Policy

Rodent tumor models are critically important experimental model systems, and tumors may result from injection of tumor cells, exposure to carcinogens, germline genetic modification, or may arise spontaneously. Regardless of origin, tumor burden may negatively impact animal well-being. The Principal Investigator (PI) is responsible for ensuring that all personnel working with animals under their protocol(s) clearly understand their individual and collective role(s) in monitoring and treating tumor-bearing animals. This Policy applies to both experimentally induced and spontaneously developing tumors.

General Guidelines

1. Tumor Burden and Location

Tumor burden is not judged on a generic size criterion, since the impact of a tumor will vary depending on its location.  Subcutaneous implantation is recommended in the flank or between the shoulder blades.  Tumor implantation should be in sites that will not interfere with normal body functions, including ambulation, eating, drinking, or elimination, unless justified in the ARC-approved protocol.

2. Euthanasia Criteria

The impact of the tumor(s) on the health and well-being of the animal is key for determining the point of euthanasia (humane endpoints). Unless otherwise justified in an approved ARC protocol (see below) animals must be euthanized before or when the following criteria are met:

  1. Tumor burden interferes with the animal’s ability to ambulate, or to reach food or water.
  2. Tumor obstructs, interferes with, or impinges on the opening of any orifice (e.g., eye, ear, nose, mouth, respiratory tract, urinary tract, or rectum).
  3. Tumor burden reaches a level that otherwise interferes with normal activity or body functions, or causes apparent distress or discomfort to the animal, including in response to palpation of the tumor (elicits a pain response).
    NOTE: While the ARC does not require euthanasia at a specified tumor size, if the protocol identifies a size limit as a criterion for premature euthanasia, that endpoint must be followed.
  4. Loss of adult body weight of 20% from tumor induction, or body condition score (BCS) of less than or equal to 2.[1]
  5. Tumor becomes ulcerated, infected, or necrotic with a break of the overlying skin.[2]
  6. Animal becomes moribund, cachectic, or exhibits any of the criteria for premature termination specified in the approved protocol for the specific study.[3]

Exceptions to the above may be allowed only after ARC approval of a detailed scientific justification and description of the procedures to be undertaken to protect the health and welfare of the animal.  Such procedures should be developed and updated as needed in collaboration with a member of the DLAM veterinary staff.

3. Monitoring

It is the PI’s responsibility to ensure that tumor-bearing animals are observed daily, including weekends and holidays, to monitor tumor development and to evaluate overall clinical condition as animals approach experimental or humane endpoints. Such monitoring must take into account loss of body condition and indications of pain, distress, or abnormal behavior and physiology, as detailed in the Guide for the Care and Use of Laboratory Animals and the approved protocol.

Changes in the animal’s clinical condition or in the integrity of the skin overlying the mass can occur rapidly.  Through daily observation, these changes should be noted by the PI/ PI’s staff.  If a cage has been identified as a health case by DLAM animal care staff, the lab must ensure that the animal is evaluated and euthanized if any of the criteria above are met.

Investigators should use the “Study Related” pink cards provided by DLAM to clearly label all cages that contain rodents into which foreign cells have been injected. It is suggested that the following information be provided on the cards:

  1. date and site of initial injection/implantation, plus any subsequent experimental treatments,
  2. cell line identity,
  3. name and phone number of the individual primarily responsible for monitoring the animals, and
  4. date and time of each observation of the animal once subcutaneous tumor(s) become visible or any clinical signs are manifest (all tumors).

For more information

  1. Indiana University Office of Research Compliance IACUC, Guidelines for Tumor Induction in Rodents. Accessed 10.2024
  2. Determining Rodent Body Condition Score
  3. P Workman et al. Guidelines for the welfare and use of animals in cancer research. British Journal of Cancer (2010)102,1555–1577
[1] Body weight is not always an accurate indicator of animal health when a tumor is present. In animals with tumors, evaluation of body condition score (BCS) is strongly recommended by DLAM veterinary staff. No animal should be allowed to reach a BCS of less than 2 out of 5 unless it is scientifically justified and approved by the ARC. For more information on body condition scoring, refer to "Determining Rodent Body Condition Score."

[2] Ulcerations represent nonviable tissue that will not heal, and they cannot be surgically repaired. An ulcerated tumor may appear as an open, moist lesion or as a scab, which is indicative of a break in the underlying epithelium. Any disruption of the skin, even pinpoint, represents ulceration. If a rodent is receiving experimental treatment that may be expected to result in ulceration or necrosis (death of a large mass of tumor cells below an intact skin surface), for example, after intra-tumoral injection of a therapeutic substance, this must be described in the ARC protocol.

[3] Tumors in body cavities, such as the cranium, orbit, abdomen, or chest, or in other restricted locations, such as bone marrow cavities or in the testes, may severely impair physiological or neurological function. Therefore, animals with these types of tumors must be euthanized when clinical signs become apparent, regardless of tumor size, unless otherwise justified in the ARC approved protocol. In such cases, investigators are expected to follow the monitoring and premature euthanasia criteria as described in their protocol.

Approved 11/13/00; Revised 2/11/02, 3/11/02, 7/26/04, 9/12/05, 4/24/06, 10/23/06, 9/23/13, 1/12/15, 11/4/24; Updated 2/11/26