Progress and future of in vitro models to study translocation of nanoparticles

Archives of Toxicology

Volumn 89, Issue 9, 2015, Pages 1469-1495

  Braakhuis, Hedwig M ^a,b   Kloet, Samantha K ^c   Kezic, Sanja ^d   Kuper, Frieke ^e   Park, Margriet V D Z ^b   Bellmann, Susann ^e   van der Zande, Meike ^c   Le Gac, Séverine ^f   Krystek, Petra ^g   Peters, Ruud J B ^c   Rietjens, Ivonne M C M ^c   Bouwmeester, Hans ^c  

^a MAASTRICHT UNIVERSITY   (Netherlands)

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

^c WAGENINGEN UNIVERSITY   (Netherlands)

^d UNIVERSITY OF AMSTERDAM   (Netherlands)

^e TNO   (Netherlands)

^f UNIVERSITY OF TWENTE   (Netherlands)

^g PHILIPS RESEARCH LABORATORIES   (Germany)

Author keywords

Dermal; In vitro models; Lung; Nanoparticles; Oral; Placenta; Toxicokinetics

Indexed keywords

NANOPARTICLE;

BLOOD PLACENTA BARRIER; CHEMICAL COMPOSITION; CIRCULATION; COMPARATIVE STUDY; CONSUMER; DIGESTION; EPITHELIUM CELL; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INHALATION; INTESTINAL BARRIER; INTESTINE ABSORPTION; LIPID BILAYER; LONG TERM EXPOSURE; LUNG ALVEOLUS MACROPHAGE; LUNG BARRIER; MICROENVIRONMENT; NONHUMAN; NUTRIENT; PERMEABILITY BARRIER; PREDICTION; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; SKIN BARRIER; STRATUM CORNEUM; ANIMAL; ANIMAL TESTING ALTERNATIVE; BIOLOGICAL MODEL; COCULTURE; METABOLISM; MICROFLUIDIC ANALYSIS; PROCEDURES; RODENT; TISSUE DISTRIBUTION;

ANIMAL TESTING ALTERNATIVES; ANIMALS; COCULTURE TECHNIQUES; HUMANS; MICROFLUIDIC ANALYTICAL TECHNIQUES; MODELS, BIOLOGICAL; NANOPARTICLES; RODENTIA; TISSUE DISTRIBUTION;

EID: 84940578935     PISSN: 03405761     EISSN: 14320738     Source Type: Journal    
DOI: 10.1007/s00204-015-1518-5     Document Type: Review

References (241)

1. Ali H, Kalashnikova I, White MA, Sherman M, Rytting E (2013) Preparation, characterization, and transport of dexamethasone-loaded polymeric nanoparticles across a human placental in vitro model. Int J Pharm 454(1):149–157. doi:10.1016/j.ijpharm.2013.07.010
2. Antunes F, Andrade F, Araujo F, Ferreira D, Sarmento B (2013) Establishment of a triple co-culture in vitro cell models to study intestinal absorption of peptide drugs. Eur J Pharm Biopharm 83(3):427–435. doi:10.1016/j.ejpb.2012.10.003
3. Arai Y, Miyayama T, Hirano S (2014) Difference in the toxicity mechanism between ion and nanoparticle forms of silver in the mouse lung and in macrophages. Toxicology 328:84–92. doi:10.1016/j.tox.2014.12.014
4. Araujo F, Shrestha N, Shahbazi MA et al (2014) The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium. Biomaterials 35(33):9199–9207. doi:10.1016/j.biomaterials.2014.07.026
5. Ardavin C, del Hoyo GM, Martin P et al (2001) Origin and differentiation of dendritic cells. Trends Immunol 22(12):691–700. doi:10.1016/S1471-4906(01)02059-2
6. Arts JH, Muijser H, Duistermaat E, Junker K, Kuper CF (2007) Five-day inhalation toxicity study of three types of synthetic amorphous silicas in Wistar rats and post-exposure evaluations for up to 3 months. Food Chem Toxicol 45(10):1856–1867. doi:10.1016/j.fct.2007.04.001
7. Asgharian B, Price O, Miller F et al (2009) Multiple-path particle dosimetry model (MPPD v 2.11): a model for human and rat airway particle dosimetry. In: Applied Research Associates (ARA) HIfHS, National Institute for Public Health and the Environment (RIVM), and Ministry of Housing, Spatial Planning and the Environment (ed). V2.11 edn. Applied Research Associates (ARA), Raleigh, North Carolina
8. Aye IL, Keelan JA (2013) Placental ABC transporters, cellular toxicity and stress in pregnancy. Chem Biol Interact 203(2):456–466. doi:10.1016/j.cbi.2013.03.007
9. Bakand S, Hayes A, Dechsakulthorn F (2012) Nanoparticles: a review of particle toxicology following inhalation exposure. Inhal Toxicol 24(2):125–135. doi:10.3109/08958378.2010.642021
10. Balasubramanian SK, Jittiwat J, Manikandan J, Ong CN, Yu LE, Ong WY (2010) Biodistribution of gold nanoparticles and gene expression changes in the liver and spleen after intravenous administration in rats. Biomaterials 31(8):2034–2042. doi:10.1016/j.biomaterials.2009.11.079
11. Baroli B (2010) Penetration of nanoparticles and nanomaterials in the skin: fiction or reality? J Pharm Sci 99(1):21–50. doi:10.1002/jps.21817
12. Bednar AJ, Poda AR, Mitrano DM et al (2013) Comparison of on-line detectors for field flow fractionation analysis of nanomaterials. Talanta 104:140–148. doi:10.1016/j.talanta.2012.11.008
13. Behrens I, Pena AI, Alonso MJ, Kissel T (2002) Comparative uptake studies of bioadhesive and non-bioadhesive nanoparticles in human intestinal cell lines and rats: the effect of mucus on particle adsorption and transport. Pharm Res 19(8):1185–1193
14. Bellmann S, Carlander D, Fasano A et al (2015) Mammalian gastrointestinal tract parameters modulating the integrity, surface properties, and absorption of food-relevant nanomaterials. Wiley Interdiscip Rev Nanomed Nanobiotechnol. doi:10.1002/wnan.1333
15. Benirschke K, Kaufmann P, Baergen RN (2006) Pathology of the human placenta. Springer, New York
16. Bermudez LE, Sangari FJ, Kolonoski P, Petrofsky M, Goodman J (2002) The efficiency of the translocation of Mycobacterium tuberculosis across a bilayer of epithelial and endothelial cells as a model of the alveolar wall is a consequence of transport within mononuclear phagocytes and invasion of alveolar epithelial cells. Infect Immun 70(1):140–146
17. Bhatia SN, Ingber DE (2014) Microfluidic organs-on-chips. Nat Biotechnol 32(8):760–772. doi:10.1038/nbt.2989
18. Bhattacharjee S, Ershov D, Gucht J et al (2013) Surface charge-specific cytotoxicity and cellular uptake of tri-block copolymer nanoparticles. Nanotoxicology 7(1):71–84. doi:10.3109/17435390.2011.633714
19. 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(3):392–405. doi:10.1089/jam.2006.19.392
20. Borm PJ, Robbins D, Haubold S et al (2006) The potential risks of nanomaterials: a review carried out for ECETOC. Part Fibre Toxicol 3:11. doi:10.1186/1743-8977-3-11
21. Bouwmeester H, Poortman J, Peters RJ et al (2011) Characterization of translocation of silver nanoparticles and effects on whole-genome gene expression using an in vitro intestinal epithelium coculture model. ACS Nano 5(5):4091–4103. doi:10.1021/nn2007145
22. Bouwmeester H, Brandhoff P, Marvin HJ, Weigel S, Peters RJ (2014) State of the safety assessment and current use of nanomaterials in food and food production. Trends Food Sci Technol 40(2):200–210
23. Braakhuis HM, Gosens I, Krystek P et al (2014a) Particle size dependent deposition and pulmonary inflammation after short-term inhalation of silver nanoparticles. Part Fibre Toxicol 11(1):16. doi:10.1186/s12989-014-0049-1
24. Braakhuis HM, Park MV, Gosens I, De Jong WH, Cassee FR (2014b) Physicochemical characteristics of nanomaterials that affect pulmonary inflammation. Part Fibre Toxicol 11(1):18. doi:10.1186/1743-8977-11-18
25. Brandenberger C, Rothen-Rutishauser B, Muhlfeld C et al (2010) Effects and uptake of gold nanoparticles deposited at the air-liquid interface of a human epithelial airway model. Toxicol Appl Pharmacol 242(1):56–65. doi:10.1016/j.taap.2009.09.014
26. Braun A, Couteau O, Franks K et al (2011) Validation of dynamic light scattering and centrifugal liquid sedimentation methods for nanoparticle characterisation. Adv Powder Technol 22:766–770
27. Brown SC, Boyko V, Meyers G, Voetz M, Wohlleben W (2013) Toward advancing nano-object count metrology: a best practice framework. Environ Health Perspect 121(11–12):1282–1291. doi:10.1289/ehp.1306957
28. Brugmann SA, Wells JM (2013) Building additional complexity to in vitro-derived intestinal tissues. Stem Cell Res Ther 4(Suppl 1):S1. doi:10.1186/scrt362
29. Brun E, Barreau F, Veronesi G et al (2014) Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo and in vitro gut epithelia. Particle Fibre Toxicol. doi:10.1186/1743-8977-11-13
30. Buerki-Thurnherr T, von Mandach U, Wick P (2012) Knocking at the door of the unborn child: engineered nanoparticles at the human placental barrier. Swiss Med Wkly 142:w13559. doi:10.4414/smw.2012.13559
31. Carr KE, Smyth SH, McCullough MT, Morris JF, Moyes SM (2012) Morphological aspects of interactions between microparticles and mammalian cells: intestinal uptake and onward movement. Prog Histochem Cytochem 46(4):185–252. doi:10.1016/j.proghi.2011.11.001
32. Cartwright L, Poulsen MS, Nielsen HM et al (2012) In vitro placental model optimization for nanoparticle transport studies. Int J Nanomed 7:497–510. doi:10.2147/ijn.s26601
33. Carvalho TC, Peters JI, Williams RO 3rd (2011) Influence of particle size on regional lung deposition—what evidence is there? Int J Pharm 406(1–2):1–10. doi:10.1016/j.ijpharm.2010.12.040
34. Cascio C, Geiss O, Franchini F et al (2015) Detection, quantification and derivation of number size distribution of silver nanoparticles in antimicrobial consumer products. J Anal At Spectrom. doi:10.1039/c4ja00410h
35. Cevc G, Vierl U (2010) Nanotechnology and the transdermal route: a state of the art review and critical appraisal. J Control Release 141(3):277–299. doi:10.1016/j.jconrel.2009.10.016
36. Chowdhury F, Howat WJ, Phillips GJ, Lackie PM (2010) Interactions between endothelial cells and epithelial cells in a combined cell model of airway mucosa: effects on tight junction permeability. Exp Lung Res 36(1):1–11. doi:10.3109/01902140903026582
37. Cone RA (2009) Barrier properties of mucus. Adv Drug Deliv Rev 61(2):75–85. doi:10.1016/j.addr.2008.09.008
38. Correia Carreira S, Walker L, Paul K, Saunders M (2013) The toxicity, transport and uptake of nanoparticles in the in vitro BeWo b30 placental cell barrier model used within NanoTEST. Nanotoxicology. doi:10.3109/17435390.2013.833317
39. Crater JS, Carrier RL (2010) Barrier properties of gastrointestinal mucus to nanoparticle transport. Macromol Biosci 10(12):1473–1483. doi:10.1002/mabi.201000137
40. Creutzenberg O, Bellmann B, Korolewitz R et al (2012) Change in agglomeration status and toxicokinetic fate of various nanoparticles in vivo following lung exposure in rats. Inhal Toxicol 24(12):821–830. doi:10.3109/08958378.2012.721097
41. Cross SE, Innes B, Roberts MS, Tsuzuki T, Robertson TA, McCormick P (2007) Human skin penetration of sunscreen nanoparticles: in vitro assessment of a novel micronized zinc oxide formulation. Skin Pharmacol Physiol 20(3):148–154. doi:10.1159/000098701
42. De Jong WH, Hagens WI, Krystek P, Burger MC, Sips AJ, Geertsma RE (2008) Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. Biomaterials 29(12):1912–1919. doi:10.1016/j.biomaterials.2007.12.037
43. De Jong WH, Burger MC, Verheijen MA, Geertsma RE (2010) Detection of the presence of gold nanoparticles in organs by transmission electron microscopy. Materials 3:4681–4694
44. Dekkers S, Krystek P, Peters RJ et al (2011) Presence and risks of nanosilica in food products. Nanotoxicology 5(3):393–405. doi:10.3109/17435390.2010.519836
45. des Rieux A, Fievez V, Theate I, Mast J, Preat V, Schneider YJ (2007) An improved in vitro model of human intestinal follicle-associated epithelium to study nanoparticle transport by M cells. Eur J Pharm Sci 30(5):380–391. doi:10.1016/j.ejps.2006.12.006
46. Desforges M, Sibley CP (2010) Placental nutrient supply and fetal growth. Int J Dev Biol 54(2–3):377–390. doi:10.1387/ijdb.082765md
47. Di Bona KR, Xu Y, Ramirez PA et al (2014) Surface charge and dosage dependent potential developmental toxicity and biodistribution of iron oxide nanoparticles in pregnant CD-1 mice. Reprod Toxicol 50:36–42. doi:10.1016/j.reprotox.2014.09.010
48. dos Santos T, Varela J, Lynch I, Salvati A, Dawson KA (2011) Effects of transport inhibitors on the cellular uptake of carboxylated polystyrene nanoparticles in different cell lines. PLoS One 6(9):e24438. doi:10.1371/journal.pone.0024438
49. Dudkiewicz A, Tiede K, Loeschner K et al (2011) Characterization of nanomaterials in food by electronmicroscopy. Trends Anal Chem 30:28–43
50. EFSA (2011) Scientific opinion on guidance on the risk assessment of the application of nanoscience and nanotechnologies in the food and feed chain. EFSA J 9(5):36. doi:10.2903/j.efsa.2011.2140
51. Elder A, Gelein R, Silva V et al (2006) Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. Environ Health Perspect 114(8):1172–1178
52. Elzey S, Tsai DH, Rabb SA, Yu LL, Winchester MR, Hackley VA (2012) Quantification of ligand packing density on gold nanoparticles using ICP-OES. Anal Bioanal Chem 403(1):145–149. doi:10.1007/s00216-012-5830-0
53. Fazlollahi F, Sipos A, Kim YH et al (2011) Translocation of PEGylated quantum dots across rat alveolar epithelial cell monolayers. Int J Nanomed 6:2849–2857. doi:10.2147/IJN.S26051
54. Filipe V, Hawe A, Jiskoot W (2010) Critical evaluation of Nanoparticle Tracking Analysis (NTA) by NanoSight for the measurement of nanoparticles and protein aggregates. Pharm Res 27(5):796–810. doi:10.1007/s11095-010-0073-2
55. Frieke Kuper C, Grollers-Mulderij M, Maarschalkerweerd T et al (2015) Toxicity assessment of aggregated/agglomerated cerium oxide nanoparticles in an in vitro 3D airway model: the influence of mucociliary clearance. Toxicol In Vitro 29(2):389–397. doi:10.1016/j.tiv.2014.10.017
56. Frohlich E, Bonstingl G, Hofler A et al (2013) Comparison of two in vitro systems to assess cellular effects of nanoparticles-containing aerosols. Toxicol In Vitro 27(1):409–417. doi:10.1016/j.tiv.2012.08.008
57. Geiser M, Kreyling WG (2010) Deposition and biokinetics of inhaled nanoparticles. Part Fibre Toxicol 7:2. doi:10.1186/1743-8977-7-2
58. Geiser M, Rothen-Rutishauser B, Kapp N et al (2005) Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environ Health Perspect 113(11):1555–1560
59. Genschow E, Spielmann H, Scholz G et al (2002) The ECVAM international validation study on in vitro embryotoxicity tests: results of the definitive phase and evaluation of prediction models. European Centre for the Validation of Alternative Methods. Altern Lab Anim 30(2):151–176
60. George R, Merten S, Wang TT, Kennedy P, Maitz P (2014) In vivo analysis of dermal and systemic absorption of silver nanoparticles through healthy human skin. Australas J Dermatol 55(3):185–190. doi:10.1111/ajd.12101
61. George I, Vranic S, Boland S, Courtois A, Baeza-Squiban A (2015) Development of an in vitro model of human bronchial epithelial barrier to study nanoparticle translocation. Toxicol In Vitro 29(1):51–58. doi:10.1016/j.tiv.2014.08.003
62. Geraets L, Oomen AG, Schroeter JD, Coleman VA, Cassee FR (2012) Tissue distribution of inhaled micro- and nano-sized cerium oxide particles in rats: results from a 28-day exposure study. Toxicol Sci 127(2):463–473. doi:10.1093/toxsci/kfs113
63. Geraets L, Oomen AG, Krystek P et al (2014) Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats. Part Fibre Toxicol 11:30. doi:10.1186/1743-8977-11-30
64. Geys J, Coenegrachts L, Vercammen J et al (2006) In vitro study of the pulmonary translocation of nanoparticles: a preliminary study. Toxicol Lett 160(3):218–226. doi:10.1016/j.toxlet.2005.07.005
65. Geys J, De Vos R, Nemery B, Hoet PH (2009) In vitro translocation of quantum dots and influence of oxidative stress. Am J Physiol Lung Cell Mol Physiol 297(5):L903–L911. doi:10.1152/ajplung.00029.2009
66. Grafmuller S, Manser P, Krug HF, Wick P, vonMandach U (2013) Determination of the transport rate of xenobiotics and nanomaterials across the placenta using the ex vivo human placental perfusion model. J Vis Exp. doi:10.3791/50401
67. Griep LM, Wolbers F, de Wagenaar B et al (2013) BBB on chip: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function. Biomed Microdevices 15(1):145–150. doi:10.1007/s10544-012-9699-7
68. Harink B, Le Gac S, Truckenmuller R, van Blitterswijk C, Habibovic P (2013) Regeneration-on-a-chip? The perspectives on use of microfluidics in regenerative medicine. Lab Chip 13(18):3512–3528. doi:10.1039/c3lc50293g
69. Hartung T, Balls M, Bardouille C et al (2002) Good cell culture practice. ECVAM good cell culture practice task force report 1. Altern Lab Anim 30(4):407–414
70. Hartung T, Luechtefeld T, Maertens A, Kleensang A (2013) Integrated testing strategies for safety assessments. ALTEX 30(1):3–18
71. Hassellov M, Readman JW, Ranville JF, Tiede K (2008) Nanoparticle analysis and characterization methodologies in environmental risk assessment of engineered nanoparticles. Ecotoxicology 17(5):344–361. doi:10.1007/s10646-008-0225-x
72. He C, Yin L, Tang C, Yin C (2012) Size-dependent absorption mechanism of polymeric nanoparticles for oral delivery of protein drugs. Biomaterials 33(33):8569–8578. doi:10.1016/j.biomaterials.2012.07.063
73. Helbig A, Silletti E, van Aken GA et al (2013) Lipid digestion of protein stabilized emulsions investigated in a dynamic in vitro gastro-intestinal model system. Food Dig 4:58–68
74. Hermanns MI, Unger RE, Kehe K, Peters K, Kirkpatrick CJ (2004) Lung epithelial cell lines in coculture with human pulmonary microvascular endothelial cells: development of an alveolo-capillary barrier in vitro. Lab Invest 84(6):736–752. doi:10.1038/labinvest.3700081
75. Hermanns MI, Kasper J, Dubruel P, Pohl C, Uboldi C, Vermeersch V, Fuchs S, Unger RE, Kirkpatrick CJ (2010) An impaired alveolar-capillary barrier in vitro: effect of proinflammatory cytokines and consequences on nanocarrier interaction. J R Soc Interface 7(Suppl 1):S41–S54. doi:10.1098/rsif.2009.0288.focus
76. Herzog F, Clift MJ, Piccapietra F et al (2013) Exposure of silver-nanoparticles and silver-ions to lung cells in vitro at the air-liquid interface. Part Fibre Toxicol 10(1):11. doi:10.1186/1743-8977-10-11
77. Hillery AM, Florence AT (1996) The effect of adsorbed poloxamer 188 and 407 surfactants on the intestinal uptake of 60-nm polystyrene particles after oral administration in the rat. Int J Pharm 132(1–2):123–130. doi:10.1016/0378-5173(95)04353-5
78. Hillery AM, Jani PU, Florence AT (1994) Comparative, quantitative study of lymphoid and non-lymphoid uptake of 60 nm polystyrene particles. J Drug Target 2(2):151–156. doi:10.3109/10611869409015904
79. Hillyer JF, Albrecht RM (2001) Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticles. J Pharm Sci 90(12):1927–1936
80. Holder AL, Marr LC (2013) Toxicity of silver nanoparticles at the air-liquid interface. Biomed Res Int 2013:328934. doi:10.1155/2013/328934
81. Huh D, Fujioka H, Tung YC et al (2007) Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems. Proc Natl Acad Sci USA 104(48):18886–18891. doi:10.1073/pnas.0610868104
82. Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE (2010) Reconstituting organ-level lung functions on a chip. Science 328(5986):1662–1668. doi:10.1126/science.1188302
83. Huh D, Torisawa YS, Hamilton GA, Kim HJ, Ingber DE (2012) Microengineered physiological biomimicry: organs-on-chips. Lab Chip 12(12):2156–2164. doi:10.1039/c2lc40089h
84. Huh D, Kim HJ, Fraser JP et al (2013) Microfabrication of human organs-on-chips. Nat Protoc 8(11):2135–2157. doi:10.1038/nprot.2013.137
85. Hussain N, Florence AT (1998) Utilizing bacterial mechanisms of epithelial cell entry: invasin-induced oral uptake of latex nanoparticles. Pharm Res 15(1):153–156
86. Hussain N, Jani PU, Florence AT (1997) Enhanced oral uptake of tomato lectin-conjugated nanoparticles in the rat. Pharm Res 14(5):613–618
87. Hussain N, Jaitley V, Florence AT (2001) Recent advances in the understanding of uptake of microparticulates across the gastrointestinal lymphatics. Adv Drug Deliv Rev 50(1–2):107–142
88. ICRP (1994) Human respiratory tract model for radiological protection. ICRP Publication 66, vol 24. International Commission on Radiological Protection, p 1–3
89. Ingels F, Deferme S, Destexhe E, Oth M, Van den Mooter G, Augustijns P (2002) Simulated intestinal fluid as transport medium in the Caco-2 cell culture model. Int J Pharm 232(1–2):183–192
90. Jakasa I, Kezic S (2008) Evaluation of in vivo animal and in vitro models for prediction of dermal absorption in man. Hum Exp Toxicol 27(4):281–288. doi:10.1177/0960327107085826
91. Janer G, Mas del Molino E, Fernandez-Rosas E, Fernandez A, Vazquez-Campos S (2014) Cell uptake and oral absorption of titanium dioxide nanoparticles. Toxicol Lett 228(2):103–110. doi:10.1016/j.toxlet.2014.04.014
92. Jani P, Halbert GW, Langridge J, Florence AT (1989) The uptake and translocation of latex nanospheres and microspheres after oral administration to rats. J Pharm Pharmacol 41(12):809–812
93. Jani P, Halbert GW, Langridge J, Florence AT (1990) Nanoparticle uptake by the rat gastrointestinal mucosa: quantitation and particle size dependency. J Pharm Pharmacol 42(12):821–826
94. Jensen KA, Kembouche Y, Christiansen E et al (2011) Final protocol for producing suitable manufactures nanomaterial exposure media. The generic NANOGENOTOX dispersion protocol, Standard Operation Procedure (SOP). http://www.nanogenotox.eu/
95. Jin Y, Song Y, Zhu X et al (2012) Goblet cell-targeting nanoparticles for oral insulin delivery and the influence of mucus on insulin transport. Biomaterials 33(5):1573–1582. doi:10.1016/j.biomaterials.2011.10.075
96. Kadiyala I, Loo Y, Roy K, Rice J, Leong KW (2010) Transport of chitosan-DNA nanoparticles in human intestinal M-cell model versus normal intestinal enterocytes. Eur J Pharm Sci 39(1–3):103–109. doi:10.1016/j.ejps.2009.11.002
97. Kandarova H, Letasiova S (2011) Alternative methods in toxicology: pre-validated and validated methods. Interdiscip Toxicol 4(3):107–113. doi:10.2478/v10102-011-0018-6
98. Kerneis S, Bogdanova A, Kraehenbuhl JP, Pringault E (1997) Conversion by Peyer’s patch lymphocytes of human enterocytes into M cells that transport bacteria. Science 277(5328):949–952
99. Kezic S, Nielsen JB (2009) Absorption of chemicals through compromised skin. Int Arch Occup Environ Health 82(6):677–688. doi:10.1007/s00420-009-0405-x
100. Kezic S, Novak N, Jakasa I et al (2014) Skin barrier in atopic dermatitis. Front Biosci (Landmark Ed) 19:542–556
101. Kim HJ, Ingber DE (2013) Gut-on-a-Chip microenvironment induces human intestinal cells to undergo villus differentiation. Integr Biol (Camb) 5(9):1130–1140. doi:10.1039/c3ib40126j
102. Klein SG, Hennen J, Serchi T, Blomeke B, Gutleb AC (2011) Potential of coculture in vitro models to study inflammatory and sensitizing effects of particles on the lung. Toxicol In Vitro 25(8):1516–1534. doi:10.1016/j.tiv.2011.09.006
103. Kong F, Singh RP (2010) A human gastric simulator (HGS) to study food digestion in human stomach. J Food Sci 75(9):E627–E635. doi:10.1111/j.1750-3841.2010.01856.x
104. Kreyling WG, Semmler-Behnke M, Seitz J et al (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. Inhal Toxicol 21(Suppl 1):55–60. doi:10.1080/08958370902942517
105. Krystek P (2012) A review on approaches to biodistribution studies about gold and silver engineered nanoparticles by inductively couples plasma mass spectrometry. Microchem J 105:39–43. doi:10.1016/j.microc.2012.02.008
106. Krystek P, Braakhuis HM, Park MVDZ, Jong WH (2013) Inductively coupled plasma-mass spectrometry in biodistribution studies of (Engineered) nanoparticles encyclopaedia of analytical chemistry. Wiley, New York
107. Krystek P, Kettler K, van der Wagt B, De Jong WH (2015) Exploring influences on the cellular uptake of medium-sized silver nanoparticles into THP-1 cells. Microchem J 120:45–50
108. Kulvietis V, Zalgeviciene V, Didziapetriene J, Rotomskis R (2011) Transport of nanoparticles through the placental barrier. Tohoku J Exp Med 225(4):225–234
109. Laborda F, Bolea E, Jimenez-Lamana J (2014) Single particle inductively coupled plasma mass spectrometry: a powerful tool for nanoanalysis. Anal Chem 86(5):2270–2278. doi:10.1021/ac402980q
110. Labouta HI, Schneider M (2013) Interaction of inorganic nanoparticles with the skin barrier: current status and critical review. Nanomedicine 9(1):39–54. doi:10.1016/j.nano.2012.04.004
111. Labouta HI, Liu DC, Lin LL et al (2011a) Gold nanoparticle penetration and reduced metabolism in human skin by toluene. Pharm Res 28(11):2931–2944. doi:10.1007/s11095-011-0561-z
112. Labouta HI, el-Khordagui LK, Kraus T, Schneider M (2011b) Mechanism and determinants of nanoparticle penetration through human skin. Nanoscale 3(12):4989–4999. doi:10.1039/c1nr11109d
113. Lager S, Powell TL (2012) Regulation of nutrient transport across the placenta. J Pregnancy 2012:179827. doi:10.1155/2012/179827
114. Lai SK, O’Hanlon DE, Harrold S et al (2007) Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc Natl Acad Sci USA 104(5):1482–1487. doi:10.1073/pnas.0608611104
115. Landsiedel R, Ma-Hock L, Hofmann T et al (2014a) Application of short-term inhalation studies to assess the inhalation toxicity of nanomaterials. Part Fibre Toxicol 11:16. doi:10.1186/1743-8977-11-16
116. Landsiedel R, Sauer UG, Ma-Hock L, Schnekenburger J, Wiemann M (2014b) Pulmonary toxicity of nanomaterials: a critical comparison of published in vitro assays and in vivo inhalation or instillation studies. Nanomedicine (Lond) 9(16):2557–2585. doi:10.2217/nnm.14.149
117. Larese FF, D’Agostin F, Crosera M et al (2009) Human skin penetration of silver nanoparticles through intact and damaged skin. Toxicology 255(1–2):33–37. doi:10.1016/j.tox.2008.09.025
118. Lefebvre DE, Venema K, Gombau L et al (2014) Utility of models of the gastrointestinal tract for assessment of the digestion and absorption of engineered nanomaterials released from food matrices. Nanotoxicology. doi:10.3109/17435390.2014.948091
119. Lehmann AD, Daum N, Bur M, Lehr CM, Gehr P, Rothen-Rutishauser BM (2011) An in vitro triple cell co-culture model with primary cells mimicking the human alveolar epithelial barrier. Eur J Pharm Biopharm 77(3):398–406. doi:10.1016/j.ejpb.2010.10.014
120. Leite-Silva VR, Le Lamer M, Sanchez WY et al (2013) The effect of formulation on the penetration of coated and uncoated zinc oxide nanoparticles into the viable epidermis of human skin in vivo. Eur J Pharm Biopharm 84(2):297–308. doi:10.1016/j.ejpb.2013.01.020
121. Lenz AG, Karg E, Lentner B et al (2009) A dose-controlled system for air-liquid interface cell exposure and application to zinc oxide nanoparticles. Part Fibre Toxicol 6:32. doi:10.1186/1743-8977-6-32
122. Lenz AG, Karg E, Brendel E et al (2013) Inflammatory and oxidative stress responses of an alveolar epithelial cell line to airborne zinc oxide nanoparticles at the air-liquid interface: a comparison with conventional, submerged cell-culture conditions. Biomed Res Int 2013:652632. doi:10.1155/2013/652632
123. Lesniak A, Campbell A, Monopoli MP, Lynch I, Salvati A, Dawson KA (2010) Serum heat inactivation affects protein corona composition and nanoparticle uptake. Biomaterials 31(36):9511–9518. doi:10.1016/j.biomaterials.2010.09.049
124. Lesniak A, Fenaroli F, Monopoli MP, Aberg C, Dawson KA, Salvati A (2012) Effects of the presence or absence of a protein corona on silica nanoparticle uptake and impact on cells. ACS Nano 6(7):5845–5857. doi:10.1021/nn300223w
125. Li H, van Ravenzwaay B, Rietjens IM, Louisse J (2013) Assessment of an in vitro transport model using BeWo b30 cells to predict placental transfer of compounds. Arch Toxicol 87(9):1661–1669. doi:10.1007/s00204-013-1074-9
126. Loeschner K, Brabrand MS, Sloth JJ, Larsen EH (2014) Use of alkaline or enzymatic sample pretreatment prior to characterization of gold nanoparticles in animal tissue by single-particle ICPMS. Anal Bioanal Chem 406(16):3845–3851. doi:10.1007/s00216-013-7431-y
127. Lozano O, Mejia J, Masereel B, Toussaint O, Lison D, Lucas S (2012) Development of a PIXE analysis method for the determination of the biopersistence of SiC and TiC nanoparticles in rat lungs. Nanotoxicology 6(3):263–271. doi:10.3109/17435390.2011.572301
128. Lozano O, Olivier T, Dogne JM, Lucas S (2013) The use of PIXE for engineered nanomaterials quantification in complex matrices. J Phys Conf Ser 429:012010
129. Lundqvist M, Stigler J, Elia G, Lynch I, Cedervall T, Dawson KA (2008) Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts. Proc Natl Acad Sci USA 105(38):14265–14270. doi:10.1073/pnas.0805135105
130. MacNicoll A, Kelly M, Aksoy H, Kramer E, Bouwmeester H, Chaudhry Q (2015) A study of the uptake and biodistribution of nano-titanium dioxide using in vitro and in vivo models of oral intake. J Nanopart Res 17(66):20
131. Madlova M, Jones SA, Zwerschke I, Ma Y, Hider RC, Forbes B (2009) Poly(vinyl alcohol) nanoparticle stability in biological media and uptake in respiratory epithelial cell layers in vitro. Eur J Pharm Biopharm 72(2):437–443. doi:10.1016/j.ejpb.2009.01.009
132. Mahler GJ, Esch MB, Glahn RP, Shuler ML (2009) Characterization of a gastrointestinal tract microscale cell culture analog used to predict drug toxicity. Biotechnol Bioeng 104(1):193–205. doi:10.1002/bit.22366
133. Mahler GJ, Esch MB, Tako E et al (2012) Oral exposure to polystyrene nanoparticles affects iron absorption. Nat Nanotechnol 7(4):264–271. doi:10.1038/nnano.2012.3
134. Ma-Hock L, Brill S, Wohlleben W et al (2012) Short term inhalation toxicity of a liquid aerosol of CdS/Cd(OH) core shell quantum dots in male Wistar rats. Toxicol Lett 208(2):115–124. doi:10.1016/j.toxlet.2011.10.011
135. Makhlof A, Werle M, Tozuka Y, Takeuchi H (2011) A mucoadhesive nanoparticulate system for the simultaneous delivery of macromolecules and permeation enhancers to the intestinal mucosa. J Control Release 149(1):81–88. doi:10.1016/j.jconrel.2010.02.001
136. Martinez-Argudo I, Sands C, Jepson MA (2007) Translocation of enteropathogenic Escherichia coli across an in vitro M cell model is regulated by its type III secretion system. Cell Microbiol 9(6):1538–1546. doi:10.1111/j.1462-5822.2007.00891.x
137. Marx U, Walles H, Hoffmann S et al (2012) ‘Human-on-a-chip’ developments: a translational cutting-edge alternative to systemic safety assessment and efficiency evaluation of substances in laboratory animals and man? Altern Lab Anim 40(5):235–257
138. Mavon A, Miquel C, Lejeune O, Payre B, Moretto P (2007) In vitro percutaneous absorption and in vivo stratum corneum distribution of an organic and a mineral sunscreen. Skin Pharmacol Physiol 20(1):10–20. doi:10.1159/000096167
139. Menjoge AR, Rinderknecht AL, Navath RS et al (2011) Transfer of PAMAM dendrimers across human placenta: prospects of its use as drug carrier during pregnancy. J Control Release 150(3):326–338. doi:10.1016/j.jconrel.2010.11.023
140. Minekus M, Marteau P, Havenaar R, Huis in’t Veld JHJ (1995) A multi compartmental dynamic computer-controlled model simulating the stomach and small intestine. Altern Lab Anim (ATLA) 23:197–209
141. Minekus M, Alminger M, Alvito P et al (2014) A standardised static in vitro digestion method suitable for food—an international consensus. Food Funct 5(6):1113–1124. doi:10.1039/c3fo60702j
142. Miquel-Jeanjean C, Crepel F, Raufast V et al (2012) Penetration study of formulated nanosized titanium dioxide in models of damaged and sun-irradiated skins. Photochem Photobiol 88(6):1513–1521. doi:10.1111/j.1751-1097.2012.01181.x
143. Miret S, Abrahamse L, de Groene EM (2004) Comparison of in vitro models for the prediction of compound absorption across the human intestinal mucosa. J Biomol Screen 9(7):598–606. doi:10.1177/1087057104267162
144. Möller W, Kreyling WG, Schmid O, Semmler-Behnke M, Schulz H (2010) Deposition, retention and clearance, and translocation of inhaled fine and nano-sized particles in the respiratory tract. In: Gehr P, Mühlfeld C, Rothen-Rutishauser B, Blank F (eds) Particle-Lung Interactions, 2nd edn. Informa Healthcare USA Inc, New York, p 338
145. 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(1):264–280. doi:10.1093/toxsci/kfr148
146. Moraes C, Mehta G, Lesher-Perez SC, Takayama S (2012) Organs-on-a-chip: a focus on compartmentalized microdevices. Ann Biomed Eng 40(6):1211–1227. doi:10.1007/s10439-011-0455-6
147. Muhlfeld C, Gehr P, Rothen-Rutishauser B (2008) Translocation and cellular entering mechanisms of nanoparticles in the respiratory tract. Swiss Med Wkly 138(27–28):387–391
148. Muller 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 R Soc Interface 7(Suppl 1):S27–S40. doi:10.1098/rsif.2009.0161.focus
149. Murdock RC, Braydich-Stolle L, Schrand AM, Schlager JJ, Hussain SM (2008) Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique. Toxicol Sci 101(2):239–253. doi:10.1093/toxsci/kfm240
150. Mwilu SK, El Badawy AM, Bradham K et al (2013) Changes in silver nanoparticles exposed to human synthetic stomach fluid: effects of particle size and surface chemistry. Sci Total Environ 447:90–98. doi:10.1016/j.scitotenv.2012.12.036
151. Myllynen PK, Loughran MJ, Howard CV, Sormunen R, Walsh AA, Vahakangas KH (2008) Kinetics of gold nanoparticles in the human placenta. Reprod Toxicol 26(2):130–137. doi:10.1016/j.reprotox.2008.06.008
152. Nalayanda DD, Wang Q, Fulton WB, Wang TH, Abdullah F (2010) Engineering an artificial alveolar-capillary membrane: a novel continuously perfused model within microchannels. J Pediatr Surg 45(1):45–51. doi:10.1016/j.jpedsurg.2009.10.008
153. Nanotechnologies PoE (2014) Consumer Products Inventory. http://www.nanotechproject.org/cpi. Accessed June 2014
154. Natoli M, Leoni BD, D’Agnano I, Zucco F, Felsani A (2012) Good Caco-2 cell culture practices. Toxicol In Vitro 26(8):1243–1246. doi:10.1016/j.tiv.2012.03.009
155. Newsome R (2014) 2013 IFT International Food Nanoscience Conference: proceedings. Compr Rev Food Sci Food Saf 13(2):190–228. doi:10.1111/1541-4337.12055
156. Nickel C, Angelstorf J, Bienert R et al (2014) Dynamic light-scattering measurement comparability of nanomaterial suspensions. J Nanopart Res 16:1–12
157. Nkabinde LA, Shoba-Zikhali LN, Semete-Makokotlela B et al (2012) Permeation of PLGA nanoparticles across different in vitro models. Curr Drug Deliv 9(6):617–627
158. Norris DA, Puri N, Sinko PJ (1998) The effect of physical barriers and properties on the oral absorption of particulates. Adv Drug Deliv Rev 34(2–3):135–154
159. Oberdorster G (1989) Dosimetric principles for extrapolating results of rat inhalation studies to humans, using an inhaled Ni compound as an example. Health Phys 57(Suppl 1):213–220
160. Oberdorster 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
161. Oberdorster G, Sharp Z, Atudorei V et al (2004) Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol 16(6–7):437–445. doi:10.1080/08958370490439597
162. OECD (2004) Guidelines for the testing of chemicals, section 4. Test no.428: skin absorption: in vitro method
163. Oomen AG, Tolls J, Sips AJ, Van den Hoop MA (2003) Lead speciation in artificial human digestive fluid. Arch Environ Contam Toxicol 44(1):107–115. doi:10.1007/s00244-002-1225-0
164. Pace HE, Rogers NJ, Jarolimek C, Coleman VA, Higgins CP, Ranville JF (2011) Determining transport efficiency for the purpose of counting and sizing nanoparticles via single particle inductively coupled plasma mass spectrometry. Anal Chem 83(24):9361–9369. doi:10.1021/ac201952t
165. Papritz M, Pohl C, Wübbeke C, Moisch M, Hofmann H, Hermanns MI, Thiermann H, Kirkpatrick CJ, Kehe K (2010) Side-specific effects by cadmium exposure: apical and basolateral treatment in a coculture model of the blood-air barrier. Toxicol Appl Pharmacol 245(3):361–369. doi:10.1016/j.taap.2010.04.002
166. Paranjpe M, Muller-Goymann CC (2014) Nanoparticle-mediated pulmonary drug delivery: a review. Int J Mol Sci 15(4):5852–5873. doi:10.3390/ijms15045852
167. Peters R, Kramer E, Oomen AG et al (2012) Presence of nano-sized silica during in vitro digestion of foods containing silica as a food additive. ACS Nano 6(3):2441–2451. doi:10.1021/nn204728k
168. Peters RJ, Rivera ZH, van Bemmel G, Marvin HJ, Weigel S, Bouwmeester H (2014a) Development and validation of single particle ICP-MS for sizing and quantitative determination of nano-silver in chicken meat. Anal Bioanal Chem 406(16):3875–3885. doi:10.1007/s00216-013-7571-0
169. Peters RJ, van Bemmel G, Herrera-Rivera Z et al (2014b) Characterization of titanium dioxide nanoparticles in food products: analytical methods to define nanoparticles. J Agric Food Chem 62(27):6285–6293. doi:10.1021/jf5011885
170. Phalen RF, Mendez LB, Oldham MJ (2010) New developments in aerosol dosimetry. Inhal Toxicol 22(Suppl 2):6–14. doi:10.3109/08958378.2010.516031
171. Pilcer G, Amighi K (2010) Formulation strategy and use of excipients in pulmonary drug delivery. Int J Pharm 392(1–2):1–19. doi:10.1016/j.ijpharm.2010.03.017
172. Poulsen MS, Rytting E, Mose T, Knudsen LE (2009) Modeling placental transport: correlation of in vitro BeWo cell permeability and ex vivo human placental perfusion. Toxicol In Vitro 23(7):1380–1386. doi:10.1016/j.tiv.2009.07.028
173. Powell JJ, Ainley CC, Harvey RS et al (1996) Characterisation of inorganic microparticles in pigment cells of human gut associated lymphoid tissue. Gut 38(3):390–395
174. Powell JJ, Faria N, Thomas-McKay E, Pele LC (2010) Origin and fate of dietary nanoparticles and microparticles in the gastrointestinal tract. J Autoimmun 34(3):J226–J233. doi:10.1016/j.jaut.2009.11.006
175. Powers KW, Brown SC, Krishna VB, Wasdo SC, Moudgil BM, Roberts SM (2006) Research strategies for safety evaluation of nanomaterials. Part VI. Characterization of nanoscale particles for toxicological evaluation. Toxicol Sci 90(2):296–303. doi:10.1093/toxsci/kfj099
176. Prow TW, Monteiro-Riviere NA, Inman AO et al (2012) Quantum dot penetration into viable human skin. Nanotoxicology 6(2):173–185. doi:10.3109/17435390.2011.569092
177. Raemy DO, Limbach LK, Rothen-Rutishauser B et al (2011) Cerium oxide nanoparticle uptake kinetics from the gas-phase into lung cells in vitro is transport limited. Eur J Pharm Biopharm 77(3):368–375. doi:10.1016/j.ejpb.2010.11.017
178. Rieux A, Ragnarsson EG, Gullberg E, Preat V, Schneider YJ, Artursson P (2005) Transport of nanoparticles across an in vitro model of the human intestinal follicle associated epithelium. Eur J Pharm Sci 25(4–5):455–465. doi:10.1016/j.ejps.2005.04.015
179. Rothen-Rutishauser BM, 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(4):281–289
180. Rothen-Rutishauser B, Mueller L, Blank F, Brandenberger C, Muehlfeld C, Gehr P (2008) A newly developed in vitro model of the human epithelial airway barrier to study the toxic potential of nanoparticles. ALTEX 25(3):191–196
181. Rothen-Rutishauser B, Grass RN, Blank F et al (2009) Direct combination of nanoparticle fabrication and exposure to lung cell cultures in a closed setup as a method to simulate accidental nanoparticle exposure of humans. Environ Sci Technol 43(7):2634–2640
182. Sadauskas E, Jacobsen NR, Danscher G et al (2009) Biodistribution of gold nanoparticles in mouse lung following intratracheal instillation. Chem Cent J 3:16. doi:10.1186/1752-153X-3-16
183. Sarlo K, Blackburn KL, Clark ED et al (2009) Tissue distribution of 20 nm, 100 nm and 1000 nm fluorescent polystyrene latex nanospheres following acute systemic or acute and repeat airway exposure in the rat. Toxicology 263(2–3):117–126. doi:10.1016/j.tox.2009.07.002
184. Saunders M (2009) Transplacental transport of nanomaterials. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1(6):671–684. doi:10.1002/wnan.53
185. Savi M, Kalberer M, Lang D et al (2008) A novel exposure system for the efficient and controlled deposition of aerosol particles onto cell cultures. Environ Sci Technol 42(15):5667–5674
186. Scaldaferri F, Pizzoferrato M, Gerardi V, Lopetuso L, Gasbarrini A (2012) The gut barrier: new acquisitions and therapeutic approaches. J Clin Gastroenterol 46(Suppl):S12–S17. doi:10.1097/MCG.0b013e31826ae849
187. Schimek K, Busek M, Brincker S et al (2013) Integrating biological vasculature into a multi-organ-chip microsystem. Lab Chip 13(18):3588–3598. doi:10.1039/c3lc50217a
188. Schimpel C, Teubl B, Absenger M et al (2014) Development of an advanced intestinal in vitro triple culture permeability model to study transport of nanoparticles. Mol Pharm 11(3):808–818. doi:10.1021/mp400507g
189. Seifert J, Haraszti B, Sass W (1996) The influence of age and particle number on absorption of polystyrene particles from the rat gut. J Anat 189:483–486
190. Semmler M, Seitz J, Erbe F et al (2004) Long-term clearance kinetics of inhaled ultrafine insoluble iridium particles from the rat lung, including transient translocation into secondary organs. Inhal Toxicol 16(6–7):453–459. doi:10.1080/08958370490439650
191. Sinha R, Le Gac S, Verdonschot N, van den Berg A, Koopman B, Rouwkema J (2015) A medium throughput device to study the effects of combinations of surface strains and fluid-flow shear stresses on cells. Lab Chip 15(2):429–439. doi:10.1039/c4lc01259c
192. Sonnegaard Poulsen M, Mose T, Leth Maroun L, Mathiesen L, Ehlert Knudsen L, Rytting E (2013) Kinetics of silica nanoparticles in the human placenta. Nanotoxicology. doi:10.3109/17435390.2013.812259
193. Striegel AM, Brewer AK (2012) Hydrodynamic chromatography. Annu Rev Anal Chem (Palo Alto Calif) 5:15–34. doi:10.1146/annurev-anchem-062011-143107
194. Sung JH, Ji JH, Park JD et al (2011) Subchronic inhalation toxicity of gold nanoparticles. Part Fibre Toxicol 8:16. doi:10.1186/1743-8977-8-16
195. Szakal C, Roberts SM, Westerhoff P et al (2014) Measurement of nanomaterials in foods: integrative consideration of challenges and future prospects. ACS Nano 8(4):3128–3135. doi:10.1021/nn501108g
196. Szentkuti L, Lorenz K (1995) The thickness of the mucus layer in different segments of the rat intestine. Histochem J 27(6):466–472
197. Takahashi S, Matsuoka O (1981) Cross placental transfer of 198Au-colloid in near term rats. J Radiat Res 22(2):242–249
198. Takenaka S, Karg E, Roth C et al (2001) Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats. Environ Health Perspect 109(Suppl 4):547–551
199. Takenaka S, Karg E, Kreyling WG et al (2006) Distribution pattern of inhaled ultrafine gold particles in the rat lung. Inhal Toxicol 18(10):733–740. doi:10.1080/08958370600748281
200. Tassinari R, Cubadda F, Moracci G et al (2014) Oral, short-term exposure to titanium dioxide nanoparticles in Sprague-Dawley rat: focus on reproductive and endocrine systems and spleen. Nanotoxicology 8(6):654–662. doi:10.3109/17435390.2013.822114
201. Taylor AJ, McClure CD, Shipkowski KA et al (2014) Atomic layer deposition coating of carbon nanotubes with aluminum oxide alters pro-fibrogenic cytokine expression by human mononuclear phagocytes in vitro and reduces lung fibrosis in mice in vivo. PLoS One 9(9):e106870. doi:10.1371/journal.pone.0106870
202. Tedja R, Lim M, Amal R, Marquis C (2012) Effects of serum adsorption on cellular uptake profile and consequent impact of titanium dioxide nanoparticles on human lung cell lines. ACS Nano 6(5):4083–4093. doi:10.1021/nn3004845
203. Tian F, Razansky D, Estrada GG et al (2009) Surface modification and size dependence in particle translocation during early embryonic development. Inhal Toxicol 21(Suppl 1):92–96. doi:10.1080/08958370902942624
204. Treuel L, Jiang X, Nienhaus GU (2013) New views on cellular uptake and trafficking of manufactured nanoparticles. J R Soc Interface 10(82):20120939. doi:10.1098/rsif.2012.0939
205. van de Stolpe A, den Toonder J (2013) Workshop meeting report Organs-on-Chips: human disease models. Lab Chip 13(18):3449–3470. doi:10.1039/c3lc50248a
206. Van de Wiele TR, Oomen AG, Wragg J et al (2007) Comparison of five in vitro digestion models to in vivo experimental results: lead bioaccessibility in the human gastrointestinal tract. J Environ Sci Health A Tox Hazard Subst Environ Eng 42(9):1203–1211. doi:10.1080/10934520701434919
207. van der Meer AD, van den Berg A (2012) Organs-on-chips: breaking the in vitro impasse. Integr Biol (Camb) 4(5):461–470. doi:10.1039/c2ib00176d
208. van der Zande M, Vandebriel RJ, Van Doren E et al (2012) Distribution, elimination, and toxicity of silver nanoparticles and silver ions in rats after 28-day oral exposure. ACS Nano 6(8):7427–7442. doi:10.1021/nn302649p
209. van der Zande M, Vandebriel RJ, Groot MJ et al (2014) Sub-chronic toxicity study in rats orally exposed to nanostructured silica. Part Fibre Toxicol 11:8. doi:10.1186/1743-8977-11-8
210. van Kesteren PCE, Cubadda F, Bouwmeester H et al (2014) Novel insights into the risk assessment of the nanomaterial synthetic amorphous silica, additive E551, in food. Nanotoxicology. doi:10.3109/17435390.2014.940408
211. Vandebriel RJ, De Jong WH (2012) A review of mammalian toxicity of ZnO nanoparticles. Nanotechnol Sci Appl 5:61–71. doi:10.2147/nsa.s23932
212. VanDussen KL, Marinshaw JM, Shaikh N et al (2014) Development of an enhanced human gastrointestinal epithelial culture system to facilitate patient-based assays. Gut. doi:10.1136/gutjnl-2013-306651
213. Vasco F, Hawe A, Jiskoot W (2010) Critical evaluation of nanoparticle tracking analysis (NTA) by nanosight for the measurement of nanoparticles and protein aggregates. Pharm Res 27:796–810
214. Versantvoort CH, Oomen AG, Van de Kamp E, Rompelberg CJ, Sips AJ (2005) Applicability of an in vitro digestion model in assessing the bioaccessibility of mycotoxins from food. Food Chem Toxicol 43(1):31–40. doi:10.1016/j.fct.2004.08.007
215. Von der Kammer F, Legros S, Hofmann T, Larsen EH, Loeschner K (2011) Separation characterization of nanoparticles in complex food and environmental samples by field-flow fractionation. Trends Anal Chem 30:425–436
216. Wagner I, Materne EM, Brincker S et al (2013) A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture. Lab Chip 13(18):3538–3547. doi:10.1039/c3lc50234a
217. Walczak AP (2015) Development of an integrated in vitro model for the prediction of oral bioavailability of nanoparticles. Wageningen University, Wageninge
218. Walczak AP, Fokkink R, Peters R et al (2013) Behaviour of silver nanoparticles and silver ions in an in vitro human gastrointestinal digestion model. Nanotoxicology 7(7):1198–1210. doi:10.3109/17435390.2012.726382
219. Walczak AP, Kramer E, Hendriksen PJ et al (2014) Translocation of differently sized and charged polystyrene nanoparticles in in vitro intestinal cell models of increasing complexity. Nanotoxicology. doi:10.3109/17435390.2014.944599
220. Walczak AP, Kramer E, Hendriksen PJ et al (2015) In vitro gastrointestinal digestion increases the translocation of polystyrene nanoparticles in an in vitro intestinal co-culture model. Nanotoxicology. doi:10.3109/17435390.2014.988664
221. Wang Y, Chen Z, Ba T et al (2013) Susceptibility of young and adult rats to the oral toxicity of titanium dioxide nanoparticles. Small 9(9–10):1742–1752. doi:10.1002/smll.201201185
222. Wang M, Zheng LN, Wang B et al (2014) Quantitative analysis of gold nanoparticles in single cells by laser ablation inductively coupled plasma-mass spectrometry. Anal Chem 86(20):10252–10256. doi:10.1021/ac502438n
223. Watkinson AC, Bunge AL, Hadgraft J, Lane ME (2013) Nanoparticles do not penetrate human skin–a theoretical perspective. Pharm Res 30(8):1943–1946. doi:10.1007/s11095-013-1073-9
224. Westerhout J, van de Steeg E, Grossouw D et al (2014) A new approach to predict human intestinal absorption using porcine intestinal tissue and biorelevant matrices. Eur J Pharm Sci 63:167–177. doi:10.1016/j.ejps.2014.07.003
225. Whitesides GM (2006) The origins and the future of microfluidics. Nature 442(7101):368–373. doi:10.1038/nature05058
226. Wick P, Malek A, Manser P et al (2010) Barrier capacity of human placenta for nanosized materials. Environ Health Perspect 118(3):432–436. doi:10.1289/ehp.0901200
227. Wickham M, Faulks R, Mills C (2009) In vitro digestion methods for assessing the effect of food structure on allergen breakdown. Mol Nutr Food Res 53(8):952–958. doi:10.1002/mnfr.200800193
228. Wolff A, Antfolk M, Brodin B, Tenje M (2015) In vitro blood-brain barrier models-an overview of established models and new microfluidic approaches. J Pharm Sci. doi:10.1002/jps.24329
229. Worth AP, Balls M (2004) The principles of validation and the ECVAM validation process. Altern Lab Anim 32(Suppl 1B):623–629
230. Worth A, Barroso J, Bremer S et al (2014) Alternative methods for regulatory toxicology—a state of the art review. JRC Sci Policy Rep EUR 26797:1–475
231. 2 nanoparticles in hairless mice and porcine skin after subchronic dermal exposure. Toxicol Lett 191(1):1–8. doi:10.1016/j.toxlet.2009.05.020
232. Xie Y, Williams NG, Tolic A et al (2012) Aerosolized ZnO nanoparticles induce toxicity in alveolar type II epithelial cells at the air-liquid interface. Toxicol Sci 125(2):450–461. doi:10.1093/toxsci/kfr251
233. Yacobi NR, Demaio L, Xie J et al (2008) Polystyrene nanoparticle trafficking across alveolar epithelium. Nanomedicine 4(2):139–145. doi:10.1016/j.nano.2008.02.002
234. Yamashita K, Yoshioka Y, Higashisaka K et al (2011) Silica and titanium dioxide nanoparticles cause pregnancy complications in mice. Nat Nanotechnol 6(5):321–328. doi:10.1038/nnano.2011.41
235. Young AM, Allen CE, Audus KL (2003) Efflux transporters of the human placenta. Adv Drug Deliv Rev 55(1):125–132
236. Yu LE, Yung L-YL, Ong C-N et al (2007) Translocation and effects of gold nanoparticles after inhalation exposure in rats. Nanotoxicology 1(3):235–242. doi:10.1080/17435390701763108
237. Zangenberg NH, Mullertz A, Kristensen HG, Hovgaard L (2001) A dynamic in vitro lipolysis model. II: evaluation of the model. Eur J Pharm Sci 14(3):237–244
238. Zattoni A, Roda B, Borghi F, Marassi V, Reschiglian P (2014) Flow field-flow fractionation for the analysis of nanoparticles used in drug delivery. J Pharm Biomed Anal 87:53–61. doi:10.1016/j.jpba.2013.08.018
239. Zhang Z, Kong F, Vardhanabhuti B, Mustapha A, Lin M (2012) Detection of engineered silver nanoparticle contamination in pears. J Agric Food Chem 60(43):10762–10767. doi:10.1021/jf303423q
240. Zhu Y, Choe CS, Ahlberg S et al (2015) Penetration of silver nanoparticles into porcine skin ex vivo using fluorescence lifetime imaging microscopy, Raman microscopy, and surface-enhanced Raman scattering microscopy. J Biomed Opt 20(5):051006. doi:10.1117/1.jbo.20.5.051006
241. Zvyagin AV, Zhao X, Gierden A, Sanchez W, Ross JA, Roberts MS (2008) Imaging of zinc oxide nanoparticle penetration in human skin in vitro and in vivo. J Biomed Opt 13(6):064031. doi:10.1117/1.3041492