國際接受之已驗證替代方法-美國環保署 Accepted List of Alternatives (U.S. EPA)(2021年更新)


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Test Guidelines – Human Health Effects1


SourceTitleInformation Gathered
OECD TG NO. 428Skin Absorption: In Vitro MethodProvides information on absorption of a test substance (can be from human or animal source)
OECD TG NO. 430In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER)Evaluates corrosivity (rat skin as source)
OECD TG NO. 431In Vitro Skin Corrosion: Reconstructed Human Epidermis (Rhe) Test MethodEvaluates corrosivity (human skin as source)
OECD TG NO. 432In Vitro 3T3 NRU Phototoxicity TestEvaluates Phototoxicity to mouse cells in culture
OECD TG NO. 435In Vitro Membrane Barrier Test Method for Skin CorrosionEvaluates corrosion using a synthetic membrane
OECD TG NO. 437Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye DamageEvaluates eye irritation/corrosivity in bovine eyes
OECD TG NO. 438Isolated Chicken Eye Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye DamageEvaluates eye irritation/corrosivity in chick eyes
OECD TG NO. 439In Vitro Skin Irritation: Reconstructed Human Epidermis Test MethodEvaluates irritation (human skin as source)
OECD TG NO. 442CIn Chemico Skin Sensitisation: Assays addressing the Adverse Outcome Pathway key event on covalent binding to proteinsNo animal or human cells used, evaluates simple binding of a chemical to a synthetic peptide
OECD TG NO. 442DIn Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test MethodSkin sensitization evaluated – human cells used
OECD TG NO. 442EIn Vitro Skin Sensitisation: In Vitro Skin Sensitisation assays addressing the Key Event on activation of dendritic cells on the Adverse Outcome Pathway for Skin SensitisationSkin sensitization evaluated – human cells used
OECD TG NO. 455Performance-based Test Guideline for Stably Transfected Transactivation In Vitro Assays to Detect Estrogen Receptor Agonists and AntagonistsEvaluates estrogenic effects – human cells used
OECD TG No. 456H295R Steroidogenesis AssayEvaluates possible endocrine effects – human cells used
OECD TG No. 458Stably Transfected Human Androgen Receptor Transcriptional Activation Assay for Detection of Androgenic Agonist and Antagonist Activity of ChemicalsEvaluates androgenic effects using chinese hamster ovary cells
OECD TG No. 460Fluorescein Leakage Test Method for Identifying Ocular Corrosives and Severe IrritantsEvaluates eye corrosivity/severe irritation with canine kidney cells
OECD TG No. 471Bacterial Reverse Mutation TestEvaluates mutagenicity in bacterial cells
OECD TG No. 473In Vitro Mammalian Chromosome Aberration TestEvaluates chromosomal effects in either human or rodent cells
OECD TG No. 476In Vitro Mammalian Cell Gene Mutation Tests using the Hprt and xprt genesEvaluates gene mutations in either human or rodent cells
OECD TG No. 487In Vitro Mammalian Cell Micronucleus TestEvaluates chromosomal effects in either human or rodent cells
OECD TG No. 490In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase GeneEvaluates gene mutations in either human or rodent cells
OECD TG No. 491Short-time Exposure In Vitro Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye DamageEvaluates eye corrosivity/severe irritation with rabbit cornea cells
OECD TG No. 492Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye DamageEvaluates eye irritation with reconstructed human cells (either eye or skin)
OECD TG No. 493Performance-Based Test Guideline for Human Recombinant Estrogen Receptor (hrER) In Vitro Assays to Detect Chemicals with ER Binding AffinityEvaluates estrogenicity in human cells
OECD TG No. 494Vitrigel-Eye Irritancy Test Method for Identifying Chemicals not requiring Classification and Labelling for Eye Irritation or Serious Eye DamageRecommended to identify chemicals not requiring classification for serious eye damage or eye irritation.
OECD TG No. 495Ros (Reactive Oxygen Species) Assay for PhotoreactivityEvaluates photoreactivity in chemico
OECD TG No. 496 4In Vitro Macromolecular Test Method for Identifying Chemicals Inducing Serious Eye Damage and Chemicals Not Requiring Classification for Eye Irritation or Serious Eye DamageRecommended as initial step of a testing strategy (see OECD Guidance Document 263 in Potentially Useful Information table) to identify chemicals that induce serious eye damage.
TM2016-08 (US) 2The ToxCast Estrogen Receptor Agonist Pathway ModelMathematical model that combines results from 18 assays to predict estrogen receptor agonism
TM2004-07 (EU) 2In Vitro BALB/c 3T3 Cell Transformation AssayAssay to measure carcinogenicity potential
TM2006-02 (EU) 2,4Ocular IrritectionAssay to predict potential eye irritation for classification/labelling purposes
TM2007-03 (EU) 23T3 Neutral Red Uptake cytotoxicity assayAssay to specifically identify non-classified chemicals (for classification/labelling purposes) with a cutoff value of 2000 mg/kg-bw (oral)
ICCVAM Eye Irritation Test 3The Cytosensor Microphysiometer Test MethodRecommended as a screening test to identify some types of water-soluble substances that may cause permanent or severe eye injuries, and for a limited range of substances, to identify chemicals and products that do not present sufficient potential to cause eye injuries to require eye hazard labeling
OPPTS 890.1200Endocrine Disruptor Screening Program Test Guidelines: Aromatase (Human Recombinant)Assay to identify chemicals that inhibit aromatase activity

1 OECD Test Guidelines (Health), ICCVAM (Alternative Methods Accepted by US Agencies; excludes methods used for evaluating other types of substances by other agencies (e.g., biologics by the U.S. Food and Drug Administration), and EURL-ECVAM source (filtered by “regulatory acceptance/Standards” by Step and “finalized” by Step Status.
2 From EURL-ECVAM (see table note 1)
3 From ICCVAM (see table note 1)
4 In the first update, the following EURL-ECVAM method was added – Ocular Irritection (link); however this same method was adopted by the OECD as TG No. 496 in October of 2019.

Test Guidelines – Effects on Biotic Systems1


SourceTitleInformation Gathered
OECD TG NO. 201Freshwater Alga and Cyanobacteria, Growth Inhibition TestEvaluates toxicity to algae
OECD TG NO. 202Daphnia sp. Acute Immobilization testEvaluates toxicity to freshwater invertebrates
OECD TG NO. 207 Earthworm Acute, Toxicity testEvaluates toxicity to soil invertebrates
OECD TG NO. 211Daphnia magna Reproduction TestEvaluates reproductive effects in freshwater invertebrates
OECD TG NO. 212Fish Short-term Toxicity Test on Embryo and Sac-Fry StagesEvaluates toxicity to fish development.
OECD TG NO. 218Sediment-Water Chironomid Toxicity Using Spiked SedimentEvaluates toxicity to sediment-dwelling invertebrates
OECD TG NO. 219Sediment-Water Chironomid Toxicity Using Spiked WaterEvaluates toxicity to sediment-dwelling invertebrates
OECD TG NO. 221Lemna sp. Growth Inhibition TestEvaluates toxicity to freshwater aquatic plants of the genus Lemna (duckweed).
OECD TG NO. 222Earthworm Reproduction Toxicity Test(Eisenia fetida/Eisenia andrei)Evaluates reproductive effects in soil invertebrates
OECD TG NO. 225Sediment-Water Lumbriculus Toxicity Test Using Spiked SedimentEvaluates toxicity of sediment-associated chemicals endobenthic living organisms
OECD TG NO. 233Sediment-Water Chironomid Life-Cycle Toxicity Test Using Spiked Water or Spiked SedimentEvaluates chronic toxicity to the life-cycle of sediment-dwelling freshwater dipteran Chironomus species.
OECD TG NO. 235Chironomus sp. Acute Immobilisation testEvaluates acute toxicity (immobilisation) to chironomid
OECD TG NO. 236Fish Embryo Acute Toxicity (FET)Evaluates toxicity to fish using zebrafish embryos
OECD TG NO. 238Sediment-free Myriophyllum spicatum Toxicity TestEvaluates toxicity to a submerged, rooted macrophyte species (water milfoil)
OECD TG NO. 239Water-Sediment Myriophyllum spicatum Toxicity TestEvaluates toxicity to a submerged, rooted macrophyte species (water milfoil)
OECD TG NO. 242Potamopyrgus antipodarum Reproduction TestEvaluates reproductive toxicity to the mudsnail
OECD TG NO. 243Lymnaea stagnalis Reproduction TestEvaluates reproductive toxicity to a freshwater snail
OECD TG NO. 319A 2Determination of In Vitro Intrinsic Clearance Using Cryopreserved Rainbow Trout Hepatocytes (RT-HEP)Evaluates the capacity for fish (rainbow trout) to metabolically clear chemical via the liver. This in vitro clearance measurement can be applied to models to predict chemical bioconcentration in fish (BCF). The application is described in the guidance document (see OECD Guidance Document [GD] No. 280, Other Useful Information table)
OECD TG NO. 319B 2Determination of In Vitro Intrinsic Clearance Using Rainbow Trout Liver S9 Sub-Cellular Fraction (RT-S9)

1 Does not include tests in terrestrial plant species.
2 The OECD includes these TGs under Section 3: Environmental Fate and Behaviour.

EPA NAM-Related Guidance Documents/Policies Which May Be Relevant to TSCA


TitleType of NAMInformation Gathered
OCSPP Skin Sensitization Policy (To be updated when finalized)Choice of Two Defined Approaches (DAs)Combination of NAMs to predict skin sensitization in humans
Guidance for Waiving Acute Dermal Toxicity Tests for Pesticide Formulations & Supporting Retrospective AnalysisWaiving dermal toxicity testing for pesticide formulations; but may be applicable to industries considering performing these studies for TSCA purposesAcute dermal toxicity
Guidance for Waiving Acute Dermal Toxicity Tests for Pesticide Technical Chemicals & Supporting Retrospective Analysis 1Waiving dermal toxicity testing for pesticide technical chemicals; but may be applicable to industries considering performing these studies for TSCA purposesAcute dermal toxicity
Final Guidance for Waiving Sub-Acute Avian Dietary Tests for Pesticide Registration and Supporting Retrospective AnalysisWaiving Sub-Acute Avian Dietary TestsPoints to consider when evaluating subacute avian dietary tests data waivers
Guidance for Waiving or Bridging of Mammalian Acute Toxicity Tests for Pesticides and Pesticide Products (Acute Oral, Acute Dermal, Acute Inhalation, Primary Eye, Primary Dermal, and Dermal Sensitization)Waiving or the use of Bridging (read-across)Acute toxicity for pesticides (by route and including irritation/sensitization)
Use of An Alternative Testing Framework for Classification of Eye Irritation Potential of EPA Pesticide ProductsDecision tree for in vitro testing for labelingEye irritation
Process for Evaluating & Implementing Alternative Approaches to Traditional In Vivo Toxicity Studies for FIFRA Regulatory UseAlternative approaches to evaluating acute toxicity in lieu of an in vivo studyDocuments a process to be followed to submit to EPA (Office of Pesticide Programs)
Use of High Throughput Assays and Computational Tools in the Endocrine Disruptor Screening ProgramUse of NAMs for endocrine disruptor screeningScreening for tiered testing for endocrine activity

1 Added to the List on Second Update (February 2021)

Other NAMs Used for TSCA1


SourceParameter/Information Gathered
The OECD QSAR ToolboxCompilation of models and information to predict physical-chemical properties and hazards of chemicals. EPA has contributed models to this tool and it is used by scientists at EPA to understand and evaluate new and existing chemicals under TSCA
OncoLogicTMHazard2,3 – Predictive system that uses knowledge-based rules to predict cancer concern for more than 52 classes of organic chemicals (Version 9.0), as well as fibers, metals, and polymers (Version 8.0).
Analog Identification Methodology (AIM)Hazard3 – Database tool to facilitate identification of analogs for read-across
Chemical Assessment Clustering Engine (ChemACE)Hazard3 – Database tool to facilitate structural clustering
New Chemical Categories DocumentHazard3 – Documentation of TSCA chemical categories
Estimation Programs Interface (EPISuiteTM)Physical/chemical properties and environmental fate4e.g., bioconcentration/bioaccumulation
Chemical Screening Tool for Exposures and Environmental Releases (ChemSTEER)Exposure4 – tools and models to estimate environmental releases and worker exposures
Exposure and Fate Assessment Screening Tool (E-FAST)Exposure4 - tools and models to estimate consumer, general public and environmental exposures to chemicals.
Approaches to Estimate Consumer ExposureExposure4 – a variety of tools and models to estimate exposure to various consumer products and materials

1 General Guidance on all approaches - https://www.epa.gov/tsca-screening-tools
2 Version 9.0 added to the List on Second Update (February 2021)
3 Hazard - https://www.epa.gov/tsca-screening-tools/using-predictive-methods-assess-hazard-under-tsca#models
4 Physical/Chemical Properties, Environmental Fate and Exposure - https://www.epa.gov/tsca-screening-tools/using-predictive-methods-assess-exposure-and-fate-under-tsca#fate

Other Useful Information


SourceTitle/Content
EPA CompTox Chemicals DashboardCompilation of publicly available information on over 850,000 chemicals.
FIFRA SAP January 2013 1Prioritizing the Universe of Endocrine Disruptor Screening Program (EDSP) Chemicals Using Computational Toxicology Tools
FIFRA SAP November, 2017Continuing Development of Alternative High-Throughput Screens to Determine Endocrine Disruption, Focusing on Androgen Receptor, Steroidogenesis, and Thyroid Pathways
FIFRA SAP December, 2018Evaluation of a Proposed Approach to Refine the Inhalation Risk Assessment for Point of Contact Toxicity: A Case Study Using a New Approach Methodology (NAM)
OECD No. 34Guidance Document on the Validation and International Acceptance of New or Updated Test Methods for Hazard Assessment
OECD No. 69Guidance documents on the validation of (Quantitative) structure-activity relationship [(Q)SAR] models
OECD No. 102Guidance document for using the OECD (Q)SAR application toolbox to develop chemical categories according to the OECD guidance on grouping chemicals
OECD No. 184Revised Guidance Document on Developing and Assessing Adverse Outcome Pathways
OECD No. 194Guidance on grouping of chemicals, second edition
OECD No. 203New Guidance Document on an Integrated Approach on Testing and Assessment (IATA) for Skin Corrosion and Irritation
OECD No. 211Guidance Document for Describing Non-Guideline In Vitro Test Methods
OECD No. 214Guidance Document on the In Vitro Syrian Hamster Embryo (SHE) Cell Transformation Assay
OECD No. 231Guidance Document on the In Vitro Bhas 42 Cell Transformation Assay
OECD No. 237Guidance Document on Considerations for Waiving or Bridging of Mammalian Acute Toxicity Tests
OECD No. 255Guidance Document on the Reporting of Defined Approaches to be Used Within Integrated Approaches to Testing and Assessment
OECD No. 256Guidance Document on the Reporting of Defined Approaches and Individual Information Sources to be Used Within Integrated Approaches to Testing and Assessment (IATA) for Skin Sensitisation, Annex 1, Annex 2
OECD No. 260Guidance Document for the Use of Adverse Outcome Pathways in Developing Integrated Approaches to Testing and Assessment (IATA)
OECD No. 263Guidance Document on an Integrated Approach on Testing and Assessment (IATA) for Serious Eye Damage and Eye Irritation
OECD No. 280Guidance Document on the Determination of In Vitro Intrinsic Clearance Using Cryopreserved Hepatocytes (RT-HEP) or Liver S9 Sub-Cellular Fractions (RT-S9) from Rainbow Trout and Extrapolation to In Vivo Intrinsic Clearance

1 FIFRA SAP = Federal Insecticide, Fungicide and Rodenticide Act, Scientific Advisory Panel. The general FIFRA SAP website is available at (Link). Although several meetings/evaluations are presented here, interested parties are encouraged to review the general FIFRA SAP link for other meetings related to NAMs.

原始檔案:https://www.epa.gov/sites/production/files/2021-02/documents/nams_list_second_update_2-4-21_final.pdf

關於美國環保署減少脊椎動物實驗之「替代測試方法」的更多資訊,可參考以下網站:https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/alternative-test-methods-and-strategies-reduce

(2021.2.18更新)

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