New Technologies for Toxicity Testing

Current Developments in Cell Culture Technology.- Embryonic Stem Cells in Safety Pharmacology and Toxicology.- Trends in Cell Culture Technology.- Tissue Engineering in the Development of Replacement Technologies.- Toxicity Testing of Nanomaterials.- Physiologically-Based Pharmacokinetic (PBPK) Models in Toxicity Testing and Risk Assessment.- In Silico Methods for Toxicity Prediction.- Luminescent Quantum Dots for Molecular Toxicology.- Engineering Quasi-Vivo(R) In-Vitro Organ Models.- ECVAM and New Technologies for Toxicity Testing.- Medium to High Throughput Screening: Microfabricat ion and Chip-Based Technology.- The Use of Genomics in Model In Vitro Systems.- The Use of Integrated and Intelligent Testing Strategies in the Prediction of Toxic Hazard and in Risk Assessment.

[1]  Thierry Lavé,et al.  Application of full physiological models for pharmaceutical drug candidate selection and extrapolation of pharmacokinetics to man. , 2005, Basic & clinical pharmacology & toxicology.

[2]  Taravat Ghafourian,et al.  Validated models for predicting skin penetration from different vehicles. , 2010, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[3]  Sushil K. Kashaw,et al.  Comparative Molecular Field Analysis (CoMFA) : A Modern Approach Towards Drug Design , 2001 .

[4]  Gerald M. Maggiora,et al.  On Outliers and Activity Cliffs-Why QSAR Often Disappoints , 2006, J. Chem. Inf. Model..

[5]  P. Tofts,et al.  Volunteer Studies Replacing Animal Experiments in Brain Research , 2000, Alternatives to laboratory animals : ATLA.

[6]  Peter Ramm,et al.  Image-based screening: a technology in transition. , 2005, Current opinion in biotechnology.

[7]  Teruo Fujii,et al.  Cell Culture in 3-Dimensional Microfluidic Structure of PDMS (polydimethylsiloxane) , 2003 .

[8]  S. Cory,et al.  The Bcl2 family: regulators of the cellular life-or-death switch , 2002, Nature Reviews Cancer.

[9]  G. Ecker,et al.  A binary QSAR model for classification of hERG potassium channel blockers. , 2008, Bioorganic & medicinal chemistry.

[10]  Tony Yuen,et al.  Method for multiplex cellular detection of mRNAs using quantum dot fluorescent in situ hybridization , 2005, Nucleic acids research.

[11]  Valérie Zuang,et al.  A proposed eye irritation testing strategy to reduce and replace in vivo studies using Bottom-Up and Top-Down approaches. , 2010, Toxicology in vitro : an international journal published in association with BIBRA.

[12]  R. Hertzberg,et al.  High-throughput screening: new technology for the 21st century. , 2000, Current opinion in chemical biology.

[13]  A. Harsch,et al.  Odor, drug and toxin analysis with neuronal networks in vitro: extracellular array recording of network responses. , 1997, Biosensors & bioelectronics.

[14]  Robert D Combes,et al.  Assessing risk to humans from chemical exposure by using non-animal test data. , 2005, Toxicology in vitro : an international journal published in association with BIBRA.

[15]  M. Knowles,et al.  Expression of hTERT immortalises normal human urothelial cells without inactivation of the p16/Rb pathway , 2006, Oncogene.

[16]  Vincent Noireaux,et al.  In Vivo Imaging of Quantum Dots Encapsulated in Phospholipid Micelles , 2002, Science.

[17]  G M Cohen,et al.  Caspases: the executioners of apoptosis. , 1997, The Biochemical journal.

[18]  Raffaella Corvi,et al.  Reduction of use of animals in regulatory genotoxicity testing: Identification and implementation opportunities-Report from an ECVAM workshop. , 2009, Mutation research.

[19]  L. Griffith,et al.  Functional behavior of primary rat liver cells in a three-dimensional perfused microarray bioreactor. , 2002, Tissue engineering.

[20]  M. D. Barratt,et al.  Prediction of toxicity from chemical structure , 2004, Cell Biology and Toxicology.

[21]  Y. Lazebnik,et al.  Caspases: enemies within. , 1998, Science.

[22]  J. Thomson,et al.  Embryonic stem cell lines derived from human blastocysts. , 1998, Science.

[23]  T. Hartung,et al.  A novel in vitro metabolomics approach for neurotoxicity testing, proof of principle for methyl mercury chloride and caffeine. , 2008, Neurotoxicology.

[24]  D. Payan,et al.  Detection of programmed cell death using fluorescence energy transfer. , 1998, Nucleic acids research.

[25]  R D Combes,et al.  Early microdose drug studies in human volunteers can minimise animal testing: Proceedings of a workshop organised by Volunteers in Research and Testing. , 2003, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[26]  V. Meidan,et al.  Validation of a Static Franz Diffusion Cell System for In Vitro Permeation Studies , 2010, AAPS PharmSciTech.

[27]  D J Beebe,et al.  Gelatin based microfluidic devices for cell culture. , 2006, Lab on a chip.

[28]  Xudong Zhang,et al.  Medium to high throughput screening: microfabrication and chip-based technology. , 2012, Advances in experimental medicine and biology.

[29]  Weihong Tan,et al.  Molecular Beacon DNA Probes and Their Bioanalytical Applications , 2004, Applied spectroscopy.

[30]  J. Hermens,et al.  Classifying environmental pollutants: Part 3. External validation of the classification system. , 2000, Chemosphere.

[31]  S. Pathak,et al.  Hydroxylated quantum dots as luminescent probes for in situ hybridization. , 2001, Journal of the American Chemical Society.

[32]  I. Giaever,et al.  Monitoring fibroblast behavior in tissue culture with an applied electric field. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[33]  George M. Whitesides,et al.  Rapid prototyping of complex structures with feature sizes larger than 20 μm , 1996 .

[34]  B Lepioufle,et al.  Study of osteoblastic cells in a microfluidic environment. , 2006, Biomaterials.

[35]  Sameer Sapra,et al.  Evolution of the electronic structure with size in II-VI semiconductor nanocrystals , 2004 .

[36]  Robert Combes,et al.  Preclinical Drug Development Planning , 2010 .

[37]  G. Peters,et al.  Postconfluent multilayered cell line cultures for selective screening of gemcitabine. , 1998, European journal of cancer.

[38]  H Hashimoto,et al.  Molecular cloning and functional expression of a mouse cytochrome P-450 (Cyp3a-13): examination of Cyp3a-13 enzyme to activate aflatoxin B1 (AFB1). , 1994, Biochimica et biophysica acta.

[39]  M. Tichy̌,et al.  Validation of QSAR models for legislative purposes , 2009, Interdisciplinary toxicology.

[40]  Xidong Jin,et al.  Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants. , 2004, Mutation research.

[41]  Ignazio Grattagliano,et al.  Current Concepts of Mechanisms in Drug-Induced Hepatotoxicity , 2009, Current medicinal chemistry.

[42]  Andrew P Worth,et al.  Report of the Workshop on the Validation of QSARs and Other Computational Prediction Models , 2004, Alternatives to laboratory animals : ATLA.

[43]  Mehmet Toner,et al.  A high-throughput microfluidic real-time gene expression living cell array. , 2007, Lab on a chip.

[44]  Michael L Shuler,et al.  Incorporation of 3T3‐L1 Cells To Mimic Bioaccumulation in a Microscale Cell Culture Analog Device for Toxicity Studies , 2008, Biotechnology progress.

[45]  Sang-Hoon Lee,et al.  Gradient generation by an osmotic pump and the behavior of human mesenchymal stem cells under the fetal bovine serum concentration gradient. , 2007, Lab on a chip.

[46]  C. Goessl,et al.  Noninvasive molecular detection of cancer -- the bench and the bedside. , 2003, Current medicinal chemistry.

[47]  Robert Combes,et al.  A Critical Assessment of the European Commission's Proposals for the Risk Assessment and Registration of Chemical Substances in the European Union , 2003, Alternatives to laboratory animals : ATLA.

[48]  B O Palsson,et al.  Effective intercellular communication distances are determined by the relative time constants for cyto/chemokine secretion and diffusion. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[49]  L. Griffith,et al.  Capturing complex 3D tissue physiology in vitro , 2006, Nature Reviews Molecular Cell Biology.

[50]  Shuming Nie,et al.  Bioconjugated quantum dots for multiplexed and quantitative immunohistochemistry , 2007, Nature Protocols.

[51]  Tsun-Po Yang,et al.  Genevar: a database and Java application for the analysis and visualization of SNP-gene associations in eQTL studies , 2010, Bioinform..

[52]  Susanne Bremer,et al.  Embryonic stem cells in safety pharmacology and toxicology. , 2012, Advances in experimental medicine and biology.

[53]  Raffaella Corvi,et al.  Toxicogenomics applied to in vitro carcinogenicity testing with Balb/c 3T3 cells revealed a gene signature predictive of chemical carcinogens. , 2010, Toxicological sciences : an official journal of the Society of Toxicology.

[54]  David Livingstone.  Building QSAR Models: A Practical Guide , 2004 .

[55]  Olaf Ellers,et al.  Scaling in biology , 2001, Complex..

[56]  Christine M. Micheel,et al.  Cell Motility and Metastatic Potential Studies Based on Quantum Dot Imaging of Phagokinetic Tracks , 2002 .

[57]  Uwe Marx,et al.  Trends in cell culture technology. , 2012, Advances in experimental medicine and biology.

[58]  Raffaella Corvi,et al.  ECVAM prevalidation of three cell transformation assays. , 2011, ALTEX.

[59]  Ivonne M C M Rietjens,et al.  Promises and pitfalls of quantitative structure-activity relationship approaches for predicting metabolism and toxicity. , 2008, Chemical research in toxicology.

[60]  George Daston,et al.  The Effects of Chemicals on Mammalian Fertility , 2005, Alternatives to laboratory animals : ATLA.

[61]  G Patlewicz,et al.  Toxmatch–a new software tool to aid in the development and evaluation of chemically similar groups , 2008, SAR and QSAR in environmental research.

[62]  M Zachary,et al.  Comparative PBT screening using (Q)SAR tools within REACH legislation , 2009, SAR and QSAR in environmental research.

[63]  B Testa,et al.  In silico pharmacology for drug discovery: applications to targets and beyond , 2007, British journal of pharmacology.

[64]  E Hulzebos,et al.  An evaluation of selected valid and mechanistically based SARs for skin sensitisation. , 2008, Toxicology in vitro : an international journal published in association with BIBRA.

[65]  Igor Nabiev,et al.  Biocompatible fluorescent nanocrystals for immunolabeling of membrane proteins and cells. , 2004, Analytical biochemistry.

[66]  Andreas Sewing,et al.  Fluorescence readouts in HTS: no gain without pain? , 2003, Drug discovery today.

[67]  Mingming Wu,et al.  A hydrogel-based microfluidic device for the studies of directed cell migration. , 2007, Lab on a chip.

[68]  Michael Balls,et al.  Statement on the application of the CORROSITEX assay for skin corrosivity testing. , 2001, Alternatives to laboratory animals : ATLA.

[69]  Igor Nabiev,et al.  Highly Stable Fluorescent Nanocrystals as a Novel Class of Labels for Immunohistochemical Analysis of Paraffin-Embedded Tissue Sections , 2002, Laboratory Investigation.

[70]  Takashi Aoi,et al.  Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts , 2008, Nature Biotechnology.

[71]  G. Whitesides,et al.  Generation of Solution and Surface Gradients Using Microfluidic Systems , 2000 .

[72]  Ivanka Tsakovska,et al.  A Mini Review of Mammalian Toxicity (Q)SAR Models , 2008 .

[73]  Patrick Poulin,et al.  Utility of physiologically based pharmacokinetic models to drug development and rational drug discovery candidate selection. , 2003, Toxicology letters.

[74]  E L LeCluyse,et al.  Human hepatocyte culture systems for the in vitro evaluation of cytochrome P450 expression and regulation. , 2001, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[75]  Holger Becker,et al.  Hot embossing as a method for the fabrication of polymer high aspect ratio structures , 2000 .

[76]  Carsten Haber,et al.  Microfluidics in commercial applications; an industry perspective. , 2006, Lab on a chip.

[77]  W. Nickel.  The mystery of nonclassical protein secretion. A current view on cargo proteins and potential export routes. , 2003, European journal of biochemistry.

[78]  H. Mattoussi,et al.  Conjugation of luminescent quantum dots with antibodies using an engineered adaptor protein to provide new reagents for fluoroimmunoassays. , 2002, Analytical chemistry.

[79]  M. Dewhirst,et al.  Comparison of tumor and normal tissue oxygen tension measurements using OxyLite or microelectrodes in rodents. , 2001, American journal of physiology. Heart and circulatory physiology.

[80]  Z. Darżynkiewicz,et al.  Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis). , 1997, Cytometry.

[81]  Robert Combes,et al.  The Availability of Human Tissue for Biomedical Research: The Report and Recommendations of the ECVAM Workshop 32. , 1998, Alternatives to laboratory animals : ATLA.

[82]  M Liebsch,et al.  The International EU/COLIPA In Vitro Phototoxicity Validation Study: Results of Phase II (Blind Trial). Part 1: The 3T3 NRU Phototoxicity Test. , 1998, Toxicology in vitro : an international journal published in association with BIBRA.

[83]  Kim H. Esbensen,et al.  Modelling data tables by principal components and PLS: class patterns and quantitative predictive relations , 1984 .

[84]  L. Samson,et al.  A microscale in vitro physiological model of the liver: predictive screens for drug metabolism and enzyme induction. , 2005, Current drug metabolism.

[85]  Gerard I. Evan,et al.  Induction of apoptosis in fibroblasts by c-myc protein , 1992, Cell.

[86]  Helene Andersson,et al.  Microfabrication and microfluidics for tissue engineering: state of the art and future opportunities. , 2004, Lab on a chip.

[87]  S. Quake,et al.  Monolithic microfabricated valves and pumps by multilayer soft lithography. , 2000, Science.

[88]  Juan G. Santiago,et al.  A review of micropumps , 2004 .

[89]  T. Hartung,et al.  Electrophysiological recording of re-aggregating brain cell cultures on multi-electrode arrays to detect acute neurotoxic effects. , 2007, Neurotoxicology.

[90]  Luke P. Lee,et al.  Continuous perfusion microfluidic cell culture array for high-throughput cell-based assays. , 2005, Biotechnology and bioengineering.

[91]  Michael Balls,et al.  A Frame Response to the European Commission Consultation on the Draft Report on Alternative (Non-animal) Methods for Cosmetics Testing: Current Status and Future Prospects — 2010 a , 2010 .

[92]  Takehiko Kitamori,et al.  An actuated pump on-chip powered by cultured cardiomyocytes. , 2006, Lab on a chip.

[93]  David A. Lawrence,et al.  Assessment of Cell Toxicity , 2006 .

[94]  A. Folch,et al.  Biology on a chip: microfabrication for studying the behavior of cultured cells. , 2003, Critical reviews in biomedical engineering.

[95]  R A Ford,et al.  Estimation of toxic hazard--a decision tree approach. , 1978, Food and cosmetics toxicology.

[96]  T Hartung,et al.  Three Rs potential in the development and quality control of pharmaceuticals. , 2001, ALTEX.

[97]  Navid Ghorashian,et al.  Microfluidic Tissue Model for Live Cell Screening , 2007, Biotechnology progress.

[98]  P. Seglen.  Preparation of isolated rat liver cells. , 1976, Methods in cell biology.

[99]  G. Whitesides,et al.  Complex Optical Surfaces Formed by Replica Molding Against Elastomeric Masters , 1996, Science.

[100]  E. Yonish-Rouach,et al.  The p53 tumour suppressor gene: a mediator of a G1 growth arrest and of apoptosis , 1996, Experientia.

[101]  N. Zghoul,et al.  Reconstructed skin equivalents for assessing percutaneous drug absorption from pharmaceutical formulations. , 2001, ALTEX.

[102]  Eric W McFarland,et al.  Microengineering neocartilage scaffolds. , 2002, Biotechnology and bioengineering.

[103]  B Allen,et al.  Design of a prototype miniature bioreactor for high throughput automated bioprocessing , 2003 .

[104]  J. Matthew Mauro,et al.  Self-Assembly of CdSe−ZnS Quantum Dot Bioconjugates Using an Engineered Recombinant Protein , 2000 .

[105]  A. M. Api,et al.  In vitro assessment of phototoxicity , 1997 .

[106]  Robert Combes,et al.  An Overall Strategy for the Testing of Chemicals for Human Hazard and Risk Assessment under the EU REACH System , 2003, Alternatives to laboratory animals : ATLA.

[107]  Alexander Tropsha,et al.  QSAR modeling of human serum protein binding with several modeling techniques utilizing structure-information representation. , 2006, Journal of medicinal chemistry.

[108]  Thomas Knacker,et al.  ECOSAR model performance with a large test set of industrial chemicals. , 2008, Chemosphere.

[109]  Jiri Aubrecht,et al.  Gene expression profile analysis: an emerging approach to investigate mechanisms of genotoxicity. , 2005, Pharmacogenomics.

[110]  George M. Whitesides,et al.  Microfabrication by microcontact printing of self‐assembled monolayers , 1994 .

[111]  W Steiling,et al.  Percutaneous penetration/dermal absorption of hair dyes in vitro. , 2001, Toxicology in vitro : an international journal published in association with BIBRA.

[112]  George M. Whitesides,et al.  Wetting characteristics of liquid drops at heterogeneous surfaces , 1994 .

[113]  Antje J Baeumner,et al.  Recirculating, passive micromixer with a novel sawtooth structure. , 2006, Lab on a chip.

[114]  Krishna Prasad,et al.  Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium , 2010, Nature Biotechnology.

[115]  George Loizou,et al.  Possibilities for a New Approach to Chemicals Risk Assessment — The Report of a FRAME Workshop a , 2006, Alternatives to laboratory animals : ATLA.

[116]  J. Bouwstra,et al.  Focus on skin as a possible port of entry for solid nanoparticles and the toxicological impact. , 2010, Journal of biomedical nanotechnology.

[117]  Uko Maran,et al.  QSAR Modeling of Mutagenicity on Non-Congeneric Sets of Organic Compounds , 2004, Artificial Intelligence Methods And Tools For Systems Biology.

[118]  Valérie Zuang,et al.  ECVAM and new technologies for toxicity testing. , 2012, Advances in experimental medicine and biology.

[119]  Stephen D Dertinger,et al.  In vivo erythrocyte micronucleus assay III. Validation and regulatory acceptance of automated scoring and the use of rat peripheral blood reticulocytes, with discussion of non-hematopoietic target cells and a single dose-level limit test. , 2007, Mutation research.

[120]  Christina Grindon,et al.  Integrated Testing Strategies for Use in the EU REACH System , 2006, Alternatives to laboratory animals : ATLA.

[121]  Shuming Nie,et al.  Quantum dot-encoded mesoporous beads with high brightness and uniformity: rapid readout using flow cytometry. , 2004, Analytical chemistry.

[122]  David Twomey,et al.  Imaging of multiple mRNA targets using quantum dot based in situ hybridization and spectral deconvolution in clinical biopsies. , 2006, Biochemical and biophysical research communications.

[123]  K. Roth,et al.  Combined Tyramide Signal Amplification and Quantum Dots for Sensitive and Photostable Immunofluorescence Detection , 2003, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[124]  T. Slaga,et al.  Improved conditions for murine epidermal cell culture , 1980, In Vitro.

[125]  Wolfgang Muster,et al.  Computational toxicology in drug development. , 2008, Drug discovery today.

[126]  Valérie Zuang,et al.  ECVAM key area topical toxicity : Update on activities , 2006 .

[127]  Paola Gramatica,et al.  In silico screening of estrogen-like chemicals based on different nonlinear classification models. , 2007, Journal of molecular graphics & modelling.

[128]  G. Whitesides,et al.  Soft lithography in biology and biochemistry. , 2001, Annual review of biomedical engineering.

[129]  M. Bawendi,et al.  Type-II quantum dots: CdTe/CdSe(core/shell) and CdSe/ZnTe(core/shell) heterostructures. , 2003, Journal of the American Chemical Society.

[130]  T. Ichisaka,et al.  Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors , 2007, Cell.

[131]  Shang-Tian Yang,et al.  Fabrication of well-defined PLGA scaffolds using novel microembossing and carbon dioxide bonding. , 2005, Biomaterials.

[132]  M. Balls.  Chapter 23:Integrated Testing Strategies and the Prediction of Toxic Hazard , 2010 .

[133]  Joel S Parker,et al.  Hepatic gene expression changes throughout the day in the Fischer rat: implications for toxicogenomic experiments. , 2005, Toxicological sciences : an official journal of the Society of Toxicology.

[134]  S M Morris,et al.  Gene expression profiles and genetic damage in benzo(a)pyrene diol epoxide-exposed TK6 cells. , 2004, Mutation research.

[135]  A. Khademhosseini,et al.  Microscale technologies for tissue engineering and biology. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[136]  A. Alivisatos.  Semiconductor Clusters, Nanocrystals, and Quantum Dots , 1996, Science.

[137]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[138]  Peter Woias,et al.  Micropumps—past, progress and future prospects , 2005 .

[139]  A. Ahluwalia,et al.  A microfluidic gradient maker for toxicity testing of bupivacaine and lidocaine. , 2008, Toxicology in vitro : an international journal published in association with BIBRA.

[140]  Marilyn J Aardema,et al.  Identification of a gene expression profile that discriminates indirect-acting genotoxins from direct-acting genotoxins. , 2004, Mutation research.

[141]  M. Bruchez,et al.  Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots , 2003, Nature Biotechnology.

[142]  D. Basketter,et al.  Skin Irritation and Sensitization: Mechanisms and New Approaches for Risk Assessment , 2008, Skin Pharmacology and Physiology.

[143]  Samir Mitragotri,et al.  Mathematical models of skin permeability: an overview. , 2011, International journal of pharmaceutics.

[144]  Alexandre Jacob,et al.  In silico platform for xenobiotics ADME-T pharmacological properties modeling and prediction. Part II: The body in a Hilbertian space. , 2009, Drug discovery today.

[145]  T Hartung,et al.  Toward an evidence-based toxicology , 2006, Human & experimental toxicology.

[146]  S. Spiekstra,et al.  Induction of cytokine (interleukin‐1α and tumor necrosis factor‐α) and chemokine (CCL20, CCL27, and CXCL8) alarm signals after allergen and irritant exposure , 2005, Experimental dermatology.

[147]  Jin-Woo Choi,et al.  Disposable smart lab on a chip for point-of-care clinical diagnostics , 2004, Proceedings of the IEEE.

[148]  George M. Whitesides,et al.  A Selective Etching Solution for Use with Patterned Self-Assembled Monolayers of Alkanethiolates on Gold , 1995 .

[149]  Wolfgang Knoll,et al.  Alloyed Zn(x)Cd(1-x)S nanocrystals with highly narrow luminescence spectral width. , 2003, Journal of the American Chemical Society.

[150]  M Liebsch,et al.  Phototoxicity of bergamot oil assessed by in vitro techniques in combination with human patch tests. , 2007, Toxicology in vitro : an international journal published in association with BIBRA.

[151]  Maykel Pérez González,et al.  Applications of 2D descriptors in drug design: a DRAGON tale. , 2008, Current topics in medicinal chemistry.

[152]  Robert D. Combes,et al.  The use of artificial intelligence systems for predicting toxicity , 1995 .

[153]  Robert Johann,et al.  Gentle cell trapping and release on a microfluidic chip by in situ alginate hydrogel formation. , 2005, Lab on a chip.

[154]  B. Efron.  Estimating the Error Rate of a Prediction Rule: Improvement on Cross-Validation , 1983 .

[155]  B. Fleischmann,et al.  The use of quantitative image analysis in the assessment of in vitro embryotoxicity endpoints based on a novel embryonic stem cell clone with endoderm-related GFP expression. , 2002, Toxicology in vitro : an international journal published in association with BIBRA.

[156]  Gerberick Frank,et al.  The intra- and inter-laboratory reproducibility and predictivity of the KeratinoSens assay to predict skin sensitizers in vitro: results of a ring-study in five laboratories. , 2011, Toxicology in vitro : an international journal published in association with BIBRA.

[157]  E Sabbioni,et al.  Cell Transformation Assays as Predictors of Human Carcinogenicity , 1999, Alternatives to laboratory animals : ATLA.

[158]  William M. Lee,et al.  Recognizing Drug-Induced Liver Injury: Current Problems, Possible Solutions , 2005, Toxicologic pathology.

[159]  M Liebsch,et al.  Quantitative in vitro assessment of phototoxicity using a human skin model, Skin2. , 1994, Photodermatology, photoimmunology & photomedicine.

[160]  Lutz Müller,et al.  Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens I. Sensitivity, specificity and relative predictivity. , 2005, Mutation research.

[161]  Thomas M Pearce,et al.  Microtechnology: meet neurobiology. , 2007, Lab on a chip.

[162]  Janusch Roi Annett,et al.  ECVAM's Database Service on Alternative Methods (DB-ALM) Online , 2005 .

[163]  M. Tichy̌,et al.  Experimental toxicology in silico. , 2005, Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia.

[164]  M Moctar,et al.  Effects of abomasal infusions of casein on N excretion and urea turnover in sheep. , 1981, Zeitschrift fur Tierphysiologie, Tierernahrung und Futtermittelkunde.

[165]  René Thierbach,et al.  Automated soft agar assay for the high-throughput screening of anticancer compounds. , 2009, Analytical biochemistry.

[166]  Igor Prudovsky,et al.  The non-classical export routes: FGF1 and IL-1alpha point the way. , 2003, Journal of cell science.

[167]  D. Morris,et al.  Analysis of cytochrome P450 and phase II conjugating enzyme expression in adult male rat hepatocytes , 1999, In Vitro Cellular & Developmental Biology - Animal.

[168]  M. Toner,et al.  Effects of oxygenation and flow on the viability and function of rat hepatocytes cocultured in a microchannel flat-plate bioreactor. , 2001, Biotechnology and bioengineering.

[169]  B. Keskinler,et al.  Bioprocess intensification in flow-through monolithic microbioreactors with immobilized bacteria. , 2005, Biotechnology and bioengineering.

[170]  Arthur M. Doweyko,et al.  QSAR: dead or alive? , 2008, J. Comput. Aided Mol. Des..

[171]  Tim Liedl,et al.  Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. , 2005, Nano letters.

[172]  P Del Castillo,et al.  Influence of fixation, exciting light and section thickness on the primary fluorescence of samples for microfluorometric analysis. , 1989, Basic and applied histochemistry.

[173]  A. Rubinstein,et al.  Zebrafish assays for drug toxicity screening , 2006, Expert opinion on drug metabolism & toxicology.

[174]  Shane Weaver,et al.  The importance of the domain of applicability in QSAR modeling. , 2008, Journal of molecular graphics & modelling.

[175]  Emilio Benfenati,et al.  A comparison of DEMETRA individual QSARs with an index for evaluation of uncertainty. , 2008, Chemosphere.

[176]  D. Acosta,et al.  Predictive value of in vitro model systems in toxicology. , 1998, Annual review of pharmacology and toxicology.

[177]  Gwo-Bin Lee,et al.  A high throughput perfusion-based microbioreactor platform integrated with pneumatic micropumps for three-dimensional cell culture , 2008, Biomedical microdevices.

[178]  Michael Balls,et al.  Translation of new technologies: from basic research to drug discovery and development. , 2008, Current drug discovery technologies.

[179]  Judith C. Madden,et al.  Formation of Structural Categories to Allow for Read‐Across for Teratogenicity , 2009 .

[180]  A A van Zeeland,et al.  Use of low temperature for growth arrest and synchronization of human diploid fibroblasts. , 1984, Mutation research.

[181]  G. Rao,et al.  Low-cost microbioreactor for high-throughput bioprocessing. , 2001, Biotechnology and bioengineering.

[182]  William H. Grover,et al.  Monolithic membrane valves and diaphragm pumps for practical large-scale integration into glass microfluidic devices , 2003 .

[183]  J. J. van de Sandt,et al.  Comparative in vitro-in vivo percutaneous absorption of the pesticide propoxur. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[184]  B. Finlayson,et al.  Combinatorial mixing of microfluidic streams. , 2004, Lab on a chip.

[185]  Robert Combes,et al.  Intelligent Testing Strategies for Chemicals Testing — A Case of More Haste, Less Speed? , 2005, Alternatives to laboratory animals : ATLA.

[186]  K. Ryan,et al.  Myc oncogenes: the enigmatic family. , 1996, The Biochemical journal.

[187]  H. Mcconnell,et al.  Screening for novel drug effects with a microphysiometer: a potent effect of clofilium unrelated to potassium channel blockade. , 1997, Life sciences.

[188]  Göran Stemme,et al.  A microfluidic device for parallel 3‐D cell cultures in asymmetric environments , 2007, Electrophoresis.

[189]  H. Ellinger-Ziegelbauer,et al.  Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver. , 2005, Mutation research.

[190]  Nam-Trung Nguyen,et al.  MEMS-Micropumps: A Review , 2002 .

[191]  A. Ahluwalia,et al.  A low shear stress modular bioreactor for connected cell culture under high flow rates , 2010, Biotechnology and bioengineering.

[192]  Takehiko Kitamori,et al.  Demonstration of a PDMS-based bio-microactuator using cultured cardiomyocytes to drive polymer micropillars. , 2006, Lab on a chip.

[193]  F. Lombardo,et al.  Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. , 2001, Advanced drug delivery reviews.

[194]  B. Lin,et al.  Parallel microfluidic networks for studying cellular response to chemical modulation. , 2007, Journal of biotechnology.

[195]  Robin H. Liu,et al.  Microfluidic tectonics: a comprehensive construction platform for microfluidic systems. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[196]  Jo Lambert,et al.  Three-dimensional skin models as tools for transdermal drug delivery: challenges and limitations , 2011, Expert opinion on drug delivery.

[197]  J. Wichard,et al.  PREDICTING AQUEOUS SOLUBILITY FROM STRUCTURE , 2009 .

[198]  Glenn E Croston,et al.  Functional cell-based uHTS in chemical genomic drug discovery. , 2002, Trends in biotechnology.

[199]  Igor V. Tetko,et al.  Combinatorial QSAR Modeling of Chemical Toxicants Tested against Tetrahymena pyriformis , 2008, J. Chem. Inf. Model..

[200]  C. Hansch.  Quantitative structure-activity relationships and the unnamed science , 1993 .

[201]  Albert van den Berg,et al.  Quantum dots based probes conjugated to annexin V for photostable apoptosis detection and imaging. , 2006, Nano letters.

[202]  G M Whitesides,et al.  Fabrication of submicrometer features on curved substrates by microcontact printing. , 1995, Science.

[203]  R. Schreiber,et al.  Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death , 1990, Nature.

[204]  Martin P. Payne,et al.  Computer-Based Methods for the Prediction of Chemical Metabolism and Biotransformation within Biological Organisms , 2004 .

[205]  Ming Lei,et al.  Hard and soft micromachining for BioMEMS: review of techniques and examples of applications in microfluidics and drug delivery. , 2004, Advanced drug delivery reviews.

[206]  Francis L Martin,et al.  Discrimination of a transformation phenotype in Syrian golden hamster embryo (SHE) cells using ATR-FTIR spectroscopy. , 2009, Toxicology.

[207]  Nicola Elvassore,et al.  Micro-bioreactor array for controlling cellular microenvironments. , 2007, Lab on a chip.

[208]  Horst Spielmann.  Ethical Environment and Scientific Rationale Towards In‐Vitro Alternatives to Animal Testing: Where Are We Going? , 2006 .

[209]  Stephen Deutsch,et al.  Physician Practice Patterns in the Treatment of Isolated Systolic Hypertension in a Primary Care Setting , 2002, Journal of clinical hypertension.

[210]  L. Griffith,et al.  A microfabricated array bioreactor for perfused 3D liver culture. , 2002, Biotechnology and bioengineering.

[211]  Bruno Michel,et al.  Lithography beyond light: Microcontact printing with monolayer resists , 1997, IBM J. Res. Dev..

[212]  Glyn Stacey,et al.  Current developments in cell culture technology. , 2012, Advances in experimental medicine and biology.

[213]  Li Xie,et al.  Microelectronic cell sensor assay for detection of cytotoxicity and prediction of acute toxicity. , 2006, Toxicology in vitro : an international journal published in association with BIBRA.

[214]  G. Neal,et al.  A comparison of the effects of pretreatment with phenobarbitone and 3-methylcholanthrene on the metabolism of aflatoxin B1 by rat liver microsomes and isolated hepatocytes in vitro. , 1981, Chemico-biological interactions.

[215]  S. McClean,et al.  An overview of membrane, cytosolic and nuclear proteins associated with the expression of resistance to multiple drugs in vitro. , 1992, Biochimica et biophysica acta.

[216]  Robert Combes,et al.  An Integrated Decision-tree Testing Strategy for Repeat Dose Toxicity with Respect to the Requirements of the EU REACH Legislation , 2008, Alternatives to laboratory animals : ATLA.

[217]  James C. Fuscoe,et al.  Preface to mutation research special issue on toxicogenomics , 2004 .

[218]  D. Balding,et al.  HLA Sequence Polymorphism and the Origin of Humans , 2006 .

[219]  Peter E Barker,et al.  Semiconductor nanocrystal probes for human metaphase chromosomes. , 2004, Nucleic acids research.

[220]  C. Hansch.  Quantitative approach to biochemical structure-activity relationships , 1969 .

[221]  Daniel A. Casciano,et al.  Use of DNA Arrays in Understanding Hepatic Test Systems , 2008 .

[222]  C C Howe,et al.  Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. , 1980, Science.

[223]  Dan V. Nicolau,et al.  Microarray technology and its applications , 2005 .

[224]  M. Toner,et al.  Microengineering of cellular interactions. , 2000, Annual review of biomedical engineering.

[225]  Igor L. Medintz,et al.  Proteolytic activity monitored by fluorescence resonance energy transfer through quantum-dot–peptide conjugates , 2006, Nature materials.

[226]  S. Ostrovidov,et al.  Membrane-Based PDMS Microbioreactor for Perfused 3D Primary Rat Hepatocyte Cultures , 2004, Biomedical microdevices.

[227]  Gordana Vunjak-Novakovic,et al.  Bioreactors mediate the effectiveness of tissue engineering scaffolds , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[228]  Carol A Marchant,et al.  An Expert System Approach to the Assessment of Hepatotoxic Potential , 2009, Chemistry & biodiversity.

[229]  Mark H Kleinman,et al.  An evaluation of chemical photoreactivity and the relationship to photogenotoxicity. , 2010, Regulatory toxicology and pharmacology : RTP.

[230]  Toshio Fujita,et al.  A Method for the Correlation of Biological Activity and Chemical Structure , 2001 .

[231]  Robert Combes,et al.  Integrated Decision-tree Testing Strategies for Acute Systemic Toxicity and Toxicokinetics with Respect to the Requirements of the EU REACH Legislation , 2008, Alternatives to laboratory animals : ATLA.

[232]  Edwin J Matthews,et al.  In silico approaches to explore toxicity end points: issues and concerns for estimating human health effects , 2007, Expert opinion on drug metabolism & toxicology.

[233]  T. Aoyama,et al.  Five of 12 forms of vaccinia virus-expressed human hepatic cytochrome P450 metabolically activate aflatoxin B1. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[234]  Z. Xue,et al.  Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes , 2003, Cell Research.

[235]  P. Watkins,et al.  The Application of Metabonomics to Predict Drug‐Induced Liver Injury , 2010, Clinical pharmacology and therapeutics.

[236]  Shuguang Zhang,et al.  Beyond the Petri dish , 2004, Nature Biotechnology.

[237]  Tadashi Nagashima,et al.  Three-dimensional Imaging of the Intracellular Localization of Growth Hormone and Prolactin and Their mRNA Using Nanocrystal (Quantum Dot) and Confocal Laser Scanning Microscopy Techniques , 2005, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[238]  Daniel A Casciano,et al.  The use of genomics in model in vitro systems. , 2012, Advances in experimental medicine and biology.

[239]  A. Tropsha,et al.  Beware of q2! , 2002, Journal of molecular graphics & modelling.

[240]  Clemens A van Blitterswijk,et al.  Cartilage Tissue Engineering: Controversy in the Effect of Oxygen , 2003, Critical reviews in biotechnology.

[241]  D Parent-Massin,et al.  Application of the CFU-GM assay to predict acute drug-induced neutropenia: an international blind trial to validate a prediction model for the maximum tolerated dose (MTD) of myelosuppressive xenobiotics. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[242]  Hedi Mattoussi,et al.  Avidin: a natural bridge for quantum dot-antibody conjugates. , 2002, Journal of the American Chemical Society.

[243]  M Liebsch,et al.  EEC/COLIPA project on in vitro phototoxicity testing: First results obtained with a Balb/c 3T3 cell phototoxicity assay. , 1994, Toxicology in vitro : an international journal published in association with BIBRA.

[244]  Terrance J Kavanagh,et al.  Luminescent quantum dots for molecular toxicology. , 2012, Advances in experimental medicine and biology.

[245]  Tejal A Desai,et al.  Layer-by-layer microfluidics for biomimetic three-dimensional structures. , 2004, Biomaterials.

[246]  J. Shay,et al.  Characterisation of telomerase immortalised normal human oesophageal squamous cells , 2003, Gut.

[247]  J Milstien,et al.  WHO activities towards the three Rs in the development and control of biological products. , 1996, Developments in biological standardization.

[248]  G. Barrett,et al.  Genetically engineered whole-cell sensing systems: coupling biological recognition with reporter genes. , 2000, Chemical reviews.

[249]  Xiaogang Peng,et al.  Control of photoluminescence properties of CdSe nanocrystals in growth. , 2002, Journal of the American Chemical Society.

[250]  Shulan Tian,et al.  Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells , 2007, Science.

[251]  Christina M Gasbarro,et al.  Bioconjugation of quantum dot luminescent probes for Western blot analysis. , 2005, BioTechniques.

[252]  Kun Wang,et al.  Advantages of in vitro cytotoxicity testing by using primary rat hepatocytes in comparison with established cell lines. , 2002, Journal of Toxicological Sciences.

[253]  D. L. Taylor,et al.  A Personal Perspective on High-Content Screening (HCS) , 2010, Journal of biomolecular screening.

[254]  Minseok S. Kim,et al.  A microfluidic platform for 3-dimensional cell culture and cell-based assays , 2007, Biomedical microdevices.

[255]  Thierry Lavé,et al.  An evaluation of the utility of physiologically based models of pharmacokinetics in early drug discovery. , 2005, Journal of pharmaceutical sciences.

[256]  C. Willis,et al.  Selective expression of immune-associated surface antigens by keratinocytes in irritant contact dermatitis. , 1991, The Journal of investigative dermatology.

[257]  A. Corrias,et al.  Arrhythmic risk biomarkers for the assessment of drug cardiotoxicity: from experiments to computer simulations , 2010, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[258]  Robert Combes,et al.  A Scientific and Animal Welfare Assessment of the OECD Health Effects Test Guidelines for the Safety Testing of Chemicals under the European Union REACH System , 2004, Alternatives to laboratory animals : ATLA.

[259]  Romualdo Benigni,et al.  The Development and Validation of Expert Systems for Predicting Toxicity The Report and Recommendations of an ECVAM / ECB Workshop ( ECVAM Workshop 24 ) , 2002 .

[260]  Thomas Scheper,et al.  Flow cytometry in biotechnology , 2001, Applied Microbiology and Biotechnology.

[261]  H C Hemker,et al.  Binding of vascular anticoagulant alpha (VAC alpha) to planar phospholipid bilayers. , 1990, The Journal of biological chemistry.

[262]  B. Teicher,et al.  Acquired multicellular-mediated resistance to alkylating agents in cancer. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[263]  Valérie Zuang,et al.  Alternative (non-animal) methods for cosmetics testing: current status and future prospects—2010 , 2011, Archives of Toxicology.

[264]  J. Eijkel,et al.  Osmosis and pervaporation in polyimide submicron microfluidic channel structures , 2005 .

[265]  Aldert Piersma,et al.  A Review of the Implementation of the Embryonic Stem Cell Test (EST) , 2009, Alternatives to laboratory animals : ATLA.

[266]  T. Lavé,et al.  A Novel Strategy for Physiologically Based Predictions of Human Pharmacokinetics , 2006, Clinical pharmacokinetics.

[267]  Jong Hwan Sung,et al.  Integration of in silico and in vitro platforms for pharmacokinetic–pharmacodynamic modeling , 2010, Expert opinion on drug metabolism & toxicology.

[268]  E. Kunkel.  Systems biology in drug discovery , 2004, Nature Biotechnology.

[269]  Naomi L. Kruhlak,et al.  In Silico Screening of Chemicals for Genetic Toxicity Using MDL-QSAR, Nonparametric Discriminant Analysis, E-State, Connectivity, and Molecular Property Descriptors , 2008, Toxicology mechanisms and methods.

[270]  Shang-Tian Yang,et al.  Microbioreactors for high-throughput cytotoxicity assays. , 2008, Current opinion in drug discovery & development.

[271]  U. Boelsterli,et al.  Diclofenac-induced liver injury: a paradigm of idiosyncratic drug toxicity. , 2003, Toxicology and applied pharmacology.

[272]  M. Gómez-Lechón,et al.  Diclofenac toxicity to hepatocytes: a role for drug metabolism in cell toxicity. , 1999, The Journal of pharmacology and experimental therapeutics.

[273]  David J Beebe,et al.  Characterization of a membrane-based gradient generator for use in cell-signaling studies. , 2006, Lab on a chip.

[274]  Francis Lin,et al.  Generation of dynamic temporal and spatial concentration gradients using microfluidic devices. , 2004, Lab on a chip.

[275]  G. Churchill,et al.  Characterization of human embryonic stem cell lines by the International Stem Cell Initiative , 2007, Nature Biotechnology.

[276]  J. Tarbell,et al.  Modeling interstitial flow in an artery wall allows estimation of wall shear stress on smooth muscle cells. , 1995, Journal of biomechanical engineering.

[277]  Stephen R. Johnson,et al.  The Trouble with QSAR (or How I Learned To Stop Worrying and Embrace Fallacy) , 2008, J. Chem. Inf. Model..

[278]  J. Parry,et al.  Detecting and predicting the activity of rodent carcinogens. , 1994, Mutagenesis.

[279]  M. Schäfer-Korting,et al.  The Phenion® Full-Thickness Skin Model for Percutaneous Absorption Testing , 2009, Skin Pharmacology and Physiology.

[280]  Noo Li Jeon,et al.  Microfluidic Multicompartment Device for Neuroscience Research. , 2003, Langmuir : the ACS journal of surfaces and colloids.

[281]  M. Eileen Dolan,et al.  Chemotherapeutic drug susceptibility associated SNPs are enriched in expression quantitative trait loci , 2010, Proceedings of the National Academy of Sciences.

[282]  M. Yarmush,et al.  Integration of technologies for hepatic tissue engineering. , 2006, Advances in biochemical engineering/biotechnology.

[283]  Naomi L Kruhlak,et al.  Combined Use of MC4PC, MDL-QSAR, BioEpisteme, Leadscope PDM, and Derek for Windows Software to Achieve High-Performance, High-Confidence, Mode of Action–Based Predictions of Chemical Carcinogenesis in Rodents , 2008, Toxicology mechanisms and methods.

[284]  Robert Combes,et al.  An Integrated Decision-tree Testing Strategy for Eye Irritation with Respect to the Requirements of the EU REACH Legislation , 2008, Alternatives to laboratory animals : ATLA.

[285]  Samuel Weiss,et al.  Production of neurons, astrocytes and oligodendrocytes from mammalian CNS stem cells , 2008, Nature Protocols.

[286]  Albrecht Poth,et al.  Bhas42 cell transformation assay as a predictor of carcinogenicity , 2008 .

[287]  A. Engler,et al.  Photopolymerization in Microfluidic Gradient Generators: Microscale Control of Substrate Compliance to Manipulate Cell Response , 2004 .

[288]  Daniel S. Miller,et al.  The annual report to the nation on the status of cancer, 1973–1997, with a special section on colorectal cancer , 2000, Cancer.

[289]  Elke Genschow,et al.  Embryotoxicity Screening Using Embryonic Stem Cells in vitro: Correlation to in vivo Teratogenicity , 1999, Cells Tissues Organs.

[290]  Jerzy Leszczynski,et al.  QSAR modeling of acute toxicity by balance of correlations. , 2008, Bioorganic & medicinal chemistry.

[291]  Moungi G. Bawendi,et al.  On the Absorption Cross Section of CdSe Nanocrystal Quantum Dots , 2002 .

[292]  A. Dorner,et al.  Transcriptional profiling of peripheral blood cells in clinical pharmacogenomic studies. , 2006, Pharmacogenomics.

[293]  C Haanen,et al.  Apoptosis and programmed cell death in health and disease. , 1994, Advances in clinical chemistry.

[294]  J. Post,et al.  Quantum dot ligands provide new insights into erbB/HER receptor–mediated signal transduction , 2004, Nature Biotechnology.

[295]  Louis Scampavia,et al.  Real-time monitoring of lactate extrusion and glucose consumption of cultured cells using a lab-on-valve system. , 2002, The Analyst.

[296]  F. Marshall,et al.  In vivo molecular and cellular imaging with quantum dots. , 2005, Current opinion in biotechnology.

[297]  Robert Combes,et al.  Integrated Decision-tree Testing Strategies for Mutagenicity and Carcinogenicity with Respect to the Requirements of the EU REACH Legislation , 2008, Alternatives to laboratory animals : ATLA.

[298]  Kathryn A Phillips,et al.  Drug withdrawals in the United States: a systematic review of the evidence and analysis of trends. , 2007, Current drug safety.

[299]  Saber M Hussain,et al.  Toxicity testing of nanomaterials. , 2012, Advances in experimental medicine and biology.

[300]  Shuming Nie,et al.  Multicolor quantum dots for molecular diagnostics of cancer , 2006, Expert review of molecular diagnostics.

[301]  David J Beebe,et al.  A plate reader-compatible microchannel array for cell biology assays. , 2007, Lab on a chip.

[302]  H Okamura,et al.  Establishment of an immortalised human ovarian surface epithelial cell line without chromosomal instability , 2005, British Journal of Cancer.

[303]  Milan Mrksich,et al.  Geometric cues for directing the differentiation of mesenchymal stem cells , 2010, Proceedings of the National Academy of Sciences.

[304]  Janet Woodcock,et al.  Empowering microarrays in the regulatory setting , 2006, Nature Biotechnology.

[305]  Maykel Pérez González,et al.  The Prediction of Carcinogenicity from Molecular Structure , 2005 .

[306]  G. Whitesides,et al.  Soft Lithography. , 1998, Angewandte Chemie.

[307]  Robert Combes,et al.  Proposed Integrated Decision-tree Testing Strategies for Mutagenicity and Carcinogenicity in Relation to the EU REACH Legislation , 2007, Alternatives to laboratory animals : ATLA.

[308]  Ivonne M C M Rietjens,et al.  On the number of EINECS compounds that can be covered by (Q)SAR models for acute toxicity. , 2009, Toxicology letters.

[309]  R. McKay,et al.  Consensus Guidance for Banking and Supply of Human Embryonic Stem Cell Lines for Research Purposes , 2009, Stem Cell Reviews and Reports.

[310]  K Enslein,et al.  Estimation of maximum tolerated dose for long-term bioassays from acute lethal dose and structure by QSAR. , 1991, Risk analysis : an official publication of the Society for Risk Analysis.

[311]  André Guillouzo,et al.  Evolving Concepts in Liver Tissue Modeling and Implications for in Vitro Toxicology 1. Introduction , 2022 .

[312]  M. Daly,et al.  HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin , 2009, Nature Genetics.

[313]  J. Fuscoe,et al.  Transcriptional profiling for understanding the basis of mitochondrial involvement in disease and toxicity using the mitochondria-specific MitoChip. , 2007, Mutation research.

[314]  Shur-Jen Wang,et al.  A parallel-gradient microfluidic chamber for quantitative analysis of breast cancer cell chemotaxis , 2006, Biomedical microdevices.

[315]  Hanry Yu,et al.  A novel 3D mammalian cell perfusion-culture system in microfluidic channels. , 2007, Lab on a chip.

[316]  Todd Thorsen,et al.  High-density microfluidic arrays for cell cytotoxicity analysis. , 2007, Lab on a chip.

[317]  Isao Yoshimura,et al.  An Inter-laboratory Collaborative Study by the Non-Genotoxic Carcinogen Study Group in Japan, on a Cell Transformation Assay for Tumour Promoters Using Bhas 42 cells , 2005, Alternatives to laboratory animals : ATLA.

[318]  A. Giuliani,et al.  Multivariate Analyses in Genetic Toxicology , 1991 .

[319]  A Paul Alivisatos,et al.  Quantum-dot-based cell motility assay. , 2003, Science's STKE : signal transduction knowledge environment.

[320]  Robert Combes,et al.  The Use of Expert Systems for Toxicity Prediction: Illustrated with Reference to the DEREK Program , 2004 .

[321]  Simon Goldbard,et al.  High-throughput cell analysis using multiplexed array technologies. , 2002, Drug discovery today.

[322]  Christopher S. Chen,et al.  Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. , 2004, Developmental cell.

[323]  Simon Thomas,et al.  Physiologically-based Simulation Modelling for the Reduction of Animal Use in the Discovery of Novel Pharmaceuticals , 2009, Alternatives to laboratory animals : ATLA.

[324]  Hengzi Wang,et al.  Optimizing layout of obstacles for enhanced mixing in microchannels , 2002 .

[325]  S. Nie,et al.  Quantum dot bioconjugates for ultrasensitive nonisotopic detection. , 1998, Science.

[326]  Xudong Zhang,et al.  3-D cell-based high-throughput screening for drug discovery and cell culture process development. , 2008 .

[327]  C. Reutelingsperger,et al.  Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. , 1998, Cytometry.

[328]  Robert Combes,et al.  Introduction to the EU REACH legislation. , 2008, Alternatives to laboratory animals : ATLA.

[329]  Ming-Hui Huang,et al.  Comparison of gene expression profiles in BALB/c 3T3 transformed foci exposed to tumor promoting agents. , 2010, Toxicology in vitro : an international journal published in association with BIBRA.

[330]  Albert Li.  Higher-Throughput Screening Assays With Human Hepatocytes for Hepatotoxicity, Metabolic Stability, and Drug–Drug Interaction Potential , 2001 .

[331]  P Sartorelli,et al.  In vitro predictions of skin absorption of caffeine, testosterone, and benzoic acid: a multi-centre comparison study. , 2004, Regulatory toxicology and pharmacology : RTP.

[332]  J. Treadway,et al.  Multiplexed SNP genotyping using the Qbead system: a quantum dot-encoded microsphere-based assay. , 2003, Nucleic acids research.

[333]  Robert Combes,et al.  Integrated Decision-tree Testing Strategies for Environmental Toxicity with Respect to the Requirements of the EU REACH Legislation , 2006, Alternatives to laboratory animals : ATLA.

[334]  C Urani,et al.  Image analysis and automatic classification of transformed foci , 2009, Journal of microscopy.

[335]  S. Jacobson,et al.  Microchip device for performing enzyme assays. , 1997, Analytical chemistry.

[336]  A. Guillouzo,et al.  Liver cell models in in vitro toxicology. , 1998, Environmental health perspectives.

[337]  B. Baroli,et al.  Penetration of nanoparticles and nanomaterials in the skin: fiction or reality? , 2010, Journal of pharmaceutical sciences.

[338]  P. Roy,et al.  Exploring the impact of size of training sets for the development of predictive QSAR models , 2008 .

[339]  Andrew Worth,et al.  Overcoming Barriers to Validation of Non-animal Partial Replacement Methods/Integrated Testing Strategies: The Report of an EPAA–ECVAM Workshop , 2009, Alternatives to laboratory animals : ATLA.

[340]  J. Niu,et al.  A QSAR Model for Predicting Mutagenicity of Nitronaphthalenes and Methylnitronaphthalenes , 2008, Bulletin of environmental contamination and toxicology.

[341]  Gerardo Perozziello,et al.  Microchemostat-microbial continuous culture in a polymer-based, instrumented microbioreactor. , 2006, Lab on a chip.

[342]  J. Urban,et al.  Development of PDMS microbioreactor with well-defined and homogenous culture environment for chondrocyte 3-D culture , 2006, Biomedical microdevices.

[343]  S A Sundberg,et al.  High-throughput and ultra-high-throughput screening: solution- and cell-based approaches. , 2000, Current opinion in biotechnology.

[344]  R. Ulrich,et al.  Profiling of hepatic gene expression in rats treated with fibric acid analogs. , 2004, Mutation research.

[345]  V. Fadok,et al.  Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. , 1992, Journal of immunology.

[346]  P. Wertz,et al.  The human epidermis models EpiSkin, SkinEthic and EpiDerm: an evaluation of morphology and their suitability for testing phototoxicity, irritancy, corrosivity, and substance transport. , 2005, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[347]  Robert Combes,et al.  Integrated Decision-tree Testing Strategies for Developmental and Reproductive Toxicity with Respect to the Requirements of the EU REACH Legislation , 2008, Alternatives to laboratory animals : ATLA.

[348]  Shuming Nie,et al.  Doping Mesoporous Materials with Multicolor Quantum Dots , 2003 .

[349]  Robert Combes,et al.  An Integrated Decision-tree Testing Strategy for Skin Sensitisation with Respect to the Requirements of the EU REACH Legislation , 2008, Alternatives to laboratory animals : ATLA.

[350]  D. Kauzlarick,et al.  Fundamentals of microfabrication, the science of miniaturization, 2nd edition [Book Review] , 2003, IEEE Engineering in Medicine and Biology Magazine.

[351]  Jos P. M. Lommerse,et al.  Some molecular descriptors for non-specific chromosomal genotoxicity based on hydrophobic interactions , 2008, Archives of Toxicology.

[352]  Marcello Imbriani,et al.  Development of QSAR models for predicting hepatocarcinogenic toxicity of chemicals. , 2009, European journal of medicinal chemistry.

[353]  R. Neubert,et al.  New nanosized technologies for dermal and transdermal drug delivery. A review. , 2010, Journal of biomedical nanotechnology.

[354]  A. M. B. DOUGLAS,et al.  X-Ray Crystallography , 1947, Nature.

[355]  Yigong Shi,et al.  Mechanisms of caspase activation and inhibition during apoptosis. , 2002, Molecular cell.

[356]  J Hadgraft,et al.  Inter- and intralaboratory variation of in vitro diffusion cell measurements: an international multicenter study using quasi-standardized methods and materials. , 2005, Journal of pharmaceutical sciences.

[357]  M. Swartz,et al.  Interstitial flow and its effects in soft tissues. , 2007, Annual review of biomedical engineering.

[358]  R. Jaeger.  Introduction to microelectronic fabrication , 1987 .

[359]  James V Jester,et al.  Extent of initial corneal injury as the mechanistic basis for ocular irritation: key findings and recommendations for the development of alternative assays. , 2002, Regulatory toxicology and pharmacology : RTP.

[360]  S. Cole,et al.  Sequences Human Induced Pluripotent Stem Cells Free of Vector and Transgene , 2012 .

[361]  Won-Gun Koh,et al.  Fabrication of cell-containing hydrogel microstructures inside microfluidic devices that can be used as cell-based biosensors , 2006, Analytical and bioanalytical chemistry.

[362]  Aniruddh Solanki,et al.  A Step Closer to Complete Chemical Reprogramming for Generating iPS Cells , 2010, Chembiochem : a European journal of chemical biology.

[363]  D. Evans,et al.  Flow cytometry in toxicity analysis , 1990, Nature.

[364]  W. Mueller‐Klieser.  Three-dimensional cell cultures: from molecular mechanisms to clinical applications. , 1997, American journal of physiology. Cell physiology.

[365]  N. Monteiro-Riviere,et al.  A linear dilution microfluidic device for cytotoxicity assays. , 2007, Lab on a chip.

[366]  Romualdo Benigni,et al.  Structure alerts for carcinogenicity, and the Salmonella assay system: a novel insight through the chemical relational databases technology. , 2008, Mutation research.

[367]  D. Chao,et al.  BCL-2 family: regulators of cell death. , 1998, Annual review of immunology.

[368]  Carl-Fredrik Mandenius,et al.  Toward Preclinical Predictive Drug Testing for Metabolism and Hepatotoxicity by Using In Vitro Models Derived from Human Embryonic Stem Cells and Human Cell Lines — A Report on the Vitrocellomics EU-project , 2011, Alternatives to laboratory animals : ATLA.

[369]  R. Vasan,et al.  Biomarkers of Cardiovascular Disease: Molecular Basis and Practical Considerations , 2006, Circulation.

[370]  Luke P. Lee,et al.  A novel high aspect ratio microfluidic design to provide a stable and uniform microenvironment for cell growth in a high throughput mammalian cell culture array. , 2005, Lab on a chip.

[371]  D. Green,et al.  Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl , 1995, The Journal of experimental medicine.

[372]  Michael Balls,et al.  Integrated Testing Strategies for Toxicity Employing New and Existing Technologies , 2011, Alternatives to laboratory animals : ATLA.

[373]  Jennifer A Hollingsworth,et al.  Pushing the band gap envelope: mid-infrared emitting colloidal PbSe quantum dots. , 2004, Journal of the American Chemical Society.

[374]  Catherine J. Murphy,et al.  Quantum Dots: A Primer , 2002 .

[375]  L. Jin,et al.  In situ hybridization: Methods and applications , 1997, Journal of clinical laboratory analysis.

[376]  Michael Balls,et al.  The Use of Integrated and Intelligent Testing Strategies in the Prediction of Toxic Hazard and in Risk Assessment , 2012, Advances in experimental medicine and biology.

[377]  W. Calder,et al.  Body Size, Physiological Time, and Longevity of Homeothermic Animals , 1981, The Quarterly Review of Biology.

[378]  George M. Whitesides,et al.  Patterned self-assembled monolayers formed by microcontact printing direct selective metalization by chemical vapor deposition on planar and nonplanar substrates , 1995 .

[379]  Milon Tichy,et al.  QSAR IN TOXICOLOGY , 1980 .

[380]  Federico Vozzi,et al.  Connected culture of murine hepatocytes and HUVEC in a multicompartmental bioreactor. , 2009, Tissue engineering. Part A.

[381]  Thomas Hartung,et al.  The value of alternative testing for neurotoxicity in the context of regulatory needs. , 2006, Environmental toxicology and pharmacology.

[382]  Aaron Sin,et al.  Development of a Microscale Cell Culture Analog To Probe Naphthalene Toxicity , 2008, Biotechnology progress.

[383]  J. Y. Kim,et al.  A cell culturing system that integrates the cell loading function on a single platform and evaluation of the pulsatile pumping effect on cells , 2008, Biomedical microdevices.

[384]  Amaya Azqueta,et al.  The influence of scoring method on variability in results obtained with the comet assay. , 2011, Mutagenesis.

[385]  P Hinsmann,et al.  Design, simulation and application of a new micromixing device for time resolved infrared spectroscopy of chemical reactions in solution. , 2001, Lab on a chip.

[386]  Robert Combes,et al.  Toxicity testing: creating a revolution based on new technologies. , 2005, Trends in biotechnology.

[387]  P. Fromherz,et al.  A neuron-silicon junction: a Retzius cell of the leech on an insulated-gate field-effect transistor. , 1991, Science.

[388]  Bas J Blaauboer,et al.  The Necessity of Biokinetic Information in the Interpretation of In Vitro Toxicity Data , 2002, Alternatives to laboratory animals : ATLA.

[389]  Christina Grindon,et al.  Integrated Decision-tree Testing Strategies for Skin Corrosion and Irritation with Respect to the Requirements of the EU REACH Legislation , 2007, Alternatives to laboratory animals : ATLA.

[390]  A. Rennie,et al.  Pumping of water with ac electric fields applied to asymmetric pairs of microelectrodes. , 2000, Physical review. E, Statistical, nonlinear, and soft matter physics.

[391]  K. Turksen,et al.  Human Embryonic Stem Cell Protocols , 2010, Methods in Molecular Biology.

[392]  J. Bruce Pitner,et al.  Novel Fluorescent Technology Platform for High Throughput Cytotoxicity and Proliferation Assays , 2000, Journal of biomolecular screening.

[393]  D. Sanderson,et al.  Computer Prediction of Possible Toxic Action from Chemical Structure; The DEREK System , 1991, Human & experimental toxicology.

[394]  Weida Tong,et al.  FDA-approved drug labeling for the study of drug-induced liver injury. , 2011, Drug discovery today.

[395]  Channing J Der,et al.  Increasing complexity of Ras signaling , 1998, Oncogene.

[396]  Christina Grindon.  The New EU REACH Regulation Has Finally Been Adopted: Is this the End of the Campaign Trail… or Just the Beginning? , 2007, Alternatives to laboratory animals : ATLA.

[397]  H. Yamasaki,et al.  Interaction and distinction of genotoxic and non-genotoxic events in carcinogenesis. , 1992, Toxicology letters.

[398]  Q. R. Yang,et al.  Effect of temperature on in vitro proliferative activity of human umbilical vein endothelial cells , 1995, Experientia.

[399]  Peter Vaupel,et al.  The role of hypoxia-induced factors in tumor progression. , 2004, The oncologist.

[400]  Jean-Claude Ourlin,et al.  Human hepatocyte culture. , 2006, Methods in molecular biology.

[401]  Martin Zenke,et al.  Insulin-producing cells from embryonic stem cells experimental considerations. , 2007, Methods in molecular biology.

[402]  William H. Grover,et al.  Development and multiplexed control of latching pneumatic valves using microfluidic logical structures. , 2006, Lab on a chip.

[403]  N. Mahajan,et al.  Novel mutant green fluorescent protein protease substrates reveal the activation of specific caspases during apoptosis. , 1999, Chemistry & biology.

[404]  M Liebsch,et al.  application of the human dermal model skin(2) ZK 1350 to phototoxicity and skin corrosivity testing. , 1995, Toxicology in vitro : an international journal published in association with BIBRA.

[405]  Willie J.G.M. Peijnenburg,et al.  Prediction of biodegradability from chemical structure: Modeling of ready biodegradation test data , 1999 .

[406]  Angela J Harris,et al.  Comparison of basal gene expression profiles and effects of hepatocarcinogens on gene expression in cultured primary human hepatocytes and HepG2 cells. , 2004, Mutation research.

[407]  M C Willingham,et al.  Advances in Cytochemical Methods for Detection of Apoptosis , 2001, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[408]  A Paul Alivisatos,et al.  Room-temperature single-nucleotide polymorphism and multiallele DNA detection using fluorescent nanocrystals and microarrays. , 2003, Analytical chemistry.

[409]  A. Wobus,et al.  Embryonic stem cell-derived cardiac, neuronal and pancreatic cells as model systems to study toxicological effects. , 2004, Toxicology letters.

[410]  J. Shaddock,et al.  Identification of differentially expressed genes in aflatoxin B1-treated cultured primary rat hepatocytes and Fischer 344 rats. , 1998, Carcinogenesis.

[411]  Thomas J Deerinck,et al.  Correlated light and electron microscopic imaging of multiple endogenous proteins using Quantum dots , 2005, Nature Methods.

[412]  J. Valentin,et al.  An introduction to QT interval prolongation and non‐clinical approaches to assessing and reducing risk , 2010, British journal of pharmacology.

[413]  Xiaogang Peng,et al.  High Quality ZnSe and ZnS Nanocrystals Formed by Activating Zinc Carboxylate Precursors , 2004 .

[414]  Shuming Nie,et al.  Peptide-linked molecular beacons for efficient delivery and rapid mRNA detection in living cells. , 2004, Nucleic acids research.

[415]  D. L. Taylor,et al.  High content screening applied to large-scale cell biology. , 2004, Trends in biotechnology.

[416]  Kannan Krishnan,et al.  Physiologically-based pharmacokinetic (PBPK) models in toxicity testing and risk assessment. , 2012, Advances in experimental medicine and biology.

[417]  Rebekah Drezek,et al.  Protease-activated quantum dot probes. , 2005, Biochemical and biophysical research communications.

[418]  Michael J. O'Brien,et al.  Rapid prototyping of active microfluidic components based on magnetically modified elastomeric materials , 2001 .

[419]  J. L. Bos,et al.  ras oncogenes in human cancer: a review. , 1989, Cancer research.

[420]  Johannes Doehmer.  The Use and Value of In Vitro Technologies in Metabolism Studies , 2009, Alternatives to laboratory animals : ATLA.

[421]  David J Beebe,et al.  Magnetically-driven biomimetic micro pumping using vortices. , 2004, Lab on a chip.

[422]  Sanjay Tyagi,et al.  Molecular Beacons: Probes that Fluoresce upon Hybridization , 1996, Nature Biotechnology.

[423]  M. Schmidt,et al.  Microfabrication in biology and medicine. , 1999, Annual review of biomedical engineering.

[424]  Andrew P. Worth,et al.  Intelligent Testing Strategies , 2007 .

[425]  H. Hogberg,et al.  Relevance of in vitro neurotoxicity testing for regulatory requirements: challenges to be considered. , 2010, Neurotoxicology and teratology.

[426]  Panos Macheras,et al.  In silico prediction of ADME and pharmacokinetics. Report of an expert meeting organised by COST B15. , 2002, European Journal of Pharmaceutical Sciences.

[427]  T. Shimada,et al.  Evidence for cytochrome P-450NF, the nifedipine oxidase, being the principal enzyme involved in the bioactivation of aflatoxins in human liver. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[428]  Graham Dellaire,et al.  Application of Quantum Dots as Probes for Correlative Fluorescence, Conventional, and Energy-filtered Transmission Electron Microscopy , 2004, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[429]  Zhiyu Zhang,et al.  Microbioreactors for Bioprocess Development , 2007 .

[430]  David A. Williams,et al.  Diffusion Dynamics of Glycine Receptors Revealed by Single – Quantum Dot Tracking , 2012 .

[431]  Paola Gramatica,et al.  Methods for reliability and uncertainty assessment and for applicability evaluations of classification- and regression-based QSARs. , 2003, Environmental health perspectives.

[432]  J. Dearden.  In silico prediction of aqueous solubility , 2006, Expert opinion on drug discovery.

[433]  D. Noble.  Modeling the Heart--from Genes to Cells to the Whole Organ , 2002, Science.

[434]  Nicola J Hewitt,et al.  International prevalidation studies of the EpiDerm 3D human reconstructed skin micronucleus (RSMN) assay: transferability and reproducibility. , 2010, Mutation research.

[435]  Aldert Piersma,et al.  The ECVAM International Validation Study on In Vitro Embryotoxicity Tests: Results of the Definitive Phase and Evaluation of Prediction Models , 2002, Alternatives to laboratory animals : ATLA.

[436]  K. BéruBé,et al.  Alternatives for Lung Research: Stuck between a Rat and a Hard Place , 2011, Alternatives to laboratory animals : ATLA.

[437]  M Bove,et al.  Coupling of organotypic brain slice cultures to silicon-based arrays of electrodes. , 1999, Methods.

[438]  A J Ryan,et al.  Development of a 3D human in vitro skin co‐culture model for detecting irritants in real‐time , 2010, Biotechnology and bioengineering.

[439]  Zvia Agur,et al.  Use of Virtual Patient Populations for Rescuing Discontinued Drug Candidates and for Reducing the Number of Patients in Clinical Trials , 2009, Alternatives to laboratory animals : ATLA.

[440]  Emilio Benfenati,et al.  SMILES in QSPR/QSAR Modeling: results and perspectives. , 2007, Current drug discovery technologies.

[441]  B Wolf,et al.  Monitoring of cellular behaviour by impedance measurements on interdigitated electrode structures. , 1997, Biosensors & bioelectronics.

[442]  Ronald E. Majors.  New developments in microplates for biological assays and automated sample preparation , 2004 .

[443]  Nicolas Szita,et al.  Membrane‐aerated microbioreactor for high‐throughput bioprocessing , 2004, Biotechnology and bioengineering.

[444]  F Lacombe,et al.  Flow cytometry: its applications in hematology. , 1995, Haematologica.

[445]  T Seidle,et al.  The development of new concepts for assessing reproductive toxicity applicable to large scale toxicological programmes. , 2007, Current pharmaceutical design.

[446]  B. Lin,et al.  Characterizing doxorubicin‐induced apoptosis in HepG2 cells using an integrated microfluidic device , 2007, Electrophoresis.

[447]  Vernon E Walker,et al.  Long-term mitochondrial toxicity in HIV-uninfected infants born to HIV-infected mothers. , 2003, Journal of acquired immune deficiency syndromes.

[448]  Thomas Hartung,et al.  Meeting Report: Validation of Toxicogenomics-Based Test Systems: ECVAM–ICCVAM/NICEATM Considerations for Regulatory Use , 2005, Environmental health perspectives.

[449]  B. J. Kane,et al.  Liver-specific functional studies in a microfluidic array of primary mammalian hepatocytes. , 2006, Analytical chemistry.

[450]  Cheng-Wey Wei,et al.  Elucidating in vitro cell-cell interaction using a microfluidic coculture system , 2006, Biomedical microdevices.

[451]  Laura Fumarola,et al.  Scoring CFU-GM colonies in vitro by data fusion: a first account. , 2007, Experimental hematology.

[452]  Pablo R. Duchowicz,et al.  Quantitative Structure‐Toxicity Models for Heterogeneous Aliphatic Compounds , 2009 .

[453]  Philip N. McFadden,et al.  Biosensors based on the chromatic activities of living, naturally pigmented cells : digital image processing of the dynamics of fish melanophores , 1997 .

[454]  Patricia McGrath,et al.  Zebrafish: a preclinical model for drug screening. , 2002, Assay and drug development technologies.

[455]  J. Hardwick,et al.  Identification of a new P450 subfamily, CYP4F1, expressed in rat hepatic tumors. , 1993, Archives of biochemistry and biophysics.

[456]  Jürgen Beuthan,et al.  Microscopical heat stress investigations under application of quantum dots. , 2005, Journal of biomedical optics.

[457]  J Jaworska,et al.  How can structural similarity analysis help in category formation? , 2007, SAR and QSAR in environmental research.

[458]  Nam-Trung Nguyen,et al.  Micromixers?a review , 2005 .

[459]  Gunnar Johanson,et al.  The Use of Biokinetics and in Vitro Methods in Toxicological Risk Evaluation , 1996 .

[460]  Peter R Braude,et al.  Generation of a human embryonic stem cell line encoding the cystic fibrosis mutation deltaF508, using preimplantation genetic diagnosis. , 2005, Reproductive biomedicine online.

[461]  Jing Zhang,et al.  High-content screening moves to the front of the line. , 2006, Drug discovery today.

[462]  C. Willis,et al.  Epidermal damage induced by irritants in man: a light and electron microscopic study. , 1989, The Journal of investigative dermatology.

[463]  Karl-Heinz Boven,et al.  Micro-Electrode Arrays in Cardiac Safety Pharmacology , 2004, Drug safety.

[464]  M. Garle,et al.  Sensory Nerves, Neurogenic Inflammation and Pain: Missing Components of Alternative Irritation Strategies? A Review and a Potential Strategy , 2003, Alternatives to laboratory animals : ATLA.

[465]  M. Maharbiz,et al.  A microsystem for sensing and patterning oxidative microgradients during cell culture. , 2006, Lab on a chip.

[466]  C Ziegler,et al.  Cell-based biosensors , 2000, Fresenius' journal of analytical chemistry.

[467]  A. Abate,et al.  Ultrahigh-throughput screening in drop-based microfluidics for directed evolution , 2010, Proceedings of the National Academy of Sciences.

[468]  Harry L. T. Lee,et al.  Microbioreactor arrays with integrated mixers and fluid injectors for high-throughput experimentation with pH and dissolved oxygen control. , 2006, Lab on a chip.

[469]  Sangeeta N. Bhatia,et al.  Intracellular Delivery of Quantum Dots for Live Cell Labeling and Organelle Tracking , 2004 .

[470]  Giovanni Vozzi,et al.  In vitro liver model using microfabricated scaffolds in a modular bioreactor , 2010, Biotechnology journal.

[471]  Tomoyuki Yasukawa,et al.  Microfluidic chip integrated with amperometric detector array for in situ estimating oxygen consumption characteristics of single bovine embryos , 2007 .

[472]  P. Olinga,et al.  Liver fibrosis in vitro: cell culture models and precision-cut liver slices. , 2007, Toxicology in vitro : an international journal published in association with BIBRA.

[473]  H. Yeh,et al.  Single-quantum-dot-based DNA nanosensor , 2005, Nature materials.

[474]  John A. Pedersen,et al.  Effects of extracellular fiber architecture on cell membrane shear stress in a 3D fibrous matrix. , 2007, Journal of biomechanics.

[475]  D. Beebe,et al.  Flow control with hydrogels. , 2004, Advanced drug delivery reviews.

[476]  M. Cestari,et al.  Genotoxicity and Mutagenicity , 2016 .

[477]  T. Hartung.  Toxicology for the twenty-first century , 2009, Nature.

[478]  Nina Jeliazkova,et al.  Toxmatch--a chemical classification and activity prediction tool based on similarity measures. , 2008, Regulatory toxicology and pharmacology : RTP.

[479]  G. Whitesides,et al.  Poly(dimethylsiloxane) as a material for fabricating microfluidic devices. , 2002, Accounts of chemical research.

[480]  Kazunari Takahashi,et al.  Growth rate suppression of cultured mammalian cells enhances protein productivity , 2004, Cytotechnology.

[481]  Gwo-Bin Lee,et al.  Development of perfusion-based micro 3-D cell culture platform and its application for high throughput drug testing , 2008 .

[482]  Ji-Yen Cheng,et al.  Performing microchannel temperature cycling reactions using reciprocating reagent shuttling along a radial temperature gradient. , 2005, The Analyst.

[483]  Laurent Griscom,et al.  Trends in the development of microfluidic cell biochips for in vitro hepatotoxicity. , 2007, Toxicology in vitro : an international journal published in association with BIBRA.

[484]  S. Cory,et al.  The Bcl-2 protein family: arbiters of cell survival. , 1998, Science.

[485]  Andrew Worth,et al.  Structural motifs modulating the carcinogenic risk of aromatic amines , 2009, Environmental and molecular mutagenesis.

[486]  Mark E. Cooper.  Current biosensor technologies in drug discovery , 2006 .

[487]  M. Toner,et al.  Microfabricated grooved substrates as platforms for bioartificial liver reactors. , 2005, Biotechnology and bioengineering.

[488]  Arun V Holden.  Development and Application of Human Virtual Excitable Tissues and Organs: From Premature Birth to Sudden Cardiac Death , 2010, Alternatives to laboratory animals : ATLA.

[489]  D. Price,et al.  Quantum dot semiconductor nanocrystals for immunophenotyping by polychromatic flow cytometry , 2006, Nature Medicine.

[490]  Petra S Kern,et al.  TIMES-SS--a promising tool for the assessment of skin sensitization hazard. A characterization with respect to the OECD validation principles for (Q)SARs and an external evaluation for predictivity. , 2007, Regulatory toxicology and pharmacology : RTP.

[491]  Toshio Miki,et al.  Use and application of stem cells in toxicology. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[492]  F. Williams,et al.  EDETOX. Evaluations and predictions of dermal absorption of toxic chemicals , 2004, International archives of occupational and environmental health.

[493]  Jehyuk Lee,et al.  Generation of functional human hepatic endoderm from human induced pluripotent stem cells , 2009, Hepatology.

[494]  Andrew Worth,et al.  Metabolism: A Bottleneck in In Vitro Toxicological Test Development , 2006, Alternatives to laboratory animals : ATLA.

[495]  Arti Ahluwalia,et al.  Engineering Quasi-Vivo in vitro organ models. , 2012, Advances in experimental medicine and biology.

[496]  G Ulrich Nienhaus,et al.  Novel fluorescent proteins for high-content screening. , 2006, Drug discovery today.

[497]  Michael L Shuler,et al.  A self-priming microfluidic diaphragm pump capable of recirculation fabricated by combining soft lithography and traditional machining. , 2004, Biotechnology and bioengineering.

[498]  Wolfgang Knoll,et al.  Composition-tunable Zn(x)Cd(1-x)Se nanocrystals with high luminescence and stability. , 2003, Journal of the American Chemical Society.

[499]  S. Nie,et al.  Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules , 2001, Nature Biotechnology.

[500]  Jonathan Balcombe,et al.  Animal Carcinogenicity Studies: 2. Obstacles to Extrapolation of Data to Humans , 2006, Alternatives to laboratory animals : ATLA.

[501]  I Gerner,et al.  Development of a Decision Support System for the Introduction of Alternative Methods into Local Irritancy/Corrosivity Testing Strategies. Development of a Relational Database , 2000, Alternatives to laboratory animals : ATLA.

[502]  Igor L. Medintz,et al.  Multiplexed toxin analysis using four colors of quantum dot fluororeagents. , 2004, Analytical chemistry.

[503]  Seth Pettie,et al.  Mind the gap , 2006, Nature Reviews Drug Discovery.

[504]  M. Dahan,et al.  Time-gated biological imaging by use of colloidal quantum dots. , 2001, Optics letters.

[505]  William Thies,et al.  Digital microfluidics using soft lithography. , 2006, Lab on a chip.

[506]  Robert Combes,et al.  In vitro models of inhalation toxicity and disease. The report of a FRAME workshop. , 2009, Alternatives to laboratory animals : ATLA.

[507]  N. Thomas.  Review Article: High-Content Screening: A Decade of Evolution , 2010, Journal of biomolecular screening.

[508]  David J Mooney,et al.  Hypoxia leads to necrotic hepatocyte death. , 2007, Journal of biomedical materials research. Part A.

[509]  S. Wold.  Validation of QSAR's , 1991 .

[510]  Arti Ahluwalia,et al.  Engineering the Stem Cell Niche and the Differentiative Micro- and Macroenvironment: Technologies and Tools for Applying Biochemical, Physical and Structural Stimuli and Their Effects on Stem Cells , 2011 .

[511]  D. Lowy,et al.  Function and regulation of ras. , 1993, Annual review of biochemistry.

[512]  D. Lewis.  Computer‐Assisted methods in the evaluation of chemical toxicity , 2007 .

[513]  Gilles Klopman,et al.  MultiCASE Expert Systems and the REACH Initiative , 2008, Toxicology mechanisms and methods.

[514]  Robert D Combes,et al.  In silico methods for toxicity prediction. , 2012, Advances in experimental medicine and biology.

[515]  E. Testai,et al.  Toxicology investigations with cell culture systems: 20 years after. , 2004, Toxicology in vitro : an international journal published in association with BIBRA.

[516]  Enrico Mombelli,et al.  An Evaluation of the Predictive Ability of the QSAR Software Packages, DEREK, HAZARDEXPERT and TOPKAT, to Describe Chemically-induced Skin Irritation , 2008, Alternatives to laboratory animals : ATLA.

[517]  Ekaterina A. Bykova,et al.  GFP-based FRET analysis in live cells , 2006, Brain Research.

[518]  Ute Drechsler,et al.  Autonomous microfluidic capillary system. , 2002, Analytical chemistry.

[519]  Valérie Zuang,et al.  The usefulness of toxicogenomics for predicting acute skin irritation on in vitro reconstructed human epidermis. , 2007, Toxicology.

[520]  S. Campbell.  The Science and Engineering of Microelectronic Fabrication , 2001 .

[521]  Lin He,et al.  Nanoparticles for bioanalysis. , 2003, Current opinion in chemical biology.

[522]  S. Free,et al.  A MATHEMATICAL CONTRIBUTION TO STRUCTURE-ACTIVITY STUDIES. , 1964, Journal of medicinal chemistry.

[523]  Yordan Kostov,et al.  Design and performance of a 24‐station high throughput microbioreactor , 2006, Biotechnology and bioengineering.

[524]  K. Shakesheff,et al.  Tissue engineering in the development of replacement technologies. , 2012, Advances in experimental medicine and biology.

[525]  S. Ekins,et al.  In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling , 2007, British journal of pharmacology.

[526]  A. Evans,et al.  Improved characterization technique for micromixers , 1999 .

[527]  Nadine Aubry,et al.  Enhancement of microfluidic mixing using time pulsing. , 2003, Lab on a chip.

[528]  Richard M Walmsley,et al.  High-specificity and high-sensitivity genotoxicity assessment in a human cell line: validation of the GreenScreen HC GADD45a-GFP genotoxicity assay. , 2006, Mutation research.

[529]  Michael Balls.  Modern Alternative Approaches to the Problem of Drug-induced Liver Injury , 2011, Alternatives to laboratory animals : ATLA.

[530]  Kirsten Peters,et al.  Cell culture models of higher complexity in tissue engineering and regenerative medicine. , 2007, Biomaterials.

[531]  M. Toner,et al.  Universal microfluidic gradient generator. , 2006, Analytical chemistry.

[532]  H Frederick Frasch,et al.  Pig and guinea pig skin as surrogates for human in vitro penetration studies: a quantitative review. , 2009, Toxicology in vitro : an international journal published in association with BIBRA.

[533]  J. Santiago,et al.  Electrokinetic instability micromixing. , 2001, Analytical chemistry.

[534]  M. Marshall,et al.  Ras target proteins in eukaryotic cells , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[535]  David J Beebe,et al.  A passive pumping method for microfluidic devices. , 2002, Lab on a chip.

[536]  Conrad D. James,et al.  Patterning Axonal Guidance Molecules Using a Novel Strategy for Microcontact Printing , 2003, Neurochemical Research.

[537]  Robert Combes,et al.  An Assessment of Progress in the Use of Alternatives in Toxicity Testing since the Publication of the Report of the Second FRAME Toxicity Committee (1991) , 2002, Alternatives to laboratory animals : ATLA.

[538]  Paola Gramatica,et al.  The Importance of Being Earnest: Validation is the Absolute Essential for Successful Application and Interpretation of QSPR Models , 2003 .

[539]  Weida Tong,et al.  Prediction of estrogen receptor binding for 58,000 chemicals using an integrated system of a tree-based model with structural alerts. , 2001, Environmental health perspectives.

[540]  Raffaella Corvi,et al.  How to reduce false positive results when undertaking in vitro genotoxicity testing and thus avoid unnecessary follow-up animal tests: Report of an ECVAM Workshop. , 2007, Mutation research.

[541]  David Twomey,et al.  Semiautomated multiplexed quantum dot-based in situ hybridization and spectral deconvolution. , 2007, The Journal of molecular diagnostics : JMD.

[542]  A. Billich,et al.  Comparison of human skin or epidermis models with human and animal skin in in-vitro percutaneous absorption. , 2001, International journal of pharmaceutics.

[543]  Valérie Zuang,et al.  Dendritic Cells as a Tool for the Predictive Identification of Skin Sensitisation Hazard , 2005, Alternatives to laboratory animals : ATLA.