  PubMed  Google Scholar 

  • Ma-Hock L, Treumann S, Strauss V, Brill S, Luizi F, Mertler M, Wiench K, Gamer AO, van Ravenzwaay B, Landsiedel R (2009) Inhalation toxicity of multiwall carbon nanotubes in rats exposed for 3 months. Toxicol Sci 112:468–481

    CAS  PubMed  Google Scholar 

  • Marchan R (2012) A special issue on nanotoxicology. (editorial). EXCLI J 11:176–177

    Google Scholar 

  • McShan D, Ray PC, Yu H (2014) Molecular toxicity mechanism of nanosilver. J Food Drug Anal 22:116–127

    CAS  PubMed  Google Scholar 

  • Monteiro-Riviere NA, Wiench K, Landsiedel R, Schulte S, Inman AO, Riviere JE (2011) Safety evaluation of sunscreen formulations containing titanium dioxide and zinc oxide nanoparticles in UVB sunburned skin: an in vitro and in vivo study. Toxicol Sci 123:264–280

    CAS  PubMed  Google Scholar 

  • Moreno-Horn M, Gebel T (2014) Granular biodurable nanomaterials: no convincing evidence for systemic toxicity. Crit Rev Toxicol 26:1–27

  • Muller J, Decordier I, Hoet PH, Lombaert N, Thomassen L, Huaux F, Lison D, Kirsch-Volders M (2008) Clastogenic and aneugenic effects of multi-wall carbon nanotubes in epithelial cells. Carcinogenesis 29:427–433

    CAS  PubMed  Google Scholar 

  • Nanotechnology Nature (2012) Editorial: join the dialogue. Nat Nanotechnol 7:545. doi:10.1038/nnano.2012.150

    Google Scholar 

  • Naya M, Kobayashi N, Ema M, Kasamoto S, Fukumuro M, Takami S, Nakajima M, Hayashi M, Nakanishi J (2012) In vivo genotoxicity study of titanium dioxide nanoparticles using comet assay following intratracheal instillation in rats. Regul Toxicol Pharmacol 62:1–6

    CAS  PubMed  Google Scholar 

  • Nel A, Xia T, Meng H, Wang X, Lin S, Ji Z, Zhang H (2013) Nanomaterial toxicity testing in the 21st century: use of a predictive toxicological approach and high-throughput screening. Acc Chem Res 46:607–621

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nohynek GJ, Lademann J, Ribaud C, Roberts MS (2007) Grey goo on the skin? Nanotechnology, cosmetic and sunscreen safety. Crit Rev Toxicol 37:251–277

    CAS  PubMed  Google Scholar 

  • Nohynek GJ, Dufour EK, Roberts MS (2008) Nanotechnology, cosmetics and the skin: is there a health risk. Skin Pharmacol Physiol 21:136–149

    CAS  PubMed  Google Scholar 

  • Nohynek GJ, Antignac E, Re T, Toutain H (2010) Safety assessment of personal care products/cosmetics and their ingredients. Toxicol Appl Pharmacol 243:239–259

    CAS  PubMed  Google Scholar 

  • Norppa H, Catalan J, Falck G, Hannukainen K, Siivola K, Savolainen K (2011) Nano-specific genotoxic effects. J Biomed Nanotechnol 7(1):19

    CAS  PubMed  Google Scholar 

  • Oberdörster G (2002) Toxicokinetics and effects of fibrous and nonfibrous particles. Inhal Toxicol 14:29–56

    PubMed  Google Scholar 

  • Oberdörster G, Ferin J, Gelein R, Soderholm SC, Finkelstein J (1992) Role of the alveolar macrophage in lung injury: studies with ultrafine particles. Environ Health Perspect 97:193–199

    PubMed Central  PubMed  Google Scholar 

  • Oberdörster G, Ferin J, Lehnert BE (1994) Correlation between particle size, in vivo particle persistence, and lung injury. Environ Health Perspect 102(Suppl 5):173–179

    PubMed Central  PubMed  Google Scholar 

  • OECD (2007) Working party on manufactured nanomaterials (WPMN). http://www.oecd.org/sti/nano/oecdworkingpartyonnanotechnologywpnvisionstatement.htm

  • OECD (2010) Series on the safety of manufactured nanomaterials, No. 27: list of manufactured nanomaterials and list of endpoints for phase one testing of the sponsorship programme for the testing of manufactured nanomaterials: revision. ENV/JM/MONO 46

  • Oesch F, Landsiedel R (2012) Genotoxicity investigations on nanomaterials. Arch Toxicol 86:985–994

    CAS  PubMed  Google Scholar 

  • Oomen AG, Bos PM, Fernandes TF, Hund-Rinke K, Boraschi D, Byrne HJ, Aschberger K, Gottardo S, von der Kammer F, Kühnel D, Hristozov D, Marcomini A, Migliore L, Scott-Fordsmand J, Wick P, Landsiedel R (2014) Concern-driven integrated approaches to nanomaterial testing and assessment: report of the NanoSafety Cluster Working Group 10. Nanotoxicology 8:334–348

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ordzhonikidze CG, Ramaiyya LK, Egorova EM, Rubanovich AV (2009) Genotoxic effects of silver nanoparticles on mice in vivo. Acta Nat 1(3):99–101

    CAS  Google Scholar 

  • Panas A, Marquardt C, Nalcaci O, Bockhorn H, Baumann W, Paur H-R, Mulhopt S, Diabaté S, Weiss C (2013) Screening of different metal oxide nanoparticles reveals selective toxicity and inflammatory potential of silica nanoparticles in lung epithelial cells and macrophages. Nanotoxicology 7:259–273

    CAS  PubMed  Google Scholar 

  • Pauluhn J (2009) Pulmonary toxicity and fate of agglomerated 10 and 40 nm aluminium oxyhydroxides following 4-week inhalation exposure of rats: toxic effects are determined by agglomerated, not primary particle size. Toxicol Sci 109:152–167

    CAS  PubMed  Google Scholar 

  • Pauluhn J (2011) Poorly soluble particulates: searching for a unifying denominator of nanoparticles and fine particles for DNEL estimation. Toxicology 279:176–188

    CAS  PubMed  Google Scholar 

  • Petrochenko PE, Zhang Q, Bayati MR, Skoog SA, Scott Phillips K, Kumar G, Narayan RJ, Goering PL (2014) Cytotoxic evaluation of nanostructured zinc oxide (ZnO) thin films and leachates. Toxicol In Vitro 28(6):1144–1152

    CAS  PubMed  Google Scholar 

  • Pinheiro T, Allon J, Alves LC, Filipe P, Silva JN (2007) The influence of corneocyte structure on the interpretation of permeation profiles of nanoparticles across the skin. Nucl Instrum Methods Phys Res B 260:119–123

    CAS  Google Scholar 

  • Pott F, Huth F, Friedrichs KH (1972) Tumors of rats after i.p. injection of powdered chrysotile and benzo(a)pyrene. Zentralbl Bakteriol Orig B 155:463–469

    CAS  PubMed  Google Scholar 

  • Pott F, Ziem U, Reiffer FJ, Huth F, Ernst H, Mohr U (1987) Carcinogenicity studies on fibres, metal compounds, and some other dusts in rats. Exp Pathol 32:129–152

    CAS  PubMed  Google Scholar 

  • Preining O (1998) The physical nature of very, very small particles and its impact on their behaviour. J Aerosol Sci 29:481–495

    CAS  Google Scholar 

  • Rehn B, Seiler F, Rehn S, Bruch J, Maier M (2003) Investigations on the inflammatory and genotoxic lung effects of two types of titanium dioxide: untreated and surface treated. Toxicol Appl Pharmacol 189:84–95

    CAS  PubMed  Google Scholar 

  • Rivera Gil P, Oberdörster G, Elder A, Puntes V, Parak WJ (2010) Correlating physico-chemical with toxicological properties of nanoparticles: the present and the future. ACS Nano 4:5527–5531

    CAS  PubMed  Google Scholar 

  • Riviere JE (2009) Pharmacokinetics of nanomaterials: an overview of carbon nanotubes, fullerenes and quantum dots. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1:26–34. Erratum in: Wiley Interdiscip Rev Nanomed Nanobiotechnol 1:685 (2009)

  • Roller M (2009) Carcinogenicity of inhaled nanoparticles. Inhal Toxicol 21(Suppl 1):144–157

    CAS  PubMed  Google Scholar 

  • Roller M (2012) Time-to-tumor dose threshold analysis for intratracheal particle instillation-induced lung tumors in a large carcinogenicity study. Int J Occup Environ Health 18:278–291

    PubMed  Google Scholar 

  • Roller M, Pott F (2006) Lung tumor risk estimates from rat studies with not specifically toxic granular dusts. Ann NY Acad Sci 1076:266–280

    CAS  PubMed  Google Scholar 

  • Ruh H, Kuhl B, Brenner-Weiss G, Hopf C, Diabaté S, Weiss C (2012) Identification of serum proteins bound to industrial nanomaterials. Toxicol Lett 208:41–50

    CAS  PubMed  Google Scholar 

  • Saber AT, Jensen KA, Jacobsen NR, Birkedal R, Mikkelsen L, Møller P, Loft S, Wallin H, Vogel U (2011) Inflammatory and genotoxic effects of nanoparticles designed for inclusion in paints and lacquers. Nanotoxicology 6:453–471

    PubMed  Google Scholar 

  • Sadeghiani NBL, Silva LP, Azevedo RB, Morais PC, Lacava ZGM (2005) Genotoxicity and inflammatory investigation in mice treated with magnetite nanoparticles surface coated with polyaspartic acid. J Magn Magn Mater 289:466–468

    CAS  Google Scholar 

  • Sadiq R, Bhalli JA, Yan J, Woodruff RS, Pearce MG, Li Y, Mustafa T, Watanabe F, Pack LM, Biris AS, Khan QM, Chen T (2012) Genotoxicity of TiO2 anatase nanoparticles in B6C3F1 male mice evaluated using Pig-a and flow cytometric micronucleus assays. Mutat Res 745:65–72

    CAS  PubMed  Google Scholar 

  • Sakamoto Y, Nakae D, Fukumori N, Tayama K, Maekawa A, Imai K, Hirose A, Nishimura T, Ohashi N, Ogata A (2009) Induction of mesothelioma by a single intrascrotal administration of multi-wall carbon nanotube in intact male Fischer 344 rats. J Toxicol Sci 34:65–76

    CAS  PubMed  Google Scholar 

  • Saleh NB, Afrooz ARM, Khan IA, Hussain SM (2013) Mechanistic heteroaggregation of gold nanoparticles in a wide range of solution chemistry. Environ Sci Technol 47:1853–1860

    PubMed  Google Scholar 

  • Sayes CM, Reed KL, Glover KP, Swain KA, Ostraat ML, Donner EM, Warheit DB (2010) Changing the dose metric for inhalation toxicity studies: short-term study in rats with engineered aerosolized amorphous silica nanoparticles. Inhal Toxicol 22:348–354

    CAS  PubMed  Google Scholar 

  • Sayes CM, Smith PA, Ivanov IV (2013) A framework for grouping nanoparticles based on their measurable characteristics. Int J Nanomedicine 8(Suppl 1):45–56

    CAS  PubMed Central  PubMed  Google Scholar 

  • SCCS (2011) Scientific committee on consumer safety: opinion on 1,3,5-triazine, 2,4,6-tris[1,1′-biphenyl]-4-yl-. SCCS/1429/11. European Union, Brussels. http://ec.europa.eu/health/scientificcommittees/consumersafety/docs/sccso070.pdf

  • SCCS (2014a) Scientific committee on consumer safety. Addendum to the opinion SCCS/1489/12 on zinc oxide (nano form) Colipa no. S76. SCCS/1518/13. European Union, Brussels. http://ec.europa.eu/health/scientificcommittees/consumersafety/docs/sccso137.pdf

  • SCCS (2014b) Scientific committee on consumer safety. Opinion on titanium dioxide (nano form). Colipa no. S75. SCCS/1516/13. European Union, Brussels. http://ec.europa.eu/health/scientificcommittees/consumersafety/docs/sccso136.pdf

  • SCCS (2014c) Scientific committee on consumer safety. Opinion on carbon black (nano-form). SCCS/1515/13. European Union, Brussels. http://ec.europa.eu/health/scientificcommittees/consumersafety/docs/sccso144.pdf

  • Schulz M, Ma-Hock L, Brill S, Strauss V, Treumann S, Gröters S, van Ravenzwaay B, Landsiedel R (2012) Investigation on the genotoxicity of different sizes of gold nanoparticles administered to the lungs of rats. Mutat Res 745:51–57

    CAS  PubMed  Google Scholar 

  • Sharma V, Singh P, Pandey AK, Dhawan A (2012) Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles. Mutat Res 745:84–91

    CAS  PubMed  Google Scholar 

  • Shi H, Magaye R, Castranova V, Zhao J (2013) Titanium dioxide nanoparticles: a review of current toxicological data. Part Fibre Toxicol 10:15

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shinohara N, Matsumoto K, Endoh S, Maru J, Nakanishi J (2009) In vitro and in vivo genotoxicity tests on fullerene C60 nanoparticles. Toxicol Lett 191:289–296

    CAS  PubMed  Google Scholar 

  • Singh N, Manshian B, Jenkins GJ, Griffiths SM, Williams PM, Maffeis TG, Wright CJ, Doak SH (2009) NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials 30:3891–3914

    CAS  PubMed  Google Scholar 

  • Sonavane G, Tomoda K, Sano A, Ohshima H, Terada H, Makino K (2008) In vitro permeation of gold nanoparticles through rat skin and rat intestine: effect of particle size. Colloids Surf B: Biointerfaces 65:1–10

    CAS  PubMed  Google Scholar 

  • Song W, Zhang J, Guo J, Zhang J, Ding F, Li L, Sun Z (2010) Role of the dissolved zinc ion and reactive oxygen species in cytotoxicity of ZnO nanoparticles. Toxicol Lett 199:389–397

    CAS  PubMed  Google Scholar 

  • Song MF, Li YS, Kasai H, Kawai K (2012) Metal nanoparticle-induced micronuclei and oxidative DNA damage in mice. J Clin Biochem Nutr 50:211–216

    CAS  PubMed Central  PubMed  Google Scholar 

  • SRU (2011a) Sachverständigenrat für Umweltfragen. Precautionary strategies for managing nanomaterials, chapt. 7: conclusions and recommendations. SRU, Berlin, pp 1–38. http://www.umweltrat.de/SharedDocs/Downloads/EN/02SpecialReports/201108PrecautionaryStrategiesformanagingNanomaterialschapter07.html

  • SRU (2011b) Sachverständigenrat für Umweltfragen. Vorsorgestrategien für Nanomaterialien. Sondergutachten. SRU, Berlin. http://www.umweltrat.de/SharedDocs/Downloads/DE/02Sondergutachten/201109SGVorsorgestrategien%20f%C3%BCr%20Nanomaterialien.pdf?blob=publicationFile

  • Stanton MF, Wrench C (1972) Mechanisms of mesothelioma induction with asbestos and fibrous glass. J Natl Cancer Inst 48:797–821

    CAS  PubMed  Google Scholar 

  • Stanton MF, Layard M, Tegeris A, Miller E, May M, Morgan E, Smith A (1981) Relation of particle dimension to carcinogenicity in amphibole asbestoses and other fibrous minerals. J Natl Cancer Inst 67:965–975

    CAS  PubMed  Google Scholar 

  • Stone V, Pozzi-Mucelli S, Tran L, Aschberger K, Sabella S, Vogel U, Poland C, Balharry D, Fernandes T, Gottardo S, Hankin S, Hartl MG, Hartmann N, Hristozov D, Hund-Rinke K, Johnston H, Marcomini A, Panzer O, Roncato D, Saber AT, Wallin H, Scott-Fordsmand JJ (2014) ITS-NANO: prioritising nanosafety research to develop a stakeholder driven intelligent testing strategy. Part Fibre Toxicol 11:9

    PubMed Central  PubMed  Google Scholar 

  • Sung JH, Ji JH, Park JD, Yoon JU, Kim DS, Jeon KS, Song MY, Jeong J, Han BS, Han JH, Chung YH, Chang HK, Lee JH, Cho MH, Kelman BJ, Yu IJ (2009) Subchronic inhalation toxicity of silver nanoparticles. Toxicol Sci 108:452–461

    CAS  PubMed  Google Scholar 

  • Sycheva LP, Zhurkov VS, Iurchenko VV, Daugel-Dauge NO, Kovalenko MA, Krivtsova EK, Durnev AD (2011) Investigation of genotoxic and cytotoxic effects of micro- and nanosized titanium dioxide in six organs of mice in vivo. Mutat Res 726:8–14

    CAS  PubMed  Google Scholar 

  • Takagi A, Hirose A, Nishimura T, Fukumori N, Ogata A, Ohashi N, Kitajima S, Kanno J (2008) Induction of mesothelioma in p53 ± mouse by intraperitoneal application of multi-wall carbon nanotube. J Toxicol Sci 33:105–116

    CAS  PubMed  Google Scholar 

  • Tavares P, Balbinot F, de Oliveira HM, Fagundes GE, Venancio M, Ronconi JVV, Merlini A, Streck EL, da Silva Paula MM, de Andrade VM (2012) Evaluation of genotoxic effect of silver nanoparticles (Ag-Nps) in vitro and in vivo. J Nanopart Res 14:791

  • Tiwari DK, Jin T, Behari J (2011) Dose-dependent in vivo toxicity assessment of silver nanoparticle in Wistar rats. Toxicol Mech Methods 21:13–24

    CAS  PubMed  Google Scholar 

  • Totsuka Y, Higuchi T, Imai T, Nishikawa A, Nohmi T, Kato T, Masuda S, Kinae N, Hiyoshi K, Ogo S, Kawanishi M, Yagi T, Ichinose T, Fukumori N, Watanabe M, Sugimura T, Wakabayashi K (2009) Genotoxicity of nano/microparticles in in vitro micronuclei, in vivo comet and mutation assay systems. Part Fibre Toxicol 6:23

    PubMed Central  PubMed  Google Scholar 

  • Trouiller B, Reliene R, Westbrook A, Solaimani P, Schiestl RH (2009) Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice. Cancer Res 69:8784–8789

    CAS  PubMed  Google Scholar 

  • van der Zande M, Vandebriel RJ, Van Doren E, Kramer E, Herrera Rivera Z, Serrano-Rojero CS, Gremmer ER, Mast J, Peters RJ, Hollman PC, Hendriksen PJ, Marvin HJ, Peijnenburg AA, Bouwmeester H (2012) Distribution, elimination, and toxicity of silver nanoparticles and silver ions in rats after 28-day oral exposure. ACS Nano 6:7427–7442

    PubMed  Google Scholar 

  • Walkey CD, Chan WCW (2012) Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment. Chem Soc Rev 41:2780–2799

    CAS  PubMed  Google Scholar 

  • Wessels A, Van Berlo D, Boots AW, Gerloff K, Scherbart AM, Cassee FR, Gerlofs-Nijland ME, Van Schooten FJ, Albrecht C, Schins RP (2011) Oxidative stress and DNA damage responses in rat and mouse lung to inhaled carbon nanoparticles. Nanotoxicology 5:66–78

    CAS  PubMed  Google Scholar 

  • Wu W, Chen B, Cheng J, Wang J, Xu W, Liu L, Xia G, Wei H, Wang X, Yang M, Yang L, Zhang Y, Xu C, Li J (2010) Biocompatibility of Fe3O4/DNR magnetic nanoparticles in the treatment of hematologic malignancies. Int J Nanomed 5:1079–1084

    Google Scholar 

  • Xu M, Zhao Y, Feng M (2012) Polyaspartamide derivative nanoparticles with tunable surface charge achieve highly efficient cellular uptake and low cytotoxicity. Langmuir 28:11310–11318

    CAS  PubMed  Google Scholar 

  • Yamashita K, Yoshioka Y, Higashisaka K, Mimura K, Morishita Y, Nozaki M, Yoshida T, Ogura T, Nabeshi H, Nagano K, Abe Y, Kamada H, Monobe Y, Imazawa T, Aoshima H, Shishido K, Kawai Y, Mayumi T, Tsunoda S, Itoh N, Yoshikawa T, Yanagihara I, Saito S, Tsutsumi Y (2011) Silica and titanium dioxide nanoparticles cause pregnancy complications in mice. Nat Nanotechnol 6:321–328

    CAS  PubMed  Google Scholar 

  • Yang AS, Creagh TA (2013) Black sentinel lymph node and ‘scary stickers’. J Plast Reconstr Aesthet Surg 66:558–560

    PubMed  Google Scholar 

  • Yen H-J, Hsu S-H, Tsai C-L (2009) Cytotoxicity and immunological response of gold and silver nanoparticles of different sizes. Small 5:1553–1561

    CAS  PubMed  Google Scholar 

  • Zhang GD, Yang Z, Lu W, Zhang R, Huang Q, Tian M, Li L, Liang D, Li C (2009) Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted mice. Biomaterials 30:1928–1936

    CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

We thank Ms. Susanne Lindemann and Ms. Silke Hankinson for valuable bibliographic support.

Conflict of interest

Heidi Foth has already performed research on safety aspects of nanoparticles and is corresponding author of the manuscript ‘Vorsorgestrategien für Nanomaterialien’. Alexius Freyberger is employed as a toxicologist by Bayer Pharma AG, Wuppertal, Germany. Pharmaceuticals are explicitly not considered in this article. A. F. previously participated in toxicological studies on other nanomaterials as a contributing scientist. Currently, he is not involved in the assessment of hazard or risk of nanomaterials. Thomas Gebel is working at the German Federal Institute for Occupational Safety and Health (BAuA) which conducts research and development in the field of safety and health at work. BAuA is a governmental research institution within the purview of the Federal Ministry of Labour and Social Affairs. T. G. is involved in the toxicological evaluation of workplace chemicals both with respect to hazard classification and occupational exposure limit setting in Germany. This includes nanomaterials. Results of such evaluations are partly published as scientific or regulatory papers or in text books. T. G. is further involved in funding extramural research on nanomaterials by BAuA. Peter-Jürgen Kramer certifies that as co-author he has no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. He has some stock ownership at the chemical-pharmaceutical company Merck KGaA, but has no knowledge, to which extend Merck is involved in the nanochemical business. In the past, until June 2008, he was an employee at Merck (Merck Pharma/Merck Serono) and worked as Ombudsman for Merck Serono R&D from August 2008 until July 2012. Today he receives standard company pension payment from Merck. Werner Lilienblum is a former official at the authority for the environment and occupational safety and health in Lower Saxony, Germany. After his retirement, he worked as a consultant in toxicology until 2012. Since 2013, he is a member of the Scientific Committee on Consumer Safety (SCCS) and of its working group on nanomaterials at the European Commission. He also contributed as an associated scientific advisor to the SCCS Guidance on Safety Assessment of Nanomaterials in Cosmetics. Working as a member or scientific advisor in the scientific committees of the European Commission requires a commitment to scientific activity only in the public interest. Claudia Röhl has been involved in research projects on nanomaterials funded by the Christiana Albertina University Kiel and the ‘Deutsche Forschungsgesellschaft’ (DFG). She has published scientific papers in this area and is working at the German Federal Institute for Risk Assessment (BfR) since August 2013, where she is not involved in risk assessment of nanomaterials. The present article exclusively represents the authors’ opinion. Thomas Schupp was employed by BASF Polyurethanes GmbH, Germany, until August 2012. Working in the product safety group, he received some general questions concerning the risk of nanomaterial from researchers of the R&D department (who were anxious about a new asbestos case). These questions were forwarded to the central product stewardship department of BASF. Thomas Schupp left the company before a reply was received and did not deal with that issue in detail. Currently, Thomas Schupp is not involved in projects dealing with nanoparticles. Carsten Weiss is an independent research group leader at the Institute of Toxicology and Genetics at KIT. C. W. studies the mechanisms of action and physico-chemical properties of nanomaterials in several model systems such as cell lines, zebrafish embryos and mice. C. W. is and has been funded by the European Commission in various projects (framework programme), German research foundation (DFG) and the German Federal Institute for Risk Assessment (BfR). C. W. is currently the deputy coordinator of the EU consortium NanoMILE (2013–2017) and published more than 10 papers on nanotoxicology and nanosafety. Klaus-Michael Wollin, Georg Damm and Jan G. Hengstler declare no conflict of interest.

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Authors and Affiliations

  1. Federal Institute for Occupational Safety and Health, 44149, Dortmund, Germany

    Thomas Gebel

  2. Institute of Environmental Toxicology, University of Halle, 06097, Halle/Saale, Germany

    Heidi Foth

  3. Department for General, Visceral and Transplantation Surgery, Campus Virchow Clinic, Charité, Universitätsmedizin Berlin, Berlin, Germany

    Georg Damm

  4. Global Early Development – Toxicology, Bayer Pharma AG, 42096, Wuppertal, Germany

    Alexius Freyberger

  5. FB7 Chemistry, Technical University Darmstadt, 64287, Darmstadt, Germany

    Peter-Jürgen Kramer

  6. 30966, Hemmingen/Han, Germany

    Werner Lilienblum

  7. Institute for Toxicology und Pharmacology, Christian-Albrechts-University Kiel, Kiel, Germany

    Claudia Röhl

  8. University of Applied Science, Muenster, 48565, Steinfurt, Germany

    Thomas Schupp

  9. Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, 76344, Eggenstein-Leopoldshafen, Germany

    Carsten Weiss

  10. Lower Saxony Governmental Institute of Public Health, 30449, Hannover, Germany

    Klaus-Michael Wollin

  11. Leibniz Research Centre for Working Environment and Human Factors (IfADo), University of Dortmund, 44139, Dortmund, Germany

    Jan Georg Hengstler

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  1. Thomas Gebel
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  11. Jan Georg Hengstler
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Corresponding authors

Correspondence to Thomas Gebel, Heidi Foth or Jan Georg Hengstler.

Additional information

The authors are members of the Advisory Committee of the German Society of Toxicology (GT), elected by the members of the Society. The Committee consists of scientists from academia, industry and administration in order to guarantee a broad range of toxicological competence. The German Society of Toxicology is the largest scientific toxicological organization in Europe, with more than 1,200 members. The annual plenary meeting had asked the advisory committee to work on a position on the safety of nanomaterials. While all members were invited to contribute to this, the authors are solely responsible for the content of the published manuscript. The advisory committee invited Dr. Carsten Weiss to join the authors as a guest expert.

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Gebel, T., Foth, H., Damm, G. et al. Manufactured nanomaterials: categorization and approaches to hazard assessment. Arch Toxicol 88, 2191–2211 (2014). https://doi.org/10.1007/s00204-014-1383-7

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Keywords

  • Nanoparticles
  • Nanotoxicology
  • Fibrous nanomaterials
  • Granular biodurable nanoparticles
  • Biodistribution
  • Genotoxicity