Bioavailability, distribution and clearance of tracheally-instilled and gavaged uncoated or silica-coated zinc oxide nanoparticles

Particle and Fibre Toxicology

Volumn 11, Issue 1, 2014, Pages

  Konduru, Nagarjun V ^a   Murdaugh, Kimberly M ^a   Sotiriou, Georgios A ^a   Donaghey, Thomas C ^a   Demokritou, Philip ^a   Brain, Joseph D ^a   Molina, Ramon M ^a  

^a HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

Bioavailability; Nanoparticles; Nanotoxicology; Pharmacokinetics; Silica coating; Zinc oxide

Indexed keywords

NANOROD; SILICON DIOXIDE; ZINC 65; ZINC OXIDE NANOPARTICLE; NANOPARTICLE; ZINC OXIDE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOAVAILABILITY; BLOOD; BONE MARROW; CECUM; COATED PARTICLE; CONTROLLED STUDY; DRUG INSTILLATION; FECES LEVEL; FEEDING; KIDNEY; LIVER; LUNG CLEARANCE; LYMPH NODE; MALE; MATERIAL COATING; NANOTOXICOLOGY; NEUTRON ACTIVATION ANALYSIS; NONHUMAN; RADIOACTIVITY; RAT; SKELETAL MUSCLE; SKIN; THORAX; TISSUE DISTRIBUTION; TOXICOKINETICS; URINARY EXCRETION; ADVERSE EFFECTS; ANALOGS AND DERIVATIVES; ANIMAL; CHEMICALLY INDUCED; CHEMISTRY; EXPOSURE; HALF LIFE TIME; LUNG; METABOLIC CLEARANCE RATE; METABOLISM; ORAL DRUG ADMINISTRATION; PNEUMONIA; SYNTHESIS; WISTAR RAT;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; HALF-LIFE; INHALATION EXPOSURE; LUNG; LYMPH NODES; MALE; METABOLIC CLEARANCE RATE; MUSCLE, SKELETAL; NANOPARTICLES; PNEUMONIA; RATS; RATS, WISTAR; SILICON DIOXIDE; TISSUE DISTRIBUTION; ZINC OXIDE;

EID: 84908102822     PISSN: 17438977     EISSN: 17438977     Source Type: Journal    
DOI: 10.1186/s12989-014-0044-6     Document Type: Article

References (85)

1. Sun B, Sirringhaus H. Solution-processed zinc oxide field-effect transistors based on self-assembly of colloidal nanorods. Nano Lett 2005, 5:2408-2413. 10.1021/nl051586w, 16351187.
2. Su YK, Peng SM, Ji LW, Wu CZ, Cheng WB, Liu CH. Ultraviolet ZnO nanorod photosensors. Langmuir 2010, 26:603-606. 10.1021/la902171j, 19894681.
3. Djurisic AB, Leung YH. Optical properties of ZnO nanostructures. Small 2006, 2:944-961. 10.1002/smll.200600134, 17193149.
4. Nohynek GJ, Dufour EK, Roberts MS. Nanotechnology, cosmetics and the skin: is there a health risk?. Skin Pharmacol Physiol 2008, 21:136-149. 10.1159/000131078, 18523411.
5. Fan Z, Lu JG. Zinc oxide nanostructures: synthesis and properties. J Nanosci Nanotechnol 2005, 5:1561-1573. 10.1166/jnn.2005.182, 16245516.
6. Beckett WS, Chalupa DF, Pauly-Brown A, Speers DM, Stewart JC, Frampton MW, Utell MJ, Huang LS, Cox C, Zareba W, Oberdorster G. Comparing inhaled ultrafine versus fine zinc oxide particles in healthy adults: a human inhalation study. Am J Respir Crit Care Med 2005, 171:1129-1135. 10.1164/rccm.200406-837OC, 15735058.
7. Sharma V, Anderson D, Dhawan A. Zinc oxide nanoparticles induce oxidative stress and genotoxicity in human liver cells (HepG2). J Biomed Nanotechnol 2011, 7:98-99. 10.1166/jbn.2011.1220, 21485822.
8. Valdiglesias V, Costa C, Kilic G, Costa S, Pasaro E, Laffon B, Teixeira JP. Neuronal cytotoxicity and genotoxicity induced by zinc oxide nanoparticles. Environ Int 2013, 55:92-100. 10.1016/j.envint.2013.02.013, 23535050.
9. Alarifi S, Ali D, Alkahtani S, Verma A, Ahamed M, Ahmed M, Alhadlaq HA. Induction of oxidative stress, DNA damage, and apoptosis in a malignant human skin melanoma cell line after exposure to zinc oxide nanoparticles. Int J Nanomed 2013, 8:983-993. 10.2217/nnm.13.80.
10. Watson C, Ge J, Cohen J, Pyrgiotakis G, Engelward BP, Demokritou P. High-throughput screening platform for engineered nanoparticle-mediated genotoxicity using CometChip technology. ACS Nano 2014, 8:2118-2133. 10.1021/nn404871p, 24617523.
11. De Berardis B, Civitelli G, Condello M, Lista P, Pozzi R, Arancia G, Meschini S. Exposure to ZnO nanoparticles induces oxidative stress and cytotoxicity in human colon carcinoma cells. Toxicol Appl Pharmacol 2010, 246:116-127. 10.1016/j.taap.2010.04.012, 20434478.
12. Vandebriel RJ, De Jong WH. A review of mammalian toxicity of ZnO nanoparticles. Nanotechnol Sci Appl 2012, 5:61-71. 10.2147/NSA.S23932, 24198497.
13. Warheit DB, Sayes CM, Reed KL. Nanoscale and fine zinc oxide particles: can in vitro assays accurately forecast lung hazards following inhalation exposures?. Environ Sci Technol 2009, 43:7939-7945. 10.1021/es901453p, 19921917.
14. Moghimi SM, Davis SS. Innovations in avoiding particle clearance from blood by Kupffer cells: cause for reflection. Crit Rev Ther Drug Carrier Syst 1994, 11:31-59. 7704918.
15. Sund J, Alenius H, Vippola M, Savolainen K, Puustinen A. Proteomic characterization of engineered nanomaterial-protein interactions in relation to surface reactivity. ACS Nano 2011, 5:4300-4309. 10.1021/nn101492k, 21528863.
16. Xia T, Zhao Y, Sager T, George S, Pokhrel S, Li N, Schoenfeld D, Meng H, Lin S, Wang X, Wang M, Ji Z, Zink JI, Madler L, Castranova V, Nel AE. Decreased dissolution of ZnO by iron doping yields nanoparticles with reduced toxicity in the rodent lung and zebrafish embryos. ACS Nano 2011, 5:1223-1235. 10.1021/nn1028482, 21250651.
17. Sotiriou GA, Watson C, Murdaugh KM, Darrah TH, Pyrgiotakis G, Elder A, Brain JD, Demokritou P. Engineering safer-by-design, transparent, silica-coated ZnO nanorods with reduced DNA damage potential. Environ Sci Nano 2014, 1:144-153. 10.1039/c3en00062a, 24955241.
18. Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Itty Ipe B, Bawendi MG, Frangioni JV. Renal clearance of quantum dots. Nat Biotechnol 2007, 25:1165-1170. 10.1038/nbt1340, 17891134.
19. Lundqvist M, Stigler J, Elia G, Lynch I, Cedervall T, Dawson KA. Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts. Proc Natl Acad Sci U S A 2008, 105:14265-14270. 10.1073/pnas.0805135105, 18809927.
20. Moghimi SM, Hunter AC, Andresen TL. Factors controlling nanoparticle pharmacokinetics: an integrated analysis and perspective. Annu Rev Pharmacol Toxicol 2012, 52:481-503. 10.1146/annurev-pharmtox-010611-134623, 22035254.
21. Lynch I, Salvati A, Dawson KA. Protein-nanoparticle interactions: what does the cell see?. Nat Nanotechnol 2009, 4:546-547. 10.1038/nnano.2009.248, 19734922.
22. Monopoli MP, Aberg C, Salvati A, Dawson KA. Biomolecular coronas provide the biological identity of nanosized materials. Nat Nanotechnol 2012, 7:779-786. 10.1038/nnano.2012.207, 23212421.
23. Alwi R, Telenkov S, Mandelis A, Leshuk T, Gu F, Oladepo S, Michaelian K. Silica-coated super paramagnetic iron oxide nanoparticles (SPION) as biocompatible contrast agent in biomedical photoacoustics. Biomed Opt Express 2012, 3:2500-2509. 10.1364/BOE.3.002500, 23082291.
24. Jana NR, Yu HH, Ali EM, Zheng Y, Ying JY: Controlled photostability of luminescent nanocrystalline ZnO solution for selective detection of aldehydes. Chem Commun (Camb) 2007, 1406-1408..
25. Chen Y-S, Wolfgang F, Seungsoo K, Pieter K, Kimberly H, Stanislav E. Silica-coated gold nanorods as photoacoustic signal nano-amplifiers. Nano Lett 2011, 11:348-354. 10.1021/nl1042006, 21244082.
26. Baber O, Jang M, Barber D, Powers K. Amorphous silica coatings on magnetic nanoparticles enhance stability and reduce toxicity to in vitro BEAS-2B cells. Inhal Toxicol 2011, 23:532-543. 10.3109/08958378.2011.592869, 21819260.
27. Moghimi SM, Hunter AC, Murray JC. Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev 2001, 53:283-318. 11356986.
28. Brunner TJ, Wick P, Manser P, Spohn P, Grass RN, Limbach LK, Bruinink A, Stark WJ. In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility. Environ Sci Technol 2006, 40:4374-4381. 10.1021/es052069i, 16903273.
29. Napierska D, Thomassen LC, Rabolli V, Lison D, Gonzalez L, Kirsch-Volders M, Martens JA, Hoet PH. Size-dependent cytotoxicity of monodisperse silica nanoparticles in human endothelial cells. Small 2009, 5:846-853. 10.1002/smll.200800461, 19288475.
30. Warheit DB, McHugh TA, Hartsky MA. Differential pulmonary responses in rats inhaling crystalline, colloidal or amorphous silica dusts. Scand J Work Environ Health 1995, 21(Suppl 2):19-21. 8929682.
31. Demokritou P, Gass S, Pyrgiotakis G, Cohen JM, Goldsmith W, McKinney W, Frazer D, Ma J, Schwegler-Berry D, Brain J, Castranova V. An in vivo and in vitro toxicological characterisation of realistic nanoscale CeO(2) inhalation exposures. Nanotoxicology 2013, 7:1338-1350. 10.3109/17435390.2012.739665, 23061914.
32. Sotiriou GA, Sannomiya T, Teleki A, Krumeich F, Voros J, Pratsinis SE. Non-toxic dry-coated nanosilver for plasmonic biosensors. Adv Funct Mater 2010, 20:4250-4257. 10.1002/adfm.201000985, 23730266.
33. Sotiriou GA, Franco D, Poulikakos D, Ferrari A. Optically stable biocompatible flame-made SiO2-coated Y2O3:Tb3+ nanophosphors for cell imaging. ACS Nano 2012, 6:3888-3897. 10.1021/nn205035p, 22509739.
34. Teleki A, Heine MC, Krumeich F, Akhtar MK, Pratsinis SE. In situ coating of flame-made TiO2 particles with nanothin SiO2 films. Langmuir 2008, 24:12553-12558. 10.1021/la801630z, 18850688.
35. Demokritou P, Buchel R, Molina RM, Deloid GM, Brain JD, Pratsinis SE. Development and characterization of a Versatile Engineered Nanomaterial Generation System (VENGES) suitable for toxicological studies. Inhal Toxicol 2010, 22(Suppl 2):107-116. 10.3109/08958378.2010.499385, 20701428.
36. Gass S, Cohen JM, Pyrgiotakis G, Sotiriou GA, Pratsinis SE, Demokritou P. A safer formulation concept for flame-generated engineered nanomaterials. ACS Sustain Chem Eng 2013, 1:843-857. 23961338.
37. Hembram K, Sivaprakasam D, Rao TN, Wegner K. Large-scale manufacture of ZnO nanorods by flame spray pyrolysis. J Nanopart Res 2013, 15:1461-1464. 10.1007/s11051-013-1461-4.
38. Beaucage G, Kammler HK, Pratsinis SE. Particle size distributions from small-angle scattering using global scattering functions. J Appl Crystallogr 2004, 37:523-535. 10.1107/S0021889804008969.
39. Height MJ, Madler L, Pratsinis SE. Nanorods of ZnO made by flame spray pyrolysis. Chem Mater 2006, 18:572-578. 10.1021/cm052163y.
40. Sotiriou GA, Schneider M, Pratsinis SE. Green, silica-coated monoclinic Y2O3:Tb3+ nanophosphors: flame synthesis and characterization. J Phys Chem C 2012, 116:4493-4499. 10.1021/jp211722z.
41. Buesser B, Pratsinis SE. Design of gas-phase synthesis of core-shell particles by computational fluid - aerosol dynamics. AIChE J 2011, 57:3132-3142. 10.1002/aic.12512, 23729817.
42. Brouwer D. Exposure to manufactured nanoparticles in different workplaces. Toxicology 2010, 269:120-127. 10.1016/j.tox.2009.11.017, 19941928.
43. Vorbau M, Hillemann L, Stintz M. Method for the characterization of the abrasion induced nanoparticle release into air from surface coatings. Aerosol Sci 2009, 40:209-217. 10.1016/j.jaerosci.2008.10.006.
44. Brain JD, Knudson DE, Sorokin SP, Davis MA. Pulmonary distribution of particles given by intratracheal instillation or by aerosol inhalation. Environ Res 1976, 11:13-33. 10.1016/0013-9351(76)90107-9, 1253768.
45. Osier M, Oberdorster G. Intratracheal inhalation vs intratracheal instillation: differences in particle effects. Fundam Appl Toxicol 1997, 40:220-227. 10.1006/faat.1997.2390, 9441718.
46. Baisch BL, Corson NM, Wade-Mercer P, Gelein R, Kennell AJ, Oberdorster G, Elder A. Equivalent titanium dioxide nanoparticle deposition by intratracheal instillation and whole body inhalation: the effect of dose rate on acute respiratory tract inflammation. Part Fibre Toxicol 2014, 11:5. 10.1186/1743-8977-11-5, 24456852.
47. Du Z, Zhao D, Jing L, Cui G, Jin M, Li Y, Liu X, Liu Y, Du H, Guo C, Zhou X, Sun Z. Cardiovascular toxicity of different sizes amorphous silica nanoparticles in rats after intratracheal instillation. Cardiovasc Toxicol 2013, 13:194-207. 10.1007/s12012-013-9198-y, 23322373.
48. Johnston CJ, Driscoll KE, Finkelstein JN, Baggs R, O'Reilly MA, Carter J, Gelein R, Oberdorster G. Pulmonary chemokine and mutagenic responses in rats after subchronic inhalation of amorphous and crystalline silica. Toxicol Sci 2000, 56:405-413. 10.1093/toxsci/56.2.405, 10911000.
49. McCarthy J, Inkielewicz-Stepniak I, Corbalan JJ, Radomski MW. Mechanisms of toxicity of amorphous silica nanoparticles on human lung submucosal cells in vitro: protective effects of fisetin. Chem Res Toxicol 2012, 25:2227-2235. 10.1021/tx3002884, 22931364.
50. Merget R, Bauer T, Kupper HU, Philippou S, Bauer HD, Breitstadt R, Bruening T. Health hazards due to the inhalation of amorphous silica. Arch Toxicol 2002, 75:625-634. 10.1007/s002040100266, 11876495.
51. Warheit DB, Webb TR, Reed KL. Pulmonary toxicity screening studies in male rats with TiO2 particulates substantially encapsulated with pyrogenically deposited, amorphous silica. Part Fibre Toxicol 2006, 3:3. 10.1186/1743-8977-3-3, 16438714.
52. Braakhuis HM, Park MV, Gosens I, De Jong WH, Cassee FR. Physicochemical characteristics of nanomaterials that affect pulmonary inflammation. Part Fibre Toxicol 2014, 11:18. 10.1186/1743-8977-11-18, 24725891.
53. Choi HS, Ashitate Y, Lee JH, Kim SH, Matsui A, Insin N, Bawendi MG, Semmler-Behnke M, Frangioni JV, Tsuda A. Rapid translocation of nanoparticles from the lung airspaces to the body. Nat Biotechnol 2010, 28:1300-1303. 10.1038/nbt.1696, 21057497.
54. Gessner A, Lieske A, Paulke B, Muller R. Influence of surface charge density on protein adsorption on polymeric nanoparticles: analysis by two-dimensional electrophoresis. Eur J Pharm Biopharm 2002, 54:165-170. 10.1016/S0939-6411(02)00081-4, 12191688.
55. Lartigue L, Wilhelm C, Servais J, Factor C, Dencausse A, Bacri JC, Luciani N, Gazeau F. Nanomagnetic sensing of blood plasma protein interactions with iron oxide nanoparticles: impact on macrophage uptake. ACS Nano 2012, 6:2665-2678. 10.1021/nn300060u, 22324868.
56. Buzea C, Pacheco II, Robbie K. Nanomaterials and nanoparticles: sources and toxicity. Biointerphases 2007, 2:MR17-71. 10.1116/1.2815690, 20419892.
57. Xia T, Kovochich M, Liong M, Madler L, Gilbert B, Shi H, Yeh JI, Zink JI, Nel AE. Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. ACS Nano 2008, 2:2121-2134. 10.1021/nn800511k, 19206459.
58. He X, Zhang H, Ma Y, Bai W, Zhang Z, Lu K, Ding Y, Zhao Y, Chai Z. Lung deposition and extrapulmonary translocation of nano-ceria after intratracheal instillation. Nanotechnology 2010, 21:285103. 10.1088/0957-4484/21/28/285103, 20562477.
59. Cullen RT, Tran CL, Buchanan D, Davis JM, Searl A, Jones AD, Donaldson K. Inhalation of poorly soluble particles. I. Differences in inflammatory response and clearance during exposure. Inhal Toxicol 2000, 12:1089-1111. 10.1080/08958370050166787, 11114783.
60. Adamcakova-Dodd A, Stebounova LV, Kim JS, Vorrink SU, Ault AP, O'Shaughnessy PT, Grassian VH, Thorne PS. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models. Part Fibre Toxicol 2014, 11:15. 10.1186/1743-8977-11-15, 24684892.
61. Mineral Tolerance of Animals 2005, The National Academic Press, Washington. D.C.
62. Environmental Health Criteria 221 Zinc 2001, Worl Health Organization, Geneva.
63. Kreyling WG, Semmler-Behnke M, Seitz J, Scymczak W, Wenk A, Mayer P, Takenaka S, Oberdörster G. Size and material dependency of translocation of inhaled iridium or carbon nanoparticles from the lungs of rats to blood. Inhal Toxicol 2009, 21:55-60. 10.1080/08958370902942517, 19558234.
64. Cho WS, Duffin R, Howie SE, Scotton CJ, Wallace WA, Macnee W, Bradley M, Megson IL, Donaldson K. Progressive severe lung injury by zinc oxide nanoparticles; the role of Zn2+ dissolution inside lysosomes. Part Fibre Toxicol 2011, 8:27. 10.1186/1743-8977-8-27, 21896169.
65. Berry JP, Arnoux B, Stanislas G, Galle P, Chretien J. A microanalytic study of particles transport across the alveoli: role of blood platelets. Biomedicine 1977, 27:354-357. 606312.
66. Cohen JM, Derk R, Wang L, Godleski J, Kobzik L, Brain J, Demokritou P. Tracking translocation of industrially relevant engineered nanomaterials (ENMs) across alveolar epithelial monolayers in vitro. Nanotoxicology 2014, 8:216-225. 10.3109/17435390.2013.879612, 24479615.
67. Geiser M, Kreyling WG. Deposition and biokinetics of inhaled nanoparticles. Part Fibre Toxicol 2010, 7:2. 10.1186/1743-8977-7-2, 20205860.
68. Geiser M, Rothen-Rutishauser B, Kapp N, Schurch S, Kreyling W, Schulz H, Semmler M, Im Hof V, Heyder J, Gehr P. Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environ Health Perspect 2005, 113:1555-1560. 10.1289/ehp.8006, 16263511.
69. Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Lunts A, Kreyling W, Cox C. Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Health A 2002, 65:1531-1543. 10.1080/00984100290071658, 12396867.
70. Semmler M, Seitz J, Erbe F, Mayer P, Heyder J, Oberdorster G, Kreyling WG. Long-term clearance kinetics of inhaled ultrafine insoluble iridium particles from the rat lung, including transient translocation into secondary organs. Inhal Toxicol 2004, 16:453-459. 10.1080/08958370490439650, 15204761.
71. Takenaka S, Karg E, Roth C, Schulz H, Ziesenis A, Heinzmann U, Schramel P, Heyder J. Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats. Environ Health Perspect 2001, 109(Suppl 4):547-551. 10.1289/ehp.01109s4547, 11544161.
72. Burch RE, Hahn HK, Sullivan JF. Newer aspects of the roles of zinc, manganese, and copper in human nutrition. Clin Chem 1975, 21:501-520. 1090398.
73. Seo J-H, Cho Y-E, Kim T, Shin H-I, Kwun I-S. Zinc may increase bone formation through stimulating cell proliferation, alkaline phosphatase activity and collagen synthesis in osteoblastic. Nutr Res Pract 2010, 4:356-361. 10.4162/nrp.2010.4.5.356, 21103080.
74. Hashizume M, Yamaguchi M. Stimulatory effect of beta-alanyl-L-histidinato zinc on cell proliferation is dependent on protein synthesis in osteoblastic MC3T3-E1 cells. Mol Cell Biochem 1993, 122:59-64. 10.1007/BF00925737, 8350864.
75. Yamaguchi M, Igarashi A, Uchiyama S. Bioavailability of zinc yeast in rats: stimulatory effect of bone calcification in vivo. J Health Sci 2004, 50(1):75-81. 10.1248/jhs.50.75.
76. Hilty FM, Arnold M, Hilbe M, Teleki A, Knijnenburg JTN, Ehrensperger F, Hurrell RF, Pratsinis SE, Langhans W, Zimmermann MB. Iron from nanocompounds containing iron and zinc is highly bioavailable in rats without tissue accumulation. Nat Nanotechnol 2010, 5:374-380. 10.1038/nnano.2010.79, 20418865.
77. Espita PJP, Soares NFF, Coimbra JSR, de Andrade NJ, Medeiros EAA. Zinc oxide nanoparticles: synthesis, antimicrobial activity and food packaging applications. Food Bioprocess Technol 2012, 5:1447-1464. 10.1007/s11947-012-0797-6.
78. Lai SK, Wang YY, Hanes J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev 2009, 61:158-171. 10.1016/j.addr.2008.11.002, 19133304.
79. Paek HJ, Lee YJ, Chung HE, Yoo NH, Lee JA, Kim MK, Lee JK, Jeong J, Choi SJ. Modulation of the pharmacokinetics of zinc oxide nanoparticles and their fates in vivo. Nanoscale 2013, 5:11416-11427. 10.1039/c3nr02140h, 23912904.
80. Chung HE, Yu J, Baek M, Lee JA, Kim MS, Kim SH, Maeng EH, Lee JK, Jeong J, Choi SJ. Toxicokinetics of zinc oxide nanoparticles in rats. J Phys: Conf Ser 2013, 429:012037.
81. Baek M, Chung HE, Yu J, Lee JA, Kim TH, Oh JM, Lee WJ, Paek SM, Lee JK, Jeong J, Choy JH, Choi SJ. Pharmacokinetics, tissue distribution, and excretion of zinc oxide nanoparticles. Int J Nanomedicine 2012, 7:3081-3097. 22811602.
82. Cohen J, Deloid G, Pyrgiotakis G, Demokritou P. Interactions of engineered nanomaterials in physiological media and implications for in vitro dosimetry. Nanotoxicology 2013, 7:417-431. 10.3109/17435390.2012.666576, 22393878.
83. Brown RP, Delp MD, Lindstedt SL, Rhomberg LR, Beliles RP. Physiological parameter values for physiologically based pharmacokinetic models. Toxicol Ind Health 1997, 13:407-484. 10.1177/074823379701300401, 9249929.
84. Schoeffner DJ, Warren DA, Muralidara S, Bruckner JV, Simmons JE. Organ weights and fat volume in rats as a function of strain and age. J Toxicol Environ Health A 1999, 56:449-462. 10.1080/009841099157917, 10201633.
85. Jaki T, Wolfsegger MJ. Estimation of pharmacokinetic parameters with the R package PK. Pharm Stat 2011, 10:288-294. 10.1002/pst.449.