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Table 1. Overview of carcinoGENOMICS deliverables as achieved during the months M37- 48. Del. No. Deliverable Name Delivery Date Completed D11.2.7 Report on newsletter M37 √ D12.19 Annual report to the M38 √ Commission: updated Description of Work D12.20 Annual report to the M38 √ Commission: Periodic Management Report D12.21 Annual report to the M38 √ Commission: Periodic Activity Report D12.22 3 monthly Project M39 √ Board mtg D3.9 Identity of most suitable cytomic assays of relevance to carcinogenicity that can be adapted to a relatively highthroughput in our cell systems M40 Postponed to M59 D2.1.10 Toxicity assessment of M42 √ the new set of chemicals in selected liver in vitro models D2.3.1 A list of carcinogens M42 √ & MOELs (Minimal Observed Effect Level) for their toxic effects in human liver slices from 5 donors D4.6 Data allowing for the M42 Still identification of novel ongoing early markers for carcinogenesis available for analysis Remark An interim deliverable being submitted & will be fully completed in the final year. Final report postponed to M59 50 PROGRESS REPORTS FROM EU-FUNDED PROJECTS Progress Report 2011 & AXLR8-2 Workshop Report
Analysis was performed for 6 compounds & promising classifiers (assumed to be ‘early’) were identified discriminating genotoxic from nongenotoxic compounds & non-carcinogens; more compounds were tested & the analysis of the data is in process D5.2 Genome wide expression profiles induced by the genotoxic & carcinogenic compounds in the various in vitro models M55 Continuously genomewide expression profiles induced by the genotoxic & carcinogenic compounds in the various in vitro models are measured by DNA microarrays; up to Nov. 2010 this has been done for >2000 RNA samples D6.6 Metabolic profiles for further sets of samples generated by WP2-4 D7.3.6.1 Meta-analysis results on project data - report D7.3.7.1 Classification analysis - report D9.2 Detailed revised SOP for each method D11.1.5 Agenda for capacity building meetings M42 M42 M42 M42 M42 M42 Postponed √ √ √ √ √ PROGRESS REPORTS FROM EU-FUNDED PROJECTS Progress Report 2011 & AXLR8-2 Workshop Report 51
Page 1 and 2: ALTERNATIVE TESTING STRATEGIES PROG
Page 3 and 4: 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 52 and 53: D12.23 3 monthly Project M42 √ Bo
Page 54 and 55: annual carcinoGENOMICS meeting in N
Page 56 and 57: M3.5 Decision of most M40 Postponed
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
Page 108 and 109:
Figure 14. Comparison of Digoxin an
Page 110 and 111:
By using the new technology of HCA
Page 112 and 113:
Figure 17. (Left panel) Phalloidin-
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limited amount of data could be pro
Page 116 and 117:
André Guillouzo Institut National
Page 118 and 119:
Objectives The overall aim of this
Page 120 and 121:
Table 2: Milestones achieved in 201
Page 122 and 123:
detected iron (µg/ml) 80 70 6
Page 124 and 125:
in the following order: uncoated ma
Page 126 and 127:
analysis of leukocytes, expression
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2011 the automated protocols will b
Page 130 and 131:
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
Page 140 and 141:
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
Page 146 and 147:
Publications 2010-11 1. Hardy B, Do
Page 148 and 149:
In vitro toxicology using isolated
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(2C-Glo-CYP2C, 3A-Glo-CYP3A) while
Page 152 and 153:
neuronal models 2D (primary culture
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10 and 14 days. The liver-specific
Page 156 and 157:
Frédéric Bois Institut National d
Page 158 and 159:
Figure 1. The Sens-it-iv sphere. 2.
Page 160 and 161:
Figure 2. The updated modular struc
Page 162 and 163:
Technology Module The aim of techno
Page 164 and 165:
Table 1: The final compound list. R
Page 166 and 167:
Table 2. The Sens-it-iv Toolbox. N
Page 168 and 169:
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:
Page 178 and 179:
S.F. Martin Universitätsklinikum F
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idging the gap to human volunteer s
Page 182 and 183:
combinations of transcriptomics, me
Page 184 and 185:
normal animals who usually exhibit
Page 186 and 187:
Workshop proposals Concepts of data
Page 188 and 189:
VITROCELLOMICS Reducing Animal Expe
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esulting of the project was the abi
Page 192 and 193:
Figure 3. Four-compartment artifici
Page 194 and 195:
embryonic stem cells differentiatin
Page 196 and 197:
196 3AXLR8-2 WORKSHOP REPORT
Page 198 and 199:
Workshop participants were divided
Page 200 and 201:
08.45 - 09.15 ACuteTox Annette Kopp
Page 202 and 203:
3.3 Workshop Presentations 202
Page 204 and 205:
Table 1. A sampling of current toxi
Page 206 and 207:
Table 2. EPA activities: a timeline
Page 208 and 209:
Why is a Consortium Needed While th
Page 210 and 211:
the development of new more relevan
Page 212 and 213:
in particular for fundamental resea
Page 214 and 215:
compared to controls. Most interest
Page 216 and 217:
epidermis to known allergens and UV
Page 218 and 219:
The Virtual Liver Spatial-Temporal
Page 220 and 221:
A B C D E Figure 2. Tissue reconstr
Page 222 and 223:
Figure 4. Mechanisms of how hepatoc
Page 224 and 225:
in rat liver in vivo (Figure 5A). H
Page 226 and 227:
The IMI eTOX Project Efforts to Dev
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deliverables, which can only be ach
Page 230 and 231:
A series of publications related to
Page 232 and 233:
Update on EPA’s ToxCast Programme
Page 234 and 235:
Phase I of ToxCast involved the eva
Page 236 and 237:
Endpoint Brief Description of Bioac
Page 238 and 239:
includes approximately 150 chemical
Page 240 and 241:
information. For each slice, distan
Page 242 and 243:
Judson RS, Houck KA, Kavlock RJ, et
Page 244 and 245:
Embryonic Stem Cell Approaches Towa
Page 246 and 247:
perhaps be tested efficiently in al
Page 248 and 249:
compared gene and protein expressio
Page 250 and 251:
cost and time, allowing more chemic
Page 252 and 253:
Toxicol Appl Pharmacol. 2011; 251,
Page 254 and 255:
functions, establish relationships
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cellular behaviours are captured fr
Page 258 and 259:
assay. PLoS One. 2011; 6, e18540. 7
Page 260 and 261:
learning algorithm called Support V
Page 262 and 263:
Compound Potency Vehicle Concentrat
Page 264 and 265:
mediated inhibition of RXR function
Page 266 and 267:
References Basketter DA, Evans P, F
Page 268 and 269:
When considering consumer exposure,
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in the induction of skin sensitisat
Page 272 and 273:
has reacted, when the peptide deple
Page 274 and 275:
of presentations and discussions, t
Page 276 and 277:
Contact Dermatitis. 2005; 53. 16. S
Page 278 and 279:
the development of in vitro assays.
Page 280 and 281:
Although the mechanisms underlying
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skin sensitisation, it will aid in
Page 284 and 285:
Figure 3. Scatter plot of robust li
Page 286 and 287:
7. De Smedt A, Van Den Heuvel R, Va
Page 288 and 289:
The OECD Adverse Outcome Pathway Ap
Page 290 and 291:
the AOP can be used in qualitative
Page 292 and 293:
Table 1. Summary of the experimenta
Page 294 and 295:
the significance of type 1 versus t
Page 296 and 297:
plus the key events that occur acro
Page 298 and 299:
Dimitrov, S.D., Low, L.K., Patlewic
Page 300 and 301:
[Supporting information and databas
Page 302 and 303:
Figure 1. Strategic R&D of chemical
Page 304 and 305:
The Bhas 42 system can sensitively
Page 306 and 307:
Table 1. Established reporter cell
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elated genes (Hand1, ADAM19, Cmyal,
Page 310 and 311:
Publications Carcinogenicity Tanaka
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Case Study Approaches for Implement
Page 314 and 315:
assay results together with CSBP mo
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them to support multi-day testing i
Page 318 and 319:
CSBP models for both receptor-media
Page 320 and 321:
Hamner Presentations in 2011 • Ch
Page 322 and 323:
human health risk assessment. Risk
Page 324 and 325:
There is a significant scientific c
Page 326 and 327:
phototoxicity and eye irritation, f
Page 328 and 329:
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
Page 336 and 337:
methods, and the generally poor und
Page 338 and 339:
3.4.3. Break-Out Group 2: Reproduct
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- Deep-sequencing of birth defect p
Page 342 and 343:
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
Page 348 and 349:
sure doses is not straightforward.
Page 350 and 351:
3.5 AXLR8 Scientific Panel Recommen
Page 352 and 353:
Workshop participants underlined th
Page 354 and 355:
could be co-ordinated in a focused
Page 356 and 357:
focusing on scientific excellence a
Page 358 and 359:
Directory of Projects & Co-ordinato
Page 360 and 361:
Glossary of Terms 2D/3D 3Rs CARDAM/
Page 362:
362
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