Standard Adverse Effects and Early Removal Criteria

IACUC Policy: 036-08, Effective Date: 11/01/2009, Last Revision: 03/18/2026

Overview/Purpose

This policy provides standard early removal criteria (ERC) which apply to all research and teaching protocols at The Ohio State University unless exceptions have been scientifically justified and approved by the Institutional Animal Care and Use Committee (IACUC). Early removal criteria are predetermined criteria, utilized as a basis for euthanasia prior to the planned study endpoint to minimize pain and/or distress to the animals while enabling scientific goals to be met.

Ideally, experimental endpoints occur with minimal or no adverse effects, pain, or distress to the animal. In some cases, however, studies will result in pain/distress in order to accomplish the scientific objectives. Furthermore, the IACUC recognizes that experimentally induced or spontaneous clinical signs in animals may be unexpected or otherwise not specifically identified in the IACUC protocol. Consultation with the veterinary staff is expected when unanticipated adverse effects are observed.

Requirements

• Investigators must ensure humane care of their research animals.
• Animals should be monitored at a frequency appropriate for the model and consistent with the protocol to ensure that animals are removed promptly when ERC are met. The frequency of monitoring is heavily dependent upon the model/study endpoints and such oversight by the research team must be clearly outlined in the animal use protocol.
• Once an animal meets the ERC, the principal investigator is responsible for promptly (< 24 hrs.) initiating treatment as outlined in the protocol or euthanizing the animal. Consultation with a veterinarian would be required to discuss alternative treatment options.
• Experiments that necessitate unrelieved pain and/or distress as approved by the IACUC must be clearly identified at the primary enclosure level. This includes, but is not limited to, protocols using moribund state or death as an endpoint.

The following criteria are considered standard ERC and apply across all protocols unless alternative criteria are identified and approved within the designated IACUC protocol. Written scientific justification must be provided if the IACUC standard ERC are not followed; this justification must be approved by the IACUC:

• Weight loss: Loss of 20% baseline body weight or compared to an age-matched control (for young growing animals or aged animals).
• Body Condition Score:
  • Rodents: Poor body condition scores (less than or equal to 2 out of 5) as determined by digital palpation.
  • Non-rodents: Poor body condition based on the species-specific reference scale.
• Weakness/inability to obtain feed or water: Inability or extreme reluctance to stand/ambulate for 24 hours.
• Ulceration: Regardless of cause, models that anticipate ulcer formation must indicate ulceration as an adverse effect, provide a maximum size for early removal, and describe how pain will be mitigated.
• Tumors:
  • Tumor size must not exceed 1.6 cm in any dimension in a mouse, or 3.6 cm dimension in a rat. When multiple tumors are present, tumor size must be based on cumulative longest dimensions.
  • Ulceration greater than 2mm.
  • Tumors that interfere with normal function of vital organs (breathing, etc.) or impede the expression of normal activities (must be able to place all four feet on the ground and walk normally).
  • Alternative endpoint criteria for tumor size/ulceration must be clearly outlined within the approved IACUC protocol, including narrative for why the alternative criteria are necessary to meet scientific needs of the study.

Additional Information/Guidance

• Mouse Body Condition Score chart (Lab Anim Sci. 1999;49(3):319-323)
• Rat Body Condition Score chart (J Am Assoc Lab Anim Sci. 2010 Mar; 49(2): 155–159)
• Recognition and Alleviation of Pain in Laboratory Animals. 2009. Chapter 5. Humane Endpoints for Animals in Pain. Bookshelf_NBK32658.pdf (nih.gov)