The term "alternative" in the context of animal testing is used to describe any change from present procedures that will result in the replacement of animals, a reduction in the numbers used, or a refinement of techniques to alleviate or minimize potential pain, distress and/or suffering. This concept—also known as the "3Rs"—was first articulated in the 1959 publication, The Principles of Humane Experimental Technique.
Alternatives to the use of animals in toxicity testing include the elimination of redundant or needless study requirements, the replacement of animal tests with non-animal methods, and the modification of animal-based tests to reduce the number of animals used and to minimize pain and distress. The Humane Society works closely with government regulators in the United States, the European Union, and internationally through the Organization for Economic Cooperation and Development (OECD), the International Conference on Harmonization (ICH) and the Veterinary International Cooperation on Harmonization (VICH), to reduce their reliance on animal testing and to become more involved in the development and use of sophisticated new non-animal test methods.
To this end, the Humane Society is actively supporting the vision of "twenty-first century toxicology" articulated by the US National Research Council, which would see animal tests that are decades old, costly, slow and of dubious relevance to people replaced by ultra-modern, efficient and human-relevant non-animal methods. We are calling for a "big biology" project to meet this challenge, akin to the Human Genome Project of the 1990s, and are forging an international, multi-stakeholder consortium to help make this landmark vision a reality as quickly as possible.
In the meantime, we are working toward the elimination of unnecessary testing requirements from international regulatory frameworks, including the deletion of 1-year dog studies from pesticide regulations and acute lethality studies from ICH test guidelines. Other opportunities include limiting cancer tests to a single species (which would spare 400 animals per test), and evaluating reproductive toxicity using only one generation of offspring instead of two (which would save at least 1,200 animals per test).
Additionally, more than two-dozen alternative methods have already been declared scientifically valid as animal replacement, reduction or refinement tools. Examples include the following:
Replacement Methods:
- EPISKIN, EpiDerm and SkinEthic tests for skin irritation
- EPISKIN, EpiDerm, SkinEthic and Transcutaneous Electrical Resistance tests for skin corrosion
- 3T3 neutral red uptake (3T3 NRU) phototoxicity test
- In vitro micronucleus test for genetic toxicity
- Colony forming unit granulocyte macrophage (CFU-GM) test for toxicity to the blood
- 5 human blood-based tests for fever-inducing "pyrogens" in intravenous drugs
- "ELISA" chemical tests to measure the potency of human tetanus and erysipelas vaccines
- Toxin binding inhibition (ToBI) test for vaccine potency
Reduction and/or Refinement Methods:
- Upper threshold concentration step-down procedure for acute aquatic toxicity testing (up to 70% reduction in fish use)
- Reduced local lymph node assay (rLLNA) for skin sensitization (up to 50% reduction relative to conventional LLNA)
- Cellular tests using "NHK" and "Balb/c 3T3" cell lines to set starting doses for acute oral toxicity studies (up to 40% reduction)
- Bovine corneal opacity and permeability (BCOP) and isolated chicken eye (ICE) tests for classifying severe eye irritants and corrosives
- Fixed dose, acute toxic class, and up-and-down procedures for acute mammalian toxicity (50% reduction relative to classical "lethal dose" tests)
- Mouse embryonic stem cell and whole embryo culture tests for embryotoxicity (a critical element in developmental toxicity testing)
For a complete list of validated and accepted alternative methods for toxicity testing, please click here.
