Strategic Vision for Adopting New Approach Methodologies

Overview

To better protect human health and the environment, EPA’s Office of Pesticide Programs (OPP) is developing and evaluating new approach methodologies (NAMs) in molecular, cellular and computational sciences to supplement or replace more traditional methods of testing chemicals — such as animal testing — for potential hazards. OPP is enhancing its ability to use these new methods such as integrated approaches to testing and assessment (IATA). IATA promotes a hypothesis-based, systematic, integrative use of exposure and hazard information.

Adopting 21^st Century Methodologies for risk assessment and toxicology review purposes is built upon the “three Rs”: reduction, replacement and refinement.

Reduction of unnecessary animal testing is primarily addressed via EPA waiver policies and guidance documents, many of which have already been released to the public, with others still under development.

Replacement pertains to the substitution of in vivoin vivo Within a living organism; a laboratory experiment performed in which the substance under study is inserted into a living organism. animal studies with alternate methods such as predictive modeling and in vitroin vitro Testing or action outside an organism (e.g. inside a test tube or culture dish.) biochemical or cellular assays.

Refinement a test method that modifies procedures to enhance animal well-being, and lessen or avoid pain and distress in animals.

OPP has focused on the need to measure successes of these strategies with metrics and active quantitative tracking of progress in reducing animal testing.

In 2009, EPA released the Strategic Plan for Evaluating the Toxicity of Chemicals. In 2011, EPA published a FIFRA Scientific Advisory Panel (SAP) consultation document titled Integrated Approaches to Testing and Assessment Strategy: Use of New Computational and Molecular Tools. The long-term goal is to move away from a paradigm requiring in vivo (animal) testing for “every possible adverse outcome” toward a hypothesis-driven paradigm where in vitro testing plays a larger role in hazard identification.

In 2016, OPP released a Letter to Stakeholders discussing EPA’s development of a process for alternatives to traditional in vivo acute toxicity studies. This letter added momentum to efforts to reduce unnecessary animal testing in collaboration with industry, non-governmental organizations, and other governmental entities.

EPA's NAMs Work Plan was created in June 2020 to prioritize Agency efforts and resources toward activities that aim to reduce the use of vertebrate animal testing while continuing to protect human health and the environment. In December 2021, EPA released an updated Work Plan that outlines the strategies the Agency will deploy through 2024 across the following objectives: evaluate regulatory flexibility, develop baselines and metrics, establish scientific confidence and applicability for regulatory decisions, address scientific challenges, fill information gaps and engage with stakeholders.

Additional links to reference documents on EPA guidance and policies may be found on the corresponding sub-pages.

21st Century Science Methodologies Anticipated Results and Benefits

Anticipated Results:

• A broader suite of computer-aided methods to better predict potential hazards and exposures that will focus testing on likely risks of concern.  
• Improved approaches to more traditional toxicity tests to minimize the number of animals used while expanding the amount of information obtained.  
• Improved understanding of toxicity pathways to allow development of non-animal tests that better predict how exposures relate to adverse effects.  
• Improved diagnostic biomonitoring and surveillance methods to detect chemical exposures and identify causes of toxic effects  
• A suite of spatial databases and geographic information tools, which will aid in developing more spatially explicit risk assessments that identify geographic areas of concern for both human health and ecological exposure.

Anticipated benefits:

• Allows evaluation of more chemicals across a broader range of potential effects in a shorter timeframe.
• Has the potential to increase the feasibility of characterizing the combined effects posed by mixtures.
• Enhances predictive ability to determine whether animal testing is needed to refine a risk assessment and inform management decisions.
• Refines and reduces animal testing by maximizing information obtained from animal studies and focusing on effects of concern.
• Enhances the sophistication and efficiency of risk assessment and risk-management decisions.

Partnerships to Replace, Reduce & Refine Animal Testing

OPP works closely with its sister office, the Office of Pollution Prevention and Toxics (OPPT),​ and the Office of Research & Development (ORD) to develop and implement strategic plans and tools that advance development and implementation of alternative testing methods.

Read the OPPT’s 2018 Strategic Plan to Promote the Development and Implementation of Alternative Test Methods Within the Toxic Substances Control Act (TSCA) Program.

Read the Strategic Research Action Plan that OCSPP and ORD developed regarding chemical safety and sustainability.

Additionally, EPA maintains a strong partnership with the National Institute of Health’s Institute of Environmental Health Science (NIEHS) and its National Toxicology Program (NTP). The NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) continues to work closely with OPP to collect and analyze data with a focus on the development of alternatives to animal use for chemical safety testing. One of the permanent committees in the NIEHS is the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), which was formally established in 2000 and is composed of representatives from 16 U.S. federal regulatory and research agencies. In January of 2018, ICCVAM released its “Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States”.  This document serves as a resource to guide federal agencies and stakeholders seeking to adopt new approaches to safety and risk assessment of chemicals and medical products that improve human relevance and replace or reduce the use of vertebrate animals for testing.

Additional Information

• EPA Efforts to Reduce Vertebrate Animal Testing
• Process for Evaluating & Implementing Alternative Approaches to Traditional in Vivo Acute Toxicity Studies for FIFRA Regulatory Use
• Safer Chemicals Research
• Strategic Plan for Alternative Test Methods Development in TSCA Program
• Integrated Approaches to Testing and Assessment
• National Academy of Sciences Report on Toxicology Testing in the 21st Century 
• Tox21 Federal Agency Consortium