Humane Endpoints

Purpose

Boston University (BU) is committed to the humane care and use of animals. The intent of this policy is to define what the BU Institutional Animal Care and Use Committee (IACUC) considers humane endpoints and to provide information on when animals must be humanely euthanized.  Adherence to this policy is mandatory unless an exception has been approved by the IACUC.

Covered Parties

 This policy is applicable to all persons responsible for conducting research, teaching, training, breeding, and related activities, hereinafter referred to collectively as “activities”, involving live vertebrate animals conducted at or under the auspices of Boston University.

University Policy

Compliance with all governing regulations involving humane care and use of animals in research is mandatory at Boston University. Legal, ethical, and regulatory guidelines obligate all personnel involved with research protocols utilizing animals to ensure that animal pain, distress, and suffering is minimized.

Definitions

A morbid state is a condition relating to, or typical of, disease or illness. Any animal exhibiting signs of morbidity should be reported to BU ASC staff.

A moribund state is defined as a state of dying. Any animal found to be exhibiting at least one of the specified characteristics is considered to have end-stage illness and should be euthanized immediately unless an exception has been specifically justified in the IACUC-approved protocol.

The IACUC requires investigators to euthanize all animals discovered to be moribund rather than allowing them to die spontaneously. Euthanasia methods must be in compliance with the investigator’s approved IACUC protocol. Rare exceptions to this policy, such as for studies in which euthanasia prior to actual death would invalidate the experiment, will only be considered by the IACUC if there is a clear scientific justification.

If tissue samples are required perimortem, investigators must consider the relative integrity of samples collected at the time of euthanasia rather than from animals allowed to expire.  If a moribund end state is required by the experiment, investigators must describe clinical staging and monitoring over the course of the disease with particular care near that humane endpoint.  In those studies, IACUC may require predicting the percentage of animals expected to expire due to the scientific requirement to assay end-stage disease.  Pilot studies are recommended where disease course is relatively unknown and may cause severe morbidity or mortality.

Humane endpoints are criteria used to end experiments on individual animals to avoid or terminate unrelieved pain or distress. Once a humane endpoint is reached, the animal should be immediately euthanized or treated as described in the approved protocol.

Once animals start to display clinical signs of illness, investigators or laboratory personnel must monitor their subjects frequently (at least once daily or as described in their protocol) to ensure timely identification of moribund animals or animals for which previously defined humane endpoints have been reached (this includes weekends and holidays). Investigators are obligated to make every effort to identify and humanely euthanize moribund animals that have not responded to treatment. In general, experiments should be designed such that all procedures are completed prior to animals reaching a moribund state, also referred to as end-stage illness.

End-stage illness is defined as signs of a debilitating physical state where death is imminent and treatment ineffectual. Animals exhibiting severe signs of morbidity or a moribund state are considered to be in end-stage illness. Investigators should be competent in judging the condition of their animal subjects, differentiating between a morbid and moribund animal, and be prepared to perform approved euthanasia when necessary. The following lists will aid investigators and laboratory personnel in identifying morbid and moribund animals. If there is any question or concern about judging the condition of animal subjects, please contact BU ASC veterinary staff.

Clinical Signs of Morbidity in Animals

Note: This list is not exhaustive.

• Hunched posture, reduced activity
• Sunken eyes, with or without discharge
• Respiration that has increased, decreased, or appears labored
• Rapid weight loss (more than 10% of body weight within a one-week period)
• Total weight loss (>20%) from baseline for mature animals on short term studies or from as age adjusted growth chart for a particular vendor strain for your or growing animals.  (Note: weight loss criteria for young, growing animals is different than for adult animals. In general, weight loss from baseline is rarely acceptable for growing animals; rather, a “reduced weight gain” protocol or a weight loss adjusted for age protocol if the strain data is published will be established on a case-by-case basis depending on the study, species, and strain.)
• A body condition score of2.5 or less on a scale of 1–5(see species-specific guidelines for assigning a body condition score)
• Decreased or no intake of food
• Hypothermia or hyperthermia
• Ruffled hair coat, erection of hair or fur, lack of grooming behavior
• Diarrhea or constipation
• Vomiting
• Unsteady gait or lameness not induced by experimental manipulation
• Ulcerated tumors
• Severe or ulcerative dermatitis
• Inability to reach food and/or water (access to food and water must be given, e.g., food on floor and Napa Nectar, or the animal humanely euthanized)

Clinical Signs of Moribund Condition in Animals

Note: This list is not exhaustive, and, in general, includes the list of clinical signs above for morbidity but with a higher degree of severity.

• Impaired mobility (the complete inability to reach food and water)
• Inability or unwillingness to remain upright
• Hunched posture for more than 48 hours
• Labored breathing and cyanosis (skin or mucous membranes have a blue color)
• Clinical dehydration and/or prolonged decreased food intake (more than 48 hours)
• Muscle atrophy and signs of lethargy and lack of physical activity
• Severe, rapid weight loss and emaciation (more than 20% of body weight from baseline; body condition score of 1.5 or less on a scale of 1–5; see species-specific guidelines for assigning a body condition score)
• Chronic diarrhea or constipation for more than 48 hours
• Hematological or biochemical values that indicate organ failure
• Prolonged bleeding from any orifice
• Self-mutilation
• No response to external stimuli

Responsible Parties

Principal investigators are responsible for: preparing and submitting applications; making modifications in applications in order secure IACUC approval; ensuring adherence to approved protocols; ensuring that all personnel have completed required training; and reporting any adverse events to the IACUC.

The Animal Welfare Program and the Institutional Animal Care and Use Committee are responsible for overseeing implementation of and ensuring compliance with this policy.

The Attending Veterinarian has been delegated authority and responsibility for ensuring compliance with this policy.

Related Policies and References

Guide for the Care and Use of Laboratory Animals, Eighth Edition

Animal Welfare Act and Regulations

Authority of the Attending Veterinarian

History

Effective Date:  07/11/2023
Next Review Date: 07/10/2026