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P. Prieto (2002)
Barriers, Nephrotoxicology and Chronic Testing In VitroAlternatives to Laboratory Animals, 30
Ryusuke Nakagiri, H. Oda, T. Kamiya (2003)
Small Scale Rat Hepatocyte Primary Culture with Applications for Screening Hepatoprotective SubstancesBioscience, Biotechnology, and Biochemistry, 67
C. Grindon, R. Combes, M. Cronin, D. Roberts, J. Garrod (2006)
Integrated Testing Strategies for Use in the EU REACH SystemAlternatives to Laboratory Animals, 34
S. Coecke, H. Ahr, B. Blaauboer, S. Bremer, S. Casati, J. Castell, R. Combes, R. Corvi, C. Crespi, M. Cunningham, G. Elaut, B. Eletti, A. Freidig, A. Gennari, J. Ghersi-Egea, A. Guillouzo, T. Hartung, P. Hoet, M. Ingelman-Sundberg, S. Munn, W. Janssens, B. Ladstetter, D. Leahy, A. Long, A. Meneguz, M. Monshouwer, S. Morath, F. Nagelkerke, O. Pelkonen, J. Ponti, P. Prieto, L. Richert, E. Sabbioni, B. Schaack, W. Steiling, E. Testai, J. Vericat, Andrew Worth (2006)
Metabolism: A Bottleneck in In Vitro Toxicological Test DevelopmentAlternatives to Laboratory Animals, 34
R. Combes, L. Schechtman, W. Stokes, D. Blakey (2002)
The International Symposium on Regulatory Testing and Animal Welfare: Recommendations on Best Scientific Practices for Animal Care in Regulatory ToxicologyIlar Journal, 43
Robert Shaw, M. Festing, I. Peers, Larry Furlong (2002)
Use of factorial designs to optimize animal experiments and reduce animal use.ILAR journal, 43 4
W. Pfaller, M. Balls, R. Clothier, S. Coecke, P. Dierickx, B. Ekwall, Bryan Hanley, T. Hartung, P. Prieto, Michael Ryan, G. Schmuck, D. Šladowski, J. Vericat, A. Wendel, A. Wolf, Jens Zimmer (2001)
Novel Advanced In Vitro Methods for Long-term Toxicity TestingAlternatives to Laboratory Animals, 29
W. Minuth, R. Dermietzel, S. Kloth, B. Hennerkes (1992)
A new method culturing renal cells under permanent superfusion and producing a luminal-basal medium gradient.Kidney international, 41 1
I. Ben-Porath, R. Weinberg (2004)
When cells get stressed: an integrative view of cellular senescence.The Journal of clinical investigation, 113 1
K. Isoda, Midori Kojima, M. Takeda, S. Higashiyama, M. Kawase, K. Yagi (2004)
Maintenance of hepatocyte functions by coculture with bone marrow stromal cells.Journal of bioscience and bioengineering, 97 5
J. Julián-Ortiz, R. García-Domènech, J. Gálvez, L. Pogliani (2005)
Predictability and prediction of lowest observed adverse effect levels in a structurally heterogeneous set of chemicalsSAR and QSAR in Environmental Research, 16
P. Pazos, S. Fortaner, P. Prieto (2002)
Long-term In Vitro Toxicity Models: Comparisons Between a Flow-cell Bioreactor, a Static-cell Bioreactor and Static Cell CulturesAlternatives to Laboratory Animals, 30
(2004)
Membrane hepatocyte bioreactor for pharmacotoxicological applications: evidence that inhibition of spontaneously produced nitric oxide improves cell
P. Prieto, A. Baird, B. Blaauboer, Jose Ripoll, R. Corvi, W. Dekant, P. Dietl, A. Gennari, L. Gribaldo, J. Griffin, T. Hartung, J. Heindel, P. Hoet, P. Jennings, L. Marocchio, J. Noraberg, P. Pazos, C. Westmoreland, A. Wolf, Jayne Wright, W. Pfaller (2006)
The Assessment of Repeated Dose Toxicity In Vitro: A Proposed ApproachAlternatives to Laboratory Animals, 34
Chong Shen, Guoliang Zhang, Q. Meng (2007)
An in vitro model for long-term hepatotoxicity testing utilizing rat hepatocytes entrapped in micro-hollow fiber reactorBiochemical Engineering Journal, 34
A. Hanley, J. McBride, S. Oehlschlager, E. Opara (1999)
Use of a flow cell bioreactor as a chronic toxicity model system.Toxicology in vitro : an international journal published in association with BIBRA, 13 4-5
(2006)
Integrated testing strat egies for use in the EU
M. Dent (2007)
Strengths and limitations of using repeat-dose toxicity studies to predict effects on fertility.Regulatory toxicology and pharmacology : RTP, 48 3
J. Davila, G. Cezar, M. Thiede, S. Strom, T. Miki, J. Trosko (2004)
Use and application of stem cells in toxicology.Toxicological sciences : an official journal of the Society of Toxicology, 79 2
M. Vinken, T. Henkens, S. Snykers, G. Elaut, P. Papeleu, V. Rogiers (2006)
Modelling Long-Term Repeat-Dose Toxicity – Challenges Faced
(2002)
Reducing the Use of Animals in Research Through Better Experimental Design, 118pp
Leila Tilaoui, B. Schilter, Liên-Anh Tran, P. Mazzatorta, M. Grigorov (2007)
Integrated Computational Methods for Prediction of the Lowest Observable Adverse Effect Level of Food‐Borne MoleculesQsar & Combinatorial Science, 26
Annette Bitsch, S. Jacobi, C. Melber, U. Wahnschaffe, N. Simetska, Inge Mangelsdorf (2006)
REPDOSE: A database on repeated dose toxicity studies of commercial chemicals--A multifunctional tool.Regulatory toxicology and pharmacology : RTP, 46 3
N. Canová, E. Kmoníčková, D. Lincová, L. Vítek, H. Farghali (2004)
Evaluation of a Flat Membrane Hepatocyte Bioreactor for Pharmacotoxicological Applications: Evidence that Inhibition of Spontaneously Produced Nitric Oxide Improves Cell FunctionalityAlternatives to Laboratory Animals, 32
H. Tähti, H. Nevala, T. Toimela (2003)
Refining In Vitro Neurotoxicity Testing — The Development of Blood–Brain Barrier ModelsAlternatives to Laboratory Animals, 31
(2005)
Differentiation of hepatocytelike cells from human embryonic stem cells and adult liver progenitors
T. Khor, S. Ibrahim, A. Kong (2006)
Toxicogenomics in Drug Discovery and Drug Development: Potential Applications and Future ChallengesPharmaceutical Research, 23
P. Prieto, C. Clemedson, A. Meneguz, W. Pfaller, U. Sauer, C. Westmoreland (2005)
3.6. Subacute and Subchronic ToxicityAlternatives to Laboratory Animals, 33
R. Combes (1999)
Summary of discussion: in vitro models for investigation of chronic toxicity and reversibility.Toxicology in vitro : an international journal published in association with BIBRA, 13 4-5
L. Buzanska, A. Habich, M. Jurga, J. Sypecka, K. Domanska-Janik (2005)
Human cord blood-derived neural stem cell line--possible implementation in studying neurotoxicity.Toxicology in vitro : an international journal published in association with BIBRA, 19 7
M. Mumtaz, L. Knauf, D. Reisman, W. Peirano, C. Derosa, Vijay Gombar, K. Enslein, J. Carter, B. Blake, K. Huque, V.M.S. Ramanujam (1995)
Assessment of effect levels of chemicals from quantitative structure-activity relationship (QSAR) models. I. Chronic lowest-observed-adverse-effect level (LOAEL).Toxicology letters, 79 1-3
R. Combes, C. Grindon, M. Cronin, D. Roberts, J. Garrod (2007)
Proposed Integrated Decision-tree Testing Strategies for Mutagenicity and Carcinogenicity in Relation to the EU REACH LegislationAlternatives to Laboratory Animals, 35
Ye Chen, Xue-jun Dong, Guo-rong Zhang, J. Shao, L. Xiang (2007)
In vitro differentiation of mouse bone marrow stromal stem cells into hepatocytes induced by conditioned culture medium of hepatocytesJournal of Cellular Biochemistry, 102
(2001)
The Way Forward — Action to End Animal Toxicity Testing, 36pp
R. Combes, C. Grindon, M. Cronin, D. Roberts, J. Garrod (2008)
Integrated Decision-tree Testing Strategies for Acute Systemic Toxicity and Toxicokinetics with Respect to the Requirements of the EU REACH LegislationAlternatives to Laboratory Animals, 36
R. Venkatapathy, C. Moudgal, R. Bruce (2004)
Assessment of the Oral Rat Chronic Lowest Observed Adverse Effect Level Model in TOPKAT, a QSAR Software Package for Toxicity PredictionJournal of chemical information and computer sciences, 44 5
N. Bhogal, C. Grindon, R. Combes, M. Balls (2005)
Toxicity testing: creating a revolution based on new technologies.Trends in biotechnology, 23 6
A. Ullrich, Christine Berg, J. Hengstler, D. Runge (2007)
Use of a standardised and validated long-term human hepatocyte culture system for repetitive analyses of drugs: repeated administrations of acetaminophen reduces albumin and urea secretion.ALTEX, 24 1
C. Grindon, R. Combes, M. Cronin, D. Roberts, J. Garrod (2006)
A review of the status of alternative approaches to animal testing and the development of integrated testing strategies for assessing the toxicity of chemicals under REACH--a summary of a DEFRA-funded project conducted by Liverpool John Moores University and FRAME.Alternatives to laboratory animals : ATLA, 34 Suppl 1
R. García-Domènech, J. Julián-Ortiz, E. Besalú (2006)
True prediction of lowest observed adverse effect levelsMolecular Diversity, 10
B. Kristensen, M. Blaabjerg, J. Noraberg, J. Zimmer (2007)
Long-term, Repeated Dose In Vitro Neurotoxicity of the Glutamate Receptor Antagonist L-AP3, Demonstrated in Rat Hippocampal Slice Cultures by Using Continuous Propidium Iodide IncubationAlternatives to Laboratory Animals, 35
V. Gombar, K. Enslein, J. Hart, B. Blake, H. Borgstedt (1991)
Estimation of maximum tolerated dose for long-term bioassays from acute lethal dose and structure by QSAR.Risk analysis : an official publication of the Society for Risk Analysis, 11 3
M. Festing, P. Overend, R. Das, M. Cortina-Borja, M. Berdoy (2002)
The Design of Animal Experiments: Reducing the use of animals in research through better experimental design. (Revised and updated edition)
R. Combes, I. Gaunt, M. Balls (2004)
A Scientific and Animal Welfare Assessment of the OECD Health Effects Test Guidelines for the Safety Testing of Chemicals under the European Union REACH SystemAlternatives to Laboratory Animals, 32
This paper presents some results of a joint research project conducted by FRAME and Liverpool John Moores University, and sponsored by Defra, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity end-points associated with REACH. This paper focuses on the use of alternative (non-animal) methods (both in vitro and in silico) for repeat dose (sub-acute, sub-chronic and chronic) toxicity testing. It reviews the limited number of in silico and in vitro tests available for this endpoint, and outlines new technologies which could be used in the future, e.g. the use of biomarkers and the ‘omics’ technologies. An integrated testing strategy is proposed, which makes use of as much non-animal data as possible, before any essential in vivo studies are performed. Although none of the non-animal tests are currently undergoing validation, their results could help to reduce the number of animals required for testing for repeat dose toxicity.
Alternatives to Laboratory Animals – SAGE
Published: Feb 1, 2008
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