A Multilaboratory Toxicological Assessment of a Panel of 10 Engineered Nanomaterials to Human Health - ENPRA Project - The Highlights, Limitations, and Current and Future Challenges

Journal of Toxicology and Environmental Health - Part B: Critical Reviews

Volumn 19, Issue 1, 2016, Pages 1-28

  Kermanizadeh, Ali ^a,b   Gosens, Ilse ^c   MacCalman, Laura ^d   Johnston, Helinor ^b   Danielsen, Pernille H ^a   Jacobsen, Nicklas R ^e   Lenz, Anke Gabriele ^f   Fernandes, Teresa ^b   Schins, Roel P F ^g   Cassee, Flemming R ^c   Wallin, Håkan ^a,e   Kreyling, Wolfgang ^f   Stoeger, Tobias ^f   Loft, Steffen ^a   Møller, Peter ^a   Tran, Lang ^d   Stone, Vicki ^b  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b HERIOT WATT UNIVERSITY   (United Kingdom)

^c NATIONAL INSTITUTE FOR PUBLIC HEALTH AND THE ENVIRONMENT   (Netherlands)

^d INSTITUTE OF OCCUPATIONAL MEDICINE   (United Kingdom)

^e NATIONAL RESEARCH CENTRE FOR THE WORKING ENVIRONMENT   (Denmark)

^f INSTITUTE OF EPIDEMIOLOGY   (Germany)

^g IUF LEIBNIZ RESEARCH INSTITUTE FOR ENVIRONMENTAL MEDICINE   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

NANOMATERIAL;

CARDIOVASCULAR SYSTEM; CYTOTOXICITY; DEVELOPMENTAL TOXICITY; DISPERSION; HAZARD ASSESSMENT; HEPATOBILIARY SYSTEM; HUMAN; IN VITRO STUDY; NANOTOXICOLOGY; NONHUMAN; RESPIRATORY SYSTEM; REVIEW; RISK ASSESSMENT; UROGENITAL SYSTEM; ANIMAL; EUROPE; NANOTECHNOLOGY; PROCEDURES; TOXICITY TESTING; TOXICOLOGY; TRENDS;

ANIMALS; EUROPE; HUMANS; IN VITRO TECHNIQUES; NANOSTRUCTURES; NANOTECHNOLOGY; RISK ASSESSMENT; TOXICITY TESTS; TOXICOLOGY;

EID: 84963635445     PISSN: 10937404     EISSN: 15216950     Source Type: Journal    
DOI: 10.1080/10937404.2015.1126210     Document Type: Review

References (115)

1. Aldieri, E., I. Fenoglio, F. Cesano, E. Gazzano, G. Gulino, D. Scarano, A. Attanasio, G. Mazzucco, D. Ghigo, and B. Fubini. 2013. The role of iron impurities in the toxic effects exerted by short multiwalled carbon nanotubes (MWCNT) in murine alveolar macrophages. Journal of Toxicology and Environmental Health, Part A 76:1056-71. doi:10.1080/15287394.2013.834855.
2. Almeida, J. P., A. L. Chen, A. Foster, and R. Drezek. 2011. In vivo biodistribution of nanoparticles. Nanomedicine 6:815-35. doi:10.2217/nnm.11.79.
3. Aschberger, K., C. Micheletti, B. Sokull-Klüttgen, and F. M. Christensen. 2011. Analysis of currently available data for characterising the risk of engineered nanomaterials to the environment and human health - Lessons learned from four case studies. Environment International 37:1143-56. doi:10.1016/j.envint.2011.02.005.
4. Asgharian, B., and O. T. Price. 2007. Deposition of ultrafine (nano) particles in the human lung. Inhalation Toxicology 19:1045-54. doi:10.1080/08958370701626501.
5. Baisch, B. L., N. M. Corson, P. Wade-Mercer, R. Gelein, A. J. Kennell, G. Oberdorster, and A. Elder. 2014. Equivalent titanium dioxide nanoparticle deposition by intratracheal instillation and whole body inhalation: The effect of dose rate on acute respiratory tract inflammation. Particle and Fibre Toxicology 11:5.
6. Balasubramanian, S. K., K.-W. Poh, C.-N. Ong, W. G. Kreyling, W.-Y. Ong, and L. E. Yu. 2013. The effect of primary particle size on biodistribution of inhaled gold nano-agglomerates. Biomaterials 34:5439-52. doi:10.1016/ j.biomaterials.2013.03.080.
7. BCC Research. 2015. http://www.bccresearch.com/marketresearch/ nanotechnology/nanotechnology-market-assess ment-report-nan031f.html (accessed January 12, 2015).
8. Benn, T. M., and P. Westerhoff. 2008. Nanoparticle silver released into water from commercially available sock fabrics. Environmental Science & Technology 42:4133-39. doi:10.1021/es7032718.
9. Braydich-Stolle, L. K., E. K. Breitner, K. K. Comfort, J. J. Schlager, and S. M. Hussain. 2014. Dynamic characteristics of silver nanoparticles in physiological fluids: Toxicological implications. Langmuir 30:15309-16. doi:10.1021/ la5036079.
10. Brocato, J., H. Sun, M. Shamy, T. Kluz, M. A. Alghamdi, M. I. Khoder, L.-C. Chen, and M. Costa. 2014. Particulate matter from Saudi Arabia induces genes involved in inflammation, metabolic syndrome and atherosclerosis. Journal of Toxicology and Environmental Health, Part A 77:751-66. doi:10.1080/15287394.2014.892446.
11. Brook, R. D., and S. Rajagopalan. 2010. Particulate matter air pollution and atherosclerosis. Current Atherosclerosis Reports 12:291-300. doi:10.1007/s11883-010-0122-7.
12. Brown, D. M., H. Johnston, E. Gubbins, and V. Stone. 2014. Serum enhanced cytokine responses of macrophages to silica and iron oxide particles and nanomaterials: A comparison of serum to lung lining fluid and albumin dispersions. Journal of Applied Toxicology 34:1177-87. doi:10.1002/jat.v34.11.
13. Cai, H., and P. Yao. 2014. Gold nanoparticles with different amino acid surfaces: Serum albumin adsorption, intracellular uptake and cytotoxicity. Colloids and Surfaces B: Biointerfaces 123:900-6. doi:10.1016/j. colsurfb.2014.10.042.
14. Cao, Y., N. R. Jacobsen, P. H. Danielsen, A. G. Lenz, T. Stoeger, S. Loft, H. Wallin, M. Roursgaard, L. Mikkelsen, and P. Moller. 2014. Vascular effects of multiwalled carbon nanotubes in dyslipidemic ApoE-/-mice and cultured endothelial cells. Toxicological Sciences 138:104-16. doi:10.1093/toxsci/kft328.
15. Chen, S.-H., F.-C. Li, J. S. Souris, C.-S. Yang, F.-G. Tseng, H.-S. Lee, C.-T. Chen, C.-Y. Dong, and L.-W. Lo. 2012. Visualizing dynamics of sub-hepatic distribution of nanoparticles using intravital multiphoton fluorescence microscopy. ACS Nano 6:4122-31. doi:10.1021/nn300558p.
16. Chen, Y.-C., Y.-H. Weng, Y.-W. Chiu, and C.-Y. Yang. 2015. Short-term effects of coarse particulate matter on hospital admissions for cardiovascular diseases: A case-crossover study in a tropical city. Journal of Toxicology and Environmental Health, Part A 78:1241-53. doi:10.1080/ 15287394.2015.1083520.
17. Chiu, H.-F.,C.-C. Chang, and C.-Y. Yang. 2014. Relationship between hemorrhagic stroke hospitalization and exposure to fine particulate air pollution in Taipei, Taiwan. Journal of Toxicology and Environmental Health, Part A 77:1154-63. doi:10.1080/15287394.2014.926801.
18. Choi, J., H. Kim, P. Kim, E. Jo, H.-M. Kim, M.-Y. Lee, S. M. Jin, and K. Park. 2015. Toxicity of zinc oxide nanoparticles in rats treated by two different routes: Single intravenous injection and single oral administration. Journal of Toxicology and Environmental Health, Part A 78:226-43. doi:10.1080/15287394.2014.949949.
19. Cohen, J., G. Deloid, G. Pyrgiotakis, and P. Demokritou. 2013. Interactions of engineered nanomaterials in physiological media and implications for in vitro dosimetry. Nanotoxicology 7:417-31. doi:10.3109/17435390.2012.666576.
20. Consumer Products Inventory. 2015. An inventory of nanotechnology-based consumer products introduced on the market. http://www.nanotechproject.org/cpi (accessed March 18, 2015).
21. Danielsen, P. H., Y. Cao, M. Roursgaard, P. Møller, and S. Loft. 2014. Endothelial cell activation, oxidative stress and inflammation induced by a panel of metal-based nanomaterials. Nanotoxicology 18:1-12.
22. Dekali, S., A. Divetain, T. Kortulewski, J. Vanbaelinghem, C. Gamez, F. Rogerieux, G. Lacroix, and P. Rat. 2013. Cell cooperation and role of the P2X7 receptor in pulmonary inflammation induced by nanoparticles. Nanotoxicology 7:1302-14. doi:10.3109/17435390.2012.735269.
23. Delfino, R. J., C. Sioutas, and S. Malik. 2005. Potential role of ultrafine particles in associations between airborne particle mass and cardiovascular health. Environmental Health Perspectives 113:934-46. doi:10.1289/ehp.7938.
24. Deloid, G., J. Cohen, T. Darrah, R. Derk, L. Rojanasakul, G. Pyrgiotakis, W. Wohlleben, and P. Demokritou. 2014. Estimating the effective density of engineered nanomaterials for in vitro dosimetry. Nature Communications 5:3514. doi:10.1038/ncomms4514.
25. Demokritou, P., S. Gass, G. Pyrgiotakis, J. M. Cohen, W. Goldsmith, W. McKinney, D. Frazer, J. Ma, D. Schwegler-Berry, J. Brain, and V. Castranova. 2012. An in vivo and in vitro toxicological characterization of realistic nanoscale CeO2 inhalation exposures. Nanotoxicology 7:1338-50. doi:10.3109/17435390.2012.739665.
26. Donaldson, K., and C. A. Poland. 2013a. Nanotoxicity: Challenging the myth of nano-specific toxicity. Current Opinion in Biotechnology 24:724-34. doi:10.1016/j. copbio.2013.05.003.
27. Donaldson, K., C. A. Poland, F. A. Murphy, M. MacFarlane, T. Chernova, and A. Schinwald. 2013b. Pulmonary toxicity of carbon nanotubes and asbestos - Similarities and differences. Advanced Drug Delivery Reviews 65:2078-86. doi:10.1016/j.addr.2013.07.014.
28. Donaldson, K., and A. Seaton. 2012. A short history of toxicology of inhaled particles. Particle and Fibre Toxicology 9:13.
29. Du, Z. J., D. L. Zhao, L. Jing, G. Q. Cui, M. H. Jin, Y. Li, X. M. Liu, Y. Liu, H. Y. Du, C. X. Guo, X. Zhou, and Z. Sun. 2013. Cardiovascular toxicity of different sizes amorphous silica nanoparticles in rats after intratracheal instillation. Cardiovascular Toxicology 13:194-207. doi:10.1007/ s12012-013-9198-y.
30. Dybdahl, M., L. Risom, J. Bornholdt, H. Autrup, S. Loft, and H. Wallin. 2004. Inflammatory and genotoxic effects of diesel particles in vitro and in vivo. Mutation Research/ Genetic Toxicology and Environmental Mutagenesis 562:119-31. doi:10.1016/j.mrgentox.2004.05.010.
31. ENPRA. 2015. http://www.enpra.eu (accessed January 18, 2015).
32. Foucaud, L., M. R. Wilson, D. M. Brown, and V. Stone. 2007. Measurement of reactive species production by nanoparticles prepared in biologically relevant media. Toxicology Letters 174:1-9. doi:10.1016/j.toxlet.2007.08.001.
33. Gangwal, S., J. S. Brown, A. Wang, K. A. Houck, D. J. Dix, R. J. Kavlock, and E. A. C. Hubal. 2011. Informing selection of nanomaterial concentrations for ToxCast in vitro testing based on occupational exposure potential. Environmental Health Perspectives 119:1539-46. doi:10.1289/ehp.1103750.
34. Gosens, I., A. Kermanizadeh, N. R. Jacobsen, A. G. Lenz, B. Bokkers, W. H. De Jong, P. Krystek, L. Tran, V. Stone, H. Wallin, T. Stoeger, and F. R. Cassee. 2015. Comparative hazard identification of zinc oxide and silver nanomaterials in mice. Plos One 10:e0126934.
35. Guo, N. L., Y. W. Wan, J. Denvir, D. W. Porter, M. Pacurari, M. G. Wolfarth, G. Castranova, and Y. Qian. 2012. Multiwalled carbon nanotube-induced gene signatures in the mouse lung: Potential predictive value for human lung cancer risk and prognosis. Journal of Toxicology and Environmental Health, Part A 75:1129-53. doi:10.1080/ 15287394.2012.699852.
36. Han, S. G., D. Howatt, A. Daugherty, and G. Gairola. 2015a. Pulmonary and atherogenic effects of multi-walled carbon nanotubes (MWCNT) in apolipoprotein-E-deficient mice. Journal of Toxicology and Environmental Health, Part A 78:244-53. doi:10.1080/15287394.2014.958421.
37. Han, S. G., J. S. Lee, K. Ahn, Y. S. Kim, J. K. Kim, J. H. Lee, J. H. Shin, K. S. Jeon, W. S. Cho, N. W. Song, M. Gulumian, B. S. Shin, and I. J. Yu. 2015. Size-dependent clearance of gold nanoparticles from lungs of Sprague-Dawley rats after short-term inhalation exposure. Archives of Toxicology 89:1083-94. doi:10.1007/s00204-014-1292-9.
38. Han, X., N. Corson, P. Wade-Mercer, R. Gelein, J. Jiang, M. Sahu, P. Biswas, J. N. Finkelstein, A. Elder, and G. Oberdörster. 2012. Assessing the relevance of in vitro studies in nanotoxicology by examining correlations between in vitro and in vivo data. Toxicology 297:1-9. doi:10.1016/j. tox.2012.03.006.
39. Hirn, S., N. Haberl, K. Loza, M. Epple, W. G. Kreyling, B. Rothen-Rutishauser, M. Rehberg, and F. Krombach. 2014. Proinflammatory and cytotoxic response to nanoparticles in precision-cut lung slices. Beilstein Journal of Nanotechnology 5:2440-49. doi:10.3762/bjnano.5.253.
40. Hirn, S., M. Semmler-Behnke, C. Schleh, M. Schffler, A. Wenk, N. Gibson, U. Holzwarth, K. Abbas, and W. G. Kreyling. 2011a. Quantitative biokinetics study in healthy adult rats over 28 days after inhalation of 20 nm titanium dioxide (TiO2) anatase nanoparticles aerosols. American Journal of Respiratory and Critical Care Medicine 183: meeting abstract A2279.
41. Hirn, S., M. Semmler-Behnke, C. Schleh, A. Wenk, J. Lipka, M. Schaffler, S. Takenaka, W. Moller, G. Schimid, U. Simon, and W. G. Kreyling. 2011b. Particle size-dependent and surface charge-dependent biodistribution of gold nanoparticles after intravenous administration. European Journal of Pharmaceutics and Biopharmaceutics 77:407-16. doi:10.1016/j.ejpb.2010.12.029.
42. Jacobsen, N. R., P. Møller, K. A. Jensen, U. Vogel, O. Ladefoged, S. Loft, and H. Wallin. 2009. Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/-mice. Particle and Fibre Toxicology 6:2. doi:10.1186/1743-8977-6-2.
43. Jacobsen, N. R., G. Pojano, H. Wallin, and K. A. Jensen. 2010. Nanomaterial dispersion protocol for toxicological studies in ENPRA. Internal report. National Research Centre for the Working Environment 6:1-10.
44. Johnston, H., D. Brown, A. Kermanizadeh, E. Gubbins, and V. Stone. 2012. Investigating the relationship between nanomaterial hazard and physicochemical properties: Informing the exploitation of nanomaterials within therapeutic and diagnostic applications. Journal of Controlled Release 164:307-13. doi:10.1016/j.jconrel.2012.08.018.
45. Johnston, H., G. Pojana, S. Zuin, N. R. Jacobsen, P. Møller, S. Loft, M. Semmler-Behnke, C. McGuiness, D. Balharry, A. Marcomini, H. Wallin, W. Kreyling, K. Donaldson, L. Tran, and V. Stone. 2013. Engineered nanomaterial risk. Lessons learnt from completed nanotoxicology studies: Potential solutions to current and future challenges. Critical Reviews in Toxicology 43:1-20. doi:10.3109/ 10408444.2012.738187.
46. JRC Nanomaterials Repository. 2015. http://ec.europa.eu/jrc/ en/scientific-tool/jrc-nanomaterials-repository (accessed March 11, 2015).
47. Kermanizadeh, A., D. Balharry, H. Wallin, S. Loft, and P. Møller. 2015b. Nanomaterial translocation - The biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs - A review. Critical Reviews in Toxicology 45:837-72. doi:10.3109/10408444.2015.1058747.
48. Kermanizadeh, A., D. M. Brown, G. Hutchison, and V. Stone. 2013d. Engineered nanomaterial impact in the liver following exposure via an intravenous route - The role of polymorphonuclear leukocytes and gene expression in the organ. Journal of Nanomedicine & Nanotechnology 4:157.
49. Kermanizadeh, A., C. Chauché, D. Balharry, D. M. Brown, N. Kanase, J. Boczkowski, S. Lanone, and V. Stone. 2014b. The role of Kupffer cells in the hepatic response to silver nanoparticles. Nanotoxicology 8:149-54. doi:10.3109/ 17435390.2013.866284.
50. Kermanizadeh, A., C. Chauché, D. M. Brown, P. Møller, and S. Loft. 2015a. The role of intracellular redox imbalance in nanomaterial induced cellular damage and genotoxicity - A review. Environmental and Molecular Mutagenesis 56:111-24. doi:10.1002/em.21926.
51. Kermanizadeh, A., B. K. Gaiser, G. R. Hutchison, and V. Stone. 2012. An in vitro liver model - Assessing oxidative stress and genotoxicity following exposure of hepatocytes to a panel of engineered nanomaterials. Particle and Fibre Toxicology 9:28. doi:10.1186/1743-8977-9-28.
52. Kermanizadeh, A., B. K. Gaiser,M. B.Ward, andV. Stone. 2013b. Primary human hepatocytes vs. hepatic cell line-assessing their suitability for in vitro nanotoxicology. Nanotoxicology 7:1255-71. doi:10.3109/17435390.2012.734341.
53. Kermanizadeh, A., M. Løhr, M. Roursgaard, S. Messner, P. Gunness, J. M. Kelm, P. Møller, V. Stone, and S. Loft. 2014a. Hepatic toxicology following single and multiple exposure of engineered nanomaterials utilising a novel primary human 3D liver microtissue model. Particle and Fibre Toxicology 11:56.
54. Kermanizadeh, A., G. Pojana, B. K. Gaiser, R. Birkedal, D. Bilaničová, H. Wallin, K. A. Jensen, B. Sellergren, G. R. Hutchison, A. Marcomini, and V. Stone. 2013a. In vitro assessment of engineered nanomaterials using C3A cells: Cytotoxicity, pro-inflammatory cytokines and function markers. Nanotoxicology 7:301-13. doi:10.3109/17435390.2011.653416.
55. Kermanizadeh, A., S. Vranic, S. Boland, K. Moreau, A. B. Squiban, B. K. Gaiser, L. A. Andrzejczuk, and V. Stone. 2013c. An in vitro assessment of panel of engineered nanomaterials using a human renal cell line: Cytotoxicity, pro-inflammatory response, oxidative stress and genotoxicity. BMC Nephrology 14:96.
56. Klein, C. L., K. Wiench, M. Wiemann, L. Ma-Hock, B. V. Ravanzwaay, and R. Landsiedel. 2012. Hazard identification of inhaled nanomaterials: Making use of short-term inhalation studies. Archives of Toxicology 86:1137-51. doi:10.1007/s00204-012-0834-2.
57. Kreyling, W. G., S. Hirn, W. Möller, C. Schleh, A. Wenk, G. Celik, J. Lipka, M. Schaffler, N. Haberl, B. D. Johnston, R. Sperling, G. Schmid, U. Simon, W. J. Parak, and M. Semmler-Behnke. 2014. Air-blood barrier translocation of tracheally instilled gold nanoparticles inversely depends on particle size. ACS Nano 8:222-33. doi:10.1021/nn403256v.
58. Kreyling, W. G., M. Semmler, F. Erbe, P. Mayer, S. Takenaka, H. Schulz, G. Oberdorster, and A. Ziesenis. 2002. Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low. Journal of Toxicology and Environmental Health, Part A 65:1513-30. doi:10.1080/ 00984100290071649.
59. Kreyling, W. G., M. Semmler-Behnke, J. Seitz, W. Scymczak, A. Wenk, P. Mayer, S. Takenaka, and G. Oberdorster. 2009. Size dependence of the translocation of inhaled iridium and carbon nanoparticle aggregates from the lung of rats to the blood and secondary target organs. Inhalation Toxicology 21:55-60. doi:10.1080/08958370902942517.
60. Krug, H. F. 2014. Nanosafety research - Are we on the right track? Angewandte Chemical 53:12304-19.
61. Kuhn, D. A., D. Vanhecke, B. Michen, F. Blank, P. Gehr, A. Petri-Fink, and B. Rothen-Rutishauser. 2014. Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages. Beilstein Journal of Nanotechnology 5:1625-36. doi:10.3762/bjnano.5.174.
62. Landsiedel, R., L. Ma-Hock, T. Hoffmann, M. Wiemann, V. Struss, S. Truemann, W. Wohlleben, S. Groters, K. Wiench, and B. Van Ravenzwaay. 2014. Application of short-term inhalation studies to assess the inhalation toxicity of nanomaterials. Particle and Fibre Toxicology 11:16.
63. Lee, Y. G., J. Jeong, J. Raftis, and W. S. Cho. 2015. Determination of adsorption affinity of nanoparticles for interleukin-8 secreted from A549 cells by in vitro cell-free and cell-based assays. Journal of Toxicology and Environmental Health, Part A 78:185-95. doi:10.1080/ 15287394.2014.955158.
64. Li, D. S., G. Johanson, C. Emond, U. Carlander, M. Philbert, and O. Jolliet. 2014b. Physiologically based pharmacokinetic modeling of polyethylene glycol-coated polyacrylamide nanoparticles in rats. Nanotoxicology 8:128-37. doi:10.3109/17435390.2013.863406.
65. Li, Y., Y. Zhang, and B. Yan. 2014a. Nanotoxicity overview: Nano-threat to susceptible populations. International Journal of Molecular Sciences 15:3671-97. doi:10.3390/ijms15033671.
66. Li, Z., T. Hulderman, R. Salmen, R. Chapman, S. S. Leonard, S. H. Young, A. Shvedova, M. I. Luster, and P. P. Simeonova. 2007. Cardiovascular effects of pulmonary exposure to single-wall carbon nanotubes. Environmental Health Perspectives 115:377-82. doi:10.1289/ehp.9688.
67. Lipka, J., M. Semmler-Behnke, R. A. Sperling, A. Wenk, S. Takenaka, C. Schleh, T. Kissel, W. J. Parak, and W. G. Kreyling. 2010. Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection. Biomaterials 31:6574-81. doi:10.1016/j. biomaterials.2010.05.009.
68. Liu, H., T. Liu, L. Li, N. Hao, L. Tan, X. Meng, J. Ren, D. Chen, and F. Tang. 2012. Size dependent cellular uptake, in vivo fate and light-heat conversion efficiency of gold nanoshells on silica nanorattles. Nanoscale 4:3523-29. doi:10.1039/c2nr30396e.
69. Liu, R., H. H. Liu, Z. Ji, C. H. Chang, T. Xia, A. E. Nel, and Y. Cohen. 2015. Evaluation of toxicity ranking of metal oxide nanoparticles via an in vitro dosimetry model. ACS Nano 9:9303-13. doi:10.1021/acsnano.5b04420.
70. Liu, X. S., H. Li, Y. J. Chen, Q. Jin, K. F. Ren, and J. Ji. 2014. Mixed-charge nanoparticles for long circulation, low reticuloendothelial system clearance and high tumor accumulation. Adv Healthcare Mater 3:1439-47. doi:10.1002/adhm.v3.9.
71. Loeschner, K., N. Hadrup, K. Qvortrup, A. Larsen, X. Gao, U. Vogel, A. Mortensen, H. R. Lam, and E. H. Larsen. 2011. Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate. Particle and Fibre Toxicology 8:18.
72. Lynch, I., and K. A. Dawson. 2008. Protein-nanoparticle interactions. Nano Today 3:40-47. doi:10.1016/S1748-0132(08)70014-8.
73. Ma-Hock, L., S. Burkhardt, V. Strauss, A. O. Gamer, K. Wiench, B. V. Ravenzwaay, and R. Landsiedel. 2008. Development of a short-term inhalation test in the rat using nano-titanium dioxide as a model substance. Inhalation Toxicology 21: 102-18. doi:10.1080/08958370802361057.
74. Marina. 2015. http://www.marina-fp7.eu (accessed May 18, 2015).
75. Miller, M. 2014. The role of oxidative stress in cardiovascular actions of particulate air pollution. Biochemical Society Transactions 42:1006-11.
76. Møller, P. 2005. Genotoxicity of environmental agents assessed by the alkaline comet assay. Basic & Clinical Pharmacology & Toxicology 96:1-42.
77. Møller, P., J. G. Hemmingsen, D. M. Jensen, P. H. Danielsen, D. G. Karottki, K. Jantzen, M. Roursgaard, Y. Cao, A. Kermanizadeh, H. Klingberg, D. V. Christophersen, L. G. Hersoug, and S. Loft. 2015b. Application of the comet assay in particle toxicology: Air pollution and engineered nanomaterials exposure. Mutagenesis 30:67-83. doi:10.1093/mutage/geu035.
78. Møller, P., D. M. Jensen, D. V. Christophersen, A. Kermanizadeh, N. R. Jacobsen, J. G. Hemmingsen, P. H. Danielsen, D. G. Karottki, M. Roursgaard, Y. Cao, K. Jantzen, L. G. Hersoug, and S. Loft. 2015a. Measurement of oxidative damage to DNA in nanomaterial exposed cells and animals. Environmental and Molecular Mutagenesis 56:97-110.
79. Møller, P., L. Mikkelsen, L. K. Vesterdal, J. K. Folkmann, L. Forchhammer, M. Roursgaard, P. H. Danielsen, and S. Loft. 2011. Hazard identification of particulate matter on vasomotor dysfunction and progression of atherosclerosis. Critical Reviews in Toxicology 41:339-68. doi:10.3109/ 10408444.2010.533152.
80. Nanogenotox Report. 2015. http://www.nanogenotox.eu/files/ PDF/Deliverables/d4.1-summary%20report.pdf (accessed March 11, 2015).
81. Nanomicex. 2015. http://cordis.europa.eu/project/rcn/ 103072-en.html (accessed May 18,2015).
82. Napierska, D., L. C. J. Thomassen, B. Vanaudenaerde, K. Luyts, D. Lison, J. A. Martens, B. Nemery, and P. H. M. Hoet. 2012. Cytokine production by co-culture exposed to monodisperse amorphous silica nanoparticles: The role of size and surface area. Toxicology Letters 211:98-104. doi:10.1016/j.toxlet.2012.03.002.
83. National Institute for Occupational Safety and Health. 2011. Occupational exposure to titanium dioxide. Current Intelligence Bulletin 63. Department of Health and Human Services, Public Health.http://www.cdc.gov/niosh/ docs/2013-145/ (accessed February 8, 2016).
84. National Institute for Occupational Safety and Health. 2013. Occupational exposure to carbon nanotubes and nanofibers. Current Intelligence Bulletin 65. Department of Health and Human Services, Public Health.http://www.cdc.gov/ niosh/docs/2011-160/ (accessed February 8, 2016).
85. NeuroNano. 2015. http://www.neuronano.eu (accessed March 16, 2015).
86. Oberdorster, G., V. Castranova, B. Asgharian, and P. Sayre. 2015. Inhalation exposure to carbon nanotubes (CNT) and carbon nanofibers (CNF): Methodology and dosimetry. Journal of Toxicology and Environmental Health, Part B 18:121-212. doi:10.1080/ 10937404.2015.1051611.
87. Oberdörster, G., E. Oberdörster, and J. Oberdörster. 2005. Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environmental Health Perspectives 113:823-39. doi:10.1289/ehp.7339.
88. Ong, K. J., T. J. MacCormack, R. J. Clark, R. J. Ede, J. D. Ede, V. A. Ortega, L. C. Felix, M. K. Dang, G. Ma, H. Fenniri, J. G. Veinot, and G. G. Goss. 2014. Widespread nanoparticle-assay interference: Implications for nanotoxicity testing. Plos One 11:9.
89. Pattan, G., and G. Kaul. 2014. Health hazards associated with nanomaterials. Toxicology and Industrial Health 30:499-519. doi:10.1177/0748233712459900.
90. Pauluhn, J. 2011. Poorly soluble particulates: Searching for a unifying denominator of nanoparticles and fine particles for DNEL estimation. Toxicology 279:176-88. doi:10.1016/ j.tox.2010.10.009.
91. Poulsen, S. S., A. T. Saber, A. Williams, A. Williams, O. Andersen, C. Købler, R. Atluri, M. E. Pozzebon, S. P. Mucelli, M. Simion, D. Rickerby, A. Mortensen, P. Jackson, Z. O. Kviovska, K. Mølhave, N. R. Jacobsen, K. A. Jensen, C. L. Yauk, H. Wallin, S. Halappanavar, and U. Vogel. 2015. MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs. Toxicology and Applied Pharmacology 284:16-32.
92. Roberts, J. R., W. McKinney, H. Kan, K. Krajnak, D. G. Frazer, T. A. Thomas, S. Waugh, A. Kenyon, R. I. MacCuspie, V. A. Hackley, and V. Castranova. 2013. Pulmonary and cardiovascular responses of rats to inhalation of silver nanoparticles. Journal of Toxicology and Environmental Health, Part A 76:651-68. doi:10.1080/ 15287394.2013.792024.
93. Rushton, E. K., J. Jiang, S. S. Leonard, S. Eberly, V. Castranova, P. Biswas, A. Elder, X. Han, R. Gelein, J. Finklestein, and G. Oberdorster. 2010. Concept of assessing nanoparticle hazards considering nanoparticle dosemetric and chemical/biological response metrics. Journal of Toxicology and Environmental Health, Part A 73:445-61. doi:10.1080/15287390903489422.
94. Saber, A. T., N. R. Jacobsen, J. Bornholdt, S. L. Kjaer, M. Dybdahl, L. Risom, S. Loft, U. Vogel, and H. Wallin. 2006. Cytokine expression in mice exposed to diesel exhaust particles by inhalation. Role of tumor necrosis factor. Particle and Fibre Toxicology 3:4. doi:10.1186/1743-8977-3-4.
95. Sadauskas, E., N. R. Jacobson, G. Danscher, M. Soltenberg, W. G. Kreyling, and W. G. Kreyling. 2009. Bio-disruption of gold nanoparticles in mouse lung following intratracheal instillation. Chemistry Central Journal 3:16-23. doi:10.1186/1752-153X-3-16.
96. Semmler-Behnke, M., W. G. Kreyling, J. Lipka, S. Fertsch, A. Wenk, S. Takenaka, G. Schmid, and W. Brandau. 2008. Biodistribution of 1.4-and 18-nm gold particles in rats. Small 4:2108-11. doi:10.1002/smll.v4:12.
97. Semmler-Behnke, M., J. Lipka, A. Wenk, S. Hirn, M. Schaffler, F. Tian, G. Schmid, G. Oberdorster, and W. G. Kreyling. 2014. Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat. Particle and Fibre Toxicology 11:33.
98. Silva, R. M., C. Teesy, L. Franzi, A. Weir, P. Westerhoff, J. E. Evans, and K. E. Pinkerton. 2013. Biological response to nano-scale titanium dioxide (TiO2): Role of particle dose, shape, and retention. Journal of Toxicology and Environmental Health, Part A 76:953-72. doi:10.1080/ 15287394.2013.826567.
99. Smith, E. P., I. Lipkovich, and K. Y. Ye. 2002. Weight-ofevidence (WOE): Quantitative estimation of probability of impairment for individual and multiple lines of evidence. Human and Ecological Risk Assessment: An International Journal 8:1585-96. doi:10.1080/20028091057493.
100. Snow, S. J., A. De Vizcaya-Ruiz, A. Osornio-Vargas, R. F. Thomas, M. C. Schladweilder, J. McGee, and U. P. Kodavanti. 2014. The effect of composition, size, and solubility on acute pulmonary injury in rats following exposure to Mexico City ambient particulate matter samples. Journal of Toxicology and Environmental Health, Part A 77:1164-82. doi:10.1080/15287394.2014.917445.
101. Snyder-Talkington, B. N., Y. Qian, V. Castranova, and N. L. Guo. 2012. New perspectives for in vitro risk assessment of multiwalled carbon nanotubes: Application of coculture and bioinformatics. Journal of Toxicology and Environmental Health, Part B 15:468-92. doi:10.1080/ 10937404.2012.736856.
102. Stone, V., S. Pozzi-Mucelli, L. Tran, K. Aschberger, S. Sabella, U. Vogel, C. Poland, D. Balharry, T. Fernandes, S. Gottardo, S. Hankin, M. G. Hartl, N. Hartmann, D. Hristozov, K. Hund-Rinke, H. Johnston, A. Marcomini, O. Panzer, D. Roncato, A. T. Saber, H. Wallin, and J. J. Scott-Fordsmand. 2014. ITS-NANO - Prioritising nanosafety research to develop a stakeholder driven intelligent testing strategy. Particle and Fibre Toxicology 11:9. doi:10.1186/1743-8977-11-9.
103. Suwa, T., J. C. Hogg, K. B. Quinlan, A. Ohgami, R. Vincent, and S. F. Van Eeden. 2002. Particulate air pollution induces progression of atherosclerosis. Journal of the American College of Cardiology 39:935-42. doi:10.1016/ S0735-1097(02)01715-1.
104. Tang, S., V. Allagadda, H. Chibli, J. L. Nadeau, and G. D. Mayer. 2013. Comparison of cytotoxicity and expression of metal regulatory genes in zebrafish (Danio rerio) liver cells exposed to cadmium sulfate, zinc sulfate and quantum dots. Metallomics 5:1411-22. doi:10.1039/c3mt20234h.
105. Teeguarden, J. G., P. M. Hinderliter, G. Orr, B. D. Thrall, and J. G. Pounds. 2007. Particokinetics in vitro: Dosimetry considerations for in vitro nanoparticle toxicity assessments. Toxicological Sciences 95:300-12. doi:10.1093/ toxsci/kfl165.
106. Tournebize, J., A. Sapin-Minet, G. Bartosz, P. Leroy, and A. Boudier. 2013. Pitfalls of assays devoted to evaluation of oxidative stress induced by inorganic nanoparticles. Talanta 116:753-63. doi:10.1016/j.talanta.2013.07.077.
107. Tran, C. L., R. Tantra, K. Donaldson, V. Stone, S. M. Hankin, B. Ross, R. J. Aitken, and A. D. Jones. 2011. A hypothetical model for predicting the toxicity of high aspect ratio nanoparticles (HARN). Journal of Nanoparticle 13:6683-98. doi:10.1007/s11051-011-0575-9.
108. Unfried, K., C. Albrecht, L.-O. Klotz, A. Von Mikecz, S. Grether-Beck, and R. P. F. Schins. 2007. Cellular responses to nanoparticles: Target structures and mechanisms. Nanotoxicology 1:52-71. doi:10.1080/00222930701314932.
109. Ursini, C. L., D. Cavallo, A. M. Fresegna, A. Ciervo, R. Maiello, P. Tassone, G. Buresti, S. Casciardi, and S. Iavicoli. 2014. Evaluation of cytotoxic, genotoxic and inflammatory response in human alveolar and bronchial epithelial cells exposed to titanium dioxide nanoparticles. Journal of Applied Toxicology 34:1209-19. doi:10.1002/jat.v34.11.
110. Van Der Zande, M., R. J. Vandebriel, E. Van Doren, E. Kramer, Z. Herrera Rivera, C. S. Serrano-Rojero, E. R. Gremmer, J. Mast, R. J. B. Peters, P. C. H. Hollman, P. J. M. Hendriksen, H. J. P. Marvin, A. A. C. M. Peijnenburg, and H. Bouwmeester. 2012. Distribution, elimination and toxicity of silver nanoparticles and silver ions in rats after 28-day oral exposure. ACS Nano 6:7427-42. doi:10.1021/ nn302649p.
111. Vietti, G., S. Ibouraadaten, M. Palmai-Pallag, Y. Yakoub, C. Bailly, I. Fenoglio, E. Marbaix, D. Lison, and S. Van Den Brule. 2013. Towards predicting the lung fibrogenic activity of nanomaterials: Experimental validation of an in vitro fibroblast proliferation assay. Particle and Fibre Toxicology 10:52.
112. Weir, A., P. Westerhoff, L. Fabricius, K. Hristovski, and N. Von Goetz. 2012. Titanium dioxide nanoparticles in food and personal care products. Environmental Science & Technology 46:2242-50. doi:10.1021/es204168d.
113. Yuta, A., M. Takamitsu, and S. Hirano. 2014. Difference in the toxicity mechanism between ion and nanoparticle forms of silver in the mouse lung and in macrophages. Toxicology 328:84-92.
114. Zhang, J., X. Nie, Y. Ji, Y. Liu, X. Wu, C. Chen, and X. Fang. 2014. Quantitative biokinetics and systemic translocation of various gold nanostructures are highly dependent on their size and shape. Journal of Nanoscience and Nanotechnology 14:4124-38. doi:10.1166/jnn.2014.8274.
115. Zhao, J., and V. Castranova. 2011. Toxicology of nanomaterials used in nanomedicine. Journal of Toxicology and Environmental Health, Part B 14:593-632. doi:10.1080/ 10937404.2011.615113.