New Approach Methodologies (NAMs) within TSCA

The Physicians Committee
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21st-Century Chemical Regulation: Ensuring Protective Chemical Regulations That Avoid Animal Testing

New Approach Methodologies (NAMs) within TSCA

 

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After 40 years, change came to the Toxic Substance Control Act (TSCA) with the Frank R. Lautenberg Chemical Safety Act for the 21st Century (LCSA) amendment. Passed in June 2016, LCSA became the first US legislation that required companies to use alternative methods or new approach methodologies (NAMs) to reduce the use of animals in chemical testing. As LCSA promises to usher in major reform in toxicology testing, the Physicians Committee for Responsible Medicine aims to provide resources to companies to help facilitate the use of non-animal methods.

The legislation outlines methods that companies can use to replace or reduce animal tests, which include:

  • computational toxicology and bioinformatics,
  • high-throughput screening methods,
  • testing of substances in chemical categories,
  • tiered testing methods,
  • in vitro studies,
  • systems biology,
  • new or revised methods identified by validation bodies such as the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) or the Organization for Economic Co-operation and Development (OECD), or
  • industry consortia that develop information submitted under this title.

Interested in Training and hearing about other Resources?

PCRM has assisted governments and companies in the use of new approach methodologies (NAMs) or nonanimal test methods for over 10 years, and we provide resources and trainings to increase the use and regulatory acceptance of reliable, cost effective, and ethical toxicological test methods.

Companies can pursue a number of approaches to ensure the products they sell are safe without testing on animals. Indeed, there are more than 40 in vitro methods approved by international regulatory bodies; however, there are other strategies that are also considered as NAMs.

  • Use of available information: Existing data on target or similar chemicals can be used instead of conducting new testing. Certain physicochemical properties can lead to waiving of testing for some endpoints. A good hazard assessment starts with gathering of data, and the eChemPortal or the AOP Knowledge Base are good places to start.
  • Threshold of Toxicological Concern: Based on knowledge about other chemicals with similar structures and some information about a target chemical, it may be possible to establish a level below which a chemical is unlikely to be harmful.
  • Computer-based methods: The potential toxicity of a chemical can be predicted by assessing the chemical structures and properties of a few or many thousands of chemicals, manually or with mathematical algorithms and supercomputing power. Start with the OECD QSAR toolbox and visit https://www.ascctox.org/resources for many more.
  • In vitro methods: From simple cell cultures to three-dimensional models of human skin, liver, and other organs, there are many methods available to assess chemical safety.

Below is a list of methods that can be used within your companies testing strategies to comply with LSCA and reduce the use of animals. Also you can sign up to receive more information about new approach methodologies under TSCA or information about PCRM’s training opportunities.

NAMs currently available for regulatory use

Many of the following methods have been approved by international validation bodies; some are appropriate when used alone and others should be used within an Integrated Approach to Testing and Assessment (IATA) in order to make a regulatory decision.

Dermal

Skin corrosion

  • OECD TG 435: In Vitro Membrane Barrier Test Method for Skin Corrosion
    • CORROSITEXTM
  • OECD TG 431: In Vitro Skin Corrosion:  formally Human Skin Model Test | Reconstructed Human Epidermis (RHE) Test Method, summary document 190 (2013)
    • EpiSkinTM
    • EpidermTM
    • SkinEthicTM
    • RHE SCT
    • epiCS ®SCT
    • Vitrolife-SkinTM
  • OECD GD 203: Guidance Document on an Integrated Approach on Testing and Assessment (IATA) for Skin Corrosion and Irritation

Skin irritation

  • OECD TG 439 : In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method
    • EpiSkinTM
    • EpidermTM SIT
    • SkinEthicTM
    • LabCyte EPO Model
  • OECD GD 203: Guidance Document on an Integrated Approach on Testing and Assessment (IATA) for Skin Corrosion and Irritation

Skin sensitization

  • EPA Draft Policy: Use of Alternative Approaches for Skin Sensitization as a Replacement for Laboratory Animal Testing
  • OECD TG 442D : In Vitro Skin Sensitization, ARE-Nrf2 Luciferase Test Method
    • KeratinoSensTM
  • OECD TG 442C : In Chemico Skin Sensitization, Direct Peptide Reactivity Assay (DPRA)
  • OECD TG 442E: In Vitro Skin Sensitization, Human Cell Line Activation Test (h-CLAT)
  • OECD Series on testing and assessment no. 168: Adverse Outcome Pathway for Skin Sensitization Initiated by Covalent Binding to Proteins
  • OECD GD 256:  On the reporting of defined approaches and individual information sources to be used within IATA for skin sensitization  
    • Annex 1: Case studies to the guidance 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 2: Information sources used within the case studies to the guidance 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
  • OECD draft TG: In Vitro Skin Sensitisation, IL-8 Luc Assay
  • OECD draft TG: In Vitro Skin Sensitisation, U937 U-SENSTM

Skin Absorption/penetration

  • OECD TG 428:  Skin Absorption: in vitro Method 
    • Dermal absorption OECD GD 28 (2004)
    • OECD Guidance notes no. 156

Occular corrosion and irritation

  • OECD TG 460: Fluorescein Leakage Test Method for Identifying Ocular Corrosives and Severe Irritants
    • Trans-Epithelial Permeability
  • Draft OECD TG: The Cytosensor Microphysiometer Test Method: An in vitro Method for Identifying Ocular Corrosive and Severe Irritant Chemicals as well as Chemicals not Classified as Ocular Irritants--- or the cytosensor mirophsiometer (CM) assay
  • OECD TG 437: Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants
  • OECD TG 438: Isolated Chicken Eye Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage
  • OECD TG 492: Reconstructed human Cornea-like Epithelium (RhCE) test method for identifying chemicals not requiring classification and labelling for eye irritation or serious eye damage
    • Epiocular
    • HCE
  • OECD TG 491: Short 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 Damage
  • Alternate Testing Framework for Classification of Eye Irritation Potential of EPA-Regulated Pesticide Products
  • NociOcular Eye Sting (only eye irritation)
  • Occular Irritection AssayValidation of the Ocular Irritection® Assay (only eye irritation)

Acute toxicity

  • 3T3 NRU cytotoxicity test to identify substances not requiring classification
  • Hematotoxicity, Colony forming unit-granulocyte/macrophage assay (CFU-GM) Assay for acute neutropenia in humans , INVITTOX n° 101

Carcinogenicity

  • OECD GD 231: in vitro Bhas 42 cell transformation assay (CTA)

Genotoxicity/Mutagenicity

  • OECD TG 471: Bacterial Reverse Mutation (Ames) Test
  • OECD TG 473: In Vitro Mammalian Chromosomal Aberration Test
  • OECD TG 487: In Vitro Mammalian Cell Micronucleus Test
  • OECD TG 490 : In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene
  • OECD TG 476: In Vitro Mammalian Cell Gene Mutation Tests using the Hprt and xprt genes

Endocrine disruptors

  • OPPTS 890.1200: Aromatase inhibition assay (Human Recombinant)
  • OECD TG 455: Performance-Based Test Guideline for Stably Transfected Transactivation In Vitro Assays to Detect Estrogen Receptor Agonists and Antagonists
  • OECD TG 456: H295R Steroidogenesis Assay
  • OECD TG 457: BG1Luc Estrogen Receptor Transactivation Test Method for Identifying Estrogen Receptor Agonists and Antagonists or BG1Luc estrogen receptor method
  • OECD TG 493: Performance-Based Test Guideline for Human Recombinant Estrogen Receptor (hrER) In Vitro Assays to Detect Chemicals with ER Binding Affinity
  • OECD TG 458: Stably Transfected Human Androgen Receptor Transcriptional Activation Assay for Detection of Androgenic Agonist and Antagonist Activity of Chemicals

Inhalation

  • Epithelix models
    • MucilAir™: 3D Human Airway Epithelia reconstituted in vitro
    • MucilAir™-HF: long shelf life co-culture model with human fibroblasts
    • SmallAir™: 3D Human Small Airway Epithelia reconstituted in vitro
    • SmallAir™-HF: 3D Human Small Airway Epithelia reconstituted in vitro
    • Human Airway Epithelial Cells of Bronchial (hAECB) and Nasal (hAECN) Origin
    • OncoCilAir™ : Human 3D in vitro lung cancer model
  • MatTek Corporation: EpiArway™

General Guidance

Contact Us

For inquiries or comments please contact, Esther Haugabrooks at ehaugabrooks@pcrm.org. Or, follow this link to sign-up for training opportunities.