Recognition and Alleviation of Pain in Laboratory Animals (2009) / Chapter Skim
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5 Humane Endpoints for Animals in Pain
5 Humane Endpoints for Animals in Pain
Pages 119-140
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From page 119... ...
GUIDELINES AND REFERENCE DOCUMENTS Moral and ethical obligations are inherent in all aspects of research, testing, and teaching that use research subjects. The question of when a study using animal models should end or the study design be changed due to animal pain, distress, or welfare considerations has been the subject of many publications, symposia, guidance documents, and regulations.
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From page 120... ...
. The OECD Guidance Document defines humane endpoints "as the earliest indicator in an animal experiment of severe pain, severe distress, suffering, or impending death.
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From page 121... ...
• The ultimate purpose of the application of humane endpoints to toxicology studies is to be able to accurately predict severe pain, severe distress, suffer ing, or impending death, before the animal experiences these effects. However, the science of toxicology is not yet to the point where such accurate predic tions can be made prior to the onset of severe pain and distress.
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From page 122... ...
. Beyond Formal Guidelines Many of the articles and recommendations that address humane endpoints focus on very specific study or research types that can cause pain to laboratory animals; for example, studies on the identification and use of humane endpoints in animal models of sepsis and shock provide an excellent overview of the methodologies to determine humane endpoints yet still achieve study objectives (Nemzek et al.
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From page 123... ...
As a corollary, it is worth emphasizing that investigators, technicians, and other staff responsible for the care of research animals should be well trained and able to make impartial judgments about an animal's well-being. OLAW approached the subject of humane endpoints in its Institutional Animal Care and Use Committee Guidebook (OLAW/ARENA 2002, p.
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From page 124... ...
. INTERNATIONAL REGULATIONS AND GUIDELINES FOR SAFETY ASSESSMENT Regulatory bodies in most countries have developed standards and guidelines to ensure the conduct of appropriate safety assessments on test substances (Hicks 1997; Merrill 2001; USEPA 2008)
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From page 125... ...
. While these efforts do not define humane endpoints, the authors of the regulation are commended for the consideration of responsible animal use in safety assessment.
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From page 126... ...
, such as the local lymph node assay in mice, whereas agencies in other countries may not accept the data in lieu of the guinea pig dermal sensitization test. While a comparison of all safety assessment guidelines is well beyond the scope of this report, differences in regulatory-driven studies can have a negative impact on the prevention and alleviation of pain in laboratory animals.
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From page 127... ...
True harmonization of guideline safety assessment tests and global adoption of the OECD humane endpoints document would be an important step toward the alleviation and avoidance of pain in laboratory animals. The NRC report Toxicity Testing in the Twenty-first Century: A Vision and a Strategy (NRC 2007)
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From page 128... ...
This approach, based on step-wise, or tiered, testing, is expected to reduce animal numbers, minimize potential pain to laboratory animals by avoiding exposure levels that produce clinical signs of toxicity, and improve the quality of data for assessments of risk to humans (Carmichael et al.
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From page 129... ...
. For this type of testing a more humane endpoint would be the onset of clinical signs in unvaccinated controls; thus for example the potency test for tetanus antitoxin is met when unvaccinated control guinea pigs are unable to stand within 24 hours postchallenge, at which point the animals may be euthanized (CFR 2006, 113.451)
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From page 130... ...
. Investigators should evaluate tumor size, tumor appearance, and animal condition to identify reliable indicators that may permit earlier termination of a study, and establish and validate endpoints that retain scientific objectives and avoid, minimize, or alleviate potential pain in the laboratory animals.
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From page 131... ...
nimals that would otherwise suffer severe or chronic pain that cannot be relieved should be painlessly killed at the end of the procedure or, if appropriate, during the procedure." There is no rigidly defined point at which euthanasia should be performed for humane reasons, as it is not possible to apply a single set of euthanasia criteria across all study designs, animal models, and experimental goals. The decision should involve a team approach among veterinarians, study directors, and animal care personnel using all available information about the affected animal(s)
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From page 132... ...
4. Efforts should continue in the development and validation of alter native procedures for incorporation in research projects and safety assessment tests to avoid or alleviate pain in laboratory animals.
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From page 133... ...
The sheet can be adapted to any protocol or animal care facility system as long as the behavioral definitions are uniform across the same facility. The second resource is a model for developing guidelines for humane endpoints that may be suitable for any protocol within a facility (Box 5A-1)
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From page 134... ...
ELSE GO TO SECTION C SECTION C KEEP MONITORING AS REQUIRED (DAILY) Date Adapted with permission from a scoring sheet developed by Fraser Darling, The Institute of Cancer Research, London, UK.
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From page 135... ...
A clear chain of command for the decision-making process should be documented, including contingency plans if said individuals are unavailable for consultation. Optimally, studies are terminated when animals begin to exhibit severe clinical signs if this endpoint is compatible with meeting the research objectives.
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From page 136... ...
2002. Humane endpoints for laboratory animals used in regulatory testing.
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2006. A tiered approach to life stages testing for agricultural chemical safety assessment.
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From page 138... ...
2006. Newcastle Consensus Meeting on Carbon Dioxide Euthanasia of Laboratory Animals.
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From page 139... ...
2000. Guidance Document on the Recognition, Assessment, and Use of Clinical Signs as Humane Endpoints for Experimental Animals Used in Safety Evaluation.
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From page 140... ...
2002. Humane endpoints for laboratory animals used in regulatory testing.
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