Refinement Database

Database on Refinement of Housing, Husbandry, Care, and Use of Animals in Research

This database, created in 2000, is updated every four months with newly published scientific articles, books, and other publications related to improving or safeguarding the welfare of animals used in research.

Tips for using the database:

  • This landing page displays all of the publications in the database.
  • Use the drop-down menus to filter these publications by Animal Type, Setting, and/or Topic.
  • Clicking on a parent category (e.g., Rodent) will include publications relating to all the items in that category (e.g., Chinchilla, Gerbil, Guinea Pig, etc.).
  • You may also add a keyword to further narrow your search.
  • Please note that at this time, only publications dated 2010 or later (with some exceptions) can be filtered by Animal Type and Topic, and only publications dated 2020 or later (with some exceptions) can be filtered by Setting. Most publications older than 2010 can only be searched by keyword. 
Kulkarni, S., Hickman, D. 2020. Isoflurane and carbon dioxide elicit similar behavioral responses in rats. Animals 10(8), 1431.

Euthanasia in rodents is an ongoing topic of debate due to concerns regarding the aversive nature of gases with anesthetic properties such as carbon dioxide (CO2) and isoflurane. The aim of this study was to...

Felgenhauer, J. L., Brune, J. E., Long, M. E. et al. 2020. Evaluation of nutritional gel supplementation in C57BL/6J mice infected with mouse-adapted Influenza A/PR/8/34 virus. Comparative Medicine 70(6), 471-486.

Mice are a common animal model for the study of influenza virus A (IAV). IAV infection causes weight loss due to anorexia and dehydration, which can result in early removal of mice from a study...

Do, J. P., Defensor, E. B., Ichim, C. V. et al. 2020. Automated and continuous monitoring of animal welfare through digital alerting. Comparative Medicine 70(4), 313-327.

A primary goal in preclinical animal research is respectful and responsible care aimed toward minimizing stress and discomfort while enhancing collection of accurate and reproducible scientific data. Researchers use hands-on clinical observations and measurements as...

Axiak Flammer, S., Eskes, C., Kohler, I. et al. 2019. Alternatives to carbon dioxide—Taking responsibility for humanely ending the life of animals. Animals 9(8), 482.

Carbon dioxide (CO2) is commonly used to kill rodents. However, a large body of research has now established that CO2 is aversive to them. A multidisciplinary symposium organized by the Swiss Federal Food Safety and...

Steiner, A. R., Axiak Flammer, S., Beausoleil, N. J. et al. 2019. Humanely ending the life of animals: Research priorities to identify alternatives to carbon dioxide. Animals 9(11), 911.

The use of carbon dioxide (CO2) for stunning and killing animals is considered to compromise welfare due to air hunger, anxiety, fear, and pain. Despite decades of research, no alternatives have so far been found...

Lutz, J., Burla, J.-B., Gygax, L. et al. 2019. Horned and dehorned dairy cows differ in the pattern of agonistic interactions investigated under different space allowances. Applied Animal Behaviour Science 218, 104819.

Limited space in dairy cattle farming is associated with frequent encounters between cows, often resulting in agonistic interactions and injuries, especially in horned cows. Previous studies with dairy cows investigated space allowances in the waiting...

Galvin, M. 2018. Refinement of tumour passage by optimisation of the tissue disaggregation protocol. Animal Technology and Welfare 17(3), 173-174 (IAT Congress 2018 Platform Presentation Abstract).

Surgical implantation of tumour pieces has been used regularly in the passage of tumour models. This involves an invasive surgical procedure, carried out under anaesthesia; ensuring mice have adequate pain relief and peri-operative care. The...

Filby, E. 2019. Give us a break! Animal Technology and Welfare 18(1), 45-48.

Literature is replete with studies on stressors to laboratory rodents; knowing the impact research and husbandry interventions, such as routine cage changing, have on rodents’ stress levels, physiology and behaviour, we hypothesised that animals recovering...

Cowley, P. M., Roberts, C. R., Baker, A. J. 2019. Monitoring the health status of mice with bleomycin-induced lung injury by using body condition scoring. Comparative Medicine 69(2), 95–102.

Well-defined, humane endpoints aid in monitoring animal health status during disease development. Body condition scoring (BCS) is a method for assessing health status in mouse studies where wasting and death are potential endpoints. Whether BCS...

Jiron, J. M., Mendieta Calle, J. L., Castillo, E. J. et al. 2019. Comparison of isoflurane, ketamine-dexmedetomidine, and ketamine-xylazine for general anesthesia during oral procedures in rice rats (Oryzomys palustris). JAALAS 58(1), 40-49.

Rice rats (Oryzomys palustris) are an unconventional laboratory species that has been used to study photoperiodicity, periodontitis, and osteonecrosis of the jaw. Interventional procedures that require anesthesia, including oral procedures, are sometimes necessary in preclinical...

Dutton III, J. W., Artwohl, J. E., Huang, X. et al. 2019. Assessment of pain associated with the injection of sodium pentobarbital in laboratory mice (Mus musculus). JAALAS 58(3), 373-379.

The AVMA Guidelines for the Euthanasia of Animals considers injection of barbiturates to be an acceptable method of euthanasia in rodents but states there is a potential for pain when administered intraperitoneally. This study examined...

Moffitt, A. D., Brignolo, L. L., Ardeshir, A. et al. 2019. The role of emotional contagion in the distress exhibited by grouped mice exposed to CO2. JAALAS 58(4), 430-437.

The 2013 AVMA Guidelines for the Euthanasia of Animals recommends a chamber volume displacement rate of 10% to 30% per minute (v/min) when euthanizing small laboratory rodents with CO2. Group euthanasia of mice is a...

Resasco, A., Carranza Martin, A. C., Ayala, M. A. et al. 2019. Non-aversive photographic measurement method for subcutaneous tumours in nude mice. Laboratory Animals 53(4), 352–361.

We have developed a new method for the measurement of subcutaneous tumour volume which consists in taking photographs of mice in their home cages, to refine the standard method of measurement with calipers. We consider...

Jensen, T. L., Kiersgaard, M. K., Mikkelsen, L. F. et al. 2019. Fasting of male mice – Effects of time point of initiation and duration on clinical chemistry parameters and animal welfare. Laboratory Animals 53(6), 587–597.

Fasting of mice is a common procedure, which can affect the outcome of the study as well as animal welfare. In this study, we assess the effects of fasting, fasting duration and fasting initiation time...

Harikrishnan, V. S., Krishnan, L. K., Abelson, K. S. P. 2019. A novel technique to develop thoracic spinal laminectomy and a methodology to assess the functionality and welfare of the contusion spinal cord injury (SCI) rat model. PLOS ONE 14(7), e0219001.

This study reports the advantage of a novel technique employing a motorised dental burr to assist laminectomy over the conventional manual technique at T10-T11 vertebra level in a rat model of spinal cord injury. Twenty-four...

Redaelli, V., Papa, S., Marsella, G. et al. 2019. A refinement approach in a mouse model of rehabilitation research. Analgesia strategy, reduction approach and infrared thermography in spinal cord injury. PLOS ONE 14(10), e0224337.

The principles of Refinement, Replacement and Reduction (3R’s) should be taken into account when animals must be used for scientific purpose. Here, a Reduction / Refinement approach was applied to the procedure of spinal cord...

Koski, S. K., Leino, S., Rannanpää, S. et al. 2019. Implementation of improved postoperative care decreases the mortality rate of operated mice after an abundant 6-hydroxydopamine lesion of nigrostriatal dopaminergic neurons. Scandinavian Journal of Laboratory Animal Science 45(1).

A mouse model of Parkinson’s disease with an abundant lesion of nigrostriatal dopaminergic neurons can be achieved by stereotactic injection of 6-hydroxydopamine into the medial forebrain bundle. However, postoperative mortality can be excessively high without...

Abdelrahman, A., Kumstel, S., Zhang, X. et al. 2019. A novel multi-parametric analysis of non-invasive methods to assess animal distress during chronic pancreatitis. Scientific Reports 9, 14084.

Ethical responsibility, legal requirements and the need to improve the quality of research create a growing interest in the welfare of laboratory animals. Judging the welfare of animals requires readout parameters, which are valid and...

Améndola, L., Ratuski, A., Weary, D. M. 2019. Variation in the onset of CO2-induced anxiety in female Sprague Dawley rats. Scientific Reports 9, 19007.

Carbon dioxide (CO2) is commonly used to kill laboratory rats. Rats find CO2 aversive and aversion varies between individuals, indicating that rats vary in CO2 sensitivity. Healthy humans experience feelings of anxiety at concentrations similar...

Ritchie, A., Collier, P., Clare, P. et al. 2019. Food for thought: The development of drug loaded diets improve both science and welfare. Animal Technology and Welfare 18(3), 222-224.

In our facility, we use several hormone dependent tumour models with supplementation delivered via slow release subcutaneously implanted pellets, implanted via trochar. For example, breast tumours which rely on 17-β-Estradiol. Administration of E2 supplementation can...

Gent, T. C., Detotto, C., Vyssotski, A. L. et al. 2018. Epileptiform activity during inert gas euthanasia of mice. PLOS ONE 13(4), e0195872.

Carbon dioxide (CO2) is one of the most commonly used euthanasia agents for mice, yet it is highly aversive and nociceptive. Inert gases are a possible alternative, however there are qualitative reports of seizures resulting...

Kells, N. J., Beausoleil, N. J., Sutherland, M. A. et al. 2018. Electroencephalographic responses of anaesthetised rats to carbon dioxide inhalation. Animal Welfare 27(3), 215-223.

Exposure to high concentrations of CO2 is a common means of stunning and killing laboratory rodents. However, there is concern regarding the potential for animals to have aversive experiences, such as pain or breathlessness, prior...

Gilliam, J. N., Woods, J., Hill, J. et al. 2018. Evaluation of the CASH Dispatch Kit combined with alternative shot placement landmarks as a single-step euthanasia method for cattle of various ages. Animal Welfare 27(3), 225-233.

Humane euthanasia of cattle under field conditions presents special challenges for veterinarians and producers. The purpose of this study was to evaluate the effectiveness of the CASH Dispatch Kit captive-bolt system combined with improved shot...

Hoffmann, M., Schwertassek, U., Seydel, A. et al. 2018. A refined and translationally relevant model of chronic DSS colitis in BALB/c mice. Laboratory Animals 52(3), 240-252.

Inflammatory bowel diseases (IBD) are chronic relapsing disorders of the gastrointestinal tract. Several mouse models for IBD are available, but the acute dextran sulfate sodium (DSS)-induced colitis model is mostly used for preclinical studies. However...

Khoo, S. Y.-S., Lay, B. P. P., Joya, J. et al. 2018. Local anaesthetic refinement of pentobarbital euthanasia reduces abdominal writhing without affecting immunohistochemical endpoints in rats. Laboratory Animals 52(2), 152-162.

Sodium pentobarbital is a commonly used agent for euthanizing laboratory rats, however its high pH can cause abdominal discomfort after intraperitoneal injection. Previous studies suggest that the addition of a local anaesthetic may alleviate this...