In vitro toxicology

In vitro toxicity testing is the scientific analysis of the effects of toxic chemical substances on cultured bacteria or mammalian cells. In vitro (literally 'in glass') testing methods are employed primarily to identify potentially hazardous chemicals and/or to confirm the lack of certain toxic properties in the early stages of the development of potentially useful new substances such as therapeutic drugs, agricultural chemicals and food additives.

In vitro assays for xenobiotic toxicity are recently carefully considered by key government agencies (e.g. EPA; NIEHS/NTP; FDA), to better assess human risks. There are substantial activities in using in vitro systems to advance mechanistic understanding of toxicant activities, and the use of human cells and tissue to define human-specific toxic effects.

Improvement over animal testing

Most toxicologists believe that in vitro toxicity testing methods can be more useful, more time and cost-effective than toxicology studies in living animals (which are termed in vivo or "in life" methods).

Due to regulatory constraints and ethical considerations, as well as concerns over human validity and sensitivity, the quest for alternatives to animal testing has gained a new momentum. In many cases the in vitro tests are better than animal tests because they can be used to develop safer products.

A 96-well microtiter plate being used for ELISA.

Examples of cell viability (cytotoxicity) assays used for In-vitro toxicology

Many methods of analysis exist for assaying test substances for cytotoxicity and other cellular responses.

In Vitro Test Technologies, Kits, Supplies, Cell Lines, Reagents and Databases

Some of the many suppliers that provide useful in vitro testing supplies, cells lines, and other biological reagents. (Courtesy of AltTox.org ):

In Vitro Test Kits

3DBiomatrix: Perfecta3D™ Hanging Drop Plate - 384-well, high-throughput format, 3D cell culture plate for life sciences research and drug discovery/testing applications that simplifies and streamlines spheroid formation and testing; Perfecta3D™ Cell Culture Scaffolds - 96-well plate inserts of synthetic hydrogel scaffolds that facilitate 3D culture

ACTIVTox®: high-throughput, in vitro human liver assay kits that measure liver toxicity or P450 CYP1A induction

ADMEcell: in vitro assay kits for drug discovery include: CacoReady Kit (Caco-2 for in vitro assessment of intestinal permeability) and MDR-1 and BCRP Kits (cell-based assays for evaluation of drug interactions with the P-gp/MDR1 transporter)

Advanced CellSystems: CellSystems® 3D skin models: EST-1000 and AST-2000

Aniara: cellular toxicology screening products: Xenometrix test systems for mutagenicity; cytotoxicity high throughput screening test kits utilizing various endpoints

APSciences: Integrated Multiple Organ Culture (idMOC), a test platform using primary human, rat, or mouse cells from multiple organs which are physically discrete but interconnected by a common medium for studying drug efficacy, metabolism, toxicity

BioSeek, Inc.: BioMAP® Systems - primary, human cell systems that generate a unique signature of the human biological response for predicting mechanisms and efficacy; BioMap profiles can be compared to company database

CCS Cell Culture Service: Princess® Instant Assays provides frozen cells in multiwell plates ready for cytotoxicity, proliferation, and inflammation assays

Cellix Ltd.: microfluidics systems capable of mimicking microcapillaries with blood flow in a robust, in vitro format; the continuous flow cell-based assays enable in vitro studies on cell adhesion, migration, and transmigration, thereby reducing the number of intravital microscopy studies; different biochips, pumping solutions, and software are available

CellSystems Biotechnologie Vertrieb GmbH: cell biology products including human primary cells, 3D skin cell systems, and cell models for angiogenesis, blood-brain-barrier and inhalation toxicology

Celsis In Vitro Technologies: InVitroSomes™, human and animal hepatocytes, microsomes, and media for in vitro ADME-Tox; human renal proximal tubule cells and media; Caco-2 cell assay kits

Epithelix Sàrl: in vitro 2D and 3D models of primary human cells: airway epithelium of different origin, keratinocytes and dermal fibroblasts

Gentaur Molecular Products: Vitotox™, a high throughput bacterial genotoxicity assay to detect DNA damage caused by genotoxic compounds

Gentronix: GreenScreen HC human cell-based genotoxicity screening assay; GreenScreen GC eukaryotic genotoxicity and cytotoxicity assay; BlueScreen HC luminescent assay

GUNZE Medical Division: Vitrolife-Skin 3D skin model

HemoGenix, Inc.: specialized tissue culture products; assay kit products for stem cell transplantation, cord blood storage processing, environmental toxicity testing, and drug discovery and development

Illumina, Inc.: VeraCode ADME Core Panel for pharmacogenetic profiling for human absorption, distribution, metabolism, and excretion (ADME) studies

In Vitro International: acellular in vitro tests: Corrositex dermal corrosion testing assay; Irritection Assay System for ocular and dermal irritation

J-TEC (Japan Tissue Engineering Co., Ltd.): LabCyte cultured human tissues, including the LabCyte EPI-MODEL cultured human epidermis for skin irritation/corrosion/metabolism/percutaneous penetration testing

Litron Laboratories: flow cytometer-based in vitro MicroFlow kits for micronucleus detection in a variety of cultured cells; assay can also provide cytotoxicity endpoints

Lonza Group Ltd: human corneal epithelial model; bovine blood brain barrier system; renal epithelial cell model

MatTek Corporation: human cell-based test kits include skin, ocular, trachael/bronchial, ectocervico-vaginal, oral epithelial, and dendritic cells, for toxicity testing, research, and drug development; some models, like EpiDerm, are validated

MD Biosciences: cell based assays such as ImmuneProfiler™ for screening of anti-inflammatory properties of substances

Millipore Corpporation: high content analysis kits for detecting neurotoxicity and neurite outgrowth in cells; ToxReporter Cell-based Toxicity ELISA consisting of cell lines containing reporter gene constructs for toxicological pathways such as HSP70, NFkB, and AP-1

MultiCell Technologies, Inc.: predictive hepatotoxicity model consisting of immortalized human hepatocyte cell lines and serum-free MFE™ culture medium to screen new drug entities for their impact upon CYP induction using high throughput assays

NCIMB Ltd: MARA Toxicity Test Kit, a microbial array for chemical and nanoparticle toxicity testing for ecotoxicology; extensive microbial culture collection is being used to develop new toxicity arrays

R&D Systems: tools for cell biology research, including ELISA assays and microplate-based antibody array for multi-protein detection

RegeneMed, Inc.: RegeneTOX, human and animal 3-D liver tissue co-cultures; monolayer cell-based products from the same donor for comparison; stem cells and 3-D tissues

Seahorse Bioscience: XF Extracellular Flu Analyzer measures effects on cell metabolism; determines basal oxygen consumption, glycolysis rates, ATP turnover, and respiratory capacity in single experiment

SimuGen Ltd: first product in 2008 will be novel hepatotoxicity platform to predict 10 sub-types of liver toxicity for test chemicals

SkinEthic Laboratories: human epidermal and epithelial models for in vitro test applications for the pharmaceutical, chemical, and consumer product industry; some models, like Episkin, are validated

Stratatech Corp.: StrataTest® human skin model composed of both an epidermis and a dermis (full thickness) for in vitro testing applications

StratiCELL: in vitro 3D skin models

Xenometrix AG: in vitro test kits include: Ames II / Ames MPF Microfluctuation Assays; Xenometrix Cytotoxicity Screening Kits - determine up to four cytotoxicity parameters from same sample; Ames MPF 98/100 AQUA - a novel mutagenicity test kit for testing water quality

XenoTech, LLC: products for in vitro drug metabolism-related research: microsomes, cryopreserved hepatocytes from human and other species, CYP antibodies directed against CYP enzymes, and more

Cells & Tissues

ADMET Technologies: cell-based products for drug discovery: characterized, fresh or cryopreserved, primary human hepatocytes available in various plated formats; non-parenchymal liver cells; liver RNA and microsomes; 3D liver bioreactor (in development)

American Type Culture Collection (ATCC): supplies many types of cells lines and bioproducts

AMS Biotechnology: products for stem cell research, including embryonic stem cells, adult stem cells, and reagents to create iPS cells

Asterand, plc.: provides human biomaterials for drug testing (human primary cells & cell lines, RNA, tissue microarrays, frozen & fixed human tissues)

ATCC-LCG Promochem Partnership: facilitates distribution of ATCC cultures and bioproducts to life science researchers in Europe

BioE, Inc.: Multi-Lineage Progenitor Cell™, a human umbilical cord blood-derived, clonal, multipotent stem cell line; unique cell reagents

Cascade Biologics: keratinocytes and other epithelial cells, endothelial cells, fibroblasts, etc.

Cell Line Database

CELLnTEC Advanced Cell Systems AG: novel culture media, primary and long-term epithelial cells (human and rodent), and methods/protocols necessary for establishment of 2D and 3D cultures for creation of specific cellular micro-environments; human primary cells currently available: epidermal keratinocytes, dermal fibroblasts, and corneal, gingival, and bladder epithelial cells

CellSystems Biotechnologie Vertrieb GmbH: cell biology products including human primary cells, 3D skin cell systems, and cell models for angiogenesis, blood-brain-barrier and inhalation toxicology

Cellular Dynamics International: iCell™ Cardiomyocytes and iCell™ Neurons derived from induced pluripotent stem cells for drug discovery and toxicity testing

CellzDirect: hepatocyte cells and cell products

Delta Robotics GmBH: Bio Factory® is a versatile and cell-friendly printing platform that allows researchers to pattern cells, biomolecules, and a range of soft and rigid materials in desirable 3D structures; a full thickness skin model based on Bio Factory® technology is available

European Collection of Cell Cultures (ECACC)

German Collection of Micro-Organisms and Cell Cultures

InSphero AG: provides scaffold-free 3-dimensional microtissues in ready-to-use 96-well microwell formats for biomedical, pharmaceutical, and toxicity testing applications; tumor, rat liver, and custom-made microtissues are available

Lonza Group Ltd: primary human and animal cells with customized media systems, Clonetics® and Poietics® Cell Systems

Millipore Corporation: many cell lines and media; primary human skin, cornea, and bladder epithelial cell kits with specialized media to enrich progenitor cells

Musculoskeletal Transplant Foundation (MTF): supplies pieces of human bone, skin, and other tissues, and FlexHD, an acellular dermal matrix, primarily for surgery

National Cancer Institute (NCI): tissue, cell lines, databases, arrays, etc. primarily for cancer research

National Cell Culture Centre (NCCC): division of Biovest International; provides customized, large scale cell culture services

National Disease Research Interchange (NDRI): not-for-profit corporation primarily funded by the NIH and dedicated to providing researchers with human cells, tissues, and organs for research purposes

National Human Neural Stem Cell Bank: provides neural stem cells harvested from the post-natal, post-mortem, human and animal brain to the research community for stem cell research; sponsored by the Children’s Hospital of Orange County

National Stem Cell Bank (NSCB) at WiCell: established to acquire, characterize and distribute the 21 human embryonic stem cell lines and their sub-clones to federally funded research programs; they currently have 13 of the 21 cell lines in the federal registry

NIH Human Embryonic Stem Cell Registry: lists the derivations of stem cells that are eligible for federal funding and provides contact information for acquiring the cell lines

OnCore UK: human specimens for cancer research

ProBioGen: specializes in mammalian cell engineering and cell culture: design of custom immortalized cell lines for vaccine and protein production, or for other customer needs

Puracyp: human hepatic microsomes and reagents for drug metabolism studies

ReachBio, LLC: primary human cell products include various types of peripheral blood, bone marrow, and cord cells; ColonyGEL™ methylcellulose-based media for colony-forming cell (CFC) assays

SciKon Innovation, Inc.: human matrix cell culture surface; human stellates; human hepatocyte cryopreserved cells

Sigma Life Science: range of quality cell lines, including genetically modified cell lines that model different types of cancer

TCS Cellworks, Ltd.: human cell-based research products and cells

tebu-bio laboratories: various cryopreserved primary cells; cell biology services such as cell amplification, differentiation, transfection, mycoplasma testing, establishes cellular models overexpressing or silencing a protein of interest

UK Human Tissue Bank: not-for-profit organization that provides human tissues for biomedical research

UK Stem Cell Bank

Vitro Diagnostics, Inc. (dba Vitro Biopharma): "Tools for Stem Cell and Drug Development™," a series of products including human stem cell lines, cell line derivatives, and medical devices for mesenchymal stem cell research, development of induced pluripotent stem cells, and stem cell therapy for cancer

Zen Bio: human adult stem cells, preadipocytes, adipocytes, primary human hepatocytes; specialized media

Media & Cell Reagents

AMS Biotechnology: products for stem cell research, including optimized growth medium and supplements, extracellular matrices, and feeder cells

Cell Preservation Solutions, LLC: develops novel solutions for preserving cells and tissues, and their storage and transportation (including stem cells); develops optimized mediums; provides DMSO-free cryopreservation solutions, and animal protein-free and serum-free media

CellSystems Biotechnologie Vertrieb GmbH: cell biology products including human primary cells and optimised cell culture media

FiberCell Systems, Inc.: hollow fiber cell culture systems for in vitrotoxicology studies of drug bio-availability

Invitrogen: Gibco® Cell Culture Systems includes serum-free and specialty cell culture media and reagents' 3D cell culture products; stem cell reagents and protocols

Lonza Group Ltd: serum-free media, cell culture reagents, cell stains

Millipore Corporation: HEScGRO animal component-free medium for culturing human embryonic stem cells in their undifferentiated state

Mirus Bio, LLC: cell transfection and electroporation reagents; new 3D Transfection System combines Reinnervate's alvetex® 3D Cell Culture Plates and Mirus Bio's TransIT®-3D Transfection Reagent

ReachBio, LLC: primary human cell products and cells; ColonyGEL™ methylcellulose-based media for colony-forming cell (CFC) assays

Reinnervate Limited: innovative new cell culture technologies including: Alvetex® - an inert polystyrene scaffold for cells to grow and form complex 3D cell structures in the laboratory, and synthetic small molecules that mediate cell differentiation in vitro - the first of these is ec23™, a synthetic retinoid that induces neurogenesis

Sigma-Aldrich Media Expert®: comprehensive source of information on cell culture media components and formulation, including primary functions for each component in cell culture applications

StemCell Technologies, Inc.: provides specialized media and cell separation products and contract services

Stemgent, Inc.: stem cell qualified reagents and tools, including cell lines, media, transfection reagents, and more

Trevigen, Inc.: kits for 3-D cell culture standardized for assessing effects on genetic alteration or cell proliferation in 3-D cultures; high-throughput 96-well format

Vitro Diagnostics, Inc. (dba Vitro Biopharma): "Tools for Stem Cell and Drug Development™," a series of products including specialized stem cell media

Worthington Biochemical Corporation: Hepatocyte Isolation System provides preoptimized combination of enzymes, buffers, and culture media to minimize lot-to-lot variation and improve quality of isolated hepatocytes; Animal Origin Free (AOF) enzymes for biopharma & vaccine production applications

ZET Serum Free Cell Culture Media - Updated Product Guide 1/2004-05: provides sources for obtaining animal-free cell culture media and reagents

Equipment & Other Resources

AbD Serotec: research and diagnostic antibodies

Affymetrix: DNA chips and microarrays

Amaxa Biosystems: Nucleofection transfection technology; cell database providing optimal transfection conditions for 570 types of cells

Applied Biosystems: instruments, consumables, software, and services for analyzing nucleic acids (DNA and RNA), small molecules, and proteins

BD Biosciences: products for research include antibodies, and reagents for western blotting, immunofluorescence, ELISA; instrumentation and reagents for flow cytometry

Beckman Coulter, Inc.: cellular automation systems to automate cellular assays

Bellbrook Labs: Transcreener™ Assay Platform, a HTS platform using proprietary fluorescent detection for screening families of enzymes at one time; uses microfluidics to bring cellular models into a fully automated high throughput environment

BioAssay Systems: biochemical and cell-based assays for both routine laboratory testing and high-throughput drug discovery: oxidative stress, cytotoxicity, cell proliferation, enzyme assays, reporter gene assays

Biocompare: large array of life science products and information

Bionas GmbH: Bionas® cell-based analyzing systems for continuous determination of cell physiology

Biontex Laboratories: mammalian cell transfection reagents

BioTek Instruments, Inc.: automation tools for ADME/Tox processes; validated microplate ADME/Tox applications include: drug permeability assessment; passive and active drug transport studies; biochemical metabolic enzyme inhibition profiling; multiplexed cell-based CYP450 induction and inhibition profiling; and cytotoxicity profiling

Cell Sciences: immunochemicals for life science research, including cytokines, ELISA and ELISPOT kits, monoclonal and polyclonal antibodies, and matched antibody pairs for do-it-yourself assays

Cell Signaling Technology: reagents and assays for studying cell signaling pathways

CellASIC: microfluidic platforms for cell and tissue based applications; innovative approach enables cells to be maintained in a more biologically relevant condition

Cellectricon: microfluidic biochips as miniaturized cell-based screening devices: Cellaxess™ electroporation technology for transfection of tissue explants and adherent cells; Dynaflow™ System for ion channel drug discovery

Cellomics, Inc.: proprietary platforms for cell-based assays

Cell Technology, Inc.: reagents and assay kits for cell-based assays

Chromocyte: online resource for the design of multi-parameter flow cytometry experiments, and for identifying reagent sources for flow cytometry and other antibody-related techniques

CompuCyte Corporation: Laser scanning Cytometry instrumentation for cell- and tissue-based analysis; advanced software tools for combining high-content quantitative data analysis with images (morphology)

CYTOO SA: micropattern-based products for cell-based assays: CYTOO chip™; CYTOO plate™; CYTOO chamber™ for live cell imaging

Delta Robotics GmBH (Switzerland): Bio Factory® is a versatile and cell-friendly printing platform that allows researchers to pattern cells, biomolecules, and a range of soft and rigid materials in desirable 3D structures.

EcoArray, Inc.: microarrays for ecotoxicity and endocrine disruptor testing: fathead minnow oligonucleotide arrays; reagents & solutions; use of EcoArray database for data interpretation, and discounts for participation in data sharing program to build capacity of predictive company database

EMD Biosciences: Calbiochem, Novabiochem, and Novagen research reagents and assays

Epigentek: tools and kits for epigenetic research

Exiqon: mRNA and microRNA research reagents and resources; bioinformatics tools ands services for probe design

FiberCell Systems, Inc.: hollow fiber cartridge systems for in vitro toxicology testing: used to model pharmacologic bio-availability and to culture epithelial cells

Fluxion Biosciences: BioFlux System for live cell analysis under shear flow for cell biology applications from high content analysis to pharmacological screening in a high throughput and low volume well-plate format

GE Healthcare: In Cell Analyzer for high content analysis (HCA)

Guava Technologies: benchtop flow cytometry systems, reagents, and software; cell cycle assay for cell cycle phase analysis at the benchtop

Harvard Apparatus: tissue slice chamber systems, isolated organ perfusion systems, and cell culture equipment; catalog of products for regenerative medicine research

Hudson Robotics, Inc.: laboratory automation and robotics equipment

Invitrogen: research supplies, tools, protocols, Gibco cell culture systems, human biological pathway maps

LabX.com: a media service for the exchange of scientific equipment, where buyers and sellers of new, used, surplus, and refurbished scientific and laboratory equipment can find items, negotiate terms, and complete transactions online

Lonza: cell viability and toxicology assays

Luminex Corporation: xMAP® technology bioassay platform; multiplexing (multiple unique assays) within a single sample

Millipore Corporation: research and cell culture supplies & reagents

Miltenyi Biotec: products for cell biology, immunology, regenerative medicine, and molecular biology

National Institute for Biological Standards and Control (NIBSC): provides International Biological Standards and other biological reference materials that are independently certified to the international quality standard BS EN ISO 9001:2000

Optometrics Corporation: SPF-290S ANALYZER SYSTEM, an UV spectrophotometer optimized for in vitro SPF assays for sunscreens, cosmetic products, and fabrics; compliant with FDA 21 CFR

OriGene Technologies: tissue qPCR arrays; transfections arrays; transfection reagents

Oxford Biomedical Research: biochemical assay kits, antibodies, cDNA probes, etc.

Perceptive Instruments, Ltd: image analysis and data processing software and instrumentation for research and testing including genetic toxicology (including Ames, MLA, and Comet Assay) and immunology assays

PerkinElmer, Inc.: cell-based assay reagents and cellular pathway mapping kits

ProBioGen: development of custom cell lines; in vitro production of monoclonal antibodies & adaptation to serum-free media

Promega: bioluminescent cytochrome P450 assays; cellular and genomic assay reagents & kits; protocols; online tools

R&D Systems: supplier of biological and research products, including antibodies and ELISA kits

SBH Sciences: cytokines and antibodies for cell-based assays; also provides bioassay testing services

Shelf Scientific: Lazar micro probes to measure ions (Na, Cl, K), pH, pO2, and pCO2; nitric oxide measurement system; ArrowDox™ Micro Oxidation-Reduction Measurement System for samples as small as 5 microliters with micro electrode that fits directly into 96-well plates or microcentrifuge tubes

Sigma Aldrich: antibodies, media, chemicals, other research reagents

tebu-bio laboratories: reagents for cell biology, drug discovery, in vitro ADME-Tox; laboratory services

Thermo Scientific: life science products include high content cell screening and cell imaging tools, and the Cellomics ToxInsight In Vitro Toxicity Platform for multiplexed assessment of toxicity targets in cells

Trevigen, Inc.: products for research: DNA damage, apoptosis, molecular biology, cell differentiation, angiogenesis

VitroCell Systems: VitroCell for in vitro culture and exposure to gases or complex mixtures

Software

ADMET Predictor™: computer software for advanced predictive modeling of ADME/Tox properties from molecular structures; builds predictive models of new properties from user's data

Aniara CelTox Software: for cytotoxicity analysis

Ariadne Genomics: Pathway Studio software for pathway and molecular interaction analysis

ArrayTrack: utilized by US FDA for review of genomic data submissions; integrated solution for managing, analyzing, and interpreting microarray gene expression data; provides statistical and visualization tools, and functional information about genes, proteins, and pathways for biological interpretation

Aureus Sciences: software applications (AurQUEST, AurPROFILER, DDI Predict, and AurPASS) for accessing information from the company's chemical and bioactivity databases relevant to drug discovery and development

Biocompare: pathway analysis and genomic sequence analysis software

Biographics Laboratory 3R (Biograf 3R) (Basel, Switzerland): software products for computational methods to replace animal testing

Cellnomica: software for modeling and simulation of multicellular systems such as tissue, organs, and organisms

CombiStats: computer program for statistical analysis of data from biological dilution assays or potency assays; can perform calculations according to: parallel line, slope ratio, probit, 4-parameter logistic curve, and more models

DART (Decision Analysis by Ranking Techniques): software tool for ranking chemicals according to their environmental and toxicological concern based on the most recent ranking theories; different kinds of order ranking methods are implemented, and can be used to rank chemicals on the basis of more than one variable

Decision Forest: novel pattern recognition method for analysis of microarray, SELDI-TOF MS, and SAR data

Decisioneering: risk analysis and data simulation software

DiscoveryQuant™ Software(Applied Biosystems): mass spectrometry software for early high-throughput ADME testing to improve speed and efficiency of drug candidate analyses

ECETOC Targeted Risk Assessment (TRA) Tools: Workers Exposure Tool, Consumer Exposure Tool, and Environmental Exposure Tool available for free download for tiered approach to calculating exposure to and risks from chemicals

Endocrine Disruptor Knowledge Base: scientific resources including a biological activity database, (Q)SAR training sets, and computational models to predict estrogen and androgen activity

US EPA ECOSAR (Ecological Structure Activity Relationships): program to estimate the toxicity of industrial chemicals discharged into water to aquatic organisms such as fish, invertebrates, and algae; toxicity is predicted using Structure Activity Relationships

US EPA Exposure Assessment Tools & Models

US EPA Toxicity Estimation Software Tool (T.E.S.T.): software available for download enables toxicity estimates from a chemical's molecular structure using (Q)SAR methodologies; User's Guide available; includes models for following endpoints: 96-hour fathead minnow 50% lethal concentration (LC50); 48-hour daphnia magna LC50; Tetrahymena pyriformis 50% growth inhibition concentration; Oral rat 50% lethal dose (LD50); Bioconcentration Factor; Developmental Toxicity (DevTox); and Ames mutagenicity (Mutagenicity)

Foodrisk.org: exposure, dose-response, statistical modeling and simulation tools, risk analysis tools and programs, and more

GlodSim: simulation software for decision and risk analysis

Ingenuity Pathway Analysis (IPA): chemical pathway analysis software and database: build pathways, assess toxicity profiles, prioritize biomarkers, metabolite data analysis

JMP: statistical software

Kinetics Calculation Tool (KinCalTool): [under Publications link] calculation tool provided by ECVAM for construction of C,t-curve using KinParDB (Kinetic Parameters DataBase)

Leadscope, Inc.: combine and build databases; build prediction models

Lhasa Limited: non-profit company specializing in the development of expert computer systems for toxicity and metabolism prediction which include Derek for Windows, Meteor and Vitic

MultiCASE, Inc.: computer programs designed to assess the potential pharmacological activity, toxicity, and metabolic transformation of new chemicals

NIEHS: free software for genomics, biostatistics, molecular biology, and more

PBT Profiler: developed as a voluntary screening tool to identify Pollution Prevention (P2) opportunities for chemicals without experimental data; uses a subset of P2 Assessment Framework computer-based tools to help identify chemicals that potentially may persist, bioaccumulate, and be toxic to aquatic life

Perceptive Instruments, Ltd: image analysis and data processing software and instrumentation for research and testing including genetic toxicology (including Ames, MLA, and Comet Assay) and immunology assays

Premier Biosoft International: lifescience software for microarrays, PCR, primer design, and more; bioinformatics software development and assay design services

Risk Assessment Information System: various risk assessment tools

SAS Institute, Inc.: data analysis software: statistical and simulation

Scorecomets: online resource for the comet assay by Perceptive Instruments Ltd; comet assay news, method, advice, and information; online interactive trouble shooting guide; download free 30-day trial of Comet Assay IV comet assay scoring system

Simcyp Population-based ADME Simulator: platform for modelling and simulation of drug absorption, distribution, metabolism and excretion (ADME) in virtual populations from in vitro data [Consortium membership required] (free ADME tools)

Simulations Plus, Inc.: ADMET Predictor™ software; GastroPlus™ software for oral absorption and pharmacokinetic simulation

Stat4tox (Software for the Statistical Evaluation of In Vitro Assays): open-source software tool that provides statistical analysis for toxicological data, including dose-response data; can be used for analysis of in vitro concentration-response curves, including estimation of EC50 values and the interpretation of both the statistical significance and biological relevance of observed effects

Syracuse Research Corporation: Environmental Science Estimation Software - variety of programs available

tebu-bio laboratories: CacoReady Software™ for analysis and management of data from in vitro studies for prediction of intestinal absorption; Noraymet ADMETM for management of in vitro ADME studies and use of in vitro ADME to predict human pharmacokinetic

Toxmatch: open-source software that encodes several chemical similarity indices to facilitate the grouping of chemicals into categories and read-across

ToxRTool (Toxicological data Reliability Assessment Tool): [under Publications link] software-based tool provided by ECVAM for evaluating quality of toxicological data

Toxtree: open-source software tool that places chemicals into categories and predicts toxicological effect by applying decision tree approaches (around 10 decision trees currently implemented)

VEGA (Virtual models for Evaluating the properties of chemicals within a Global Architecture): new and open-source platform for (Q)SAR and read across for REACH; includes models for phys-chem, environmental, ecotoxicological, and toxicological properties

VirtualToxLab™: in silico tool for predicting toxic potential of drugs and chemicals; simulates and quantifies chemical interactions with human protein via (Q)SAR; includes 12 validated models

MTT

MTT assay is used often in determining cell viability and has been validated for use by international organisations. MTT assay involves two steps of introducing the assay to the chemicals and then a solubilisation step

MTS

The colourimetric MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium) in vitro assay is an updated version of the validated MTT method, MTS assay has the advantage of being soluble and hence no solubilisation step is required.

ATP

ATP assay has the main advantage of providing results quickly (within 15 minutes) and only requires fewer sample cells. The assay performs lysis on the cells and the following chemical reaction between the assay and ATP content of cells produces luminescence. The amount of luminescence is then measured by a photometer and can be translated into number cells alive since

• ATP assay assumes alive cells still have ATP inside it.
• Luminescence level recorded is proportional to the ATP content in the sample cells

Neutral Red

Another cell viability endpoint can be Neutral Red uptake. Neutral Red(NR), a weak cationic dye penetrates cellular membranes by non-diffusion and accumulates intercelluarly in lysosomes. Viable cells take up the NR dye, damaged or dead cells do not.

Enzyme-linked immunosorbent assay (ELISA)

ELISA kits can be used to examine up and down regulation of proinflammatory mediators such as cytokines (IL-1, TNF alpha, PGE2)....

Measurement of these types of cellular responses can be windows into the interaction of the test article on the test models (monolayer cell cultures, 3D tissue models, tissue explants).

External links

• AltTox.org: Non-animal Methods for Toxicity Testing - Toxicity Testing Resource Center
• Introduction to Genetic Toxicology
• Alt Web
• The Johns Hopkins Center for Alternatives to Animal Testing (CAAT)
• 3-D, Human Cell-Derived TISSUES for Tox. Testing - MatTek Corp.
• In Vitro and Alternative Methods Specialty Section
• In Vitro Phototoxicity Testing
• Integrated_Discrete_Multiple_Organ_CoCulture_Assays for toxicity
• Informational source on types of in vitro assays