The National Toxicology Program (NTP) oversees a federal committee that Congress put in charge of implementing non-animal test methods within the government. The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) was established as a permanent committee of the National Institute of Environmental Health Sciences (NIEHS) under the NTP’s Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). The mission of ICCVAM, which is composed of representatives from 15 U.S. federal regulatory and research agencies, is to promote the regulatory acceptance of test methods that protect human and animal health and the environment while reducing, refining, or replacing the use of animal tests. ICCVAM had a long history of working against its congressionally mandated mission to validate reliable test methods that would have reduced the number of animals killed in toxicity tests. The following are just a few of the obstacles that ICCVAM presented:
- Actively campaigned to prohibit the U.S. from adopting the Globally Harmonized System of labeling, which would have allowed the use of non-animal methods to assess skin irritation
- Insisted on the use of rabbits for testing chemical effects on eyes
- Failed to review any of the non-animal methods used by the Environmental Protection Agency (EPA) for its Endocrine Disruptor Screening Program
- Actively excluded experts in non-animal testing methods from its advisory committee
ICCVAM lagged behind its European counterparts in approving new chemical test methods that did not involve animal subjects. The committee either moved slowly or took no action on reviewing methods to be used by the EPA, the Food and Drug Administration, and other federal agencies. You can read more about the history of problems with ICCVAM in PETA’s 2008 report, the resulting front-page Washington Post exposé of ICCVAM, and our 2010 detailed review of 33 alternative methods for which ICCVAM had inaccurately claimed credit. PETA called for the dismissal of ICCVAM head William Stokes, who, for more than a decade, undermined the use of scientifically reliable and humane non-animal test methods. Fortunately, in early 2013, Dr. Warren Casey, director of NICEATM, was appointed acting director of ICCVAM, and under his leadership, a new vision and direction for ICCVAM has flourished. The new approach is designed to align with the vision laid out in the 2007 National Academy of Sciences report Toxicity Testing in the 21st Century: A Vision and a Strategy. One of the first changes in ICCVAM procedure was to require that a member agency sponsor proposed assays or projects in order to ensure that the work done by ICCVAM would be aligned with the needs of the agencies. This is critical because it ensures that the methods ICCVAM is evaluating will be implemented at the regulatory level. Three areas that ICCVAM and its member agencies immediately identified as short-term high priorities are the following:
- Acute oral and dermal toxicity testing: ICCVAM and the EPA are spearheading an effort to evaluate the feasibility of waiving dermal toxicity testing based on acute oral toxicity data and are also assessing the ability of in vitro assays (e.g., 3T3 Neutral Red Uptake assay) to predict acute oral toxicity.
- Skin sensitization: Thanks in part to the development of an adverse outcome pathway(AOP) on skin sensitization, much progress has been made in developing integrated approaches to testing and assessment based on non-animal test methods (e.g., the direct peptide reactivity assay, the KeratinoSens assay and the h-CLAT assay). ICCVAM is closely monitoring progress in this field and is developing a strategy for evaluating skin sensitization test methods.
- Leptospirosis vaccine potency: The U.S. Department of Agriculture’s Animal and Plant Health Inspection Service (USDA-APHIS) is developing strategies to decrease the number of hamsters used in leptospirosis vaccine potency testing and in the maintenance of the leptospirosis challenge cultures.
We are optimistic that under the leadership of Dr. Casey, ICCVAM will continue to implement proactive and innovative approaches to developing and implementing non-animal testing methods throughout the government.