Tweet
ShareIn silico, in chemico, in vitro, and ex vivo test methods endorsed by the Organisation for Economic Co-operation and Development (OECD), the European Union Reference Laboratory for alternatives to animal testing (EURL ECVAM), the Japanese Center for the Validation of Alternative Methods (JaCVAM), the Korean Center for the Validation of Alternative Methods (KoCVAM), and/or the U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and/or other organisations are listed below. To download a pdf version, click on the format option here: A4 or 8.5×11. You can also download a printable version of the table below and skin and eye irritation and corrosion factsheets here.
See here for an 11×17 printable poster describing non-animal test strategies for eye irritation, skin irritation, and skin sensitisation.
See also individual factsheets on:
3D TISSUE MODELS (here)
EPA OPP EYE HAZARD (here)
EYE IRRITATION (here)
GENOTOXICITY (here)
MEDICAL DEVICES (here)
ORGANS-ON-CHIPS (here)
PHOTOTOXICITY (here)
PYROGENICITY (here)
QSARS, GROUPING & READ-ACROSS (here)
SKIN IRRITATION (here, training tool also available here)
SKIN SENSITISATION (here)
The following factsheets are available in French:
Les fiches de renseignements suivantes sont disponibles en français:
IRRITATION OCULAIRE (ici)
IRRITATION DE LA PEAU (ici)
SENSIBILISATION DE LA PEAU (ici)
PYROGÉNICITÉ (ici)
| TOXICITY ENDPOINT | TEST METHODS AND APPROACHES | RECOMMENDATIONS AND STANDARD METHODS | ||
|---|---|---|---|---|
| OECD | OTHER AUTHORITY | |||
| SERIOUS EYE DAMAGE AND IRRITATION | Integrated approach on testing and assessment (IATA) for serious eye damage and irritation | OECD guidance document (GD) 263, published in 2019 | _ | |
| Guideline on defined approaches on eye irritation | OECD test guideline (TG) 467, published in 2022 | _ | ||
| Chemical toxicity assessment strategy | _ | European Chemicals Agency guidance Chapter R.7a., R.7.2.8–R.7.2.11 (2017) | ||
| Use of a testing framework employing cytosensor microphysiometer (CM), BCOP, and the EpiOcular™ model for classification of pesticide products | _ | US Environmental Protection Agency policy (2015) | ||
| Reconstructed human cornea-like epithelium (RhCE) test method | EpiOcular™ (MatTek, US) | OECD TG 492, revised in 2019 | ESAC statement (2014); JaCVAM statements (2017 and 2018); KoCVAM guideline (2016) | |
| SkinEthic™ (L’Oréal, France) | ||||
| LabCyte (J-TEC, Japan) | ||||
| MCTT HCE™ (Biosolution, South Korea) | ||||
| Reconstructed human cornea-like epithelium (RhCE) test method (SkinEthic™) | OECD TG 492B, published in 2022 | _ | ||
| Fluorescein leakage (FL) test method | OECD TG 460, revised in 2017 | ESAC statement (2009); JaCVAM statement (2013) | ||
| Short time exposure (STE) in vitro test method | OECD TG 491, revised in 2020 | ICCVAM report (2013); JaCVAM statement (2016); KoCVAM guideline (2017) | ||
| Vitrigel-eye irritancy test (EIT) method | OECD TG 494, revised in 2021 | - | ||
| In vitro macromolecular test method | OECD TG 496, published in 2019 | - | ||
| Bovine corneal opacity and permeability (BCOP) test method | OECD TG 437, revised in 2020 | ICCVAM report (2006); ESAC statement (2007); JaCVAM statements (2009 and 2014); KoCVAM guideline (2011) | ||
| Isolated chicken eye (ICE) test method | OECD TG 438, revised in 2018 | ICCVAM report (2006); ESAC statement (2007); JaCVAM statement (2009) | ||
| Cytosensor microphysiometer (CM) assay | - | ESAC statement (2009); ICCVAM report (2010) | ||
| SKIN CORROSION AND IRRITATION | Integrated approach on testing and assessment (IATA) for skin corrosion and irritation | OECD GD 203, published in 2014 | - | |
| Chemical toxicity assessment strategy for skin corrosion and irritation | - | European Chemicals Agency guidance Chapter R.7a., R.7.2 (2017) | ||
| In vitro membrane barrier test Corrositex for skin corrosion | OECD TG 435, revised in 2015 | ICCVAM report (1999); ESAC statement (2000); JaCVAM statement (2017) | ||
| In vitro skin corrosion: Reconstructed human epidermis (RhE) test | EpiSkin™ (L’Oréal, France) | OECD TG 431, revised in 2019 | ICCVAM report (2002); ESAC statement (1998); JaCVAM statement (2017) | |
| EpiDerm™ (MatTek, US) | ICCVAM report (2002); ESAC statement (2000); JaCVAM statement (2017) | |||
| SkinEthic™ (L’Oréal, France) | ESAC statement (2006); JaCVAM statement (2017) | |||
| epiCS® (Phenion, Germany) | ESAC statement (2009); JaCVAM statement (2017) | |||
| LabCyte EPI-MODEL24 SCT (J-TEC, Japan) | - | |||
| Vitrolife-Skin™ | - | JaCVAM statement (2008) | ||
| In vitro skin irritation: Reconstructed human epidermis (RhE) test | EpiSkin™ (L’Oréal, France) | OECD TG 439, revised in 2021 | ESAC statement (2007); JaCVAM statement (2010); KoCVAM guideline (2014) | |
| EpiDerm™ (MatTek, US) | ESAC statement (2008); JaCVAM statement (2013); KoCVAM guideline (2017) | |||
| SkinEthic™ (L’Oréal, France) | ESAC statement (2008); JaCVAM statement (2013); KoCVAM guideline (2017) | |||
| LabCyte EPI-MODEL24 SIT (J-TEC, Japan) | JaCVAM statement (2013); KoCVAM guideline (2017) | |||
| Skin+® (Sterlab, France) | - | |||
| epiCS® (Phenion, Germany) | ||||
| KeraSkin™ (Biosolution, South Korea) | ||||
| SKIN SENSITISATION | Adverse outcome pathway (AOP) for skin sensitisation | OECD GD 168 (Part 1, Part 2), published in 2012 | - | |
| Guideline on defined approaches on skin sensitisation | OECD Guideline 497, published in 2021 | - | ||
| Guidance on reporting of defined approaches and individual information sources to be used within integrated approaches to testing and assessment (IATA) | OECD GD 256 (Annex I, Annex II), published in 2016 | - | ||
| Use of alternative approaches for skin sensitisation as a replacement for animal testing | - | US Environmental Protection Agency policy (2018) | ||
| Chemical toxicity assessment strategy | - | European Chemicals Agency guidance Chapter R.7a., R.7.3.4–R.7.3.7 (2017) | ||
| OECD QSAR Toolbox | Implementing AOP workflow for skin sensitisation | OECD training manual, released in 2017 | - | |
| Example for predicting skin sensitisation of a mixture | ||||
| Example of how to predict the skin sensitisation potential of a chemical by read-across based on an analogue approach |
||||
| In chemico assays addressing the adverse outcome pathway (AOP) key event on covalent binding to proteins | Direct peptide reactivity assay (DPRA) | OECD TG 442C, revised in 2022 | EURL ECVAM recommendation (2013); JaCVAM statement (2015); KoCVAM guideline (2016) | |
| Kinetic DPRA | ||||
| Amino acid derivative reactivity assay (ADRA) | ||||
| ARE-Nrf2 luciferase test method | KeratinoSens™ | OECD TG 442D, revised in 2018 | EURL ECVAM recommendation (2014); JaCVAM statement (2015); KoCVAM guideline (2017) | |
| LuSens | ||||
| In vitro assays addressing the adverse outcome pathway (AOP) key event on activation of dendritic cells | Human cell line activation test (h-CLAT) | OECD TG 442E, revised in 2022 | EURL ECVAM recommendation (2015); JaCVAM statement (2017); KoCVAM guideline (2017) | |
| IL-8 Luc assay | - | |||
| U937 skin sensitization test (U-SENS™) | ||||
| GARD™ skin assay | ||||
| PHOTOTOXICITY | 3T3 neutral red uptake (NRU) phototoxicity test | OECD TG 432, revised in 2019 | ESAC statement (1997); ICH S10; KoCVAM guideline (2007) | |
| Reactive oxygen species (ROS) assay | OECD TG 495, published in 2019 | JaCVAM statement (2016); ICH S10 | ||
| Reconstructed human epidermis phototoxicity test method | OECD TG 498, published in 2021 | ICH S10 | ||
| SKIN ABSORPTION/PENETRATION | In vitro diffusion method | OECD TG 428, published in 2004 | JaCVAM statement (2014); KoCVAM guideline (2009) | |
| ACUTE SYSTEMIC TOXICITY | Guidance for waiving tests for pesticide formulations | - | Canada Pest Management Regulatory Agency guidance (2013); US Environmental Protection Agency guidance for acute dermal toxicity tests (2016) | |
| Strategy to replace, reduce, and refine the use of animals in the assessment of acute mammalian systemic toxicity | - | EURL ECVAM guidance (2014) | ||
| Collaborative Acute Toxicity Modeling Suite (CATMoS) | - | NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) (2019) | ||
| 3T3 neutral red uptake (NRU) cytotoxicity test to identify substances not requiring classification | - | EURL ECVAM recommendation (2013) | ||
| GENOTOXICITY/MUTAGENICITY | OECD QSAR Toolbox: Example for predicting Ames mutagenicity using read-across | OECD training manual, released in 2017 | - | |
| In vitro micronucleus test | OECD TG 487, revised in 2016 | ESAC statement (2006); ICH S2(R1) | ||
| Bacterial reverse mutation test | OECD TG 471, revised in 2020 | ICH S2(R1) | ||
| In vitro mammalian chromosome aberration test | OECD TG 473, revised in 2016 | ICH S2(R1) | ||
| In vitro mammalian cell gene mutation test | OECD TG 476, revised in 2016 | - | ||
| In vitro mammalian cell gene mutation tests using the thymidine kinase gene | OECD TG 490, revised in 2016 | ICH S2(R1) | ||
| CARCINOGENICITY | In vitro cell transformation assays (CTA) | OECD GD 214, published in 2015; OECD GD 231, published in 2016 | EURL ECVAM recommendations (2012 and 2013) | |
| PYROGENICITY | In vitro monocyte activation tests (MAT) | - | ICCVAM report (2008); ESAC statement (2006); European Pharmacopoeia general chapter 2.6.30; US Food and Drug Administration guidance (2012) | |
| HAEMATOTOXICITY | CFU-GM assay | - | ESAC statement (2006) | |
| REPRODUCTIVE TOXICITY | Embryonic stem cell test (EST) | - | ESAC statement (2001) | |
| Micromass embryotoxicity assay (Note: Animal embryos are used, therefore this test should be used only if replacing a regulatory requirement for a live-animal test using later life stages.) | ||||
| Whole rat embryotoxicity assay (Note: Animal embryos are used, therefore this test should be used only if replacing a regulatory requirement for a live-animal test using later life stages.) | ||||
| ENDOCRINE DISRUPTOR SCREENING | Stably transfected transactivation in vitro assays to detect oestrogen receptor agonists and antagonists | OECD TG 455, revised in 2021 | JaCVAM statement (2016) | |
| H295R steroidogenesis assay | OECD TG 456, published in 2011 | - | ||
| Stably transfected human androgen receptor transcriptional activation assay | OECD TG 458, revised in 2020 | - | ||
| Human recombinant oestrogen receptor (hrER) in vitro assays to detect chemicals with ER binding affinity | OECD TG 493, published in 2015 | - | ||
| Xenopus eleutheroembryonic thyroid assay (XETA) (Note: Animal embryos are used, therefore this test should be used only if replacing a regulatory requirement for a live-animal test using later life stages.) | OECD TG 248, published in 2019 | - | ||
| AQUATIC TOXICITY | OECD QSAR Toolbox: Example for predicting acute aquatic toxicity to fish of mixture with known components | OECD training manual, released in 2017 | - | |
| EnviroTox database to calculate threshold values | - | Health and Environmental Sciences Institute (2018) | ||
| Freshwater alga and cyanobacteria growth inhibition test | OECD TG 201, published in 2011 | - | ||
| Daphnia sp acute immobilisation test | OECD TG 202, published in 2004 | - | ||
| Fish cell line acute toxicity - the RTgill-W1 cell line assay | OECD TG 249, published in 2021 | ISO 21115 standard (2019) | ||
| In vitro intrinsic clearance test using cryopreserved rainbow trout hepatocytes (Note: Animal primary cells are used, therefore this test should be used only if replacing a regulatory requirement for a live-animal test.) | OECD TG 319A, published in 2018; OECD GD 280, published in 2018 | - | ||
| In vitro intrinsic clearance test using rainbow trout liver S9 sub-cellular fraction (Note: Animal primary cells are used, therefore this test should be used only if replacing a regulatory requirement for a live-animal test.) | OECD TG 319B, published in 2018; OECD GD 280, published in 2018 | - | ||
| Fish embryo acute toxicity test (FET) (Note: Animal embryos are used, therefore this test should be used only if replacing a regulatory requirement for a live-animal test using later life stages.) | OECD TG 236, published in 2013 | EURL ECVAM recommendation (2014) | ||
| MULTIPLE ENDPOINTS | Guidance on considerations for waiving or bridging of mammalian acute toxicity tests | OECD GD 237, published in 2016 | - | |
| Guidance for waiving or bridging of acute toxicity tests for pesticides | - | Health Canada guidance (2013) | ||
| Guidance on the reporting of defined approaches to be used within integrated approaches to testing and assessment | OECD GD 255, published in 2016 | - | ||
| Guidance on the validation of (Q)SAR models | OECD GD 69, published in 2007 | - | ||
| OECD QSAR Toolbox: Guidance documents and training materials | OECD, revised in 2018 | - | ||
| QSAR Model Database | - | Maintained by the European Commission Joint Research Centre | ||
| Various modelling programs | - | For example, programs from Lhasa Limited, Instem, ScitoVation, and Simulations Plus | ||
| Guidance on the grouping of chemicals | OECD GD 194, published in 2014 | - | ||
| Read-across assessment framework | - | European Chemicals Agency guidance (2017) | ||
| Guidance on good in vitro method practices | OECD GD 286, published in 2018 | - | ||
| Guidance for describing non-guideline in vitro test methods | OECD GD 211, published in 2014 | - | ||
| Classification of mixtures based on the toxicity of ingredients | - | United Nations “Globally Harmonized System of Classification and Labelling of Chemicals” guidance (2015); US Environmental Protection Agency pilot program | ||
| ENDPOINT | REPLACEMENT METHOD OR STRATEGY | REGULATORY ACCEPTANCE |
| Biologics testing | In vitro leptospirosis vaccine potency assay | USDA Supplemental Assay Methods (SAM) 624, 625, 626 and 627 |
| In vitro erysipelas vaccine potency assay | USDA SAM 612 and 613 | |
| In vitro clostridial vaccine potency assay | USDA draft SAM 220 | |
| In vitro tetanus toxoid potency assay | USDA SAM 217 | |
| In vitro recombinant antibody production methods | www.thepsci.eu/antibodies/ | |
| Veterinary target animal batch safety test (TABST) | Can be waived following demonstration of compliance; USDA CVB memorandum 800.116 | |
| Revocation of general safety tests (GST)/abnormal toxicity tests (ATT) | FDA amended biologics regulations to revoke GST (2015); all European Pharmacopoeia monographs revised to revoke the ATT (2017) |
|
For all endpoints, in vitro methods developed in-house should always be used. Researchers should make every effort to use available non-animal methods. If these methods are not accepted by regulatory agencies, information on additional replacement, reduction, and refinement methods can be found here: NICEATM Accepted Alternative Methods EURL ECVAM Tracking System for Alternative Methods Towards Regulatory Acceptance EURL ECVAM Dataset on Alternative Methods to Animal Experimentation
|
Detailed information on the guidance documents and test methods described in this document can be found at the following sites: