Skip to main content
Log in

Nanotoxicology: a perspective and discussion of whether or not in vitro testing is a valid alternative

  • Review Article
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Despite the many proposed advantages related to nanotechnology, there are increasing concerns as to the potential adverse human health and environmental effects that the production of, and subsequent exposure to nanoparticles (NPs) might pose. In regard to human health, these concerns are founded upon the plethora of knowledge gained from research relating to the effects observed following exposure to environmental air pollution. It is known that increased exposure to environmental air pollution can cause reduced respiratory health, as well as exacerbate pre-existing conditions such as cardiovascular disease and chronic obstructive pulmonary disease. Such disease states have also been associated with exposure to the NP component contained within environmental air pollution, raising concerns as to the effects of NP exposure. It is not only exposure to accidentally produced NPs however, which should be approached with caution. Over the past decades, NPs have been specifically engineered for a wide range of consumer, industrial and technological applications. Due to the inevitable exposure of NPs to humans, owing to their use in such applications, it is therefore imperative that an understanding of how NPs interact with the human body is gained. In vivo research poses a beneficial model for gaining immediate and direct knowledge of human exposure to such xenobiotics. This research outlook however, has numerous limitations. Increased research using in vitro models has therefore been performed, as these models provide an inexpensive and high-throughput alternative to in vivo research strategies. Despite such advantages, there are also various restrictions in regard to in vitro research. Therefore, the aim of this review, in addition to providing a short perspective upon the field of nanotoxicology, is to discuss (1) the advantages and disadvantages of in vitro research and (2) how in vitro research may provide essential information pertaining to the human health risks posed by NP exposure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Abbey DE, Nishino N, McDonnell WF, Knutsen SF, Burchette RJ, Beeson WL, Yang JX (1999) Long-term inhalable particles and other air pollutants related to mortality in nonsmokers. Am J Respir Crit Care Med 159:373–382

    PubMed  CAS  Google Scholar 

  • Aga E, Samoili E, Touloumi G, Anderson HR, Cadum E, Forsber B, Goodman P, Goren A, Kotesovec F, Kriz B, Macarol-Hiti M, Medina S, Paldy A, Schindler C, Sunyer J, Tittanen P, Wojtyniak B, Zmiorou D, Schwartz J, Katsouyanni K (2003) Short-term effects of ambient particles on mortality in the elderly: results from 28 cities in the APHEA2 project. Eur Respir J 21:28s–33s

    Article  CAS  Google Scholar 

  • Alfaro-Moreno E, Nawrot TS, Vanaudenaerde BM, Hoylaerts MF, Vanoirbeek JA, Nemery B, Hoet PHM (2008) Co-cultures of multiple cell types mimic pulmonary cell communication in response to urban PM10. Eur Respir J 32:1184–1194

    Article  PubMed  CAS  Google Scholar 

  • Bhabra G, Sood A, Fisher B, Cartwright L, Saunders M, Evans WH, Surprenant A, Lopez-Castejon G, Mann S, Davis SA, Hails LA, Ingham E, Verkade P, Lane J, Heesom K, Newson R, Case CP (2009) Nanoparticles can cause DNA damage across a cellular barrier. Nat Nanotech 4:876–883

    Article  CAS  Google Scholar 

  • Bivas-Benita M, Romeijn S, Junginger HE, Borchard G (2004) PLGA-PEI nanoparticles for gene delivery to pulmonary epithelium. Eur J Pharm Biopharm 58:1–6

    Article  PubMed  CAS  Google Scholar 

  • Blank F, Rothen-Rutishauser BM, Schurch S, Gehr P (2006) An optimized in vitro model of the respiratory tract wall to study particle cell interactions. J Aerosol Med 19:392–405

    Article  PubMed  Google Scholar 

  • Blank F, Rothen-Rutishauser B, Gehr P (2007) Dendritic cells and macrophages form a transepithelial network against foreign particulate antigens. Am J Respir Cell Mol Biol 36:669–677

    Article  PubMed  CAS  Google Scholar 

  • Blank F, Gehr P, Rothen-Rutishauser B (2009) In vitro human lung cell culture models to study the toxic potential of nanoparticles. In: Sahu SC (ed) Nanotoxicity: From in vitro, in vivo models to health risks s. Wiley, Chichester, England, pp 379–395

    Google Scholar 

  • Bouwmeester H, Lynch I, Marvin HJP, Dawson KA, Berges M, Braguer D, Byrne HJ, Casey A, Chambers G, Clift MJD, Elia G, Fernandes TF, Fjellsbø LB, Hatto P, Juillerat L, Klein C, Kreyling WG, Nickel C, Riediker M, Stone V (2010) Minimal analytical characterisation of engineered nanomaterials needed for hazard assessment in biological matrices. Accepted by Nanotoxicology

  • Braga ALF, Zanobetti A, Schwartz J (2000) Do respiratory epidemics confound the association between air pollution and daily deaths? Eur Respir J 16:723–728

    Article  PubMed  CAS  Google Scholar 

  • Brandenberger C, Rothen-Rutishauser B, Muhlfeld C, Schmid O, Ferron GA, Maier KL, Gehr P, Lenz AG (2010) Effects and uptake of gold nanoparticles deposited at the air-liquid interface of a human epithelial airway model. Toxicol appl Pharm 242:56–65

    Article  CAS  Google Scholar 

  • Bremner SA, Anderson HR, Atkinson RW, McMichael AJ, Strachan DP, Bland JM, Bower JS (1999) Short-term associations between outdoor air pollution and mortality in London 1992–4. Occ Environ Med 56:237–244

    Article  CAS  Google Scholar 

  • Brown DM, Wilson MR, MacNee W, Stone V, Donaldson K (2001) Size-dependent proinflammatory effects of ultrafine polystyrene particles: a role for surface area and oxidative stress in the enhanced activity of ultrafines. Toxciol Appl Pharm 175:191–199

    Article  CAS  Google Scholar 

  • Brzoska M, Langer K, Coester C, Loitsch S, Wagner TO, Mallinckrodt C (2004) Incorporation of biodegradable nanoparticles into human airway epithelium cells-in vitro study of the suitability as a vehicle for drug or gene delivery in pulmonary diseases. Biochem Biophys Res Commun 318:562–570

    Article  PubMed  CAS  Google Scholar 

  • Carterson AJ, Honer zu BK, Ott CM, Clarke MS, Pierson DL, Vanderburg CR, Buchanan KL, Nickerson CA, Schurr MJ (2005) A549 lung epithelial cells grown as three-dimensional aggregates: alternative tissue culture model for Pseudomonas aeruginosa pathogenesis. Infect Immun 73:1129–1140

    Article  PubMed  CAS  Google Scholar 

  • Chen HW, Su SF, Chien CT, Lin WH, Yu SL, Chou CC, Chen JJ, Yang PC (2006) Titanium dioxide nanoparticles induce emphysema-like lung injury in mice. FASEB J 20:2393–2395

    Article  PubMed  CAS  Google Scholar 

  • Choudhury AH (1997) Associations between respiratory illness and PM10 air pollution. Arc Environ Health 52:113–117

    Article  CAS  Google Scholar 

  • Clift MJD, Brown DM, Rothen-Ruthishauser B, Duffin R, Donaldson K, Proudfoot L, Guy K, Stone V (2008) Comparing a panel of commercially available quantum dots and polystyrene nanoparticles with differing surface characteristics; an analysis of their uptake and toxicity in a murine macrophage cell line. Toxicol Appl Pharm 232:418–427

    Article  CAS  Google Scholar 

  • Diabaté S, Mülhopt S, Paur HR, Krug HF (2008) The response of a co-culture lung model to fine and ultrafine particles of incinerator fly ash at the air-liquid interface. Altern Lab Anim 36:285–298

    PubMed  Google Scholar 

  • Dockery DW, Pope CA, Xu X, Spengler JD, Ware JH, Fay ME, Ferris BG, Speizer FE (1993) An association between air pollution and mortality in six U.S. cities. N Eng J Med 329:1753–1759

    Article  CAS  Google Scholar 

  • Donaldson K, Tran CL (2004) An introduction to the short-term toxicology of respirable industrial fibres. Mut Res/Fundamen Mol Mechan Mutagen 553:5–9

    Article  CAS  Google Scholar 

  • Donaldson K, Stone V, Borm PJ, Jimenez LA, Gilmour PS, Schins RPF, Knaapen AM, Rahman I, Faux SP, Brown DM, MacNee W (2003) Oxidative stress and calcium signalling in the adverse effects of environmental particles (PM10). Free Rad Biol Med 34:1369–1382

    Article  PubMed  CAS  Google Scholar 

  • Donaldson K, Stone V, Tran CL, Kreyling W, Borm PJA (2004) Nanotoxicology. Occ Environ Med 61:727–728

    Article  CAS  Google Scholar 

  • Donaldson K, Aitken R, Tran L, Stone V, Duffin R, Forrest G, Alexander A (2006) Carbon Nanotubes: a review of their properties in relation to pulmonary toxicology and workplace safety. Toxicol Sci 92:5–22

    Article  PubMed  CAS  Google Scholar 

  • Dörger M, Münzing S, Allmeling A-M, Messmer K, Krombach F (2001) Differential Responses of Rat Alveolar and Peritoneal Macrophages to Man-Made Vitreous Fibers in Vitro. Environ Res 85:207–214

    Article  PubMed  Google Scholar 

  • Duffin R, Tran CL, Clouter A, Brown DM, MacNee W, Stone V, Donaldson K (2002) The importance of surface area and specific reactivity in the acute pulmonary inflammatory response to particles. Ann Occ Hyg 46:242–245

    Google Scholar 

  • Duffin R, Tran L, Brown D, Stone V, Donaldson K (2007) 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 19:849–856

    Article  PubMed  CAS  Google Scholar 

  • Ece GD, Shah LK, Devalapally H, Amiji MM, Carrier RL (2008) A model predicting delivery of saquinavir in nanoparticles to human monocyte/macrophage (Mo/Mac) cells. 2008. Biotechnol Bioeng 101:1072–1082

    Article  Google Scholar 

  • European Science Foundation (ESF) Report (2005) Nanomedicine; An ESF—European Medical Research Councils (EMRC) Forward Look Report

  • European Union Cosmetics directive 76/768/EEC; Amended document 2008

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

    PubMed  CAS  Google Scholar 

  • Goulaouic S, Foucaud L, Bennasroune A, Laval-Gilly P, Falla J (2008) Effect of polycyclic aromatic hydrocarbons and carbon black particles on pro-inflammatory cytokine secretion: impact of PAH coating onto particles. J Immunotoxicol 5:337–345

    Article  PubMed  CAS  Google Scholar 

  • Grenha A, Grainger CI, Dailey LA, Seijo B, Martin GP, Remunan-Lopez C, Forbes B (2007) Chitosan nanoparticles are compatible with respiratory epithelial cells in vitro. Eur J Pharm Sci 31:73–84

    Article  PubMed  CAS  Google Scholar 

  • Herzog E, Casey A, Lyng FM, Chambers G, Byrne HJ, Davoren M (2007) A new approach to the toxicity testing of carbon-based nanomaterials—the clonogenic assay. Toxicol Lett 174:49–60

    Article  PubMed  CAS  Google Scholar 

  • Holder AL, Lucas D, Goth-Goldstein R, Koshland CP (2008) Cellular response to diesel exhaust particles strongly depends on the exposure method. Toxicol Sci 103:108–115

    Article  PubMed  CAS  Google Scholar 

  • International Organization for Standardization (ISO) Technical Specification (ISO/TS) 27687:2008; Nanotechnologies—Terminology and definitions for nano-objects—Nanoparticle, nanofibre and nanoplate; First published 2008-08-15

  • Jang M, Ghio AJ, Cao G (2006) Exposure of BEAS-2B cells to secondary organic aerosol coated on magnetic nanoparticles. Chem Res Toxicol 19:1044–1050

    Article  PubMed  CAS  Google Scholar 

  • Kaiser JP, Wick P, Manser P, Spohn P, Bruinink A (2008) Single walled carbon nanotubes (SWCNT) affect cell physiology and cell architecture. J Mater Sci Mater Med 19:1523–1527

    Article  PubMed  CAS  Google Scholar 

  • Kemp SJ, Thorley AJ, Gorelik J, Seckl MJ, O’Hare MJ, Arcaro A, Korchev Y, Goldstraw P, Tetley TD (2008) Immortalisation of Human Alveolar Epithelial Cells to Investigate Nanoparticle Uptake. Am J Respir Cell Mol Biol 39:591–597

    Article  PubMed  CAS  Google Scholar 

  • Knol AB, de Hartog JJ, Boogaard H, Slottje P, van der Sluijs JP, Lebret E, Cassee FR, Wardekker JA, Ayres JG, Borm PJ, Brunekreef B, Donaldson K, Forastiere F, Holgate ST, Kreyling WG, Nemery B, Pekkanen J, Stone V, WichmannH-E HoekG (2009) Expert elicitation on ultrafine particles: likelihood of health effects and causal pathways. Part Fibre Toxicol 6:19

    Article  PubMed  Google Scholar 

  • Lehmann AD, Blank F, Baum O, Gehr P, Rothen-Rutishauser BM (2009) Diesel exhaust particles modulate the tight junction protein occluding in lung cells in vitro. Part Fibre Toxicol 6:26

    Article  PubMed  Google Scholar 

  • Lehmann AD, Daum N, Lehr C-M, Bur M, Gehr P, Rothen-Rutishauser B (2010) An in vitro triple cell co-culture model with primary cells mimicking the human alveolar epithelial barrier. Submitted to J Roy Soc Inter

  • Lenz AG, Karg E, Lentner B, Dittrich V, Brandenberger C, Rothen-Rutishauser B, Schulz H, Ferron GA, Schmid O (2009) A dose-controlled system for air-liquid interface cell exposure and application to zinc oxide nanoparticles. Part Fibre Toxciol 6:32

    Article  Google Scholar 

  • Li XY, Gilmour PS, Donaldson K, MacNee W (1997) In Vivo and In Vitro proinflammatory effects of particulate air pollution (PM10). Environ Health Perspec 105:1279–1283

    CAS  Google Scholar 

  • Li XY, Brown DM, Smith S, MacNee W, Donaldson K (1999) Short-term inflammatory responses following intratracheal instillation of fine and ultrafine carbon black in rats. Inhal Toxicol 11:709–731

    Article  PubMed  Google Scholar 

  • Limbach LK, Li Y, Grass RN, Brunner TJ, Hintermann MA, Muller M, Gunther D, Stark WJ (2005) Oxide nanoparticle uptake in human lung fibroblasts: effects of particle size, agglomeration, and diffusion at low concentrations. Environ Sci Technol 39:9370–9376

    Article  PubMed  CAS  Google Scholar 

  • Lovric J, Bazzi HS, Cuie Y, Fortin GRA, Winnik FM, Maysinger D (2005) Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots. J Mol Med 83:377–385

    Article  PubMed  Google Scholar 

  • Maynard AD (2007) Nanotechnology: the next big thing, or much ado about nothing? Ann Occ Hyg 51:1–12

    Article  CAS  Google Scholar 

  • Maysinger D, Lovric J, Eisenberg A, Savic R (2007) Fate of micelles and quantum dots in cells. Eur J Pharm Biopharm 65:270–281

    Article  PubMed  CAS  Google Scholar 

  • Medina S, Plasencia A, Ballester F, Mucke HG, Schwartz J (2004) Apheis: public health impact of PM10 in 19 European cities. J Epidemiol Com Health 58:831–836

    Article  CAS  Google Scholar 

  • Mueller L, Riediker M, Wick P, Mohr M, Gehr P, Rothen-Rutishauser B (2010) Oxidative stress and inflammation response after nanoparticle exposure: differences between human lung cell monocultures and an advanced three-dimensional model of the human epithelial airways. J Roy Soci Inter 7:S27–S40

    Article  CAS  Google Scholar 

  • Muhlfeld C, Rothen-Rutishauser B, Blank F, Vanhecke D, Ochs M, Gehr P (2008) Interactions of nanoparticles with pulmonary structures and cellular responses. Am J Physiol; Lung, Cell Mol Physiol 294:L817–L829

    Article  CAS  Google Scholar 

  • Mühlfeld C, Gehr P, Rothen-Rutishauser B (2008) Translocation and cellular entering mechanisms of nanoparticles in the respiratory tract. Swiss Medical Weekly 138:387–391

    PubMed  Google Scholar 

  • Oberdorster G, Ferin J, Morrow PE (1992) Volumetric loading of alveolar macrophages (AM): a possible basis for diminished AM-mediated particle clearance. Exp Lung Res 18:87–104

    Article  PubMed  CAS  Google Scholar 

  • Oberdorster G, Oberdorster E, Oberdorster J (2005) Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environ Health Perspec 113:823–839

    Article  CAS  Google Scholar 

  • Oberdorster G, Stone V, Donaldson K (2007) Toxicology of nanoparticles: a historical perspective. Nanotox 1:2–25

    Article  CAS  Google Scholar 

  • Park S, Lee YK, Jung M, Kim KH, Chung N, Ahn EK, Lim Y, Lee KH (2007) Cellular toxicity of various inhalable metal nanoparticles on human alveolar epithelial cells. Inhal Toxicol 19(Suppl 1):59–65

    Article  PubMed  CAS  Google Scholar 

  • Peters A, Wichmann HE, Tuch T, Heinrich J, Heyder J (1997) Respiratory effects are associated with the number of ultrafine particles. Am J Respir Crit Care Med 155:1376–1383

    PubMed  CAS  Google Scholar 

  • Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WAH, Seaton A, Stone V, Brown S, MacNee W, Donaldson K (2008) Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nat Nanotech 3:423–428

    Article  CAS  Google Scholar 

  • Pope CA, Dockery DW (1999) Epidemiology of particle effects. Air Poll Health 31:674–705

    Google Scholar 

  • Pope CA, Ezzati M, Dockery DW (2009) Fine-particulate air pollution and life expectancy in the United States. N Eng J Med 360:376–386

    Article  CAS  Google Scholar 

  • Rothen-Rutishauser B, Kiama SG, Gehr P (2005) A three-dimensional cellular model of the human respiratory tract to study the interaction with particles. Am J Respir Cell Mol Biol 32:281–289

    Article  PubMed  CAS  Google Scholar 

  • Rothen-Rutishauser B, Schurch S, Gehr P (2007) Interaction of particles with membranes. In: Donaldson K, Borm P (eds) The toxicology of particles. CRC Press LCC, New York, pp 139–160

    Google Scholar 

  • Rothen-Rutishauser B, Blank F, Ch Muehlfeld, Gehr P (2008a) In vitro models of the human epithelial airway barrier to study the toxic potential of particulate matter. Exp Opin Drug Metab Toxicol 4:1075–1089

    Article  CAS  Google Scholar 

  • Rothen-Rutishauser B, Müller L, Blank F, Ch Mühlfeld, Gehr P (2008b) A newly developed in vitro model of the human epithelial airway barrier to study the toxic potential of nanoparticles. ALTEX 25:191–196

    PubMed  Google Scholar 

  • Rotoli BM, Bussolati O, Bianchi MG, Barilli A, Balasubramanian C, Bellucci S, Bergamaschi E (2008) Non-functionalized multi-walled carbon nanotubes alter the paracellular permeability of human airway epithelial cells. Toxicol Lett 178:95–102

    Article  PubMed  CAS  Google Scholar 

  • Ryman-Rasmussen JP, Cesta MF, Brody AR, Shipley-Phillips JK, Everitt JI, Tewksbury EW, Moss OR, Wong BA, Dodd DE, Andersen ME, Bonner JC (2009) Inhaled carbon nanotubes reach the subpleural tissue in mice. Nat Nanotech 4:747–751

    Article  CAS  Google Scholar 

  • Schins RP, Knaapen AM (2007) Genotoxicity of poorly soluble particles. Inhal Toxicol 19:189–198

    Article  PubMed  CAS  Google Scholar 

  • Schulz H, Harder V, Ibald-Mulli A, Khandoga A, Koenig W, Krombach F, Radykewicz R, Stampfl A, Thorand B, Peters A (2005) Cardiovascular effects of fine and ultrafine particles. J Aero Med 18:1–22

    Article  CAS  Google Scholar 

  • Schwartz J (2004) The effects of particulate air pollution on daily deaths: a multi-city case cross over analysis. Occ Environ Med 61:956–961

    Article  CAS  Google Scholar 

  • Seaton A, MacNee W, Donaldson K, Godden D (1995) Particulate air pollution and acute health effects. Lancet 345:176–178

    Article  PubMed  CAS  Google Scholar 

  • Service RF (2004) Nanotoxicology. Nanotechnology grows up. Science 304:1732–1734

    Article  PubMed  CAS  Google Scholar 

  • Stearns RC, Paulauskis JD, Godleski JJ (2001) Endocytosis of ultrafine particles by A549 cells. Am J Respir Cell Mol Biol 24:108–115

    PubMed  CAS  Google Scholar 

  • Stoeger T, Reinhard C, Takenaka S, Schroeppel A, Karg E, Ritter B, Heyder J, Schulz H (2006) Instillation of six different ultrafine carbon particles indicates a surface areas threshold dose for acute lung inflammation in mice. Environ Health Perspec 114:328–333

    Article  Google Scholar 

  • Stone V, Johnston H, Schins RPF (2009) Development of in vitro systems for nanotoxicology: methodological considerations. Crit Rev Toxicol 39:613–626

    Article  PubMed  CAS  Google Scholar 

  • Timbrell J (1999) Principles of biochemical toxicology. Taylor and Francis, CRC Press

    Google Scholar 

  • Tippe A, Heinzmann U, Roth C (2002) Deposition of fine and ultrafine aerosol particles during exposure at the air/cell interface. Aero Sci 33:207–218

    Article  CAS  Google Scholar 

  • Unfried K, Albrecht C, Klotz LO, von Mikecz A, Grether-Beck S, Schins RPF (2007) Cellular responses to nanoparticles: target structures and mechanisms. Nanotox 1:1–20

    Article  Google Scholar 

  • Veranth JM, Kaser EG, Veranth MM, Koch M, Yost GS (2007) Cytokine responses of human lung cells (BEAS-2B) treated with micron-sized and nanoparticles of metal oxides compared to soil dusts. Part Fibre Toxicol 4:2

    Article  PubMed  Google Scholar 

  • Waldman WJ, Kristovich R, Knight DA, Dutta PK (2007) Inflammatory properties of iron-containing carbon nanoparticles. Chem Res Toxicol 20:1149–1154

    Article  PubMed  CAS  Google Scholar 

  • Wichmann HE, Spix C, Tuch T, Wolke G, Peters A, Heinrich J, Kreyling WG, Heyder J (2000) Daily mortality and fine and ultrafine particles in Erfurt, Germany part I: role of particle number and particle mass. Research Report/Health Effects Institute 98:5–86

    Google Scholar 

  • Wick P, Manser P, Limbach LK, Dettlaff-Weglikowska U, Krumreich F, Roht S, Stark WJ, Bruinink A (2007) The degree and kind of agglomeration affect carbon nanotube cytotoxicity. Toxicol Lett 168:121–131

    Article  PubMed  CAS  Google Scholar 

  • Worle-Knirsch JM, Pulskamp K, Krug HF (2006) Oops they did it again! Carbon nanotubes hoax scientists in viability assays. Nano Lett 6:1261–1268

    Article  PubMed  CAS  Google Scholar 

  • Wottrich R, Diabaté S, Krug HF (2004) Biological effects of ultrafine model particles in human macrophages and epithelial cells in mono- and co-culture. Int J Hyg Environ Health 207:353–361

    Article  PubMed  CAS  Google Scholar 

  • Zanobetti A, Schwartz J, Samoli E, Gryparis A, Touloumi G, Peacock J, Anderson RH, Tertre A, Bobros J, Celko M, Goren A, Forsberg B, Michelozzi P, Rabczenko D, Perzhoyso S, Wichmann HE, Katsouyanni K (2003) The temporal pattern of respiratory and heart disease mortality in response to air pollution. Environ Health Perspec 111:118–1214

    Article  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Christina Brandenberger, Andrea Lehmann, Loretta Mueller, Michael Gasser, David Raemy, Kirsten Dobson, Dagmar Kuhn, Andrea Stokes, Mohammed Ouanella and Barbara Tschirren for their vital input to the ongoing research of the laboratory of Prof. P. Gehr, as well as their assistance for the routine and helpful discussion from which this review has been partially based upon.

Conflict of interest statement

The authors would like to report no conflict of interests. The authors are entirely responsible for the content and writing of the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Martin J. D. Clift.

Additional information

This article is published as part of Special Issue on Nanotoxicology.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Clift, M.J.D., Gehr, P. & Rothen-Rutishauser, B. Nanotoxicology: a perspective and discussion of whether or not in vitro testing is a valid alternative. Arch Toxicol 85, 723–731 (2011). https://doi.org/10.1007/s00204-010-0560-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-010-0560-6

Keywords

Navigation