ICCVAM Biennial Report 2024-2025

We are pleased to share with you the many accomplishments of the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), and the 18 ICCVAM agencies in the 2024–2025 Biennial Report. These accomplishments address needs and priorities identified in the “Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States.”

We congratulate the ICCVAM Validation Workgroup on the March 2024 publication of “Validation, Qualification, and Regulatory Acceptance of New Approach Methodologies.” This update of the original ICCVAM criteria for new approach methodologies (NAMs) validation reflects the advancement of alternative toxicological testing tools. It places less emphasis on replacement of in vivo tests with a single alternative method and instead emphasizes integrating evidence from multiple in vitro and in chemico assays and in silico approaches. This document is already proving to be a key resource in U.S. and international initiatives to bring state-of-the-science approaches to bear on development and validation of test methods.

The period covered by this report has been remarkable in the number and visibility of federal government initiatives to advance alternative methods to complement or replace animal use in testing and research. Policy shifts announced in 2025 by the U.S. Food and Drug Administration and the National Institutes of Health (NIH) will prioritize the development of predictive systems that use computer modeling and in vitro testing in these areas. Initiatives by the U.S. Environmental Protection Agency (EPA), the U.S. Department of the Interior, the U.S. Department of Transportation, and other ICCVAM member agencies to complement, reduce, or replace animal use are also described in this report.

ICCVAM and NICEATM also continue to be at the forefront of developing new approaches to address specific chemical safety testing needs. We congratulate NICEATM on the acceptance of the Skin Allergy Risk Assessment – Integrated Chemical Environment (SARA-ICE) defined approach for skin sensitization (Reinke et al. 2025) by OECD in an update to its Guideline 497 for defined approaches to identify skin sensitizers. SARA-ICE, developed by NICEATM in collaboration with the consumer products company Unilever, is the first defined approach that provides a numerical estimate of potency to be accepted as an OECD guideline test. ICCVAM also sponsored an EPA-led interlaboratory validation study of a thyroid 3D microtissue model for evaluating chemical effects on thyroid hormone synthesis and tissue viability (Deisenroth et al. 2026). This model is an important advance in assessing thyroid hormone interference, filling a notable gap in determining the potential of chemicals to affect the endocrine system.

A key area of the Strategic Roadmap is communication. During 2024-2025, NICEATM and ICCVAM continued to effectively connect with stakeholders, as demonstrated by the high attendance and strong participation at ICCVAM-sponsored virtual public events such as the Communities of Practice webinars and the Public Forums. In response to stakeholder requests, NICEATM and ICCVAM member agencies such as EPA and the U.S. Department of Agriculture are increasing efforts to provide training on computational tools and data resources and highlight available information on NAMs. Details and outcomes of many of these outreach efforts are described herein.

NIEHS and NTP have been proud to be the home of ICCVAM and NICEATM since their inception over 20 years ago and to support their important work to advance NAMs. Reflecting the increasingly central role of ICCVAM and NICEATM to NIH efforts to develop, validate, and scale the use of NAMs, we announced in 2026 plans for NICEATM to move to the newly created Office of Research Innovation, Validation, and Application (ORIVA) within the Division of Program Coordination, Planning, and Strategic Initiatives in the NIH Office of the Director. Within ORIVA, NICEATM would become the Division of the National Interagency Center for the Evaluation of Alternative Test Methods (D-NICEATM) and work alongside ORIVA’s Division for Accelerating Innovation in Biomedical Research. NIEHS and NTP are actively supporting this planned transition and look forward to continued fruitful collaborations with ORIVA in the future.

The activities in this 2024–2025 Biennial Report illustrate the outstanding contributions of ICCVAM to advance alternative methodologies and the 3Rs. We invite you to read this report to learn about all that ICCVAM has accomplished in the past two years.

Kyle Walsh, Ph.D.
Director, National Institute of Environmental Health Sciences and National Toxicology Program

Heather Patisaul, Ph.D.
Scientific Director, Division of Translational Toxicology, National Institute of Environmental Health Sciences