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. 
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...

Lidster, K., Readman, G. D., Prescott, M. J. et al. 2017. International survey on the use and welfare of zebrafish Danio rerio in research. Journal of Fish Biology 90(5), 1891-1905.

A survey was conducted regarding zebrafish Danio rerio use for scientific research with a focus on: anaesthesia and euthanasia; housing and husbandry; breeding and production; refinement opportunities. A total of 98 survey responses were received...

Tucker, R. D. 2017. Woodchuck College. Laboratory Animal Science Professional 5(2) (June), 33-36.

Marmota monax is a valuable laboratory animal species used in studies of Hepatitis B virus (HBV), food intake, obesity, hibernation, and circannual cycles. This article describes the woodchuck’s (also known as groundhog) natural behavior and...

Miller, A. L., Golledge, H. D. R., Leach, M. C. 2016. The influence of isoflurane anaesthesia on the rat grimace scale. PLOS ONE 11(11), e0166652.

Over 234,000 rats were used in regulated procedures in the UK in 2014, many of which may have resulted in some degree of pain. When using animals in research, there is an ethical and legal...

Schmitz, S., Tacke, S., Guth, B. et al. 2016. Comparison of physiological parameters and anaesthesia specific observations during isoflurane, ketamine-xylazine or medetomidine-midazolam-fentanyl anaesthesia in male guinea pigs. PLOS ONE 11(9), e0161258.

Guinea pigs (GPs) are difficult to anaesthetize successfully, the choices for anaesthesia are limited and physiological parameters are likely to be influenced substantially under anaesthesia. We implanted blood pressure radio-telemetry devices into 16 male GPs...

Martins, T., Valentim, A. M., Pereira, L. N. et al. 2016. Anaesthesia and analgesia in laboratory adult zebrafish: a question of refinement. Laboratory Animals 50(6), 476-488.

Anaesthesia is used daily in fish experimental procedures; however, the use of an inadequate anaesthetic protocol can compromise not only the animal’s welfare but also the reliability of results. The use of zebrafish (Danio rerio)...

Norton, W. B., Scavizzi, F., Smith, C. D. et al. 2016. Refinements for embryo implantation surgery in the mouse: Comparison of injectable and inhalant anesthesias – tribromoethanol, ketamine and isoflurane – on pregnancy and pup survival. Laboratory Animals 50(5), 335-343.

An essential aspect of genetically-engineered mice (GEM) is the ability to produce live animals after the appropriate injection procedure. Animals are produced by implantation of manipulated embryos into pseudopregnant females for gestation, parturition, and growth...

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...

Moheban, A. A., Chang, H. H., Havton, L. A. 2016. The suitability of propofol compared with urethane for anesthesia during urodynamic studies in rats. JAALAS 55(1), 89–94.

Urethane anesthesia preserves many reflex functions and is often the preferred anesthetic for urodynamic studies in rats. Because of the toxicity profile of urethane, its use as an anesthetic typically is limited to acute and...

Gardiner, P. 2016. Going outside ASPA guidelines. Animal Technology and Welfare 15(1), 47-52.

This article will discuss an improved and refined technique used for working and caring for a group of diabetic mice. As a team of animal technologists, academics and named veterinary surgeon, we developed a new...

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...

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...

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...

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...

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...

Readman, G. D., Owen, S. F., Murrell, J. C. et al. 2013 Do fish perceive anaesthetics as aversive? PLOS ONE. 8(9), e73773.

This study addresses a fundamental question in fish welfare: are the anaesthetics used for fish aversive? Despite years of routine general use of many agents, within both scientific research and aquaculture, there is a paucity...

Walters, S. L., Torres-Urbano, C. J., Chichester, L. et al. 2012. The impact of huts on physiological stress: A refinement in post-transport housing of male guinea pigs (Cavia porcellus). Laboratory Animals 46(3), 220-224.

The ideal animal model would contribute no confounding variables in experimental science. Variables affect experimental design resulting in increased animal use or repeated studies. We demonstrated a simple refinement which may reduce the number of...

Coleman, K. 2012. Individual differences in temperament and behavioral management practices for nonhuman primates. Applied Animal Behaviour Science 137(3-4), 106-113.

This review will examine how individual differences in temperament might affect, or be affected by, behavioral management practices for captive primates. Measuring temperament may help us predict the outcome of social introductions. It can also...