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. 
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...

Sutherland, M. A., Watson, T. J., Millman, S. T. 2017. Technical contribution: evaluation of the efficacy of a non-penetrating captive bolt to euthanase dairy goat kids up to 30 days of age. Animal Welfare 26(3), 277-280.

The objective of this study was to evaluate the effectiveness of a non-penetrating captive bolt (NPCB) to euthanase previously disbudded Saanen dairy goat kids (Capra hircus) up to 30 days of age and 9 kg...

Lipták, B., Kaprinay, B., Gáspárová, Z. 2017. A rat-friendly modification of the non-invasive tail-cuff to record blood pressure. Lab Animal 46(6), 251-253.

In animal models, blood pressure measurement methods can be either invasive (direct) or non-invasive (indirect). The non-invasive alternative involves applying a tail-cuff for blood pressure measurement. Current standardized restraint methods involve confining the laboratory animal...

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...

Scott, K. E., Bracchi, L. A., Lieberman, M. T. et al. 2017. Evaluation of best practices for the euthanasia of zebra finches (Taeniopygia guttata). JAALAS 56(6), 802-806.

Although zebra finches (Taeniopygia guttata) have been used in biomedical research for many years, no published reports are available about euthanizing these small birds. In this study, we compared 5 methods for zebra finch euthanasia...

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...

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...

Sutherland, M. A., Watson, T. J., Johnson, C. B. et al. 2016. Evaluation of the efficacy of a non-penetrating captive bolt to euthanase neonatal goats up to 48 hours of age. Animal Welfare 25(4), 471-479.

Manual blunt force trauma is a common method of euthanasia or culling of goat kids, however it is difficult to apply consistently and may vary in effectiveness. Therefore, a controlled mechanical method is needed. The...

Martin, J. E., McKeegan, D. E. F., Sparrey, J. et al. 2016. Comparison of novel mechanical cervical dislocation and a modified captive bolt for on-farm killing of poultry on behavioural reflex responses and anatomical pathology. Animal Welfare 25(2), 227-241.

An alternative emergency method for killing poultry on-farm is required following European legislation changes (EU 1099/2009), which heavily restricts the use of manual cervical dislocation. This study investigated the kill efficacy of two mechanical methods...

Karrberg, L., Andersson, L., Kastenmayer, R. J. et al. 2016. Refinement of habituation procedures in diet-induced obese mice. Laboratory Animals 50(5), 397-399.

Orogastric gavage, while a common method for delivering experimental substances in mice, has been shown to induce stress. To minimize the associated stress with this procedure, sham gavage prior to the start of experiment is...

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...

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...

Hickman, D., Fitz, S., Bernabe, C. et al. 2016. Evaluation of low versus high volume per minute displacement CO2 methods of euthanasia in the induction and duration of panic-associated behavior and physiology. Animals 6(8), 45.

Current recommendations for the use of CO 2 as a euthanasia agent for rats require the use of gradual fill protocols (such as 10% to 30% volume displacement per minute) in order to render the...

Zatroch, K. K., Knight, C. G., Reime, J. N. et al. 2017. Refinement of intraperitoneal injection of sodium pentobarbital for euthanasia in laboratory rats (Rattus norvegicus). BMC Veterinary Research 13, 60.

Background: The Canadian Council on Animal Care and American Veterinary Medical Association classify intraperitoneal (IP) pentobarbital as an acceptable euthanasia method in rats. However, national guidelines do not exist for a recommended dose or volume...

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...

Boulanger Bertolus, J., Nemeth, G., Makowska, I. J. et al. 2015. Rat aversion to sevoflurane and isoflurane. Applied Animal Behaviour Science 164, 73-80.

Virtually all rodents used in research are eventually euthanized. Best practice is to anaesthetize these animals before euthanasia using a halogenated anaesthetic such as isoflurane. Exposure to isoflurane is aversive, but less so than exposure...

Stuart, S., Robinson, E. S. J. 2015. Reducing the stress of drug administration: Implications for the 3Rs. Scientific Reports 5, 14288.

Restraint in animals is known to cause stress but is used during almost all scientific procedures in rodents, representing a major welfare and scientific issue. Administration of substances, a key part of most scientific procedures...

Hall, L. E., Robinson, S., Buchanan-Smith, H. E. 2015. Refining dosing by oral gavage in the dog: A protocol to harmonise welfare. Journal of Pharmacological and Toxicological Methods 72, 35-46.

Introduction: The dog is a frequently-used, non-rodent species in the safety assessment of new chemical entities. We have a scientific and ethical obligation to ensure that the best quality of data is achieved from their...

Bode, A. E., Barber, H. 2014. Use of vinyl nonadhesive tape as an alternative for positioning rodents in small animal imaging. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 597-598. (Abstract #P185).

Specific positioning for different imaging modalities is essential in our small animal imaging core. While we have different animal holders designed to position the animal inside the MRI, additional securing of the animal to the...

Tupper, T., Manning, H., Turner, D. et al. 2014. An innovative restraint device for the placement of intravenous tail vein catheters in anesthetized mice. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 584. (Abstract #P136).

Consistently accurate intravenous tail vein administration of radiopharmaceuticals in anesthetized mice is a critical component of successful PET/CT imaging in the preclinical setting. Injectable anesthetics are often not suitable for PET imaging and commercially available...

McMillan, J. L., Perlman, J. E., Galvan, A. et al. 2014. Refining the pole-and-collar method of restraint: Emphasizing the use of positive training techniques with rhesus macaques (Macaca mulatta). JJAALAS 53(1), 61-68.

The pole-and-collar method is one of several techniques that enable the safe transfer of a nonhuman primate from its home environment into a restraint chair without the need for sedation. It has been used within...