EPA Releases NAMs to Curb Animal Testing

On June 2, the U.S. Environmental Protection Agency released an expanded list of recognized New Approach Methods (NAMs)[EF1]  for chemical assessments under the Toxic Substances Control Act (TSCA) and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The agency also announced a new streamlined pathway for stakeholders to nominate additional methods for EPA consideration.

The action signals renewed EPA momentum toward replacing, reducing, and refining mammalian animal testing while creating practical opportunities for companies to use alternative methods in regulatory submissions and product safety evaluations.

What is the significance of EPA's expanded NAMs list? 

This is the first time EPA has updated its list of NAMs since 2021 and the first time the agency has opened   a formal process for companies, researchers, NGOs, and other stakeholders to nominate additional methods for regulatory consideration. This creates a near-term opportunity for regulated companies to reassess testing strategies, identify where NAMs may support TSCA or FIFRA obligations, and potentially help shape EPA's future accepted-method toolbox. 

With this new announcement and nomination process, NAMs are no longer just a scientific innovation topic; they are increasingly a regulatory strategy, product development, and compliance planning issue.

Manufacturers face regulatory pressure to reduce animal testing while maintaining scientifically robust safety assessments. Many have increased the use of human-relevant models, including reconstructed human tissues, in vitro assays, in chemico methods, computational toxicology, and integrated approaches to testing and assessment. Companies are also more heavily relying on the Organization for Economic Co-operation and Development (OECD) for validated methods and internationally recognized testing frameworks. 

There is a growing need for faster and more cost-effective chemical safety decisions, especially for innovation pipelines and product registrations. Corporate sustainability and animal welfare commitments — relevant to investors, customers, and downstream product users — are also becoming more important. These factors increase demand for regulatory certainty, as companies seek clarity on which non-animal methods EPA will accept for particular endpoints and decision contexts.

How to nominate a NAM 

The EPA is collecting short descriptions of NAMs for review through email at nam@epa.gov. If the agency decides to pursue the submitted NAM, organizations will be asked to complete a form and provide supporting scientific information. EPA scientists and subject-matter experts will assess the form submission and accompanying documentation for relevance, reliability, transparency, reproducibility, and fitness-for-purpose. 

Overall, EPA will consider three main factors when assessing NAMs:

• Context of use: How the NAM will support a specific TSCA or FIFRA regulatory decision context (screening new chemicals, prioritizing existing chemicals, or conducting risk evaluations) and the type of endpoint it addresses (e.g., physicochemical properties, fate, exposure, ecological effects, or human health). The Agency will also evaluate whether the information the NAM provides is adequate for the intended regulatory application. 
• Biological relevance: The scientific basis of the method, including biological or mechanistic understanding, and the reference chemicals used to evaluate and anchor the NAM.
• Reliability: Quality assurance practices, applicability domain, predictivity and statistical performance, reproducibility within and across laboratories, and whether the method has undergone independent review. 

EPA expects to evaluate nominated NAMs across a range of TSCA and FIFRA decision contexts[SH2] . Under TSCA, NAMs may be relevant to new chemical review, prioritization of existing chemicals, risk evaluations, and risk management decisions. Under FIFRA, NAMs may be relevant to pesticide registration and registration review, data requirement waivers, bridging arguments, hazard characterization, exposure assessment, ecological risk assessment, and weight-of-evidence evaluations for pesticide active ingredients and formulated products. 

The regulatory considerations may differ between TSCA and FIFRA. TSCA reviews often focus on whether a chemical presents an unreasonable risk under its conditions of use, including manufacturing, processing, distribution, use, and disposal. FIFRA reviews, by contrast, evaluate whether a pesticide can be registered or remain registered without causing unreasonable adverse effects on the environment, considering labeled uses, exposure scenarios, efficacy where relevant, and human health and ecological risk. As a result, the same NAM may have different utility depending on whether it is being used to support a TSCA chemical assessment, a FIFRA pesticide submission, or both.

The EPA will apply a fit-for-purpose framework, recognizing that a method suitable for one regulatory use may not be appropriate for another. Most NAMs currently on the list are likely to be used as part of a weight-of-evidence approach to characterize hazards or modes of action, although some may be combined to meet specific regulatory needs, such as OECD defined approaches that integrate multiple methods[KD3] .

What companies should consider when applying or nominating NAMs

Companies considering whether to apply an existing NAM or nominate a new NAM should first define the intended regulatory context of use. This includes identifying the relevant statute, decision point, chemical or product type, endpoint, exposure scenario, and whether the NAM is intended to replace, reduce, refine, or supplement traditional animal testing. Companies should also consider the method's applicability domain, data quality, reproducibility, biological relevance, performance against reference chemicals, and alignment with EPA, OECD, or other internationally recognized guidance.