Purpose

UConn Health’s Institutional Animal Care and Use Committee (IACUC) and the Attending Veterinarian are responsible for ensuring that all research animals are provided adequate veterinary care. This policy details requirements regarding tumor production to include implantable/inducible tumors, evaluating tumor growth, ascites produced by tumors, and endpoints and exemptions.

Action

Implantable/Inducible Tumors

1. Tumor implantation sites should be chosen to minimize damage to adjacent normal structures. The IACUC recommends implanting tumors on the dorsum or flank of an animal, as these areas will likely have minimal or no site-related morbidity.
2. Sites involving the face, limbs, or perineum should be avoided as there is little to no space for tumor growth and expansion.
3. Intramuscular implantation should be avoided as this is considered to be painful due to the distention of the muscle by the tumor.
4. Tumor implantation on the ventral surface of the body should also be avoided due to the risk of irritation to the tumor site in contact with the bedding and floor of the cage.

Evaluating Tumor Growth

1. Animals that are on a tumor production study must be monitored by the PI staff at least once a week during the time when the tumor is not yet detectable, to observe when tumor growth has begun.
2. After a visual or palpable tumor is evident, the animals must be monitored by the PI staff at least twice weekly. More frequent observations may be necessary based on tumor growth rate, study parameters, and general condition of the animals and will be detailed in the approved animal protocol.
3. The general physical condition of the animals is the most important factor in effectively following the progression of tumors in rodents.
4. When on the dorsum or flank of an adult rodent, tumors may be allowed to grow to mean diameters of 2.0cm in mice and 4.0cm in rats as long as the rodent remains otherwise healthy.
5. Evaluating tumors in central areas of the rodents (e.g., bone, lung) can be challenging. Tumor size will likely not be useful and, because of the sensitivity of areas, a small tumor may cause severe clinical signs. For tumor models studying central body tumors, clinical evaluation of the animals take priority over the measured size of the tumor. The expected clinical signs and the humane endpoints of those signs must be clearly described in the protocol. The evaluation of clinical signs in an animal with a tumor burden of this type should include consultation with the attending veterinarian.
6. Multiple tumors present other challenges. The concern of size for individual tumors is related to central necrosis, ulceration of skin overlying tumors, and abrasions. Multiple tumors that are individually smaller than the single tumor limit may not have the same negative sequelae as a single tumor. Multiple tumors may be allowed to grow up to 150% of the volume compared with the volume of a single tumor. Please note that the limitation on a single tumor will still be valid.
7. Tumor ulceration may not necessarily require euthanasia, but it does potentially require more frequent monitoring and treatment of the ulcerated tumor. The care for ulcerated tumors is based on both the size of the ulceration and the clinical judgment of the veterinarian.
   • Pinpoint (<=2mm) ulcerations at the site of tumor injection must be monitored at least 3 times per week for worsening of the ulceration site.
   • Ulcerations up to approximately 25% of the surface area of the tumor must be monitored at least 3 times per week and must be reported to the CCM veterinary staff for evaluation and potential treatment. If animals with ulcerated tumors of this size are not under veterinary care, these animals must be euthanized.
   • Ulcerations of greater than 25% of the surface of the tumor must be euthanized.

Species	Single tumor (max volume)	Multiple tumors (max volume)
Mouse	4.2cm3	6.3cm3
Rat	33.5cm3	50.25cm3

Ascites Produced by Tumors

1. In cases where tumors are expected to grow with an accumulation of ascites, rodents must be weighed prior to inoculation and subsequently be followed by weight measurements at regular intervals and this must be described in the approved protocol and based on the expected rate of fluid accumulation.
2. When the body weight exceeds 120% of the initial weight, the rodents must be euthanized or the animal tapped. Ascites pressure should be relieved before abdominal distention is great enough to cause discomfort or interfere with normal activity.
3. The abdominal tap should be performed by trained personnel using proper aseptic technique, with manual restraint or anesthesia, and by using the smallest needle possible that allows for good flow. This procedure must be described in the approved protocol.

Endpoints and Exemptions

1. Endpoints must be determined and specified in the experimental protocol.
2. If there is a strong scientific justification for maintaining tumors exceeding any of the guidelines described above, this must be detailed in the animal protocol and approved by the IACUC.
3. For studies that involve some degree of morbidity – Pain/Distress category D or E should be checked and the applicable sections filled out in the Animal Care and use Protocol.

References

1. The Guide for the Care and Use of Laboratory Animals, 8th Edition, 2012. National Research Council

2. IACUC Guideline on Rodent Tumor Production, University of Pennsylvania.

3. Ulman-Cullere MH and CJ Foltz. 1999. Body Condition Scoring: A Rapid and Accurate Method for Assessing Health Status in Mice. Lab Anim Sci 49(3): 319-323.

Effective Dates:      December 7, 2023 through December 31, 2026

Purpose

The Animal Welfare Act, Animal Welfare Regulations, and PHS Policy state that no animal work may be performed on protocols without IACUC approval which includes protocols that have expired. In addition, all approved protocols must completely describe the disposition of animals.

Action

1. All Principal Investigators (PI) who wish to transfer animals from an approved protocol to an approved protocol of another PI must have, in the original protocol, a statement that the disposition of animals includes the transfer of animals to another approved protocol.

2. The PI will need to inform the Center for Comparative Medicine (CCM) and the IACUC office of the request to transfer animals. The PI will need to give the following information: species and number of animals to be transferred, the name of the PI to whom the animals will be transferred, and the new IACUC protocol number. The IACUC office will confirm that the new protocol is approved.

3. This process may require that the original protocol be modified to include transfer of animals as a disposition method; this modification will require the approval of the Institutional Animal Care and Use Committee (IACUC) according to established procedures.

Effective Dates:  June 5, 2025 through June 30, 2028

 

Purpose

In order to ensure adequate review of animal care and use protocols, and to be compliant with both PHS Policy and recent clarification from the USDA, UConn Health’s IACUC has established a policy on assigning reviewers to new protocols.

Action

1. All protocols are submitted to the IACUC via the current electronic animal protocol and development system by the Principal Investigator.

2. The IACUC office will initially assign a primary (scientific) reviewer to the protocol. The primary reviewer assignment will be on a rotating basis with consideration of a reviewer’s particular area of expertise. In addition, the Attending Veterinarian (AV) and the Biological Safety Officer (BSO) and/or Chemical Safety Specialist (CSS) will also review all submitted protocols. If there are more than one AV, BSO and/or CSS on the IACUC, this assignment will be performed on a rotating basis.

3. The primary reviewers will remain for the life of the protocol; the initial primary reviewers will serve as the reviewers for all subsequent modifications to the protocol. If the initial primary reviewer is no longer a voting member of the IACUC when a future modification is received, the primary reviewer will be the Chair or Vice-Chair of the IACUC.  If the initial AV, BSO, or CSS reviewer not be a voting member of the IACUC when a future modification is received, these reviews will be performed by the current AV, BSO, or CSS on the IACUC committee.

Effective Dates: June 1, 2023 through June 30, 2026

This policy has been approved by a majority vote of the IACUC members.

Purpose

The Animal Welfare Act, Animal Welfare Regulations, and PHS Policy state that no animal work may be performed on protocols without IACUC approval which includes protocols that have expired. The Center for Comparative Medicine (CCM) has holding protocols on which animals may be temporarily transferred from a previously approved protocol (which has expired) so that the maintenance of these animals can be assured.

Action

1. All Principal Investigators (PI) are informed when any of their protocols expire. The PI is expected to comply with federal law that no experimental procedures may be performed on animals when the approved protocol expires. CCM is also informed when any protocol expires.

2. All animals under an expired protocol will automatically be transferred to the institutional holding protocol by CCM. While animals are being housed under this protocol, no experimental procedures- this includes breeding- are allowed. The holding protocol provides for routine husbandry and any veterinary care actions that may be required.

3. Once animals are transferred to the institutional holding protocol, there will be a card placed over the cage card which identifies the cage as being housed under the holding protocol. This should serve as a reminder that no experimental procedures may be performed on any animal in the cage.

4. The transfer of animals to the holding protocol will be allowed for three months ONLY. This will allow the PI time to write a new animal care and use protocol and have it approved by the Institutional Animal Care and Use Committee.

5. Animals transferred to the institutional holding protocol will be euthanized, or otherwise appropriately disposed of, once the three months expiration date is reached unless the PI of the original expired protocol requests a one-time extension of an additional three months.

Effective Dates:  June 5, 2025 through June 30, 2028

Purpose

In order to ensure a safe environment for both employees of the Health Center, and the laboratory animals, the Institutional Animal Care and Use Committee (IACUC) has implemented a policy regarding the transport of animals in the Health Center.

Action

1. Animals must be transferred into clean caging prior to removal from the animal facility.

2. Animals must be transported in closed caging (either microisolator lids or soft bonnet type covers) and covered with an opaque material (e.g., sheet, towel, etc.).

3. If more than 1 cage of animals is being transported, transport must be on a cart because of the possibility of dropping the cages.

4. Animals may not be transported on a common-use elevator. CCM elevators only are to be used to transport animals between floors.

5. Animal caging (with or without animals) may NOT be placed, unsupervised, in the hallways. All caging must be kept in the laboratory areas.

6. Animals are to be transported in commercial or CCM-operated vehicles ONLY unless a modification of an approved protocol to transport animals in personal cars has been approved by the IACUC.  Please refer to the IACUC Policy on Mouse/Rat Transportation Outside UConn Health for transport of animals outside the institution.

 

Effective Dates: June 6, 2024 thru June 30, 2027

Purpose

In order to comply with government regulations and to simplify the approval process, the IACUC has established a policy on the ability to utilize the designated member review (DMR) for approval of new protocols.

Action

IF THE ORIGINAL FULL COMMITTEE REVIEW RESULT IS “MODIFICATIONS REQUIRED”, THEN:

1. The changes requested to the protocol are sent to the Principal Investigator (PI) of the protocol through the InfoEd eRA portal Animal Use / IACUC module.

2. When the PI has responded to the request for changes, the PI’s changes are sent to the reviewers (Primary, veterinarian, research safety) of the protocol via InfoEd with a request to review the changes by a specified date (generally one week).

3. All reviewers must agree to the changes made. If there is no consensus to the changes, the protocol will go back to the full committee.

4. When all three (3) reviewers have indicated approval of the change(s) in InfoEd, the IACUC office will approve the protocol.

Effective Dates:  June 1, 2023 through June 30, 2026

Purpose

The use of expired medical materials such as drugs, fluids, or sutures on animals is not considered to be acceptable veterinary practice and does not constitute adequate veterinary care as required by current animal care and use regulations.

Action

1. No expired drugs, fluid replacements, or surgical/medical materials used for analgesic or anesthetic purposes are allowed for use in animals utilized for research, testing, or teaching purposes.

2. All expired materials must be discarded on, or before, their expiration date.

3. Expired drugs or materials are not allowed for use in terminal procedures unless described and justified in the animal care and use protocol and approved by the IACUC.

Effective Dates:  December 5, 2024 through December 31, 2027

Purpose

In order to comply with government regulations (PHS and USDA), AAALAC, The Guide for the Care and Use of Laboratory Animals, and standard veterinary care techniques, UConn Health’s Institutional Animal Care and Use Committee (IACUC) has implemented a policy concerning retro-orbital eye bleeding.

Action

1. All animals must be appropriately anesthetized prior to performing procedure.

2. Maximum blood collection volumes (mouse):

• Weekly sampling (0.6% body weight):                             115μL (25g mouse)
• Every other week sampling (0.8% body weight):          200μL (25g mouse)
• Monthly sampling (no fluid replacement, 0.6%):          200μL (25g mouse)
• Monthly sampling (with fluid replacement, 1.5%):       350μL (25g mouse)

3. Maximum blood collection volumes (rat):

• Every other week sampling (1.5% body weight):           3.5 mL (250g rat)

4. Multiple retro-orbital plexus bleeding requires the use of alternate eyes each time the procedure is performed.

5. No bleeding may be performed from a damaged eye. In the event that both eyes are damaged, eye bleeding must cease.

6. Volumes greater than the maximum volumes listed above require scientific justification and prior approval by the IACUC.

7. Investigators should maintain familiarity with the Center for Comparative Medicine guidelines regarding retro-orbital plexus bleeding.

Effective Dates:  June 1, 2023 through June 30, 2026

This policy has been approved by a majority vote of the IACUC members

Purpose

In order to comply with federal regulations (USDA and PHS) and the Guide for the Care and Use of Laboratory Animals, 8th edition, 2011, the UConn Health’s Institutional Animal Care and Use Committee (IACUC) has established a policy on death as an endpoint in research projects.

Action

1. Studies should be terminated when animals begin to exhibit adverse clinical signs if this endpoint is compatible with meeting research objectives.

2. Protocols requiring death as an endpoint must contain the following:

• Scientific rationale
• Consideration of alternate endpoints
• Number of animals used for this endpoint and why it is the minimum necessary
• Plan describing the monitoring of these animals
• What information is to be gained in the interval between moribundity and death

3. The use of death as an endpoint must be approved by the IACUC prior to the initiation of the research project.

4. Under no circumstances may the use of death as an endpoint be applied simply because it is an unambiguous and easy criterion to apply.

Effective Dates:  June 5, 2025 through June 30, 2028

Purpose

In order to comply with government regulations (PHS and USDA) and the American Association for the Accreditation of Laboratory Animal Care (AAALAC) the UConn Health’s Institutional Animal Care and Use Committee (IACUC) has implemented a policy regarding a code of ethics for the care and use of animals.

Action

1. It is recognized that in many research protocols there is simply no alternative to the use of live animals. Despite this social imperative for animal experimentation, all investigators have an ethical obligation to explore ways in which animals can be partially or totally replaced by other biological or mathematical/computer systems. When a research question can be pursued using reasonably available non-animal or in vitro models and still result in sound scientific conclusions, the investigator should choose these alternatives.

2. When live animals are used in research or biological testing, there must be a reasonable expectation that such utilization will contribute to the enhancement of human or animal health, the advancement of knowledge, and/or the good of society. The relative value of the study is a particularly important consideration in potentially painful experiments where there is an ethical imperative that the benefits of the research clearly outweigh any pain, discomfort, and distress experienced by the animals.

3. Selection of an appropriate animal model is an important consideration, particularly at a time when alternative models for animal research are being emphasized. It is the investigator’s responsibility to select the optimal species for a particular project. In addition, the number of animals utilized in a protocol should be minimized consistent with sound scientific and statistical standards. It is also the investigator’s responsibility to consider the source of the animal and ensure that all animals used for experimental research are lawfully acquired.

4. When animals are used in a research project, the investigator has an ethical obligation to seek the least painful techniques feasible that will allow the protocol objective(s) to be pursued adequately. If a procedure has associated pain, discomfort, or distress, it is imperative that the investigator estimate the probably occurrence, magnitude, and duration of the pain, discomfort, or distress in order to adequately plan for the treatment of pain.

5. In potentially painful procedures, the investigator must take all necessary steps to assess and monitor pain as well as discomfort and distress. In assessing pain, the investigator should use behavioral signs based on the normal behavior pattern of the species under study.

6. If a procedure will cause more than momentary slight pain or distress to the animal, the pain must be minimized both in intensity and duration through the administration of appropriate anesthetics, analgesics, and tranquilizers consistent with acceptable standards of veterinary medicine. It should be emphasized that the requirement for the alleviation/reduction of pain applies not only at the time the procedure is being conducted, but also following the procedure until such time when the pain is either alleviated or reduced to an acceptable tolerance level.

7. Potentially painful experiments should not be conducted on an awake animal under the influence of a paralytic or curarizing drug without the concomitant use of an appropriate anesthetic.

8. Research in which painful stimuli are used should be so designed as to provide a means of escape from that pain by the animals.

9. It is recognized that in certain research protocols, the administration of appropriate anesthetics and/or analgesics will compromise the scientific validity of the experiment. Such experiments must be justifiable in terms of scientific design and value, and the deletion of these drugs should be based on referenceable scientific fact or experimental data and not intuition. In addition, pain, discomfort, and distress levels should be carefully monitored. There is a limitation on the pain to which an experimental animal may be exposed. Investigators should choose the earliest possible end-point in order to minimize pain and discomfort. An animal that is observed to be in a state of severe pain that cannot be alleviated or reduced to an acceptable tolerance level should be immediately euthanized.

10. No animal should be subjected to multiple survival surgeries, except where they are inter-related and essential to the primary research objective.

11. Physical restraint procedures should be used on an awake animal only after alternative procedures have been considered and found to be inadequate. If a restraint will be utilized, the animal should be trained or conditioned to the restraining device, using positive reinforcement, prior to the beginning of the experiment. The restraining device should provide the minimum restraint consistent with the maximum security and comfort of the animal. In addition, the restraining device should provide the animal with the greatest possible opportunity to assume its normal postural adjustments. Awake animals should not be subjected to prolonged physical restraint.

12. It is the responsibility of the investigator to ensure that adequate post-surgical/procedural care is provided to all animals. This care must meet acceptable standards of veterinary medicine and be provided as long as necessary, including during non-duty hours.

13. Euthanasia is the act of inducing painless death. The proposed method of euthanasia must be consistent with the recommendations of the American Veterinary Medical Association (AVMA) Panel on Euthanasia (2013).  If an animal will not be subjected to euthanasia at the completion of a research protocol, it is the responsibility of the investigator to ensure that the final disposition of the animal is both humane and acceptable.

14. Procedures involving the use of animals should be performed by or under the immediate supervision of an individual with the appropriate training and experience relative to the procedures to be carried out on live animals.

Effective Dates:  June 5, 2025 through June 30, 2028