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. 
Bailoo, J. D., Murphy, E., Varholick, J. A. et al. 2018. Evaluation of the effects of space allowance on measures of animal welfare in laboratory mice. Scientific Reports 8, 713.

We studied how space allowance affects measures of animal welfare in mice by systematically varying group size and cage type across three levels each in both males and females of two strains of mice (C57BL/6ByJ...

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...

Champneys, T., Castaldo, G., Consuegra, S., et al. 2018. Density dependent changes in neophobia and stress-coping styles in the world’s oldest farmed fish. Royal Society Open Science 5(12), 181473.

Farmed fish are typically reared at densities much higher than those observed in the wild, but to what extent crowding results in abnormal behaviours that can impact welfare and stress coping styles is subject to...

Benedict, D., Megrath, B. 2018. Upgrades to nonhuman primate tethered infusion system. Laboratory Animal Science Professional 6(3) (September), 62-64.

Continuous tethered infusions in any animal model pose a unique set of problems. These problems are amplified when nonhuman primates are the model. A high tolerance to the tether system by an animal model is...

Marquardt, N., Feja, M., Hünigen, H. et al. 2018. Euthanasia of laboratory mice: Are isoflurane and sevoflurane real alternatives to carbon dioxide? PLOS ONE 13(9), e0203793.

In the European Union (EU) millions of laboratory mice are used and killed for experimental and other scientific purposes each year. Although controversially discussed, the use of carbon dioxide (CO2) is still permitted for killing...

Cronin, K. A., Bethell, E. J., Jacobson, S. L. et al. 2018. Evaluating mood changes in response to anthropogenic noise with a response-slowing task in three species of zoo-housed primates. Animal Behavior and Cognition 5(2), 209–221.

In the zoo environment, anthropogenic noise is common as sound levels fluctuate due to visitors, construction, habitat design, and special events. In this study, changes in the mood of three species of zoo-housed primates in...

Walsh, J., Percival, A., Turner, P. 2017. Efficacy of blunt force trauma, a novel mechanical cervical dislocation device, and a non-penetrating captive bolt device for on-farm euthanasia of pre-weaned kits, growers, and adult commercial meat rabbits. Animals 7(12), 100.

The commercial meat rabbit industry is without validated on-farm euthanasia methods, potentially resulting in inadequate euthanasia protocols. We evaluated blunt force trauma (BFT), a mechanical cervical dislocation device (MCD), and a non-penetrating captive bolt device...

Boivin, G. P., Hickman, D. L., Creamer-Hente, M. A. et al. 2017. Review of CO2 as a euthanasia agent for laboratory rats and mice. JAALAS 56(5), 491-499.

Selecting an appropriate, effective euthanasia agent is controversial. Several recent publications provide clarity on the use of CO2 in laboratory rats and mice. This review examines previous studies on CO2 euthanasia and presents the current...

de Souza Dyer, C., Brice, A. K., Marx, J. O. 2017. Intraperitoneal administration of ethanol as a means of euthanasia for neonatal mice (Mus musculus). JAALAS 56(3), 299-306.

The humane euthanasia of animals in research is of paramount importance. Neonatal mice frequently respond differently to euthanasia agents when compared with adults. The AVMA's Guidelines for the Euthanasia of Animals includes intraperitoneal injection of...

Boivin, G. P., Bottomley, M. A., Schiml, P. A. et al. 2017. Physiologic, behavioral, and histologic responses to various euthanasia methods in C57BL/6NTac male mice. JAALAS 56(1), 69-78.

Rodent euthanasia using exposure to increasing concentrations of CO2 has come under scrutiny due to concerns of potential pain during the euthanasia process. Alternatives to CO2, such as isoflurane and barbiturates, have been proposed as...

Polissidis, A., Zelelak, S., Nikita, M. et al. 2017. Assessing the exploratory and anxiety-related behaviors of mice. Do different caging systems affect the outcome of behavioral tests? Physiology & Behavior 177, 68-73.

Ample studies have shown that housing can affect the health, welfare and behavior of mice and therefore, the outcomes of certain experiments. The aim of this study was to investigate if three widely used housing...

Guedes, S. R., Valentim, A. M., Antunes, L. M. 2017. Mice aversion to sevoflurane, isoflurane and carbon dioxide using an approach-avoidance task. Applied Animal Behaviour Science 189, 91-97.

Euthanasia of laboratory animals is one of the main concerns for animal welfare, especially the use of carbon dioxide (CO2) which has been described to induce aversive-like behaviours. In order to refine mass euthanasia in...

Adams, S. C., Guyot, C. M., Berry, K. M. et al. 2017. Hypercortisolemia and depressive-like behaviors in a rhesus macaque (Macaca mulatta) involved in visual research. Comparative Medicine 67(6), 529–536.

A 10-y-old cranially implanted rhesus macaque (Macaca mulatta) involved in visual research was presented for dull mentation and weight loss. Physical examination revealed alopecia and poor body conditioning, and bloodwork revealed marked hypercortisolemia (23 μg/dL)...

Valentim, A. M., Guedes, S. R., Pereira, A. M. et al. 2016. Euthanasia using gaseous agents in laboratory rodents. Laboratory Animals 50(4), 241-253.

Several questions have been raised in recent years about the euthanasia of laboratory rodents. Euthanasia using inhaled agents is considered to be a suitable aesthetic method for use with a large number of animals simultaneously...

Jang, Y., Park, Y. E., Yun, C.-W. et al. 2016. The vest-collar as a rodent collar to prevent licking and scratching during experiments. Laboratory Animals 50(4), 296-304.

Various types of restraint collars have been used for research animals, and the Elizabethan collar (E-collar) is the most commonly used. However, animals can be choked by the E-collar or they tend to remove it...

Powell, K., Ethun, K., Taylor, D. K. 2016. The effect of light level, CO2 flow rate, and anesthesia on the stress response of mice during CO2 euthanasia. Lab Animal 45(10), 386-395.

Euthanasia protocols are designed to mitigate the stress experienced by animals, and an environment that induces minimal stress helps achieve that goal. A protocol that is efficient and practical in a typical animal research facility...

Hawkins, P., Prescott, M., Carbone, L. et al. 2016. A good death? Report of the second Newcastle meeting on laboratory animal euthanasia. Animals 6(9), 50.

Millions of laboratory animals are killed each year worldwide. There is an ethical, and in many countries also a legal, imperative to ensure those deaths cause minimal suffering. However, there is a lack of consensus...

Sánchez-Muros, M. J., Sánchez, B., Barroso, F. G. et al. 2016. Effects of culture densities on feed demand, behavioural tests and on the hepatic and cerebral oxidative status in tilapia (Oreochromis sp.). Applied Animal Behaviour Science 185, 137-145.

The present study examines whether fish density affects behavioural tests, feed demand, and different parameters indicative of the oxidative status of the liver and brain of Orechromis sp. to identify welfare indicators for fish culturing...

Prior, H., Bottomly, A., Champéroux, P. et al. 2016. Social housing of non-rodents during cardiovascular recordings in safety pharmacology and toxicology studies. Journal of Pharmacological and Toxicological Methods 81, 75-87.

Introduction: The Safety Pharmacology Society (SPS) and National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs) conducted a survey and workshop in 2015 to define current industry practices relating to housing...

Slater, H., Milne, A. E., Wilson, B. et al. 2016. Individually customisable non-invasive head immobilisation system for non-human primates with an option for voluntary engagement. Journal of Neuroscience Methods 269, 46-60.

Background: Head immobilisation is often necessary for neuroscientific procedures. A number of Non-invasive Head Immobilisation Systems (NHIS) for monkeys are available, but the need remains for a feasible integrated system combining a broad range of...

Moody, C. M., Makowska, I. J., Weary, D. M. 2015. Testing three measures of mouse insensibility following induction with isoflurane or carbon dioxide gas for a more humane euthanasia. Applied Animal Behaviour Science 163, 183-87.

Laboratory mice are commonly killed via exposure to gradually increasing concentrations of isoflurane and carbon dioxide (CO2) gas. Once rendered insensible using isoflurane or CO2, a high concentration of CO2 is used to decrease time...

Xing, G., Lu, J., Hu, M. et al. 2015. Effects of group housing on ECG assessment in conscious cynomolgus monkeys. Journal of Pharmacological and Toxicological Methods 75, 44-51.

Assessing the cardiovascular safety of new chemical or biological entities is important during pre-clinical development. Electrocardiogram (ECG) assessments in non-human primate (NHP) toxicology studies are often made using non-invasive telemetry systems. We investigated whether ECG...

Brown, C. 2015. Fish intelligence, sentience and ethics. Animal Cognition 18(1), 1-17.

Fish are one of the most highly utilised vertebrate taxa by humans; they are harvested from wild stocks as part of global fishing industries, grown under intensive aquaculture conditions, are the most common pet and...

Bethell, E. J., Koyama, N. F. 2015. Happy hamsters? Enrichment induces positive judgement bias for mildly (but not truly) ambiguous cues to reward and punishment in Mesocricetus auratus. Royal Society Open Science 2, 140399.

Recent developments in the study of animal cognition and emotion have resulted in the ‘judgement bias’ model of animal welfare. Judgement biases describe the way in which changes in affective state are characterized by changes...

Brown, C. 2015. Fish intelligence, sentience and ethics. Animal Cognition 18(1), 1–17.

Fish are one of the most highly utilised vertebrate taxa by humans; they are harvested from wild stocks as part of global fishing industries, grown under intensive aquaculture conditions, are the most common pet and...