EPA added 13 New Approach Methodologies to its approved list in June 2026, the first update since 2021. What it means for TSCA and FIFRA registrants.
EPA recently released a renewed commitment to eliminate animal testing by 2035 under Administrator Lee Zeldin, updating the approved list for New Approach Methods (NAMs) for the first time since 2021 by adding 13 new methods and a streamlined pathway to nominate additional methods.
NAMs are emerging testing methods intended to replace the use of animal testing for products and materials under regulatory assessment without sacrificing study or data quality. Typically, companies submitting a product or material to the EPA conduct a full battery of human health and environmental toxicology testing to demonstrate safety or accurately measure any risks that may be present. Some products have explicit data requirements for EPA evaluation, which may be very costly in terms of time and resources, so NAMs could be a solution to cut down on both time and cost while also sacrificing less animals.
The three categories on EPA's list
EPA’s list of accepted NAMs is divided into three categories: OECD and EPA test guidelines, computational tools and models, and policy related documents. Each of these categories represents a different method of replacing a traditional animal study.
Test guidelines: in vitro and in chemico replacements
Generally, the OECD and EPA test guideline NAMs take an in vitro approach to replacing animal models, often using cultured human or animal cell lines rather than a whole animal. For instance, specific guidelines offer targeted solutions for evaluating topical safety. Guideline OECD TG No. 431 offers an in vitro method to test dermal corrosion via a three-dimensional human skin model with a functional stratum corneum, which may be helpful for your product’s data package as a preliminary hazard identification or if skin contact is a primary safety concern for end users.
OECD and EPA guideline NAMs sometimes also take an in chemico approach for evaluating a material. In chemico studies evaluate how a chemical interacts with certain materials instead of using any human or animal cells. OECD TG No. 495 measures photoreactivity using Reactive Oxygen Species (ROS) instead of cell lines to predict potential phototoxicity. Although further work is needed to validate positive results, negative assay results have been cross-validated to accurately reflect those for in vivo studies, which could reduce unnecessary testing based on a specific test chemical.
Computational models: in silico predictions
Computational tools and modeling NAMs are also called in silico, and aim to remove the biological component of testing altogether. One such in silico modelling tool is the Toxicity Estimation Software Tool (TEST). The software includes models for six toxicity endpoints: 96-hour fathead minnow 50 percent lethal concentration (LC50), 48-hour Daphnia magna 50 percent lethal concentration (LC50), Tetrahymena pyriformis 50 percent growth inhibition concentration (IGC50), oral rat 50 percent lethal dose (LD50), developmental toxicity, and Ames mutagenicity. TEST estimates these endpoints through a method called Quantitative Structure Activity Relationships (QSARs), which uses the known characteristics of chemical structures to make predictions about how a substance will behave in the environment, as well as within an animal’s bodily system.
Newly added to the NAMs list, ECOTOX is a database used to investigate the toxic effects of a chemical or substance on both aquatic and terrestrial species in the environment. This tool allows you to search published data for a specific substance as well as browse all data according to chemical class, toxicological effects, and species affected. While there are some limitations to this database, its single-chemical, peer-reviewed toxicity data serves as a strong starting point for a product’s data package or addressing regulatory questions.
These types of models have the potential to not only replace animal models, but also could play a part in a product’s data package by helping to select the dosing range for animal testing that is deemed necessary.
Policy and framework documents
The policy related documents included as part of the NAMs list includes guides to fully utilizing the different types of listed NAMs, as well as regulatory framework to aid in completing different risk or hazard assessments without the use of animal models. These documents help piece together information from NAMs, alongside the collective scientific intelligence built by global researchers and regulatory submissions, to fully assess a material or product.
Applying NAMs in Practice
While NAMs are growing, they still represent a relatively small portion of total submissions, and sometimes it can be unclear how your material or product fits into a regulatory framework or an existing NAM, especially if you are developing a new technology. This can lead to uncertainty whether or not EPA will accept a NAM study that is conducted in lieu of a traditional animal model.
NAMs are mainly applicable to products or materials under The Toxic Substances Control Act (TSCA), but products regulated under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) may still utilize NAMs as part of a weight-of-evidence (WOE) approach for a product’s safety and stewardship data package.
Contact Compass
Contact our experts at Compass to learn more about NAMs, data requirements, and explore your product’s options.
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