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...

Van Wijk, H., Haida, D., Duncan, C. et al. 2020. Surgery refinements improve success rates in rat bile collection. Animal Technology and Welfare 19(3), 251-254.

This poster compares the model success rates using 2 different housing regimes during recovery from surgery. Catheters were placed in the bile duct to collect bile; a second catheter was secured into the duodenum where...

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...

Lee, L. Y., Lee, D., Ryu, H. et al. 2019. Capnography-guided endotracheal intubation as an alternative to existing intubation methods in rabbits. JAALAS 58(2), 240-245.

Rabbits provide a unique challenge for routine endotracheal intubation in clinical practice because of various distinctive anatomic and physiologic features. Many previously proposed methods for endotracheal intubation in rabbits are limited by several factors, including...

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...

Falkenberg, M. K., Teilmann, A. C., Henriksen, T. et al. 2019. Clinical, physiologic, and behavioral evaluation of permanently catheterized NMRI mice. JAALAS 58(3), 380-389.

Vascular catheterization is becoming a popular technique in laboratory rodents, facilitating repetitive blood sampling and infusion in individual animals. In mice, catheterization is complicated by their small body size, which may increase the risk of...

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...

Animal Welfare Institute. 2019. A new beginning for retired laboratory rabbits. Animal Welfare Institute (AWI) Quarterly 68(4) Winter, 10-11.

This article describes the rehoming of 10 laboratory female rabbits now living as a group in a private shelter.

Ijichi, C., Green, S., Squibb, K. et al. 2019. Zylkéne to load? The effects of alpha-casozepine on compliance and coping in horses during loading. Journal of Veterinary Behavior 30, 80-87.

Horses are routinely transported for access to safe off-road riding, veterinary care, breeding, sale, or moving to a new home environment. However, transport is a known stressor in horses. For this reason, problem behavior when...

Nosaka, N., Crother, T. R., Chen, S. et al. 2019. Optimal tube length of orotracheal intubation for mice. Laboratory Animals 53(1), 79–83.

Endotracheal tube (ETT) management is an essential technique in handling mice with mechanical ventilators. Malposition into bronchi causes not only lethal complications for them but also less efficient mechanical ventilation. However, in general, it is...

Gjendal, K., Lund Ottesen, J., Olsson, I. A. S. et al. 2019. Burrowing and nest building activity in mice after exposure to grid floor, isoflurane or ip injections. Physiology & Behavior 206, 59-66.

Burrowing and nest building are examples of highly motivated innate behaviours in rodents. Assessments based on these behaviours can be used as non-invasive indicators of pain, distress and suffering. In this study, we investigated the...

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...

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...

Peric, T., Comin, A., Corazzin, M., et al. 2018. Hair cortisol concentrations in New Zealand white rabbits subjected to surgery. Animal Welfare 27(1), 13-20.

The aim of this study was to assess hair cortisol concentrations in New Zealand white rabbits (Oryctolagus cuniculus) that were subjected to relocation and surgery to evaluate HPA-axis activity; in addition, we used this marker...

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...

Dudley, E. S., Boivin, G. P. 2018. Evaluation of a commercially available euthanasia solution as a voluntarily ingested euthanasia agent in laboratory mice. JAALAS 57(1), 30-34.

All currently accepted methods of euthanasia for laboratory mice involve some degree of stress, fear, anxiety, or pain. We evaluated the voluntary oral administration of a euthanasia drug in 99 male and 81 female mice...

Lahger, C., Laska, M. 2018. Behavioral responses of CD-1 mice to conspecific and heterospecific blood odors and to a blood odor component. Physiology & Behavior 184, 2015-210.

The odor of blood may have both aversive and attractive properties for mammals, depending on the species of the odor donor and the species perceiving the odor. To better understand the informational content of blood...

Galvin, M., Lallo, A., Brown, S. et al. 2018. Refinement of tumour passage by optimisation of the tissue disaggregation protocol. Animal Technology and Welfare 17(2), 101-103.

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...

Read, H., Perry, R. 2018. A refinement to Schedule 1. Animal Technology and Welfare 17(2), 117-120.

There are varying methods used for animal restraint and angle of injection. It remains unclear whether one method is more accurate than others. The primary objectives were to examine whether inverted restraint of rats resulted...

Beamish, G., Chapman, C., Lomax, A. 2018. Design by intravenous injection in the Syrian hamster. Animal Technology and Welfare 17(2), 124-125.

Repeated injections in rats and mice are typically done via the tail vein. For hamsters, the tail is not an option. In this paper we explore the development and refinement of IV dosing in the...

van Wijk, H., Crossman, L., Adjin-Tettey, G. et al. 2018. Advances in animal welfare and scientific outcomes of the bile duct cannulated rat model utilised in ADME studies. Animal Technology and Welfare 17(1), 64-67.

Since rats lack a gall bladder, they are an ideal model for investigating continuous biliary excretion and biotransformation. The design and implementation of a modified tail cuff and cannula system introduced at Covance permits the...

Creamer-Hente, M. A., Lao, F. K., Dragos, Z. P. et al. 2018. Sex- and strain-related differences in the stress response of mice to CO₂ euthanasia. JAALAS 57(5), 513–519.

The 2013 edition of the AVMA Guidelines for the Euthanasia of Animals recommends a 10% to 30% volume displacement rate (VDR) per minute for CO2 euthanasia of rodents. Here we sought to evaluate behavior and...

Hickman D. L. 2018. Interpreting neuroendocrine hormones, corticosterone, and blood glucose to assess the wellbeing of anesthetized rats during euthanasia. JAALAS 57(6), 725–728.

Current recommendations for assessing animal wellbeing during euthanasia suggest that measuring neuroendocrine hormones—such as ACTH, noradrenaline, and adrenaline—is preferable to measuring corticosterone and blood glucose because of the sensitivity of neuroendocrine hormones to the acute...