Plan Overview	Preface
Executive Summary	Introduction
CHAPTER 1 - Research, Development, Translation, and Validation Activities for Priority Test Methods to Reduce, Refine, and Replace Animals in Regulatory Testing
CHAPTER 2 - Incorporating New Science and Technology
CHAPTER 3 - Fostering Acceptance and Appropriate Use of Alternative Test Methods
CHAPTER 4 - Developing Partnerships and Strengthening Interactions with ICCVAM Stakeholders
References - Acronyms and Abbreviations - Glossary	Appendices
Acknowledgements - ICCVAM Roster - About NICEATM and ICCVAM

References - Acronyms and Abbreviations - Glossary

References and Information Resources

Note: References cited as webpages in the hard copy/PDF version of the Five-Year Plan can be accessed here by selecting the active link in the reference listing.

• Animal Welfare Act, as amended. 1990. Public Law 89-544.
• Fowler BA, Socha M and Sonawane B. 2005. International Conference on Biomarkers for Toxicology and Molecular Epidemiology, March 15–17, 2004. Toxicol Appl Pharmacol 206:98-101.
• Health Research Extension Act of 1985. 1985. Public Law 99-158.
• ICCVAM. 1997. Validation and Regulatory Acceptance of Toxicological Test Methods: A Report of the ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods. NIH Publication No. 97-3981. Research Triangle Park, NC: National Institute for Environmental Health Sciences.
ICCVAM Authorization Act of 2000. 2000. Public Law 106-545.
• ICCVAM. 2003. ICCVAM Guidelines for the Nomination and Submission of New, Revised, and Alternative Test Methods. NIH Publication No. 03-4508. Research Triangle Park, NC: National Institute for Environmental Health Sciences.
• ICCVAM. 2004. ICCVAM: Mission, Vision and Strategic Priorities.
• National Research Council. 2004. Science, Medicine, and Animals. Washington, DC: National Academy of Sciences.
• National Research Council. 2007. Toxicity Testing in the Twenty-first Century: A Vision and a Strategy. Washington, DC: National Academy of Sciences. Available: [accessed 10 August 2007].
• NIH Revitalization Act of 1993. 1993. Public Law 103-43.
• National Toxicology Program. 2004. Toxicology in the 21st Century: The Role of the National Toxicology Program.
• Organisation for Economic Co-operation and Development (OECD). 2005. OECD Series on Testing and Assessment Number 34: Guidance Document on the Validation and International Acceptance of New Test Methods for Hazard Assessment. Paris: OECD.
• Office of Laboratory Animal Welfare. 2002. Public Health Service Policy on Humane Care and Use of Laboratory Animals. Bethesda, MD: National Institutes of Health.
• Russell WMS, Birch RL. 1959. The Principles of Humane Experimental Technique. 1st ed. London: Methuen and Co.

A full listing of all ICCVAM publications can be found on the NICEATM-ICCVAM website.

Acronyms and Abbreviations

Glossary of Terms¹

• Accuracy: (a) The closeness of agreement between a test method result and an accepted reference value. (b) The proportion of correct outcomes of a test method. It is a measure of test method performance and one aspect of “relevance” and is a term that is often used interchangeably with “concordance”.
• Acute toxicity²: Adverse effects occurring within a short time (usually up to 14 days) after administration of a single dose (or exposure to a given concentration) of a test substance or after multiple doses (exposures), usually within 24 hours; OR the ability of a substance to cause adverse effects within a short time of dosing or exposure.
• Assay: The experimental system used. Often used interchangeably with “test” and “test method”.
• Biological products or Biologics: Includes a wide range of products such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, therapeutic antibodies, and recombinant therapeutic proteins. Biologics can be composed of sugars, proteins, or nucleic acids, or complex combinations of these substances, or may be living entities such as cells and tissues. Biologics are isolated from a variety of natural sources - human, animal, or microorganism - and may be produced by biotechnology methods and other cutting-edge technologies. Gene-based and cellular biologics, for example, often are at the forefront of biomedical research, and may be used to treat a variety of medical conditions for which no other treatments are available.
• Biomarker³: A distinctive biological or biologically derived indicator (as a biochemical metabolite in the body) of a process, event, or condition (as aging, disease, or exposure to a toxic substance).
• Chronic Toxicity: Adverse effects following chronic exposure; OR effects which persist over a long period of time whether or not they occur immediately upon exposure or are delayed.
• Concordance: The proportion of all chemicals tested that are correctly classified as positive or negative. It is a measure of test method performance and one aspect of “relevance”. The term is often used interchangeably with “accuracy”.
• Endpoint: The biological or chemical process, response, or effect assessed by a test method.
• Hazard: The potential for an adverse health or ecological effect. A hazard potential results only if an exposure occurs that leads to the possibility of an adverse effect being manifested.
• In vitro: Outside the living body and in an artificial environment: “growth of cells in vitro”, “in vitro studies”.
• In vivo: In the living body of a plant or animal: “in vivo synthesis of DNA”, “microorganisms are not ordinarily destroyed in vivo by bacteriostatic drugs”.
• Mechanistically based methods: Methods that provide a direct relationship between the biological effects observed and the biological effects of interest.
• Performance: The accuracy and reliability characteristics of a test method (see “accuracy”, “reliability”).
• Reduction alternative: A new or modified test method that reduces the number of animals required.
• Reference species: The species used in the reference (or traditional) test method to which a new or modified test is being compared. This may be the target species when it is also the species of interest, or it may be a surrogate species when it is not possible to perform testing on the target species.
• Reference test method: The accepted in vivo test method used for regulatory purposes to evaluate the potential of a test substance to be hazardous to the species of interest.
• Refinement alternative: A new or modified test method that refines procedures to lessen or eliminate pain or distress in animals or enhances animal well-being.
• Relevance: The extent to which a test method correctly predicts or measures the biological effect of interest in humans or another species of interest. Relevance incorporates consideration of the “accuracy” or “concordance” of a test method.
• Reliability: A measure of the degree to which a test method can be performed reproducibly within and among laboratories over time. It is assessed by calculating intra- and inter-laboratory reproducibility and intralaboratory repeatability.
• Replacement alternative: A new or modified test method that replaces animals with nonanimal systems or one animal species with a phylogenetically lower one (for example, a mammal with an invertebrate).
• Risk: The probability or degree of concern that exposure to an agent will cause an adverse effect in the species of interest.
• Risk assessment⁴: Evaluation of the potential adverse health and environmental effects to a target species from exposures to certain substances.
• Screen/screening test: A rapid, simple test conducted for the purposes of a general classification of substances according to general categories of hazard. The results of a screen generally are used for preliminary decision-making and to set priorities for more definitive tests. A screening test may have a truncated response range (for example, be able to reliably identify active chemicals but not inactive chemicals).
• Substitute method: A new or modified test method proposed for use in lieu of a currently used test method, regardless of whether that test method is for a definitive, screening, or adjunct purpose.
• Test: The experimental system used; used interchangeably with “test method” and “assay”.
• Test method: A process or procedure used to obtain information on the characteristics of a substance or agent. Toxicological test methods generate information regarding the ability of a substance or agent to produce a specified biological effect under specified conditions. Used interchangeably with “test” and “assay”. See also “validated test method” and “reference test method”.
• Test method nomination: Test methods proposed to ICCVAM for review and evaluation for which a complete test method submission is not available. Four examples are (1) test methods for which adequate validation studies presumably have been completed but lack a complete submission package; (2) test methods that appear promising based on limited revalidation or validation data and are proposed for additional validation studies; (3) test methods that have been developed and are proposed for revalidation or validation studies; and (4) test methods that are recommended for a workshop or other activity.
• Test method nominator: The organization or individual that submits a test method nomination to ICCVAM for consideration.
• Test method sponsor: The organization or individual that puts forward a test method submission to ICCVAM for consideration.
• Test method submission: A test method proposed to ICCVAM for consideration for which adequate validation studies have been completed to characterize the usefulness and limitations of the test method for a specific proposed regulatory testing requirement or application, and adequate documentation of the scientific validity has been prepared in accordance with ICCVAM test method submission guidelines.
• Toxicology⁵: The study of the adverse effects of chemicals on living organisms. It is the study of symptoms, mechanisms, treatments and detection of poisoning of humans, animals, or the environment.
• Transferability: The ability of a test method or procedure to be accurately and reliably performed in different laboratories.
• Translation: For the purposes of this document, ICCVAM considers translation as activities that are carried out to characterize if there is evidence of relevance and applicability of a test method for a specific testing purpose. If so, then the test method may be considered for evaluation in a formal validation study.
• Validated test method: An accepted test method for which validation studies were conducted and the demonstrated relevance and reliability were sufficient for the test method's intended purpose.
• Validation: The process by which the reliability and relevance of a procedure are established for a specific purpose.

Footnotes

¹ Unless otherwise indicated, definitions are from ICCVAM Guidelines for the Nomination and Submission of New, Revised, and Alternative Test Methods (NIH Publication No. 03-4508, September 2003)

² From National Library of Medicine Toxicology Glossary

³ From Medline Plus Medical Dictionary

⁴ Modified from Validation and Regulatory Acceptance of Toxicological Test Methods: A Report of the ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods (NIH 97-3981, March 1997).

⁵ Modified from Medline Plus Medical Dictionary

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