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. 
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...

Ferguson, R. 3Rs improvements in the Bexsero® (Meningitis B) vaccine. Animal Technology and Welfare 16(2), 150-152.

Bexsero® is a new vaccine in the UK which since September 2015 has been added to the childhood immunisation programme for the prevention of Meningitis B. The in-vivo test as performed in Biological Services Division...

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...

Jeger, V., Hauffe, T., Nicholls-Vuille, F. et al. 2016. Analgesia in clinically relevant rodent models of sepsis. Laboratory Animals 50(6), 418-426.

Postoperative analgesia in rodent sepsis models has been considerably neglected in the past. However, intentions to model clinical practice, increasing awareness of animal ethics, efforts to apply the 3Rs (replacement, reduction, refinement), and stricter legislation...

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...

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...

Blankenship-Paris, T. L., Dutton, J. W., Goulding, D. R. et al. 2016. Evaluation of buprenorphine hydrochloride Pluronic® gel formulation in male C57BL/6NCrl mice. Lab Animal 45(10), 370-379.

Providing adequate analgesia while minimizing handling and stress post-surgery can be challenging. Recently, there have been commercial products made available for providing long acting analgesia in rodents. However, we find there are limitations for use...

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...

Kendall, L. V., Wegenast, D. J., Smith, B. J. et al. 2016. Efficacy of sustained-release buprenorphine in an experimental laparotomy model in female mice. JAALAS 55(1), 66–73.

Mice purportedly require dosing with the opioid buprenorphine (Bup-HCl) at least every 8 to 12 h to maintain an adequate plane of analgesia. Here we used an experimental laparotomy model to determine the clinical efficacy...

Sauer, M., Fleischmann, T., Lipiski, M. et al. 2016. Buprenorphine via drinking water and combined oral-injection protocols for pain relief in mice. Applied Animal Behaviour Science 185, 103-112.

Buprenorphine is the opioid analgesic most commonly used in laboratory mice. However, to maintain therapeutically effective serum levels, repeated injections are required. To overcome negative aspects of restraint and injection, oral self-administration is a promising...

Herndon, N. L., Bandyopadhyay, S., Hod, E. A. et al. 2016. Sustained-release buprenorphine improves postsurgical clinical condition but does not alter survival or cytokine levels in a murine model of polymicrobial sepsis. Comparative Medicine 66(6), 455–462.

Cecal ligation and perforation (CLP) is a common technique for studying sepsis in mice. Because of the invasiveness of the procedure and its effects on clinical condition, many animal care and use committees require the...

Miller, A., Kitson, G., Skalkoyannis, B. et al. 2015. The effect of isoflurane anaesthesia and buprenorphine on the mouse grimace scale and behaviour in CBA and DBA/2 mice. Applied Animal Behaviour Science 172, 58-62.

Prevention or alleviation of pain in laboratory mice is a fundamental requirement of in vivoresearch. The mouse grimace scale (MGS) has the potential to be an effective and rapid means of assessing pain and analgesic...

Miller, A. L., Leach, M. C. 2015. Using the mouse grimace scale to assess pain associated with routine ear notching and the effect of analgesia in laboratory mice. Laboratory Animals 49(2), 117-120.

Social housing is recommended where possible for laboratory mice. In order to achieve this, mice must be individually identifiable. Although, various methods are available, permanent identification is often required, such as ear notching. This method...

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...

Bayne, K. A., Beaver, B. V., Mench, J. A. et al. 2015. Laboratory animal behavior. In: Laboratory Animal Medicine, 3rd edition. Fox, J. G., Anderson, L., Otto, G., et al. (eds). Elsevier, Inc., Amsterdam, NL. pp. 1617-1651.

The study of laboratory animal behavior has increased steadily over the last decade, with expanding emphasis on a variety of commonly used species. In the United States, this trend was initially focused on species for...

Cesarovic, N., Arras, M., Jirkof, P. 2014. Impact of inhalation anaesthesia, surgery and analgesic treatment on home cage behaviour in laboratory mice. Applied Animal Behaviour Science. 157, 137-145.

Anaesthesia and analgesia are used frequently in laboratory routine to ensure animal welfare and good scientific outcomes in experiments that may elicit pain or require immobilisation of the animal. However, there is concern regarding the...

Young, M., Lawson, G. W., Duarte-Vogel, S. et al. 2014. Minimizing symptoms and stress in seizure-prone mice by using acupressure during routine handling. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 555 (Abstract #P29).

Many laboratory mice used in research experience spontaneous seizures during cage changing and routine handling. The triggers are usually the abrupt sound and sudden motion of the cage. These seizures can range from mild to...

Vaughan, L. M., Dawson, J. S., Porter, P. R. et al. 2014. Castration promotes welfare in group-housed male Swiss outbred mice maintained in educational institutions. JAALAS 53(1), 38-43.

Educational institutions maintain group-housed mice of both sexes for training veterinarians and technicians in husbandry, medication, and sampling procedures. Mice kept in all-male groups may experience poor welfare due to fighting. Castrated mice may be...

Lambeth, S. P., Schapiro, S. J., Bernacky, B. J. et al. 2013. Establishing 'quality of life' parameters using behavioural guidelines for humane euthanasia of captive non-human primates. Animal Welfare 22(4) 429-435.

Chronic pain and distress are universally accepted conditions that may adversely affect an animal’s quality of life (QOL) and lead to the humane euthanasia of an animal. At most research institutions and zoological parks in...

Coleman, K. 2011. Caring for nonhuman primates in biomedical research facilities: Scientific, moral and emotional considerations. American Journal of Primatology 73(3), 220-225.

Animal care for nonhuman primates (NHPs) in biomedical facilities has undergone major changes in the past few decades. Today, most primate facilities have dedicated and highly trained animal care technicians who go to great efforts...

Moreau, E. 2010. To squeeze or not to squeeze? A Discussion on LAREF, September, 2009. Laboratory Primate Newsletter 49(2), 3-4.

The discussion was started by the following questions: "Is the squeeze-back mechanism more or less stressful than the pole and collar system for removing a macaque from his cage for an IM (intramuscular) injection?" and...

Stewart, K. 2010. Effects of increased interaction between research rodents and their handlers. Animal Welfare Institute (AWI) Quarterly 59(1) Winter, 28-29.

We conclude that handling experimental animals more often than only at the time their cage is changes is beneficial.

Howard, B., Nevalainen, T., Perretta, G. (ed). 2010. The COST Manual of Laboratory Animal Care and Use: Refinement, Reduction, and Research (1st Ed). CRC Press, Boca Raton, FL.

COST Action B-24 established four working groups to research and discuss issues relevant to laboratory animal science. These included the housing of animals, environmental needs, refinement of procedures, genetically modified animals, and cost-benefit analysis. Based...