Standard on Humane Endpoints in Rodents

Title

University of North Carolina at Chapel Hill Standard on Humane Endpoints in Rodents

Introduction

Purpose

The standards and procedures described below provide guidance to all researchers and animal handlers regarding the humane endpoints for laboratory rodents utilized in research, teaching, or testing.

Scope of Applicability

Applies to all personnel engaged in hands-on husbandry or research involving laboratory rodents. It is essential that humane endpoints be described within the approved Institutional Animal Care and Use Committee (IACUC) protocol and that personnel understand and adhere to those endpoints.

The UNC-CH IACUC expects that anyone involved in animal work at the University will comply with this Standard. Requests for exceptions to this Standard must be reviewed and approved by the IACUC.

Standard

“The Experimental Endpoint of a study occurs when the scientific aims and objectives have been reached. The Humane Endpoint is the point at which pain or distress in an experimental animal is prevented, terminated, or relieved. The use of humane endpoints contributes to refinement by providing an alternative to experimental endpoints that result in unrelieved or severe animal pain and distress, including death.” (8th edition of the Guide for the Care and Use of Laboratory Animals, 2011). The following table outlines the humane endpoints outlined in the relevant UNC Standards. Any deviations from these values must be approved by the IACUC.

1. Efforts should be made to either alleviate pain or distress or the animal should be euthanized. Federal guidelines require that the humane endpoints take into consideration the scientific requirements of the research, the time course and progression of any expected or potential adverse effects the animals may experience, and the earliest and most predictive indicators of impending adverse effects or morbidity. In certain specialized models, where there are expected levels of morbidity or mortality (e.g., experimental autoimmune encephalitis [EAE]), humane endpoints should be developed on a case-by-case basis in conjunction with the clinical veterinarians and the IACUC. The UNC-CH IACUC requires that all animals be monitored at least once daily by personnel trained and experienced in recognizing signs of illness, injury, or abnormal behavior to determine whether any of the following apply:

1. Abnormal appearance: abnormal posture, rough coat, head tucked into abdomen, exudate around eyes and/or nose, skin lesions, abnormal breathing.
2. Abnormal activity: lethargy, abnormal movement, decreased food or water intake, self-mutilation.
3. Body weight: The humane endpoint (euthanasia required) for body weight loss is 20% (as compared to the original body weight of an adult animal).  Body weight loss may not exceed 20% without an approved Exception request (Section 8.)
4. Body Condition Score (BCS): the humane endpoint (euthanasia required) for BCS is 2.0. The BCS may not go below 2.0 without an approved Exception request (Section 8.)

(DCM staff perform daily monitoring as part of the normal husbandry duties; however, lab staff are also required to monitor their animals according to the approved protocol.)

2. If DCM notes an animal requires attention, the animal may be removed from group housing and housed individually to provide easy access to food and water. Laboratory personnel will be notified to make an assessment whether to continue to use the animal in the study. If the DCM caretaker cannot reach laboratory personnel listed on the emergency contact sheet in the animal housing area, veterinary services will be contacted to assess the animal. It is good practice for the investigator to determine, in advance of an emergency, what procedures should be used to care for abnormal animals. In all instances, veterinary services will be notified if animals are showing clinical signs of disease. Veterinarians have authority to euthanize research animals when they have exceeded the humane endpoints described in the approved protocol.

3. Moribund implies a severely debilitated state that precedes imminent death and is often interpreted to mean an animal that is prostrate and unresponsive. Moribund is NOT considered an appropriate experimental endpoint.  Less severe clinical signs, such as decreased body temperature or rapid weight loss, are often accurate predictors of death in experimental systems. and investigators should identify less severe endpoints that will meet the scientific needs of the study. All animals discovered to be moribund must be euthanized.

4. Animals showing any of the following signs should be euthanized by approved methods, regardless of whether they are endpoints specifically listed in the protocol:

1. Inability to ambulate or maintain an upright position that prevents the animal's easy access to food and/or water.
2. Agonal breathing and cyanosis.
3. Severe muscular atrophy or other signs of emaciation (BCS equal to 2). See Figure 1.
4. Severe ulceration of skin or uncontrolled bleeding.

(Note: the humane endpoints described in the approved protocol are endpoints which should result in euthanasia and that would be expected to happen before any of the above occurred.)

Figure 1: Body Condition Scoring (BCS) Guide

5. As animals approach the humane endpoints described in the protocol, or if any animals in the study are moribund or die, the IACUC requires a minimum of twice daily monitoring at least six (6) hours apart.  In these cases, the frequency of monitoring should increase as the conditions worsen. Animals exhibiting these clinical signs are not expected to survive until the next scheduled evaluation and should be euthanized immediately.

6. Written records of monitoring sessions are required, depending on the protocol and the endpoints and should be made available to the clinical veterinarian or the IACUC staff on request.

7. Unexpected phenotypes that affect the morbidity or that cause mortality should be reported to IACUC and the protocol amended to describe the unexpected condition. If a protocol is approved prior to observing unexpected phenotypes, the investigator is required to amend the protocol to describe the new phenotype and humane endpoints. In addition, more frequent monitoring of the animals may be needed. (p 28, 8^th edition of the Guide for the Care and Use of Laboratory Animals, 2011).

8. Studies that require animals to experience unrelieved pain or distress prior to reaching the endpoint or those requiring morbidity or death as the endpoint will not be considered by the IACUC unless an exception to policy is requested, scientifically justified, and approved.

Exceptions

Requests for exceptions to this Standard must be reviewed and approved by the IACUC.

Related Requirements

External Regulations and Consequences

• National Research Council. 2011. Guide for the Care and Use of Laboratory Animals: Eighth Edition. Washington, DC: The National Academies Press. https://doi.org/10.17226/12910.

University Policies, Standards, and Procedures

• For more general guidance, please refer to the University Policy on the Care and Use of Vertebrate Animals for Research, Training and Teaching Purposes
• Standard on Tumor Production and Cancer Research In Mice and Rats

Contact Information

Important Dates

• Effective Date and title of Approver: 01/27/1999; UNC IACUC
• Revision and Review Dates, Change notes, title of Reviewer or Approver: March 16, 2007, March, 2014; UNC IACUC

Approved by: UNC IACUC