Alternatives to Animal Testing
Questions and Answers about ICCVAM
Alternatives to Animal Testing
What are alternative test methods?
Alternative test methods are test methods that reduce, refine, or replace animal use in research and testing. Reduction, refinement, and replacement are commonly referred to as “the 3Rs”. The 3Rs concept was first described by William Russell and Rex Burch in their 1959 book The Principles of Humane Experimental Technique.
What do "reduce, refine, or replace" mean in the context of animal use in research and testing?
- A test method that reduces animal use decreases the number of animals required for testing while still achieving testing objectives.
- A test method that refines animal use lessens or eliminates pain or distress in animals, or enhances animal well-being.
- A test method that replaces animals substitutes traditional animal models with nonanimal systems such as computer models or biochemical or cell-based systems, or replaces one animal species with a less highly developed one (for example, replacing a mouse with a worm).
Why is safety testing performed on chemical products?
U.S. regulatory agencies require testing of consumer products, medicines, and industrial and agricultural chemicals to identify potential health and safety hazards. Testing these substances enables appropriate hazard classification and labeling, which in turn enables informed decisions about responsible use, storage, and disposal. All toxicity test methods used for regulatory purposes must be based on sound science and able to adequately identify hazards.
Is there a requirement to consider alternative methods before animals are used for testing?
Yes. U.S. laws require that alternatives must be considered before using animals for research and testing.
- The Animal Welfare Act requires that Institutional Animal Care and Use Committees in facilities where research and testing using animals is done approve proposed animal use and ensure that alternatives are being used where appropriate.
- The Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals addresses the use of animals by NIH grantees and within NIH and other institutions under the Public Health Service. The PHS Policy requires that proposals justify the animal use, the number of animals to be used, and the specific procedures to be used.
Are Federal agencies required to support the development of alternative test methods?
- The NIH Revitalization Act of 1993 directed NIH to support research to reduce, refine, and replace animal use in biomedical research, and to develop and validate methods that will reduce and replace animals in acute and chronic safety testing.
- The ICCVAM Authorization Act of 2000 established the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) to coordinate activities within the Federal government relevant to new test method evaluation, acceptance, and use. ICCVAM is made up of representatives of 15 U.S. Federal agencies that use or generate toxicity testing information.
Why are animals still used for safety testing?
Human and animal responses to chemicals are complex and difficult to accurately assess using only biochemical or cell-based (“in vitro”) systems or computer models. No single in vitro test method is currently available to serve all regulatory needs for a specific testing area. In some areas, such as identification of severe eye irritants and substances that could cause allergic contact dermatitis, major progress has been made in reducing and replacing animal use. For other hazards, such as identification of substances that can cause cancer or birth defects, development of in vitro tests that reliably identify hazards is more difficult because of the number of different mechanisms involved in these complex biological processes.
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How does NIEHS support the development and use of alternative test methods?
NIEHS supports the development and use of alternative methods:
- By adhering to the requirements outlined in the PHS Policy
- As a member institution of ICCVAM
- Through the activities of the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) , an office within the Division of the NTP at NIEHS
- Through its participation in the U.S. government’s interagency high-throughput screening initiative known as Tox21
What NIEHS is Doing on Alternatives to Animal Testing
- Plan to replace animal use shared at public forum
- Kleinstreuer highlights groundbreaking approaches to safety testing
- Groundbreaking EPA testing plan builds on NTP work to replace animal use
- Public forum highlights progress on replacing animals used in safety testing
- Symposium strengthens efforts to ensure replacement chemicals are safer
What is ICCVAM’s mission and purpose?
ICCVAM's mission is to facilitate development, validation, and regulatory acceptance of new, revised, and alternative regulatory safety testing methods that reduce, refine, and replace the use of animals in testing while maintaining and promoting scientific quality and the protection of human health, animal health, and the environment.
The ICCVAM Authorization Act of 2000 states that the purposes of ICCVAM are to:
- Increase the efficiency and effectiveness of Federal agency test method review
- Eliminate duplication of effort between Federal agencies
- Optimize use of scientific expertise outside the Federal government
- Ensure that new and revised test methods are validated to meet the needs of Federal agencies
- Reduce, refine, and/or replace the use of animals in testing where feasible
What activities does ICCVAM conduct to accomplish these purposes?
To accomplish its purposes, ICCVAM is charged with the following functions:
- Coordinate the technical review and evaluation of new, revised, or alternative test methods
- Foster interagency and international harmonization of test protocols that encourage reducing, refining, and replacing animal test methods
- Facilitate and provide guidance on validation criteria and processes
- Promote the acceptance of scientifically valid test methods
- Promote awareness of accepted test methods
- Submit ICCVAM test recommendations to appropriate U.S. Federal agencies
- Consider requests from the public to review and evaluate new, revised, or alternative test methods that have evidence of scientific validity
- Make ICCVAM final test recommendations available to the public
- Prepare reports on ICCVAM progress and accomplishments under the Act and make these available to the public
Who are ICCVAM’s members?
ICCVAM is made up of one or more Federal employees from each of the following Federal agencies or offices .
- Consumer Product Safety Commission (CPSC)
- Department of Defense (DOD)
- Department of Energy (DOE)
- Agency for Toxic Substances and Disease Registry (ATSDR)
- National Institute for Occupational Safety and Health (NIOSH)
- Food and Drug Administration (FDA)
- National Institutes of Health (NIH)
- National Cancer Institute (NCI)
- National Institute of Environmental Health Sciences (NIEHS)
- National Library of Medicine (NLM)
- Department of the Interior (DOI)
- Occupational Safety and Health Administration (OSHA)
- Department of Transportation (DOT)
- Environmental Protection Agency (EPA)
ICCVAM members are selected to represent their agency on ICCVAM because they are knowledgeable about their agency’s activities or requirements relevant to safety testing. ICCVAM members attend monthly ICCVAM committee meetings or teleconferences and engage in other ICCVAM activities in addition to their other duties within their agencies.
About the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)
What is NICEATM?
NICEATM is an office within the Division of the NTP (DNTP) at NIEHS. The office has two Federal employees, Director Warren Casey, Ph.D., and Toxicologist Elizabeth Maull, Ph.D. Additional NICEATM support is provided through an NIEHS contractor.
What does NICEATM do?
NICEATM’s activities include
- Supporting DNTP activities, especially those contributing to Tox21
- Conducting evaluations and coordinating independent validation studies of novel and high-priority alternative test methods and approaches
- Providing information to test method developers, regulators, and regulated industry through its website and email list and by sponsoring workshops on topics of interest
- Providing scientific and operational support to ICCVAM
What is the role of NICEATM and ICCVAM in gaining regulatory acceptance of new and alternative test methods?
When a test method is submitted to ICCVAM for evaluation, NICEATM and ICCVAM work together to evaluate that method’s usefulness and limitations for specific testing purposes. ICCVAM then develops recommendations for Federal agencies regarding appropriate uses of the method. Each Federal agency determines whether the test method is acceptable for its specific program.
Does ICCVAM or NICEATM conduct alternative methods research or validation studies?
No. ICCVAM is an interagency committee that meets monthly; NICEATM is an office with limited staff and no laboratory facilities. ICCVAM depends on stakeholders with appropriate capabilities and resources to carry out alternative test method research, development, and validation studies and to submit the results to ICCVAM.
Stakeholders, Nominations and Outreach
Who are ICCVAM's stakeholders?
ICCVAM's stakeholders are any person or organization that uses, develops or has an interest in toxicity testing methods or the data that is generated from toxicity testing. They include:
- U.S. Federal agencies that generate or use toxicity data
- Agencies within governments of other countries that use or generate toxicity data
- Researchers and Institutional Animal Care and Use Committee (IACUC) members in companies or research institutions that perform toxicity testing
- Companies that develop toxicity tests for sale
- Animal welfare organizations
- Consumer protection organizations
- Any member of the public interested in human and environmental health and related animal welfare issues
How does ICCVAM communicate with its stakeholders?
- NICEATM announces ICCVAM activities and requests input from ICCVAM stakeholders by publication of notices in the Federal Register, posting announcements on the NTP website , and sending emails to members of the ICCVAM-all mailing list .
- ICCVAM members interact with their international counterparts through the International Cooperation on Alternative Test Methods (ICATM) and the Organisation for Economic Co-operation and Development (OECD).
- ICCVAM members participate in national and international scientific meetings.
- NICEATM organizes workshops on topics relevant to alternative methods development. ICCVAM or ICCVAM agencies cosponsor these workshops and ICCVAM members participate as presenters or organizing committee members.
- The Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) advises the NIEHS Director, NICEATM, and ICCVAM about NICEATM and ICCVAM activities. SACATM is made up of representatives from various ICCVAM stakeholder groups. SACATM meetings are open to the public, and public comments are invited on agenda topics.
Who can make test method submissions?
ICCVAM welcomes submissions of relevant new, revised, and alternative test methods from any of its stakeholders, including government agencies, academics, companies developing new test methods, and animal welfare organizations. However, to maximize the potential for effective implementation of new test methods or approaches, ICCVAM will only conduct evaluations and prepare recommendations on test method submissions proposed for regulatory uses that align with ICCVAM member agency needs and priorities.
Test method sponsors are encouraged to consult with NICEATM and ICCVAM throughout the test method research, development, translation, and validation process, as well as during preparation of submissions. These interactions ensure that:
- The test method aligns with the needs and priorities of one or more ICCVAM agencies, and there is at least one agency willing to sponsor the test method for evaluation
- Validation studies that are conducted using the test method adequately characterize its usefulness and limitations for a particular regulatory application
- The test method submission package contains the data and information that sponsoring agencies require to determine the extent to which a test method can generate information that will meet their regulatory needs
Progress and Plans
How has ICCVAM's work replaced, reduced, or refined animal use in toxicity testing?
ICCVAM has evaluated many alternative methods for regulatory use and made a number of formal recommendations to Federal agencies . ICCVAM’s recommendations to Federal agencies include:
- An approach to the standard animal test used to assess acute oral systemic toxicity (poisoning) that reduces the number of animals used
- Use of assays employing cultured cells to set starting doses for acute oral systemic toxicity testing to further reduce the number of animals required for each test
- Nonanimal models that simulate human skin to assess the potential of chemicals to cause skin burns
- A mouse method to assess the potential of substances to cause allergic contact dermatitis that uses fewer animals and eliminates pain and distress compared to traditional guinea pig methods
- Assays employing tissue isolated from food animal species (cows or chickens) during processing to screen chemicals and products for their potential to cause blindness or other severe eye injuries; substances that test positive do not require testing on live animals
These recommendations can potentially reduce the number of animals used for these types of toxicity testing and refine animal use to lessen or avoid animal pain and distress.
How are ICCVAM and NICEATM changing to better respond to stakeholder needs and changes in the science of toxicology?
ICCVAM stakeholders have raised concerns that the methods recommended by ICCVAM were not being used for regulatory decision-making. Expectations for real reductions in animal use for toxicity testing were not being matched by documented progress. In a February 2013 Environmental Health Perspectives editorial, NIEHS and NTP Director Dr. Linda Birnbaum announced that NIEHS would move forward with a different philosophy toward ICCVAM whereby the partner regulatory agencies would drive ICCVAM’s activities. At the same time, NICEATM would expand its scope to provide bioinformatic and computational toxicology support to the DNTP. The goal of these activities would be to better position ICCVAM to address how data from the Tox21 collaboration could be integrated into the existing regulatory framework.
In response to this new philosophy, ICCVAM developed a draft document titled “ A New Vision and Direction for ICCVAM ”. The document presented ICCVAM’s (1) areas of priority and scientific focus for immediate resource investment; (2) plans to improve communications with stakeholders and the public; and (3) interest in exploring new paradigms for the validation and utilization of alternative toxicological methods. This document was released for public comment in August 2013 and discussed at the September 2013 SACATM meeting . ICCVAM is carefully considering public and SACATM comments on the draft document as it develops new operating procedures and plans activities for the near future.