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. 
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...

Salyards, G. W., Lemoy, M.-J., Knych, H. K. et al. 2017. Pharmacokinetics of a novel, transdermal fentanyl solution in rhesus macaques (Macaca mulatta). JAALAS 56(4), 443-451.

Rhesus macaques (Macaca mulatta) are the most commonly used NHP biomedical model and experience both research and clinical procedures requiring analgesia. Opioids are a mainstay of analgesic therapy. A novel, transdermal fentanyl solution (TFS) has...

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...

Martin-Flores, M., Singh, B., Walsh, C. A. 2017. Effects of buprenorphine, methylnaltrexone, and their combination on gastrointestinal transit in healthy New Zealand White rabbits. JAALAS 56(2), 155-159.

Among the many analgesic agents available, buprenorphine appears to be the analgesic used most often in rabbits. Unfortunately, deleterious side effects of opioids, such as gastrointestinal stasis and anorexia, may discourage the use of these...

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...

Johnston, J. M., Wilson, J. M., Smith, A. L. et al. 2017. Using a cageside device for testing glycosylated hemoglobin in cynomolgus macaques (Macaca fascicularis). JAALAS 56(1), 90-94.

Recording an accurate body temperature is important to assess an animal's health status. We compared temperature data from sedated cynomolgus macaques (Macaca fascicularis) to evaluate differences between rectal, infrared (inguinal and chest), and implanted telemetry...

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...

McMillan, J. L., Bloomsmith, M. A., Prescott, M. J. 2017. An international survey of approaches to chair restraint of nonhuman primates. Comparative Medicine 67(5), 442–451.

Specifically designed restraint chairs are the preferred method of restraint for research studies that require NHP to sit in place for sustained periods of time. In light of increasing emphasis on refinement of restraint to...

Grant, C., Marks, L., Prior, H. 2017. Provision of food and water in rodent whole body plethysmography safety pharmacology respiratory studies – Impact on animal welfare and data quality. Journal of Pharmacological and Toxicological Methods 88(Part 1), 79-84.

Introduction: We evaluated the feasibility of providing food and water to rodents during whole body plethysmography (WBP) studies as a welfare improvement to standard conditions. Methods: Male Han Wistar rats or CD1 mice (n=8) were...

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...

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...

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...

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...

Pizzi, R., Dowling, A., Brown, D. et al. 2015. Facial thermography is not useful in assessing body temperature in common squirrel monkeys (Saimiri sciureus) in comparison to rectal temperatures. Journal of Zoo and Aquarium Research 3(3), 94-98.

A group of 39 captive common squirrel monkeys (Saimiri sciureus) had their body temperature measurements compared by rectal thermometry and facial infrared thermal imaging (Flir i3, Flir Systems Inc). Squirrel monkeys were caught up and...