In vivo-in vitro comparison of acute respiratory tract toxicity using human 3D airway epithelial models and human A549 and murine 3T3 monolayer cell systems

Toxicology in Vitro

Volumn 27, Issue 1, 2013, Pages 174-190

  Sauer, Ursula G ^a   Vogel, Sandra ^b   Hess, Annemarie ^b   Kolle, Susanne N ^b   Ma Hock, Lan ^b   van Ravenzwaay, Bennard ^b   Landsiedel, Robert ^b  

^a Scientific Consultancy Animal Welfare   (Germany)

^b BASF SE   (Germany)

Author keywords

3T3 Mouse embryonic fibroblast cell line; A549 Human alveolar epithelial cell line; Acute inhalation toxicity; Globally Harmonised System; Hazard categories; Three dimensional human airway epithelial tissue models

Indexed keywords

ACETIC ANHYDRIDE; ACETONE; ALCOHOL; ANILINE; DODECYL SULFATE SODIUM; FORMALDEHYDE; GLUTARALDEHYDE; HEXACHLOROPLATINATE AMMONIUM; ISOPHORONE DIICYANATE; LACTOSE; METHACRYLIC ACID METHYL ESTER; N,N DIMETHYLFORMAMIDE; OCTANOYL CHLORIDE; PARACETAMOL; PARAQUAT; TOLUENE DIISOCYANATE; TOXIC SUBSTANCE; TRIMELLITIC ANHYDRIDE; UNCLASSIFIED DRUG; ZINC OXIDE;

ACUTE RESPIRATORY TRACT DISEASE; ACUTE TOXICITY; ANIMAL CELL; ARTICLE; CONTROLLED STUDY; EMPHYSEMA; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; LUNG ALVEOLUS CELL; LUNG EDEMA; LUNG MODEL; MOUSE; NONHUMAN; PREDICTION; RESPIRATORY EPITHELIUM; SENSITIVITY AND SPECIFICITY; TOXIC INHALATION;

3T3 CELLS; ADMINISTRATION, INHALATION; ANIMAL TESTING ALTERNATIVES; ANIMALS; CELL CULTURE TECHNIQUES; CELL LINE, TUMOR; DRUG TOXICITY; HUMANS; LETHAL DOSE 50; LUNG; MICE; MODELS, BIOLOGICAL; RATS; TOXICITY TESTS, ACUTE;

MURINAE; RATTUS;

EID: 84869387623     PISSN: 08872333     EISSN: 18793177     Source Type: Journal    
DOI: 10.1016/j.tiv.2012.10.007     Document Type: Article

References (64)

1. Andersen M.E., Dennison J.E. Mode of action and tissue dosimetry in current and future risk assessments. Sci. Total Environ. 2001, 274:3-14.
2. Anon., 2004. Annexes A and B to Council Directive 94/55/EC as announced in Commission Directive 2001/7/EC adapting for the third time to technical progress Council Directive 94/55/EC on the approximation of the laws of the Member States with regard to the transport of dangerous goods by road. O.J. L 18, 26 January 2004.
3. Anon., 2006. Regulation (EC) No. 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC. O.J. L 396/1, 30 December 2006.
4. Anon., 2008. Regulation (EC) No. 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006. O.J. L 353/1, 31 December 2008.
5. Anon., 2010. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. O.J. L 276/33, 20 October 2010.
6. Anon., 2011. Commission Regulation (EU) No. 545/2011 of 10 June 2011 implementing Regulation (EC) No. 1107/2009 of the European Parliament and of the Council as regards the data requirements for plant protection products. O.J. L 155/67, 11 June 2011.
7. Aufderheide M., Knebel J.W., Ritter D. Novel approaches for studying pulmonary toxicity in vitro. Toxicol. Lett. 2003, 140-141:205-211.
8. Bakand S., Winder C., Khalil C., Hayes A. Toxicity assessment of industrial chemicals and airborne contaminants: transition from in vivo to in vitro test methods: a review. Inhal. Toxicol. 2005, 17:775-787.
9. Baldrick P., Bamford D.G. A toxicological review of lactose to support clinical administration by inhalation. Food Chem. Toxicol. 1997, 35(7):719-733.
10. Balharry D., Sexton K., BéruBé K.A. An in vitro approach to assess the toxicity of inhaled tobacco smoke components: nicotine, cadmium, formaldehyde and urethane. Toxicology 2008, 244:66-76.
11. Castell J.V., Donato M.T., Gomez-Lechon M.J. Metabolism and bioactivation of toxicants in the lung. The in vitro cellular approach. Exp. Toxicol. Pathol. 2005, 57:189-204.
12. Checkoway H., Ray R.M., Lundin J.I., Astrakianakis G., Seixas N.S., Camp J.E., Wernli K.J., Fitzgibbons E.D., Li W., Feng Z., Gao D.L., Thomas D.B. Lung cancer and occupational exposures other than cotton dust and endotoxin among women textile workers in Shanghai. China Occup. Environ. Med. 2011, 68:425-429.
13. EPA, undated. United States Environmental Protection Agency. Label review manual. Chapter 7: Precautionary statements. 18pp. Available at: http://www.epa.gov/oppfead1/labeling/lrm/chap-07.pdf.
14. Fujino A., Satoh T., Takebayashi T., Nakashima H., Sakurai H., Higashi T., Matumura H., Minaguchi H., Kawai T. Biological monitoring of workers exposed to acetone in acetate fibre plants. Br. J. Ind. Med. 1992, 49:654-657.
15. Gannon P.F., Bright P., Campbell M., O'Hickey S.P., Burge P.S. Occupational asthma due to glutaraldehyde and formaldehyde in endoscopy and X ray departments. Thorax 1995, 50:156-159.
16. Hartung T. Food for thought... on cell culture. ALTEX 2007, 24:143-147.
17. Hayes A., Bakand S. Inhalation toxicology. Mol. Clin. Exp. Toxicol. Experientia Suppl. 2010, 100:461-488.
18. Health Canada, 2001. Reference Manual for the Consumer Chemicals and Containers Regulations of the Hazardous Products Act. Available at: http://www.hc-sc.gc.ca/cps-spc/pubs/indust/cccr-2001-rpccc/ref_man/sec-35-article-eng.php.
19. Hirsh A.J., Zhang J., Zamurs A., Fleegle J., Thelin W.R., Caldwell R.A., Sabater J.R., Abraham W.M., Donowitz M., Cha B., Johnson K.B., St.George J.A., Johnson M.R., Boucher R.C. Pharmacological properties of N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N'-4-[4-(2,3-dihydroxy-propoxy)phenyl]butyl-guanidine methane-sulfonate (552-02), a novel epithelial sodium channel blocker with potential clinical efficacy for CYSTIC cystic fibrosis. J. Pharmacol. Exp. Ther. 2008, 325:77-78.
20. Huang S., Constant S., Wiszniewski L., Derouette J.P. MucilAir: a novel human 3D airway epithelium model for acute or long term toxicity testing of chemicals. ALTEX 2008, 25(Suppl. 1):30-31.
21. Huang S., Wiszniewski L., Constant S. The use of in vitro 3D cell models in drug development for respiratory diseases. Drug Discovery and Development - Present and Future 2011, 169-190. InTech - open access company. I.M. Kapetanovic (Ed.).
22. ICCVAM, 2006. ICCVAM test method evaluation report (TMER) (2006). In vitro cytotoxicity test methods for estimating starting doses for acute oral systemic toxicity testing. NIH Publication No. 07-4519.
23. Jackson Jr., G.R., Bolmarcich, J., Oldach, J., Klausner, M., Hayden, P.J., 2011. In vitro evaluation of airway toxicity using the EpiAirway organotypic in vitro human airway model. SOT 2011, Abstract No. 2567. available from Mattek Corporation, USA.
24. Jírová D., Basketter D., Liebsch M., Bendová H., Kejlová K., Marriott M., Kandárová H. Comparison of human skin irritation patch test data with in vitro skin irritation assays and animal data. Contact Dermatitis 2010, 62:109-116.
25. Kim H., Lee S.W., Baek K.M., Park J.S., Min J.H. Continuous hypoxia attenuates paraquat-induced cytotoxicity in the human A549 lung carcinoma cell line. Exp. Mol. Med. 2011, 43:494-500.
26. Kirkham S., Kolsum U., Rousseau K., Singh D., Vestbo J., Thornton D.J. MUC5B is the major mucin in the gel phase of sputum in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2008, 178:1029-1033.
27. Klimisch H.-J., Andreae M., Tillmann U. A systematic approach for evaluating the quality of experimental toxicological and ecotoxicological data. Regul. Toxicol. Pharmacol. 1997, 25:1-5.
28. Krewski D., Acosta D., Andersen M., Anderson H., Bailar J.C., Boekelheide K., Brent R., Charnley G., Cheung V.G., Green S., Kelsey K.T., Kerkvliet N.I., Li A.A., McCray L., Meyer O., Patterson R.D., Pennie W., Scala R.A., Solomon G.M., Stephens M., Yager J., Zeise L. Toxicity testing in the 21st century: a vision and a strategy. J. Toxicol. Environ. Health B. Crit. Rev. 2010, 13:51-138.
29. Kroll A., Dierker C., Rommel C., Hahn D., Wohlleben W., Schulze-Isfort C., Göbbert C., Voetz M., Hardinghaus F., Schnekenburger J. Cytotoxicity screening of 23 engineered nanomaterials using a test matrix of ten cell lines and three different assays. Part. Fibre Toxicol. 2011, 8:9.
30. Landsiedel R., Ma-Hock L., Kroll A., Hahn D., Schnekenburger J., Wiench K., Wohlleben W. Testing metal-oxide nanomaterials for human safety. Adv. Mater. 2010, 22:2601-2627.
31. Larsen C.P., Regal J.F. Trimellitic anhydride (TMA) dust induces airway obstruction and eosinophilia in non-sensitized guinea pigs. Toxicology 2002, 178:89-99.
32. Lefebvre M.A., Meuling W.J., Engel R., Coroama M.C., Renner G., Pape W., Nohynek G.J. Consumer inhalation exposure to formaldehyde from the use of personal care products/cosmetics. Regul. Toxicol. Pharmacol. 2012, 63:171-176.
33. Lenz A.G., Karg E., Lentner B., Dittrich V., Brandenberger C., Rothen-Rutishauser B., Schulz H., Ferron G.A., Schmid O. A dose-controlled system for air-liquid interface cell exposure and application to zinc oxide nanoparticles. Part. Fibre Toxicol. 2009, 16:32.
34. Lieber M., Smith B., Szakal A., Nelson-Rees W., Todaro G. A continuous tumor-cell line from a human lung carcinoma with properties of type II alveolar epithelial cells. Int. J. Cancer 1976, 17:62-70.
35. Mainwaring G., Foster J.R., Lund V., Green T. Methyl methacrylate toxicity in rat nasal epithelium: studies of the mechanism of action and comparisons between species. Toxicology 2001, 158:109-118.
36. Martin M.T., Knudsen T.B., Judson R.S., Kavlock R.J., Dix D.J. Economic benefits of using adaptive predictive models of reproductive toxicity in the context of a tiered testing program. Syst. Biol. Reprod. Med. 2012, 58:3-9.
37. Martinez V., Corsini E., Mitjans M., Pinazo A., Vinardell M.P. Evaluation of eye and skin irritation of arginine derivative surfactants using different in vitro endpoints as alternatives to the in vivo assays. Toxicol. Lett. 2006, 164:259-267.
38. Mikoczy Z., Welinder H., Tinnerberg H., Hagmar L. Cancer incidence and mortality of isocyanate exposed workers from the Swedish polyurethane foam industry: updated findings 1959-98. Occup. Environ. Med. 2004, 61:432-437.
39. Miller F.J., Kimbell J.S., Preston R.J., Overton J.H., Groß E.A., Conolly R.B. The fractions of respiratory tract cells at risk in formaldehyde carcinogenesis. Inhal. Toxicol. 2011, 23:689-706.
40. Nakashima K., Takeshita T., Morimoto K. Review of the occupational exposure to isocyanates: mechanisms of action. Environ. Health Prev. Med. 2002, 7:1-6.
41. OECD, 2009a. OECD guidelines for the testing of chemicals, Section 4. Test No. 403: Acute inhalation toxicity. Adopted 7 September 2009.
42. OECD, 2009b. OECD guidelines for the testing of chemicals, Section 4. Test No. 436: Acute inhalation toxicity - acute toxic class method. Adopted 8 September 2009.
43. OECD, 2009c. Guidance document on acute inhalation toxicity testing. Series on testing and assessment, Number 39. ENV/JM/MONO(2009) 28. Adopted 21 July 2009.
44. OECD, 2010. OECD guidelines for the testing of chemicals, Section 4. Test No. 439: In vitro skin irritation - reconstructed human epidermis test method. Adopted 23 July 2010.
45. Pauluhn J., Bury D., Föst U., Gamer A., Hoernicke E., Hofmann T., Kunde M., Neustadt T., Schlede E., Schnierle H., Wettig K., Westphal D. Acute inhalation toxicity testing: considerations of technical and regulatory aspects. Arch. Toxicol. 1996, 71:1-10.
46. Pauluhn J. Issues of dosimetry in inhalation toxicity. Toxicol. Lett. 2003, 140-141:229-238.
47. Pauluhn J. Subacute inhalation toxicity of aniline in rats: analysis of time-dependence and concentration-dependence of hematotoxic and splenic effects. Toxicol. Sci. 2004, 81:198-215.
48. Plantier L., Boczkowski J., Crestani B. Defect of alveolar regeneration in pulmonary emphysema: role of lung fibroblasts. Int. J. Chron. Obstruct. Pulmon. Dis. 2007, 2:463-469.
49. Plitnick L.M., Loveless S.E., Ladics G.S., Holsapple M.P., Smialowicz R.J., Woolhiser M.R., Anderson P.K., Smith C., Selgrade M.J. Cytokine mRNA profiles for isocyanates with known and unknown potential to induce respiratory sensitization. Toxicology 2005, 207:487-499.
50. Ren D., Daines D.A. Use of the EpiAirway model for characterising long-term host-pathogen interactions. J. Vis. Exp. 2011, 55:e3261.
51. Roggen E.L., Soni N.K., Verheyen G.R. Respiratory immunotoxicity. An in vitro assessment. Toxicol. In Vitro 2006, 20:1249-1264.
52. Rothen-Rutishauser B.M., Kiama S.G., Gehr P. A three-dimensional cellular model of the human respiratory tract to study the interaction with particles. Am. J. Respir. Cell. Mol. Biol. 2005, 32:281-289.
53. Russell, W.M.S., Burch, R.L., 1959. The principles of humane experimental technique. London, UK. Methuen. Reprinted by UFAW, 1992: 8 Hamilton Close, South Mimms, Potters Bar, Herts EN6 3QD England. 238 pp.
54. Sayes C.M., Reed K.L., Warheit D.B. Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. Toxicol. Sci. 2007, 97:163-180.
55. Sexton K., Balharry D., Brennan P., McLaren J., Brewis I.A., BéruBé K.A. Proteomic profiling of human respiratory epithelia by iTRAQ reveals biomarkers of exposure and harm by tobacco smoke components. Biomarkers 2011, 16:567-576.
56. Shaheen S.O., Sterne J.A., Songhurst C.E., Burney P.G. Frequent paracetamol use and asthma in adults. Thorax 2000, 55:266-270.
57. Sharma M., Schoop R., Hudson J.B. The efficacy of Echinacea in a 3D tissue model of human airway epithelium. Phytother. Res. 2010, 24:900-904.
58. Siadaty M.S., Shu J. Proportional odds ratio model for comparison of diagnostic tests in meta-analysis. BMC Med. Res. Methodol. 2004, 4:27.
59. Singer M.M., Tjeerdema R.S. Fate and effects of the surfactant sodium dodecyl sulfate. Rev. Environ. Contam. Toxicol. 1993, 133:95-149.
60. Smith L.L., Lewis C.P.L., Wyatt I., Cohen G.M. The importance of epithelial uptake systems in lung toxicity. Environ. Health Perspect. 1990, 85:25-30.
61. Snipes M.B. Species comparisons for pulmonary retention of inhaled particles. Concepts in Inhalation Toxicology 1988, 196. Hemisphere Publishing Corp, New York, (Chapter 7). first ed. R.O. McClelland, R.F. Henderson (Eds.).
62. Tung J.N., Lang Y.D., Wang L.F., Chen C.M. Paraquat increases connective tissue growth factor and collagen expression via angiotensin signaling pathway in human lung fibroblasts. Toxicol. In Vitro 2010, 24:803-808.
63. United Nations, 2011. Globally Harmonised System of classification and labelling of chemicals, fourth revised edition. United Nations, New York and Geneva, ST/SG/AC.10/30/Rev. 4. 561pp. available at: <>. http://www.unece.org/fileadmin/DAM/trans/danger/publi/ghs/ghs_rev04/English/ST-SG-AC10-30-Rev4e.pdf.
64. VCI, 2010. Verband der Chemischen Industrie - German Chemical Industry Association. Ableitung von DNEL für lokal reizende Stoffe mit guter Datenlage zur systemischen Toxizität, aber limitierter Datenlage zur Inhalationstoxizität - Derivation of DNEL for locally irritating substances with satisfactory data on systemic toxicity, but limited data on inhalation toxicity. VCI Arbeitskreis Toxikologie, 21.01.2010, available from VCI: www.vci.de.