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)
Revision History
- 036-01 – New policy approved 11/01/2009
- 036-02 – This policy was retitled and formerly known as the Early Removal Criteria and Non- CO2 Euthanasia. In addition, the policy was revised and includes criteria from the tumor production policy. IACUC approved this policy on 06/20/2014.
- 036-03 – This revision reflects the early removal criteria for weight loss, body condition scores, and clarifies tumor production models by defining the size of ulcerations. Approved 02/19/2016
- 036-04 – This revision reflects the requirement that investigators must ensure humane care of their research animals by checking animals at least weekly to utilize ERC as listed in their protocol. Revised multiple tumor production to emphasize endpoint criteria being described in the protocol. Approved 06/16/2017
- 036-05 – This revision reflects a requirement being added for experiments that necessitate unrelieved pain and/or distress as approved by the IACUC must be clearly identified at the cage level. This includes but is not limited to protocols using moribund as sole criteria for removal and death as an endpoint. Approved 01/19/2018
- 036-06 – Policy was revised to remove the requirement for immobile and remove the weight limit related with the tumor size for rodent tumor production models; Approved 11/20/2020
- 036-07 – Policy revised requirement 4a for tumor production to clarify that alternative endpoint criteria will be considered by the IACUC if justified and clearly described in the protocol.
- 036-08 – Policy revised and reviewed; approved 11/17/2023
- 036-09 – Policy revised including requirements on monitoring frequency, elimination of ≥4 BCS removal criteria for rodents, addition of ulceration requirement and update of tumors requirement. Approved 03/18/2026
Article ID: 43
Created: May 20, 2024
Last Updated: May 8, 2026
Online URL: https://ohiostateresearch.knowledgebase.co/article/standard-adverse-effects-and-early-removal-criteria-43.html