Institutional Animal Care & Use Committee Policy of Humane Experimental Endpoints in Rodent Research P6.08 The Institutional Animal Care and Use Committee (IACUC) of Tulane University has adopted the following policy regarding humane experimental endpoints in rodent research: Introduction: Animals used in biomedical research may sometimes be subject to pain and/or distress while undergoing experimental procedures. All animal research must be reviewed and approved by the IACUC and must be in accordance with the Animal Welfare Act and the Public Health Service Policy on Humane Care and Use of Laboratory Animals. To be in accordance with these regulations, all research, testing, and teaching that utilize animals must be performed to minimize discomfort, distress, and pain. When laboratory animals experience pain and/or distress they may advance to the moribund condition or death. Although each scientific study is unique, the IACUC has established this set of guidelines to assist principal investigators in looking for clinical signs in rodents indicative of a humane experimental endpoint. However, these guidelines cannot be articulated satisfactorily to cover every research proposal; therefore, the IACUC reserves the right to evaluate protocols on an individual basis. Humane experimental endpoints: The humane endpoint is the point at which pain/distress is terminated, minimized or reduced by taking actions such as euthanizing the animal, giving the animal treatment to relieve pain and/or distress, or terminating a painful procedure. a. Weight loss – A 15-20 % weight loss over a few days would be considered rapid. This requires frequent monitoring. A gradual weight loss over an extended period of time (weeks to months), which leads to emaciation, would also be grounds for euthanasia. Degree of weight loss should be defined in terms of percentage weight lost, and should account for growth/pregnancy weight gains in animals fitting those criteria. In addition, PI should recognize that certain disease conditions like ascites or tumor growth may mask true weight loss. *Strong scientific justification is required for any weight loss exceeding 20%. b. Inability to rise or ambulate – This condition would indicate that an animal would not be able to reach for food and/or water and this condition is easily determined. *Animals should be euthanized within 24 hours of not being able to rise or ambulate. c. Tumor size – Usually the diameter of the mass measured with a caliper or as a percentage of body weight. Tumor burden should not exceed 10% body weight in an adult rodent and/or specifically 1.5 cm diameter in an adult mouse or 3 cm in an adult rat. Tumor endpoints should also take into account the location of the tumor and the ability of the animal to ambulate. In addition, an endpoint is reached if the tumor ulcerates or is necrotic. *Strong scientific justification is required for exceeding tumor size or allowing tumors to become ulcerated and/or necrotic. d. Labored respiration - A humane endpoint may be reached when animals show an altered respiratory rate and/or effort. Labored breathing is often accompanied by a strong abdominal component to breathing. e. Dehydration – Severe dehydration is manifested when an animal’s skin loses elasticity. Skin pinched over the back that does not return to normal is called “tenting” and if this is excessive, it is considered a humane endpoint. Policy of Humane Experimental Endpoints in Rodents P6.08 Page 1 of 1 f. Abdominal distension – May occur during ascites production, secondary to tumor growth, or during severe hypoproteinemia or hypoalbuminemia. Animals will have enlarged abdomens and may have a difficult time breathing and/or ambulating. g. Other clinical signs that may lead to an humane endpoint, depending on severity and duration – Diarrhea, if debilitating; progressive dermatitis; rough hair coat; hunched posture; jaundice and/or anemia; neurologic signs; bleeding from any orifice; or self-trauma. Other Considerations for Establishing a Humane Endpoint Principal investigators should refine their procedures by identifying experimental endpoints that minimize pain, distress, or discomfort by choosing the earliest possible endpoint to obtain valid scientific data. Experimental endpoints must be clearly defined and should be based on objective criteria. a. Moribund State: Moribund is defined as the condition that occurs immediately prior to death. The moribund state is preferred to death as an endpoint because it is assumed that euthanizing a moribund animal will help to reduce terminal pain and/or distress, however defining moribundity is usually subjective. The continuation of a study until an animal dies is almost never acceptable. Strong scientific justification is required for such a study. b. Monitoring Frequency: The frequency of observations should be increased as the potential for pain and/or distress increases. The monitoring frequency can vary greatly, from weekly to several times a day. The protocol should clearly state monitoring frequency and define conditions when frequency will increase as the potential for pain and/or distress increases. c. Pilot Study: The selection of appropriate humane endpoints requires a detailed knowledge of the impact of the procedure on the animal. The IACUC reserves the right to request a pilot study if these factors are unknown. Additional Reading: • Institute for Laboratory Animal Research Journal (2000), Humane Endpoints for Animals Used in Biomedical Research and Testing. 41(2). • Ullman-Cullere, MH, CJ Foltz. 1999. Body Condition Scoring: A Rapid and Accurate Method for Assessing Health Status in Mice. LAS. 49(3): 319-323. • Canadian Council on Animal Care (1998) guidelines on: Choosing an Appropriate Endpoint in Experiments Using Animals for Research, Teaching, and Testing. Ottawa, Canada. Approved: July 2007 Policy of Humane Experimental Endpoints in Rodents P6.08 Page 2 of 2
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