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M3.5 Decision of most M40 Postponed suitable cytomic assays to M59 The results to date indicate that glucose/ lactate; cell cycle analysis & epithelial cell cilia are the most promising; interim report available within the consortium M11.1.9 Organising a workshop M42 Postponed Postponed and rena- depending upon final to Year 5 med into: M11.1.10: input of WG result Organising a work- reports & recommen- shop and setting up dations an agenda depending upon final input of WG result reports and recommendations M2.2.7 Establishment of M42 √ definitive endoderm derived from feeder-free hESC M2.3.5 Omics data combined M42 Postponed with genotypes for the first 5 donors M52 Trancriptomic data are all available & statistical analyses are ongoing. Metabolomic samples sent to Imperial College for analysis; so far no experiments have been undertaken. This Milestone renamed ‘Omics data combined with epigenotypes for the first 5 donors’ & postponed to M52 56 PROGRESS REPORTS FROM EU-FUNDED PROJECTS Progress Report 2011 & AXLR8-2 Workshop Report
M2.3.7 Select classic bioactivable carcinogens for testing in HepG2 with ‘risky’ phenotype. Define time & dose M5.4 Continuation of uploading transcriptome data sets onto the central data warehouse at EMBL-EBI M55 Continuously transcriptome data are uploaded onto the central data warehouse at EMBL- EBI. Up to November 2010 this has been done for >2000 RNA samples. Still in progress & postponed to M55 M6.6 Analytical data generated for further sets of samples from WP2-4 M7.3.7 Detailed characterisation of compounds M9.2 Selection of participating laboratories & validation Management Team M11.2.10 Dissemination of information through the electronic newsletter, based on input of the partners M11.2.7 Updating of the list of relevant publications M2.1.5 Based on the results obtained in phase I study, re-define time & dose of the different compounds in phase II M42 M42 M42 M42 M42 M43 M44 M44 √ Postponed √ √ √ √ √ √ PROGRESS REPORTS FROM EU-FUNDED PROJECTS Progress Report 2011 & AXLR8-2 Workshop Report 57
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ALTERNATIVE TESTING STRATEGIES PROG
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ALTERNATIVE TESTING STRATEGIES PROG
Page 5 and 6: TABLE OF CONTENTS 1. 2. EXECUTIVE S
Page 7: Update on EPA’s ToxCast Programme
Page 10 and 11: challenges, needs, and priorities f
Page 13 and 14: 1INTRODUCTION It is the aim of the
Page 15 and 16: and progress of these multidiscipli
Page 17 and 18: Table 2. Members of the AXLR8 Scien
Page 19: • OECD Joint Meeting Special Sess
Page 22 and 23: ACuteTox Optimisation & Pre-Validat
Page 24 and 25: to robotic screening platforms; and
Page 26 and 27: ased on functional parameters inclu
Page 28 and 29: Table 1. Outliers identified by com
Page 30 and 31: showed that for some compounds the
Page 32 and 33: Computer-based prediction of metabo
Page 34 and 35: three reference compounds revealed
Page 36 and 37: a calibration curve constructed. Th
Page 38 and 39: cell lines) or 48 hours (A704 cells
Page 40 and 41: multivariate CART results did not c
Page 42 and 43: probability) ~50% of the substances
Page 44 and 45: Publications 2010-11 Hoffmann S, Ki
Page 46 and 47: Per Artursson Uppsala University Up
Page 48 and 49: their genotoxic and carcinogenic po
Page 50 and 51: Table 1. Overview of carcinoGENOMIC
Page 52 and 53: D12.23 3 monthly Project M42 √ Bo
Page 54 and 55: annual carcinoGENOMICS meeting in N
Page 58 and 59: M3.4 Identification of most suitabl
Page 60 and 61: WP1 with input from other partners
Page 62 and 63: Partners Project Co-ordinator Jos K
Page 64 and 65: combine knowledge of critical proce
Page 66 and 67: defined and published in the form o
Page 68 and 69: WP6 is devoted to the setup of a so
Page 70 and 71: Partners Co-ordinator Bart van der
Page 72 and 73: obustness, comparing results obtain
Page 74 and 75: 6. Candéias S, Pons B, Viau M, et
Page 76 and 77: ESNATS Embryonic Stem Cell-Based No
Page 78 and 79: Table 1. List of deliverables due i
Page 80 and 81: D3.3.1 Toxicity gene expression sig
Page 82 and 83: Table 2. List of milestones due in
Page 84 and 85: Table 3. Test systems corresponding
Page 86 and 87: Publications 2010-11 1. Peters SJ,
Page 88 and 89: Marcel Leist Universität Konstanz
Page 90 and 91: The most significant achievements o
Page 92 and 93: Figure 3. The Sensor Dish Reader (S
Page 94 and 95: LIINTOP Optimisation of Liver & Int
Page 96 and 97: cells express most of the functions
Page 98 and 99: Figure 3. Scheme of lentivirus gene
Page 100 and 101: Figure 5. Co-culture set-up. Functi
Page 102 and 103: Figure 9. Phalloidin-TRITC staining
Page 104 and 105: Table 1. Values are expressed as pe
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formed with mannitol, atenolol, pro
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Figure 14. Comparison of Digoxin an
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By using the new technology of HCA
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Figure 17. (Left panel) Phalloidin-
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limited amount of data could be pro
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André Guillouzo Institut National
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Objectives The overall aim of this
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Table 2: Milestones achieved in 201
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detected iron (µg/ml) 80 70 6
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in the following order: uncoated ma
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analysis of leukocytes, expression
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2011 the automated protocols will b
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OpenTox Promotion, Development, Acc
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Results The OpenTox Framework The O
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Figure 1. ToxPredict: OpenTox Appli
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scientifically sound manner, so as
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Figure 4. Creating a QPRF report wi
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Figure 7. MaxTox model-building app
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Figure 8. Bioclipse interaction wit
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and model predictions, which they m
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Publications 2010-11 1. Hardy B, Do
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In vitro toxicology using isolated
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(2C-Glo-CYP2C, 3A-Glo-CYP3A) while
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neuronal models 2D (primary culture
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10 and 14 days. The liver-specific
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Frédéric Bois Institut National d
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Figure 1. The Sens-it-iv sphere. 2.
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Figure 2. The updated modular struc
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Technology Module The aim of techno
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Table 1: The final compound list. R
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Table 2. The Sens-it-iv Toolbox. N
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Figure 4. A gene profile for identi
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Figure 7. In vitro T cell priming a
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sessions at congress and meetings (
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7. Gibbs S, van Montfrans C, Kroeze
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vitro assessment of allergens. Eds:
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S.F. Martin Universitätsklinikum F
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idging the gap to human volunteer s
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combinations of transcriptomics, me
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normal animals who usually exhibit
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Workshop proposals Concepts of data
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VITROCELLOMICS Reducing Animal Expe
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esulting of the project was the abi
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Figure 3. Four-compartment artifici
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embryonic stem cells differentiatin
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196 3AXLR8-2 WORKSHOP REPORT
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Workshop participants were divided
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08.45 - 09.15 ACuteTox Annette Kopp
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3.3 Workshop Presentations 202
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Table 1. A sampling of current toxi
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Table 2. EPA activities: a timeline
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Why is a Consortium Needed While th
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the development of new more relevan
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in particular for fundamental resea
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compared to controls. Most interest
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epidermis to known allergens and UV
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The Virtual Liver Spatial-Temporal
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A B C D E Figure 2. Tissue reconstr
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Figure 4. Mechanisms of how hepatoc
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in rat liver in vivo (Figure 5A). H
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The IMI eTOX Project Efforts to Dev
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deliverables, which can only be ach
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A series of publications related to
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Update on EPA’s ToxCast Programme
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Phase I of ToxCast involved the eva
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Endpoint Brief Description of Bioac
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includes approximately 150 chemical
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information. For each slice, distan
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Judson RS, Houck KA, Kavlock RJ, et
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Embryonic Stem Cell Approaches Towa
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perhaps be tested efficiently in al
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compared gene and protein expressio
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cost and time, allowing more chemic
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Toxicol Appl Pharmacol. 2011; 251,
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functions, establish relationships
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cellular behaviours are captured fr
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assay. PLoS One. 2011; 6, e18540. 7
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learning algorithm called Support V
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Compound Potency Vehicle Concentrat
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mediated inhibition of RXR function
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References Basketter DA, Evans P, F
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When considering consumer exposure,
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in the induction of skin sensitisat
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has reacted, when the peptide deple
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of presentations and discussions, t
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Contact Dermatitis. 2005; 53. 16. S
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the development of in vitro assays.
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Although the mechanisms underlying
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skin sensitisation, it will aid in
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Figure 3. Scatter plot of robust li
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7. De Smedt A, Van Den Heuvel R, Va
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The OECD Adverse Outcome Pathway Ap
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the AOP can be used in qualitative
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Table 1. Summary of the experimenta
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the significance of type 1 versus t
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plus the key events that occur acro
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Dimitrov, S.D., Low, L.K., Patlewic
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[Supporting information and databas
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Figure 1. Strategic R&D of chemical
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The Bhas 42 system can sensitively
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Table 1. Established reporter cell
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elated genes (Hand1, ADAM19, Cmyal,
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Publications Carcinogenicity Tanaka
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Case Study Approaches for Implement
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assay results together with CSBP mo
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them to support multi-day testing i
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CSBP models for both receptor-media
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Hamner Presentations in 2011 • Ch
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human health risk assessment. Risk
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There is a significant scientific c
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phototoxicity and eye irritation, f
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allergy risk assessment rather than
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‘toolbox’ of non-animal methods
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332 3.4 Breakout Group Reports
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Figure 1. An illustration of the me
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methods, and the generally poor und
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3.4.3. Break-Out Group 2: Reproduct
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- Deep-sequencing of birth defect p
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Figure 2. Specific stages of the ma
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3.4.4 Break-Out Group 3: Skin Sensi
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for further progress. Better tools
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sure doses is not straightforward.
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3.5 AXLR8 Scientific Panel Recommen
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Workshop participants underlined th
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could be co-ordinated in a focused
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focusing on scientific excellence a
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Directory of Projects & Co-ordinato
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Glossary of Terms 2D/3D 3Rs CARDAM/
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362
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