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D12.23 3 monthly Project M42 √ Board mtg D11.2.8 Report on the M43 √ newsletter D2.2.10 Carcinogenicity testing M44 √ with compounds from the extended list D3.8 Comparison of dose M44 √ -response relationships to selected carcinogens in cell models with & without introduction of xenobiotic metabolising capability D4.5 A procedure based M44 Still This procedure upon immortalised ongoing seems to be estab- primary human lung lished, but perfor- cells for screening mance of the cell carcinogens line as compared to the primary cell remains to be established D7.1.6 Report on testing and M44 √ training phase & local installation deployed D7.1.7 Report of consortium M44 √ datasets, annotated & loaded in the infrastructure D9.1 A list of promising M44 √ methods to enter pre-validation D9.3 A list of chemicals for M44 √ pre-validation D9.4 Kick-off pre-validation M44 √ meeting with participating labs D11.1.6 Report of the M44 √ invitational conference on risk assessment 52 PROGRESS REPORTS FROM EU-FUNDED PROJECTS Progress Report 2011 & AXLR8-2 Workshop Report
D11.1.8 Production of a final version manuscript for publication out of Workshop M20 D2.3.7 Incubation of ‘risky phenotype’ HepG2 with selected classic bioactivable carcinogens; cytotoxicity assessment D12.24 3 monthly Project Board mtg D7.2.11 Completed 4th analysis of a limited selected transcriptomics & metabolomics dataset within pathway context D2.2.11 A feeder-free protocol to derive hepatocytelike cells from hESC D7.2.10 Report on completed 4th analysis of limited transcriptomics & metabolomics dataset within pathway context, provided sufficient data are generated in the consortium to justify compilation of 2nd analysis (otherwise only Deliverable D7.2.3 will stand) D4.9 Report on the Epithelix tests & decision D6.7 Multivariate statistical models of further sets of metabonomic data D7.3.5D Modelling of carcinogenic effects of compounds - report M44 M45 M45 M46 M47 M47 M48 M48 M48 √ √ √ √ √ √ √ √ √ PROGRESS REPORTS FROM EU-FUNDED PROJECTS Progress Report 2011 & AXLR8-2 Workshop Report 53
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 50 and 51: Table 1. Overview of carcinoGENOMIC
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
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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
Page 120 and 121:
Table 2: Milestones achieved in 201
Page 122 and 123:
detected iron (µg/ml) 80 70 6
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in the following order: uncoated ma
Page 126 and 127:
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
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.
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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
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combinations of transcriptomics, me
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normal animals who usually exhibit
Page 186 and 187:
Workshop proposals Concepts of data
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VITROCELLOMICS Reducing Animal Expe
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esulting of the project was the abi
Page 192 and 193:
Figure 3. Four-compartment artifici
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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
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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
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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
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cost and time, allowing more chemic
Page 252 and 253:
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
Page 262 and 263:
Compound Potency Vehicle Concentrat
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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
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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
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
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Figure 3. Scatter plot of robust li
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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
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Dimitrov, S.D., Low, L.K., Patlewic
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[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
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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
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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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