Here - Stiftung Forschung 3R

More documents

Recommendations

Info

Judson RS, Houck KA, Kavlock RJ, et al. Predictive in vitro screening of environmental chemicals: The ToxCast project. Environ Hlth Perspect. 2010; 118, 485-92. Judson R, Kavlock RJ, Setzer W, et al. Estimating toxicity-related biological pathway altering doses for high-throughput chemical risk assessment. Chem Res Toxicol. 2011; 24, 451-62. Kavlock RJ, Austin CP, Tice RR. Toxicity testing in the 21 st century: Implications for human health risk assessment. Risk Anal. 2009; 29, 485-7. Kleinstreuer N, Judson R, Reif D, et al. Environmental impact on vascular development predicted by high throughput screening (HTS). Environ Hlth Perspect. [In press]. Knight AW, Little S, Houck K, et al. Evaluation of high-throughput genotoxicity assays used in profiling the US EPA ToxCast chemicals. Regulat Toxicol Pharmacol. 2009; 55, 188-99. Knudsen TB, Martin MT, Kavlock RJ, et al. Profiling the activity of environmental chemicals in prenatal developmental toxicity studies using the US EPA’s ToxRefDB. Reprod Toxicol. 2009; 28, 209-19. Knudsen TB, Houck KA, Sipes NS, et al. Activity profiles of 309 ToxCast chemicals evaluated across 292 biochemical targets. Toxicol. 2011; 282, 1-15. Martin MT, Mendez E, Corum DG, et al. Profiling the reproductive toxicology of chemicals from multigeneration studies in ToxRefBD. Toxicol Sci. 2009a; 11, 181-90. Martin MT, Judson RS, Reif DM, et al. Profiling chemicals based on chronic toxicity results from the US EPA ToxRef database. Environ. Hlth Perspect. 2009b; 117, 392-9. Martin MT, Dix DJ, Judson RS, et al. Impact of environmental chemicals on key transcription regulators and correlation to toxicity end points within EPA’s ToxCast program. Chem Res Toxicol. 2010; 23, 578-90. Martin MT, Knudsen TB, Reif D, et al. Predictive model of rat reproductive toxicity from ToxCast high throughput screening. Biology Reprod. 2011; 85, 327-39. NRC. Toxicity Testing in the 21st Century: A Vision and a Strategy. Washington, DC: National Academies Press, 2007. NTP. A National Toxicology Program for the 21st Century: A roadmap to achieve the NTP Vision. Research Triangle Park, NC: National Institute of Environmental Health Sciences, 2004, 4 pp. Padilla S, Corum D, Padnos B, et al. Zebrafish developmental screening of the ToxCast Phase I chemical library. [In preparation]. Rief D, Martin M, Tan S, et al. Endocrine profiling and prioritization of environmental chemicals using ToxCast data. Environ Hlt Perspect. 2010; 118, 1714-20 242 AXLR8-2 WORKSHOP REPORT Progress Report 2011 & AXLR8-2 Workshop Report
Rotroff DM, Beam AL, Dix DJ, et al. Xenobiotic-metabolizing enzyme and transporter gene expression in primary cultures of human hepatocytes modulated by ToxCast chemicals. J Toxicol Environ Health B Crit Rev. 2010; 13, 329-46. Rotroff DM, Wetmore BA, Dix DJ, et al. Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening. Toxicol Sci. 2010; 117, 348-58. Sipes NS, Martin MT, Reif DM, et al. Predictive models of prenatal developmental toxicity from ToxCast high-throughput screening data. Toxicol Sci. [Epub ahead of print]. Xia M, Huang R, Witt KL, et al.Compound cytotoxicity profiling using quantitative highthroughput screening. Toxicol Sci. 2009; 112, 153-63. AXLR8-2 WORKSHOP REPORT Progress Report 2011 & AXLR8-2 Workshop Report 243
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 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
Page 106 and 107:
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-
Page 114 and 115:
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
Page 128 and 129:
2011 the automated protocols will b
Page 130 and 131:
OpenTox Promotion, Development, Acc
Page 132 and 133:
Results The OpenTox Framework The O
Page 134 and 135:
Figure 1. ToxPredict: OpenTox Appli
Page 136 and 137:
scientifically sound manner, so as
Page 138 and 139:
Figure 4. Creating a QPRF report wi
Page 140 and 141:
Figure 7. MaxTox model-building app
Page 142 and 143:
Figure 8. Bioclipse interaction wit
Page 144 and 145:
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
Page 150 and 151:
(2C-Glo-CYP2C, 3A-Glo-CYP3A) while
Page 152 and 153:
neuronal models 2D (primary culture
Page 154 and 155:
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
Page 170 and 171:
Figure 7. In vitro T cell priming a
Page 172 and 173:
sessions at congress and meetings (
Page 174 and 175:
7. Gibbs S, van Montfrans C, Kroeze
Page 176 and 177:
vitro assessment of allergens. Eds:
Page 178 and 179:
S.F. Martin Universitätsklinikum F
Page 180 and 181:
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
Page 190 and 191:
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
Page 228 and 229: 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 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
Page 256 and 257: 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,
Page 270 and 271: 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
Page 282 and 283: 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
Page 308 and 309:
elated genes (Hand1, ADAM19, Cmyal,
Page 310 and 311:
Publications Carcinogenicity Tanaka
Page 312 and 313:
Case Study Approaches for Implement
Page 314 and 315:
assay results together with CSBP mo
Page 316 and 317:
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
Page 330 and 331:
‘toolbox’ of non-animal methods
Page 332 and 333:
332 3.4 Breakout Group Reports
Page 334 and 335:
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
Page 340 and 341:
- Deep-sequencing of birth defect p
Page 342 and 343:
Figure 2. Specific stages of the ma
Page 344 and 345:
3.4.4 Break-Out Group 3: Skin Sensi
Page 346 and 347:
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
show all

Here - Stiftung Forschung 3R

Create successful ePaper yourself

Delete template?

Save as template?