Opportunities for an alternative integrating testing strategy for carcinogen hazard assessment?

Critical Reviews in Toxicology

Volumn 42, Issue 2, 2012, Pages 91-106

  Doktorova, Tatyana Y ^a   Pauwels, Marleen ^a   Vinken, Mathieu ^a   Vanhaecke, Tamara ^a   Rogiers, Vera ^a  

^a VRIJE UNIVERSITEIT BRUSSEL   (Belgium)

Author keywords

3R alternatives to carcinogenicity testing; Carcinogen hazard assessment; Integrated testing strategies; Rodent carcinogenicity bioassay

Indexed keywords

CARCINOGEN; ANEUGEN; CLASTOGEN;

BIOASSAY; CARCINOGENICITY; GENE MUTATION; GENOTOXICITY; HAZARD ASSESSMENT; HUMAN; IN VITRO STUDY; IN VIVO STUDY; METHODOLOGY; MUTAGENICITY; NONHUMAN; REVIEW; STRUCTURE ACTIVITY RELATION; ANEUGENICITY; CARCINOGEN TESTING; CELL TRANSFORMATION; CLASTOGENICITY; DNA MODIFICATION; FEASIBILITY STUDY; GENOTOXICITY ASSAY; MUTAGEN TESTING; RISK ASSESSMENT; TOXICOGENETICS;

ANIMAL TESTING ALTERNATIVES; ANIMALS; ANIMALS, GENETICALLY MODIFIED; BIOLOGICAL ASSAY; CARCINOGENICITY TESTS; CARCINOGENS; CELL LINE; CELL TRANSFORMATION, NEOPLASTIC; HUMANS; MUTAGENICITY TESTS; RISK ASSESSMENT; RODENTIA; TOXICOGENETICS;

ANIMALIA; RODENTIA;

EID: 84856139798     PISSN: 10408444     EISSN: 15476898     Source Type: Journal    
DOI: 10.3109/10408444.2011.623151     Document Type: Review

References (137)

1. Ames BN, Lee FD, Durston WE. (1973). An improved bacterial test system for the detection and classification of mutagens and carcinogens. Proc Natl Acad Sci USA 70:782-786.
2. Ao L, Liu JY, Liu WB, Gao LH, Hu R, Fang ZJ, Zhen ZX, Huang MH, Yang MS, Cao J. (2010). Comparison of gene expression profiles in BALB/c 3T3 transformed foci exposed to tumor promoting agents. Toxicol In Vitro 24:430-438.
3. Balls M. (2009). The origins and early days of the Three Rs concept. Altern Lab Anim 37:255-265.
4. Benfenati E, Benigni R, Demarini DM, Helma C, Kirkland D, Martin TM, Mazzatorta P, Ouédraogo-Arras G, Richard AM, Schilter B, Schoonen WG, Snyder RD, Yang C. (2009). Predictive models for carcinogenicity and mutagenicity: frameworks, state-of-theart, and perspectives. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 27:57-90.
5. Benigni R, Bossa C, Netzeva T, Rodomonte A, Tsakovska I. (2007a). Mechanistic QSAR of aromatic amines: new models for discriminating between homocyclic mutagens and nonmutagens, and validation of models for carcinogens. Environ Mol Mutagen 48:754-771. (Pubitemid 350305012)
6. Benigni R, Bossa C. (2008). Predictivity and reliability of QSAR models: the case of mutagens and carcinogens. Toxicol Mech Methods 18:137-147. (Pubitemid 351414963)
7. Benigni R, Conti L, Crebelli R, Rodomonte A, Varí MR. (2005). Simple and alpha,beta-unsaturated aldehydes: correct prediction of genotoxic activity through structure-activity relationship models. Environ Mol Mutagen 46:268-280. (Pubitemid 43107948)
8. Benigni R, Netzeva TI, Benfenati E, Bossa C, Franke R, Helma C, Hulzebos E, Marchant C, Richard A, Woo YT, Yang C. (2007b). The expanding role of predictive toxicology: an update on the (Q) SAR models for mutagens and carcinogens. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 25:53-97. (Pubitemid 46393120)
9. Benigni R. (2005). Structure-activity relationship studies of chemical mutagens and carcinogens: mechanistic investigations and prediction approaches. Chem Rev 105:1767-1800. (Pubitemid 40773667)
10. Bercu JP, Jolly RA, Flagella KM, Baker TK, Romero P, Stevens JL. (2010). Toxicogenomics and cancer risk assessment: a framework for key event analysis and dose-response assessment for nongenotoxic carcinogens. Regul Toxicol Pharmacol 58:369-381.
11. Berwald Y, Sachs L. (1963). In vitro cell transformation with chemical carcinogens. Nature 200:1182-1184.
12. Besaratinia A, Pfeifer GP. (2010). Applications of the human p53 knock-in (Hupki) mouse model for human carcinogen testing. FASEB J 24:2612-2619.
13. Beyer LA, Beck BD, Lewandowski TA. (2011). Historical perspective on the use of animal bioassays to predict carcinogenicity: evolution in design and recognition of utility. Crit Rev Toxicol 41:321-338.
14. Boobis AR, Cohen SM, Doerrer NG, Galloway SM, Haley PJ, Hard GC, Hess FG, Macdonald JS, Thibault S, Wolf DC, Wright J. (2009). A data-based assessment of alternative strategies for identification of potential human cancer hazards. Toxicol Pathol 37:714-732.
15. Bruce ED, Autenrieth RL, Burghardt RC, Donnelly KC, McDonald TJ. (2008). Using quantitative structure-activity relationships (QSAR) to predict toxic endpoints for polycyclic aromatic hydrocarbons (PAH). J Toxicol Environ Health Part A 71:1073-1084. (Pubitemid 352000674)
16. Chaible LM, Corat MA, Abdelhay E, Dagli ML. (2010). Genetically modified animals for use in research and biotechnology. Genet Mol Res 9:1469-1482.
17. Cohen SM, Robinson D, MacDonald J. (2001). Alternative models for carcinogenicity testing. Toxicol Sci 64:14-19. (Pubitemid 33062183)
18. Cohen SM. (2010). An enhanced 13-week bioassay as an alternative for screening for carcinogenesis factors. Asian Pacific J Cancer Prev 10:5-17.
19. Cohen SM, Arnold LL. (2011). Chemical carcinogenesis. Toxicol Sci 120 Suppl 1:S76-S92.
20. Colbert LH, Westerlind KC, Perkins SN, Haines DC, Berrigan D, Donehower LA, Fuchs-Young R, Hursting SD. (2009). Exercise effects on tumorigenesis in a p53-deficient mouse model of breast cancer. Med Sci Sports Exerc 41:1597-1605.
21. COM. (2011). Committee on Mutagenicity of Chemicals in Food, Consumer products and the Environment. Guidance on a strategy for carcinogenicity testing and mutagenic hazard assessment of chemical substances. [Online] Available at: http://www.iacom. org.uk/ Accessed on 3 August 2011.
22. Combes R, Grindon C, Cronin MT, Roberts DW, Garrod J. (2007). Proposed integrated decision-tree testing strategies for mutagenicity and carcinogenicity in relation to the EU REACH legislation. Altern Lab Anim 35:267-287. (Pubitemid 46883166)
23. Contrera JF, DeGeorge JJ. (1998). In vivo transgenic bioassays and assessment of the carcinogenic potential of pharmaceuticals. Environ Health Perspect 106 Suppl 1:71-80. (Pubitemid 28196037)
24. Crettaz P, Benigni R. (2005). Prediction of the rodent carcinogenicity of 60 pesticides by the DEREKfW expert system. J Chem Inf Model 45:1864-1873. (Pubitemid 41784761)
25. Dass SB, Bucci TJ, Heflich RH, Casciano DA. (1999). Evaluation of the transgenic p53+/- mouse for detecting genotoxic liver carcinogens in a short-term bioassay. Cancer Lett 143:81-85. (Pubitemid 29327193)
26. ECHA. (2009). New study inaccurate on the number of test animals for REACH. [Online] Available at: http://echa.europa.eu/doc/press/pr-09-11-animal- testing-20090828.pdf. Accessed on 3 August 2011.
27. EFSA. (2011). EFSA Scientific Committee. Scientific opinion on genotoxicity testing strategies applicable in food and feed safety assessment. [Online] Available at: http://www.efsa.europa.eu/Accessed on 3 August 2011.
28. Ellinger-Ziegelbauer H, Fostel JM, Aruga C, Bauer D, Boitier E, Deng S, Dickinson D, Le Fevre AC, Fornace AJ Jr, Grenet O, Gu Y, Hoflack JC, Shiiyama M, Smith R, Snyder RD, Spire C, Tanaka G, Aubrecht J. (2009). Characterization and interlaboratory comparison of a gene expression signature for differentiating genotoxic mechanisms. Toxicol Sci 110:341-352.
29. Ellinger-Ziegelbauer H, Gmuender H, Bandenburg A, Ahr HJ. (2008). Prediction of a carcinogenic potential of rat hepatocarcinogens using toxicogenomics analysis of short-term in vivo studies. Mutat Res 637:23-39. (Pubitemid 350256758)
30. Ellinger-Ziegelbauer H, Stuart B, Wahle B, Bomann W, Ahr HJ. (2005). Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver. Mutat Res 575:61-84. (Pubitemid 40733311)
31. EMEA. (2004). CHMP SWP Conclusions and recommendations on the use of genetically modified animal models for carcinogenicity assessment. 1-12.
32. Engelhardt G, Schwind KR, Mussler B. (2004). The testing of chemicals in the Syrian hamster embryo (SHE) cell transformation assay for assessment of carcinogenic potential. Toxicol In Vitro 18:213-218. (Pubitemid 38125201)
33. EPA. (2005). EPA/630/P-03/001F.Environmental Protection Agency Guidelines for Carcinogen Risk Assessment. EPA. (Online). Available at: http://www.epa.gov/oppt/sf/pubs/oncologic.htm. Accessed on 3 August 2011.
34. EU. (1986). Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes. Official J L358:1.
35. EU. (2003). Directive 2003/15/EC of the European parliament and of the council of 27 February 2003 amending Council directive 76/768/EEC on the approximation of the laws of the member states relating to cosmetic products. Official J L066:26-35.
36. EU. (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. Official J L396:1-849.
37. EU. (2008a). B.33 Combined chronic toxicity/carcinogenicity test. COUNCIL REGULATION (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH). Official J L142:344-350.
38. EU. (2008b). B.13/14 Mutagenicity: Reverse mutation test using bacteria COUNCIL REGULATION (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH). Official J L142:248-255.
39. EU. (2008c). B.17 Mutagenicity: in vitro mammalian cell gene mutation test COUNCIL REGULATION (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH). Official J L142:262-270.
40. EU. (2008d). B.10 Mutagenicity: in vitro mammalian chromosome aberration test COUNCIL REGULATION (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH). Official J L142:225-232.
41. EU. (2008e). B.10 Mutagenicity: in vitro mammalian micronucleus test COUNCIL REGULATION (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH). Official J L142:225-232.
42. EU. (2008f). B21. In vitro mammalian cell transformation tests. Council Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH). Official J L142:282-284.
43. EU. (2010a). 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. Official J L276:33-79.
44. EU. (2010b). JRC Draft report on Alternative (non-animal) methods for cosmetics testing: current status and future perspects-2010. [Online] Available at: http://ec.europa.eu/consumers/sectors/cosmetics/files/pdf/animal-testing/ chapter-3-carcinogenicity- en.pdf. Accessed on 3 August 2011.
45. Fan X, Shi L, Fang H, Harris S, Perkins R, Tong W. (2009). Investigation of reproducibility of differentially expressed genes in DNA microarrays through statistical simulation. BMC Proc 3 Suppl 2:S4.
46. Fielden MR, Brennan R, Gollub J. (2007). A gene expression biomarker provides early prediction and mechanistic assessment of hepatic tumor induction by nongenotoxic chemicals. Toxicol Sci 99:90-100. (Pubitemid 47250370)
47. Fjodorova N, Vracko M, Novic M, Roncaglioni A, Benfenati E. (2010). New public QSAR model for carcinogenicity. Chem Cent J 4 Suppl 1:S3.
48. Foster WR, Chen SJ, He A, Truong A, Bhaskaran V, Nelson DM, Dambach DM, Lehman-McKeeman LD, Car BD. (2007). A retrospective analysis of toxicogenomics in the safety assessment of drug candidates. Toxicol Pathol 35:621-635. (Pubitemid 47123742)
49. Galloway S, Lorge E, Aardema MJ, Eastmond D, Fellows M, Heflich R, Kirkland D, Levy DD, Lynch AM, Marzin D, Morita T, Schuler M, Speit G. (2011). Workshop summary: Top concentration for in vitro mammalian cell genotoxicity assays; and report from working group on toxicity measures and top concentration for in vitro cytogenetics assays (chromosome aberrations and micronucleus). Mutat Res 723:77-83.
50. Gama Sosa MA, De Gasperi R, Elder GA. (2010). Animal transgenesis: an overview. Brain Struct Funct 214:91-109.
51. Ghanayem BI, Hoffler U. (2007). Investigation of xenobiotics metabolism, genotoxicity, and carcinogenicity using Cyp2e1(-/-) mice. Curr Drug Metab 8:728-749. (Pubitemid 47578121)
52. Goodsaid FM, Amur S, Aubrecht J, Burczynski ME, Carl K, Catalano J, Charlab R, Close S, Cornu-Artis C, Essioux L, Fornace AJ Jr, Hinman L, Hong H, Hunt I, Jacobson-Kram D, Jawaid A, Laurie D, Lesko L, Li HH, Lindpaintner K, Mayne J, Morrow P, Papaluca-Amati M, Robison TW, Roth J, Schuppe-Koistinen I, Shi L, Spleiss O, Tong W, Truter SL, Vonderscher J, Westelinck A, Zhang L, Zineh I. (2010). Voluntary exploratory data submissions to the US FDA and the EMA: experience and impact. Nat Rev Drug Discov 9:435-445.
53. Guyton KZ, Kyle AD, Aubrecht J, Cogliano VJ, Eastmond DA, Jackson M, Keshava N, Sandy MS, Sonawane B, Zhang L, Waters MD, Smith MT. (2009). Improving prediction of chemical carcinogenicity by considering multiple mechanisms and applying toxicogenomic approaches. Mutat Res 681:230-240.
54. Harris AJ, Shaddock JG, Delongchamp R, Dragan Y, Casciano DA. (2004). Comparison of Basal gene expression in cultured primary rat hepatocytes and freshly isolated rat hepatocytes. Toxicol Mech Methods 14:257-270. (Pubitemid 39122143)
55. Hayashi K, Sasaki K, Asada S, Tsuchiya T, Hayashi M, Yoshimura I, Tanaka N, Umeda M. (2008). Technical modification of the Balb/c 3T3 cell transformation assay: the use of serum-reduced medium to optimise the practicability of the protocol. Altern Lab Anim 36:653-665.
56. Hoenerhoff MJ, Hong HH, Ton TV, Lahousse SA, Sills RC. (2009). A review of the molecular mechanisms of chemically induced neoplasia in rat and mouse models in National Toxicology Program bioassays and their relevance to human cancer. Toxicol Pathol 37:835-848.
57. Hu T, Kaluzhny Y, Mun GC, Barnett B, Karetsky V, Wilt N, Klausner M, Curren RD, Aardema MJ. (2009). Intralaboratory and interlaboratory evaluation of the EpiDerm 3D human reconstructed skin micronucleus (RSMN) assay. Mutat Res 673:100-108.
58. Hu T, Khambatta ZS, Hayden PJ, Bolmarcich J, Binder RL, Robinson MK, Carr GJ, Tiesman JP, Jarrold BB, Osborne R, Reichling TD, Nemeth ST, Aardema MJ. (2010). Xenobiotic metabolism gene expression in the EpiDermin vitro 3D human epidermis model compared to human skin. Toxicol In Vitro 24:1450-1463.
59. Huff J, Jacobson MF, Davis DL. (2008). The limits of two-year bioassay exposure regimens for identifying chemical carcinogens. Environ Health Perspect 116:1439-1442.
60. Humble MC, Trempus CS, Spalding JW, Cannon RE, Tennant RW. (2005). Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review. Oncogene 24:8217-8228. (Pubitemid 43250914)
61. Jacobson-Kram D. (2010). Cancer risk assessment approaches at the FDA/CDER: Is the era of the 2-year bioassay drawing to a close? Toxicol Pathol 38: 169-170.
62. Jennen DG, Magkoufopoulou C, Ketelslegers HB, van Herwijnen MH, Kleinjans JC, van Delft JH. (2010). Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci 115:66-79.
63. Jonker MJ, Bruning O, van Iterson M, Schaap MM, van der Hoeven TV, Vrieling H, Beems RB, de Vries A, van Steeg H, Breit TM, Luijten M. (2009). Finding transcriptomics biomarkers for in vivo identification of (non-)genotoxic carcinogens using wild-type and Xpa/p53 mutant mouse models. Carcinogenesis 30:1805-1812.
64. Kakunaga T. (1973). A quantitative system for assay of malignant transformation by chemical carcinogens using a clone derived from BALB-3T3. Int J Cancer 12:463-473.
65. Kawai M, Jin M, Nishimura J, Dewa Y, Saegusa Y, Matsumoto S, Taniai E, Shibutani M, Mitsumori K. (2008). Hepatocarcinogenic susceptibility of fenofibrate and its possible mechanism of carcinogenicity in a two-stage hepatocarcinogenesis model of rasH2 mice. Toxicol Pathol 36:950-957.
66. Kerckaert GA, Isfort RJ, Carr GJ, Aardema MJ, LeBoeuf RA. (1996). A comprehensive protocol for conducting the Syrian hamster embryo cell transformation assay at pH 6.70. Mutat Res 356:65-84. (Pubitemid 26308723)
67. Kirkland D, Aardema M, Henderson L, Müller L. (2005). Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens I. Sensitivity, specificity and relative predictivity. Mutat Res 584:1-256. (Pubitemid 40922793)
68. Kirkland D, Pfuhler S, Tweats D, Aardema M, Corvi R, Darroudi F, Elhajouji A, Glatt H, Hastwell P, Hayashi M, Kasper P, Kirchner S, Lynch A, Marzin D, Maurici D, Meunier JR, Müller L, Nohynek G, Parry J, Parry E, Thybaud V, Tice R, van Benthem J, Vanparys P, White P. (2007). How to reduce false positive results when undertaking in vitro genotoxicity testing and thus avoid unnecessary follow-up animal tests: Report of an ECVAM Workshop. Mutat Res 628:31-55.
69. Kirkland D, Fowler P. (2010). Further analysis of Ames-negative rodent carcinogens that are only genotoxic in mammalian cells in vitro at concentrations exceeding 1 mM, including retesting of compounds of concern. Mutagenesis 25:539-553.
70. Kirkland D. (2010a). Evaluation of different cytotoxic and cytostatic measures for the in vitro micronucleus test (MNVit): introduction to the collaborative trial. Mutat Res 702:135-138.
71. Kirkland D. (2010b). Evaluation of different cytotoxic and cytostatic measures for the in vitro micronucleus test (MNVit): summary of results in the collaborative trial. Mutat Res 702:139-147.
72. Kirkland D, Reeve L, Gatehouse D, Vanparys P. (2011). A core in vitro genotoxicity battery comprising the Ames test plus the in vitro micronucleus test is sufficient to detect rodent carcinogens and in vivo genotoxins. Mutat Res 721:27-73.
73. Kissling GE, Malarkey DE, Vallant MK, Johnson JD, Hejtmancik MR, Herbert RA, Boorman GA. (2009). Evaluation of dichloroacetic acid for carcinogenicity in genetically modified Tg.AC hemizygous and p53 haploinsufficient mice. Toxicol Sci 107:19-26.
74. Knight A, Bailey J, Balcombe J. (2006). Animal carcinogenicity studies: 2. Obstacles to extrapolation of data to humans. Altern Lab Anim 34:29-38. (Pubitemid 43378978)
75. LeBoeuf RA, Kerckaert GA, Aardema MJ, Gibson DP, Brauninger R, Isfort RJ. (1996). The pH 6.7 Syrian hamster embryo cell transformation assay for assessing the carcinogenic potential of chemicals. Mutat Res 356:85-127. (Pubitemid 26308724)
76. LeBoeuf RA, Kerckaert KA, Aardema MJ, Isfort RJ. (1999). Use of Syrian hamster embryo and BALB/c 3T3 cell transformation for assessing the carcinogenic potential of chemicals. IARC Sci Publ 409-425.
77. Long GG, Morton D, Peters T, Short B, Skydsgaard M. (2010). Alternative mouse models for carcinogenicity assessment: industry use and issues with pathology interpretation. Toxicol Pathol 38:43-50.
78. Lynch D, Svoboda J, Putta S, Hofland HE, Chern WH, Hansen LA. (2007). Mouse skin models for carcinogenic hazard identification: utilities and challenges. Toxicol Pathol 35:853-864.
79. Maire MA, Bazin E, Fessard V, Rast C, Humpage AR, Vasseur P. (2010). Morphological cell transformation of Syrian hamster embryo (SHE) cells by the cyanotoxin, cylindrospermopsin. Toxicon 55:1317-1322.
80. Mascolo MG, Perdichizzi S, Rotondo F, Morandi E, Guerrini A, Silingardi P, Vaccari M, Grilli S, Colacci A. (2010). BALB/c 3T3 cell transformation assay for the prediction of carcinogenic potential of chemicals and environmental mixtures. Toxicol In Vitro 24:1292-1300.
81. Mathijs K, Brauers KJ, Jennen DG, Boorsma A, van Herwijnen MH, Gottschalk RW, Kleinjans JC, van Delft JH. (2009). Discrimination for genotoxic and nongenotoxic carcinogens by gene expression profiling in primary mouse hepatocytes improves with exposure time. Toxicol Sci 112:374-384.
82. Mathijs K, Brauers KJ, Jennen DG, Lizarraga D, Kleinjans JC, van Delft JH. (2010). Gene expression profiling in primary mouse hepatocytes discriminates true from false-positive genotoxic compounds. Mutagenesis 25:561-568.
83. Matsumoto H, Yakabe Y, Saito K, Sumida K, Sekijima M, Nakayama K, Miyaura H, Saito F, Otsuka M, Shirai T. (2009). Discrimination of carcinogens by hepatic transcript profiling in rats following 28-day administration. Cancer Inform 7:253-269.
84. Mauthe RJ, Gibson DP, Bunch RT, Custer L. (2001). The syrian hamster embryo (SHE) cell transformation assay: review of the methods and results. Toxicol Pathol 29 Suppl:138-146.
85. Maurici D, Aardema M, Corvi R, Kleber M, Krul C, Laurent C, Loprieno N, Pasanen M, Pfuhler S, Phillips B, Sabbioni E, Sanner T, Vanparys P. (2005). Genotoxicty and mutagenicity. Altern Lab Anim 33 Suppl 1:117-130.
86. Mayer J, Cheeseman MA, Twaroski ML. (2008). Structure-activity relationship analysis tools: validation and applicability in predicting carcinogens. Regul Toxicol Pharmacol 50:50-58.
87. McKinney JD, Richard A, Waller C, Newman MC, Gerberick F. (2000). The practice of structure activity relationships (SAR) in toxicology. Toxicol Sci 56:8-17. (Pubitemid 30441460)
88. Mortensen HM, Euling SY. (2011). Integrating mechanistic and polymorphism data to characterise human genetic susceptibility for environmental chemical risk assessment in the 21st century. Toxicol Appl Pharmacol [Epup ahead of print]
89. Morton D, Alden CL, Roth AJ, Usui T. (2002). The Tg rasH2 mouse in cancer hazard identification. Toxicol Pathol 30:139-146. (Pubitemid 34194572)
90. Morton D, Bailey KL, Stout CL, Weaver RJ, White KA, Lorenzen MJ, Ball DJ. (2008). N-Methyl-N-Nitrosourea (MNU): A positive control chemical for p53+/- mouse carcinogenicity studies. Toxicol Pathol 36:926-931.
91. Nakayama K, Kawano Y, Kawakami Y, Moriwaki N, Sekijima M, Otsuka M, Yakabe Y, Miyaura H, Saito K, Sumida K, Shirai T. (2006). Differences in gene expression profiles in the liver between carcinogenic and non-carcinogenic isomers of compounds given to rats in a 28-day repeat-dose toxicity study. Toxicol Appl Pharmacol 217:299-307. (Pubitemid 44855817)
92. OECD. (1997a). OECD Guidelines for the Testing of Chemicals Test No. 471 Bacterial Reverse Mutation Test.
93. OECD. (1997b). OECD Guidelines for the Testing of Chemicals Test No. 476 In vitro Mammalian Cell Gene Mutation Test.
94. OECD. (1997c). OECD Guidelines for the Testing of Chemicals Test No. 473 In vitro Mammalian Chromosome Aberration Test.
95. OECD. (1997d). OECD Guidelines for the Testing of Chemicals Test No. 474 In Vitro Mammalian Cell Micronucleus Test.
96. OECD. (2007). Detailed review paper on non-genotoxic carcinogen detection: The performance of the in vitro cell transformation assay.
97. OECD. (2009). OECD Guidelines for the Testing of Chemicals Test No. 453 Combined Chronic Toxicity/Carcinogenicity Studies.
98. Ohmori K, Umeda M, Tanaka N, Takagi H, Yoshimura I, Sasaki K, Asasda S, Sakai A, Araki H, Asakura M, Baba H, Fushiwaki Y, Hamada S, Kitou N, Nakamura T, Nakamura Y, Oishi H, Sasaki S, Shimada S, Tsuchiya T, Uno Y, Washizuka M, Yajima S, Yamamoto Y, Yamamura E, Yatsushiro T; Non-Genotoxic Carcinogen Study Group in the Environmental Mutagen Society of Japan. (2005). An inter-laboratory collaborative study by the Non-Genotoxic Carcinogen Study Group in Japan, on a cell transformation assay for tumour promoters using Bhas 42 cells. Altern Lab Anim 33:619-639. (Pubitemid 43151818)
99. Palazzi X, Kergozien-Framery S. (2009). Use of rasH2 transgenic mice for carcinogenesis testing of medical implants. Exp Toxicol Pathol 61:433-441.
100. Pant K, Sly JE, Bruce SW, Leung C, San RH. (2008). Syrian hamster embryo (SHE) cell transformation assay with conditioned media (without X-ray irradiated feeder layer) using 2,4-diaminotoluene, 2,6-diaminotoluene and chloral hydrate. Mutat Res 654:108-113.
101. Pant K, Sly JE, Bruce SW, Scott AD, Carmichael PL, San RH. (2010). Syrian Hamster Embryo (SHE) cell transformation assay with and without X-ray irradiation of feeder cells using Di(2-ethylhexyl) phthalate (DEHP) and N-nitroso-N-methylnitroguanidine (MNNG). Mutat Res 698:6-10.
102. Pennie W, Pettit SD, Lord PG. (2004). Toxicogenomics in risk assessment: an overview of an HESI collaborative research program. Environ Health Perspect 112:417-419. (Pubitemid 38404551)
103. Pfuhler S, Kirkland D, Kasper P, Hayashi M, Vanparys P, Carmichael P, Dertinger S, Eastmond D, Elhajouji A, Krul C, Rothfuss A, Schoening G, Smith A, Speit G, Thomas C, van Benthem J, Corvi R. (2009). Reduction of use of animals in regulatory genotoxicity testing: Identification and implementation opportunities-Report from an ECVAM workshop. Mutat Res 680:31-42.
104. Pfuhler S, Kirst A, Aardema M, Banduhn N, Goebel C, Araki D, Costabel-Farkas M, Dufour E, Fautz R, Harvey J, Hewitt NJ, Hibatallah J, Carmichael P, Macfarlane M, Reisinger K, Rowland J, Schellauf F, Schepky A, Scheel J. (2010). A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: genotoxicity. A COLIPA analysis. Regul Toxicol Pharmacol 57:315-324.
105. Pritchard JB, French JE, Davis BJ, Haseman JK. (2003). The role of transgenic mouse models in carcinogen identification. Environ Health Perspect 111:444-454. (Pubitemid 36546520)
106. Reddy MV, Sistare FD, Christensen JS, Deluca JG, Wollenberg GK, Degeorge JJ. (2010). An evaluation of chronic 6- and 12-month rat toxicology studies as predictors of 2-year tumor outcome. Vet Pathol 47:614-629.
107. Rhomberg LR, Baetcke K, Blancato J, Bus J, Cohen S, Conolly R, Dixit R, Doe J, Ekelman K, Fenner-Crisp P, Harvey P, Hattis D, Jacobs A, Jacobson-Kram D, Lewandowski T, Liteplo R, Pelkonen O, Rice J, Somers D, Turturro A, West W, Olin S. (2007). Issues in the design and interpretation of chronic toxicity and carcinogenicity studies in rodents: approaches to dose selection. Crit Rev Toxicol 37:729-837. (Pubitemid 350034876)
108. Rogiers V, Garthoff B, Webb S, Pauwels M, Müller K, Devolder T, Spielmann H (2007). The Impact of REACH, The report of the CONAM / ecopa Chemical Policy Working Group.
109. Rohrbeck A, Salinas G, Maaser K, Linge J, Salovaara S, Corvi R, Borlak J. (2010). Toxicogenomics applied to in vitro carcinogenicity testing with Balb/c 3T3 cells revealed a gene signature predictive of chemical carcinogens. Toxicol Sci 118:31-41.
110. Rothfuss A, O'Donovan M, De Boeck M, Brault D, Czich A, Custer L, Hamada S, Plappert-Helbig U, Hayashi M, Howe J, Kraynak AR, van der Leede BJ, Nakajima M, Priestley C, Thybaud V, Saigo K, Sawant S, Shi J, Storer R, Struwe M, Vock E, Galloway S. (2010). Collaborative study on fifteen compounds in the rat-liver Comet assay integrated into 2- and 4-week repeat-dose studies. Mutat Res 702:40-69.
111. Rothfuss A, Honma M, Czich A, Aardema MJ, Burlinson B, Galloway S, Hamada S, Kirkland D, Heflich RH, Howe J, Nakajima M, O'Donovan M, Plappert-Helbig U, Priestley C, Recio L, Schuler M, Uno Y, Martus HJ. (2011). Improvement of in vivo genotoxicity assessment: combination of acute tests and integration into standard toxicity testing. Mutat Res 723:108-120.
112. Ruiz P, Faroon O, Moudgal CJ, Hansen H, De Rosa CT, Mumtaz M. (2008). Prediction of the health effects of polychlorinated biphenyls (PCBs) and their metabolites using quantitative structure-activity relationship (QSAR). Toxicol Lett 181:53-65.
113. Russell WMS, Burch RL. (1959). The principle of humane experimental technique. London, United Kingdom: Methuen and Co. Ltd.
114. Sakai A, Sasaki K, Muramatsu D, Arai S, Endou N, Kuroda S, Hayashi K, Lim YM, Yamazaki S, Umeda M, Tanaka N. (2010). A Bhas 42 cell transformation assay on 98 chemicals: the characteristics and performance for the prediction of chemical carcinogenicity. Mutat Res 702:100-122.
115. SCCP. (2008). Scientific committee on Consumer Products, Health and Environmental Risk and Emerging and Newly Identified Health Risks. Draft opinion on use of the Threshold of Toxicological Concern (TTC) approach for the safety assessment of chemical substances. [Online] Available at: http://ec.europa.eu/ health/ph-risk/committees/documents/sc-o-001.pdf. Accessed on 3 August 2011.
116. Sistare FD. (2010). An analysis of pharmaceutical experience with decades of rat carcinogenicity testing. Oral presentation during meeting with EMA SWP&EFPIA, 12 February 2010.
117. Storer RD, Sistare FD, Reddy MV, DeGeorge JJ. (2010). An industry perspective on the utility of short-term carcinogenicity testing in transgenic mice in pharmaceutical development. Toxicol Pathol 38:51-61.
118. Thomas RS, Pluta L, Yang L, Halsey TA. (2007a). Application of genomic biomarkers to predict increased lung tumor incidence in 2-year rodent cancer bioassays. Toxicol Sci 97:55-64. (Pubitemid 47072155)
119. Thomas RS, Allen BC, Nong A, Yang L, Bermudez E, Clewell HJ 3rd, Andersen ME. (2007b). A method to integrate benchmark dose estimates with genomic data to assess the functional effects of chemical exposure. Toxicol Sci 98:240-248. (Pubitemid 47073836)
120. Thomas RS, Clewell HJ 3rd, Allen BC, Wesselkamper SC, Wang NC, Lambert JC, Hess-Wilson JK, Zhao QJ, Andersen ME. (2011). Application of transcriptional benchmark dose values in quantitative cancer and noncancer risk assessment. Toxicol Sci 120:194-205.
121. Toyoda-Hokaiwado N, Inoue T, Masumura K, Hayashi H, Kawamura Y, Kurata Y, Takamune M, Yamada M, Sanada H, Umemura T, Nishikawa A, Nohmi T. (2010). Integration of in vivo genotoxicity and short-term carcinogenicity assays using F344 gpt delta transgenic rats: in vivo mutagenicity of 2,4-diaminotoluene and 2,6-diaminotoluene structural isomers. Toxicol Sci 114:71-78.
122. Tsuchiya T, Umeda M, Tanaka N, Sakai A, Nishiyama H, Yoshimura I, Ajimi S, Asada S, Asakura M, Baba H, Dewa Y, Ebe Y, Fushiwaki Y, Hagiwara Y, Hamada S, Hamamura T, Iwase Y, Kajiwara Y, Kasahara Y, Kato Y, Kawabata M, Kitada E, Kaneko K, Kizaki Y, Kubo K, Miura D, Mashiko K, Mizuhashi F, Muramatsu D, Nakajima M, Nakamura T, Oishi H, Sasaki T, Shimada S, Takahashi C, Takeda Y, Wakuri S, Yajima N, Yajima S, Yatsushiro T. (2010). Application of the improved BALB/c 3T3 cell transformation assay to the examination of the initiating and promoting activities of chemicals: the second interlaboratory collaborative study by the non-genotoxic carcinogen study group of Japan. Altern Lab Anim 38:11-27.
123. Tsuchiya T, Umeda M. (1995). Improvement in the efficiency of the in vitro transformation assay method using BALB/3T3 A31-1-1 cells. Carcinogenesis 16:1887-1894.
124. Tsujimura K, Asamoto M, Suzuki S, Hokaiwado N, Ogawa K, Shirai T. (2006). Prediction of carcinogenic potential by a toxicogenomic approach using rat hepatoma cells. Cancer Sci 97:1002-1010. (Pubitemid 44322546)
125. Urani C, Stefanini FM, Bussinelli L, Melchioretto P, Crosta GF. (2009). Image analysis and automatic classification of transformed foci. J Microsc 234:269-279.
126. van Delft JH, van Agen E, van Breda SG, Herwijnen MH, Staal YC, Kleinjans JC. (2004). Discrimination of genotoxic from nongenotoxic carcinogens by gene expression profiling. Carcinogenesis 25:1265-1276. (Pubitemid 38976470)
127. Vinken M, Doktorova T, Decrock E, Leybaert L, Vanhaecke T, Rogiers V. (2009). Gap junctional intercellular communication as a target for liver toxicity and carcinogenicity. Crit Rev Biochem Mol Biol 44:201-222.
128. Walsh MJ, Bruce SW, Pant K, Carmichael PL, Scott AD, Martin FL. (2009). Discrimination of a transformation phenotype in Syrian golden hamster embryo (SHE) cells using ATR-FTIR spectroscopy. Toxicology 258:33-38.
129. Ward JM. (2010). Evolution of the uses of rats and mice for assessing carcinogenic risk from chemicals in humans. Asian Pac J Cancer Prev 11:18.
130. Waters MD, Jackson M, Lea I. (2010). Characterizing and predicting carcinogenicity and mode of action using conventional and toxicogenomics methods. Mutat Res 705:184-200.
131. Wells MY, Williams ES. (2009). The transgenic mouse assay as an alternative test method for regulatory carcinogenicity studies-implications for REACH. Regul Toxicol Pharmacol 53:150-155.
132. Westerink WM, Stevenson JC, Lauwers A, Griffioen G, Horbach GJ, Schoonen WG. (2009). Evaluation of the Vitotox and RadarScreen assays for the rapid assessment of genotoxicity in the early research phase of drug development. Mutat Res 676:113-130.
133. Westerink WM, Stevenson JC, Horbach GJ, Schoonen WG. (2010). The development of RAD51C, Cystatin A, p53 and Nrf2 luciferasereporter assays in metabolically competent HepG2 cells for the assessment of mechanism-based genotoxicity and of oxidative stress in the early research phase of drug development. Mutat Res 696:21-40.
134. Wilson VS, Keshava N, Hester S, Segal D, Chiu W, Thompson CM, Euling SY. (2011). Utilizing toxicogenomic data to understand chemical mechanism of action in risk assessment. Toxicol Appl Pharmacol [Epub ahead of print].
135. Wolf T, Niehaus-Rolf C, Banduhn N, Eschrich D, Scheel J, Luepke NP. (2008). The hen's egg test for micronucleus induction (HET-MN): novel analyses with a series of well-characterized substances support the further evaluation of the test system. Mutat Res 650:150-164.
136. Yamagiwa K, Ichikawa K. (1915). Experimental study of the pathogenesis of carcinoma. J Cancer Res 3:1.
137. Zeiger E. (2010). Historical perspective on the development of the genetic toxicity test battery in the United States. Environ Mol Mutagen 51:781-791.