Humane Endpoints

Guidelines for Selecting Humane Endpoints during Experiments Using Living Animals

The Animal Care and Use Committee is committed to minimizing pain and suffering in experimental animals, irregardless of the species of animal in which an experiment is conducted. The Committee recognizes that all vertebrate animals are capable of experiencing pain and distress. It is essential that the principal investigator consider the welfare of the animals when planning experiments. Section C and Item 9 of the Animal Care and Use Application form require investigators to provide specific information about humane cut-off points for experimental animals and to address the issues of pain and distress and how they can be minimized. These guidelines were prepared to assist investigators when completing these sections of the application form.

What types of studies may cause significant pain or distress for experimental animals?

Studies in which transgenic animals are created, tumors are propagated, toxic drugs are administered, and most models of chronic diseases have the potential to produce suffering, and ultimately death, in experimental animals.

The principal investigator's responsibilities when proposing to conduct these types of studies are the following:

Know the clinical features of the disease well enough to predict the course and degree of illness.
Observe the animals frequently (at least daily), and more often if illness can be acute or sudden.
Plan the project so that the most critical times for animals occur when staff are present.
Define intervention times/signs in the protocol (see table for sample criteria for euthanasia).
Design the project with animal well-being in mind, considering minimization of suffering and reduction of animal numbers. For example, locate tumor implants in areas that will not impair the animal or in areas where the animal cannot self-mutilate.
Assure that tumor cells or other materials injected into animals are not contaminated with potentially pathogenic organisms.

What information does the Animal Care and Use Committee require to approve an experiment in which death of the animal is a data point (also called a death as the endpoint experiment)?

The types of studies in which death of the animal may be a data point include: acute toxicity studies, infectious disease studies, vaccine trials, virulence assays, and some cancer treatment studies.

To gain approval to conduct studies in which death of the animal is an endpoint, the principal investigator must provide the following information under Item 9 of the application form:

A strong scientific justification
The number of animals per group is clearly defined and justified by an appropriate statistical method.
There are clear reasons why the experiment cannot be modified toward a more humane termination point, and these are included in the application. The table below was prepared to help investigators select humane cut-off points for experiments in which animals may experience pain and distress. The criteria that are selected as cut-off points should be relevant to the clinical symptoms seen in the animals.