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...

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...

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...

Flint, M., Mills, P. C., Loban, F. et al. 2017. Development of a humane slaughter device for green turtles for use by traditional owners in the Torres Strait Islands, Australia. PLOS ONE 12(1), e0167849.

Marine turtles are caught and slaughtered for consumption as part of traditional indigenous community harvest in Australia as well as in many countries in which marine turtles can be found. However, changes to the Animal...

Roth, B., Grimsbø, E. 2016. Electrical stunning of edible crabs (Cancer pagurus): from single experiments to commercial practice. Animal Welfare 25(4), 489-497.

To determine the optimal electrical stunning conditions for edible crabs (Cancer pagurus) their impedance was investigated along with currents with the potential to render the animal insensible within 1 s. This information was used to...

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...

Reinhardt, V. (ed.) 2013. Compassion Makes a Difference - Discussions by the Laboratory Animal Refinement & Enrichment Forum [LAREF], Volume III. Animal Welfare Institute, Washington, DC.

This is the third volume of discussions that took place on the Laboratory Animal Refinement & Enrichment Forum (LAREF). This forum is dedicated to the exchange of personal experiences of refining the conditions under which...

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...

Wong, D., Makowska, I. J., Weary, D. M. 2013. Rat aversion to isoflurane versus carbon dioxide. Biology Letters 9(1), 20121000.

Some experts suggest that sedation of laboratory rodents with isoflurane before euthanasia with carbon dioxide (CO2) is a humane alternative to euthanasia with CO2 alone, but little research has compared aversion with these agents. Albino...

Chisholm, J., De Rantere D., Fernandez, N. J. et al. 2013. Carbon dioxide, but not isoflurane, elicits ultrasonic vocalizations in female rats. Laboratory Animals 47(4), 324-7.

Gradual filling of a chamber with carbon dioxide is currently listed by the Canadian Council on Animal Care guidelines as a conditionally acceptable method of euthanasia for rats. Behavioural evidence suggests, however, that exposure to...

Abelson, K. S. P., Jacobsen, K. R., Sundbom, R. et al. 2012. Voluntary ingestion of nut paste for administration of buprenorphine in rats and mice. Laboratory Animals 46(4), 349-351.

An adequate analgesic strategy is important to improve the postoperative recovery and welfare of laboratory rats and mice. It is desirable that the method for administering the drug is non-invasive and stress-free. We have previously...

Corbett, A., McGowin, A., Sieber, S. et al. 2012. A method for reliable voluntary oral administration of a fixed dosage (mg/kg) of chronic daily medication to rats. Laboratory Animals 46(4), 318-324.

Stress can influence a number of physiological processes including adult neurogenesis, metabolism, cardiovascular function, immune function, neurophysiological function, endocrine function and inflammatory processes following injury. In testing drugs which may be used to treat various...

Blyth, L. 2012. A safe, gentle and effective method of oral dosing guinea-pigs. Animal Technology and Welfare 11, 187-188.

Guinea pigs are difficult to oral gavage dose. Previous adverse effects from this dosing method, using rigid catheters, had caused an earlier endpoint to studies and loss of data. We therefore developed a prototype gag...

Ali, A., Dua, Y., Constance, J. E. et al. 2012. A once-per-day, drug-in-food protocol for prolonged administration of antiepileptic drugs in animal models. Epilepsia 53(1), 199-206.

Purpose: Convenient and effective methods for administering potential antiepileptic drugs (AEDs) chronically should facilitate many experiments in animal models of chronic epilepsy with spontaneous recurrent seizures. This proof-of-principle study aimed to optimize a once-per-day, drug-in-food...

Hawkins, P., Burn, C., Hurst, J. et al. 2011. Report of the 2010 RSPCA/UFAW rodent welfare group meeting - The effect of husbandry on welfare and promoting good practice. Animal Technology and Welfare 10(2), 105-114.

The RSPCA/UFAW Rodent Welfare Group holds a one-day meeting every autumn so that its members can discuss current welfare research, exchange views on rodent welfare issues and share experiences of the implementation of the 3Rs...