EPA New Approach Methods: Efforts to Reduce Use of Vertebrate Animals in Chemical Testing

The Environmental Protection Agency is prioritizing ongoing efforts to develop and use New Approach Methods (NAMs) to test chemicals for health effects. Using NAMs will help reduce the use of vertebrate animals in chemical testing while ensuring protection of human health and the environment.

The definition of NAMs has evolved over time. Currently, it is broadly descriptive reference to any non-vertebrate animals technology, methodology, approach, or combination thereof that can be used to provide information on chemical hazard and risk assessment. These include in vitro tests, in chemico assays, and in silico models. NAMs are functionally equivalent to “alternatives" to mammal testing.

• Why Develop New Approach Methods?
• NAMs Research Approaches
• Additional Resources

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Why Develop New Approaches?

EPA uses many types of information to evaluate the potential risks of chemicals to human and ecological health. Due to the large number of chemicals regulated by EPA, better, faster, and more cost effective methods are needed for chemical evaluation. Associated with this need, is the goal of reducing, refining, and replacing the use of animals in testing. The increased application of NAMs holds the potential of meeting both the need and the goal.

NAMs Research Approaches

EPA’s Office of Research and Development (ORD) is actively developing, testing and applying NAMs to improve Agency approaches to evaluate the potential impacts of chemicals on human and ecological health. Working collaboratively with federal partners and other stakeholders, EPA is developing NAMS that will provide data to fill critical information gaps and build confidence for the use of these new approaches in regulatory decisions. EPA has developed a three-part strategy that: 1) characterizes the scientific quality and relevance of existing animal tests, 2) develops recommended reporting requirements, and 3) demonstrates application of the NAMs to regulatory decisions through case studies. These efforts are focused on developing information of “equivalent or better” scientific quality and relevance to animal test-based results.

High-Throughput Toxicology

ORD has developed a computational NAM model to evaluate potential estrogenic activity for the Agency’s Endocrine Disruptor Screening Program (EDSP). The model is being used to evaluate the potential estrogenic activity of over 1800 environmental chemicals and will reduce the use of low-throughput in vitro and in vivo assays. Looking forward, EPA will continue to modernize the EDSP by developing: computational models for estrogen receptor activity, androgen receptor activity, and steroidogenesis; high-throughput thyroid assays and associated models; species extrapolation approaches; and interactive dashboard tools, such as the CompTox Chemicals Dashboard, for data interpretation, translation, and chemical prioritization. Learn more about High-Throughput Toxicology research.

Virtual Tissue Models

Chemical assessments include consideration of risks to vulnerable subpopulations and life stages. NAMs help to address potential adverse developmental outcomes that reflect the best available knowledge of human developmental biology and do so with less reliance on traditional animal testing. EPA is exploring evaluating the effects of chemical exposure during human development on phenotypic responses in human-based in vitro and virtual tissue model systems to predict chemical hazard. In addition, EPA is developing and applying in silico virtual tissue models, agent-based models, and organotypic cell culture models to evaluate and model the effects of chemicals on reproductive and developmental endpoints. Learn more about Virtual Tissue Model research.

Adverse Outcome Pathways

Successful adoption and use of NAMs in risk assessments and regulatory decision making depends upon developing confidence that new methods and approaches provide equivalent or better scientific quality and relevance compared to existing approaches. To achieve this confidence, an understanding of both chemistry and biology is needed to establish the scientific rationale that support the use of NAMs in evaluating potential chemical impacts. EPA is actively developing Adverse Outcome Pathways (AOPs) for high-priority pathways and chemicals, designing relevant case studies, and disseminating the results through an AOP knowledgebase. Additionally, EPA is conducting in vitro and in vivo studies for high-priority AOPs to support predictive model development. EPA’s work on AOP will help to understand and define biological points of departure, actionable effect levels, and susceptibility factors for important chemicals of interest. Learn more about Adverse Outcome Pathways research.

Additional Resources

• List of NAMs per Section 4(h)(2)(C) of TSCA
• Alternative Toxicity Testing Report to Congress
• TSCA Alternative to Mammal Testing
• Pesticides

• Work Plan

  Prioritizing agency efforts to reduce vertebrate animal testing.

  EPA New Approach Methods Work Plan

• Conferences

  EPA will be hosting the 4th NAMs Conference November 5-6, 2024.

  EPA NAMs Conferences

• Training

  Access resources like recordings, worksheets, and user guides for EPA NAMs tools.

  Catalog of Training Materials