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. 
Steiner, A. R., Axiak Flammer, S., Beausoleil, N. J. et al. 2019. Humanely ending the life of animals: Research priorities to identify alternatives to carbon dioxide. Animals 9(11), 911.

The use of carbon dioxide (CO2) for stunning and killing animals is considered to compromise welfare due to air hunger, anxiety, fear, and pain. Despite decades of research, no alternatives have so far been found...

Animal Welfare Institute. 2019. A new beginning for retired laboratory rabbits. Animal Welfare Institute (AWI) Quarterly 68(4) Winter, 10-11.

This article describes the rehoming of 10 laboratory female rabbits now living as a group in a private shelter.

Améndola, L., Ratuski, A., Weary, D. M. 2019. Variation in the onset of CO2-induced anxiety in female Sprague Dawley rats. Scientific Reports 9, 19007.

Carbon dioxide (CO2) is commonly used to kill laboratory rats. Rats find CO2 aversive and aversion varies between individuals, indicating that rats vary in CO2 sensitivity. Healthy humans experience feelings of anxiety at concentrations similar...

Kells, N. J., Beausoleil, N. J., Sutherland, M. A. et al. 2018. Electroencephalographic responses of anaesthetised rats to carbon dioxide inhalation. Animal Welfare 27(3), 215-223.

Exposure to high concentrations of CO2 is a common means of stunning and killing laboratory rodents. However, there is concern regarding the potential for animals to have aversive experiences, such as pain or breathlessness, prior...

Peric, T., Comin, A., Corazzin, M., et al. 2018. Hair cortisol concentrations in New Zealand white rabbits subjected to surgery. Animal Welfare 27(1), 13-20.

The aim of this study was to assess hair cortisol concentrations in New Zealand white rabbits (Oryctolagus cuniculus) that were subjected to relocation and surgery to evaluate HPA-axis activity; in addition, we used this marker...

Khoo, S. Y.-S., Lay, B. P. P., Joya, J. et al. 2018. Local anaesthetic refinement of pentobarbital euthanasia reduces abdominal writhing without affecting immunohistochemical endpoints in rats. Laboratory Animals 52(2), 152-162.

Sodium pentobarbital is a commonly used agent for euthanizing laboratory rats, however its high pH can cause abdominal discomfort after intraperitoneal injection. Previous studies suggest that the addition of a local anaesthetic may alleviate this...

Read, H., Perry, R. 2018. A refinement to Schedule 1. Animal Technology and Welfare 17(2), 117-120.

There are varying methods used for animal restraint and angle of injection. It remains unclear whether one method is more accurate than others. The primary objectives were to examine whether inverted restraint of rats resulted...

Hickman D. L. 2018. Interpreting neuroendocrine hormones, corticosterone, and blood glucose to assess the wellbeing of anesthetized rats during euthanasia. JAALAS 57(6), 725–728.

Current recommendations for assessing animal wellbeing during euthanasia suggest that measuring neuroendocrine hormones—such as ACTH, noradrenaline, and adrenaline—is preferable to measuring corticosterone and blood glucose because of the sensitivity of neuroendocrine hormones to the acute...

Hickman D. L. 2018. Home cage compared with induction chamber for euthanasia of laboratory rats. JAALAS 57(6), 729–733.

This study compared behavioral and physiologic changes in Sprague–Dawley and Brown Norway rats that were euthanized by using a 30% volume displacement rate of CO2 in either their home cage or an induction chamber; rats...

Byrd, R., Boyd, S., Buckmaster, C. 2018. Rat thunder jacket— A zen experience. Laboratory Animal Science Professional 6(3) (September), 55-57.

Germ-free rats are fairly uncommon, relative to germ-free mice, and restraining these animals safely and effectively for compound administration and blood collection can be challenging. There are many commercially available varieties of restraint devices, but...

Peric, T., Comin, A., Corazzin, M. et al. 2017. Relocation and hair cortisol concentrations in New Zealand White rabbits. Journal of Applied Animal Welfare Science 20(1), 1-8.

To investigate how long relocation modified hair cortisol concentrations in New Zealand white rabbits, 19 rabbits were subjected to a change in their breeding facility at the beginning of the trial and then were kept...

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...

Simpson, D. 2017. Investigation of transportation on rat acclimatisation using novel cage side recording equipment (Rodent Big Brother). Animal Technology and Welfare 16(1), 1-12.

The transportation of animals from supplier to experimental facility is one of the biggest stressors to animals in research. Transportation unavoidably causes stress and when the animals arrive at the testing facility they require a...

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...

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...

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...

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...

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...

Cloutier, S., Wahl, K., Newberry, R. C. 2010. Playful handling mitigates the stressfulness of injections in laboratory rats. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 721 (Abstract #P126).

Rats can be playfully handled (tickled) in a manner that mimics playful social contact with conspecifics. We hypothesized that the timing of tickling in relation to an intraperitoneal injection would affect the efficacy of tickling...

Reed, B., Hawkins, P., Latham, N. et al. 2008. Report of the 2006 RSPCA/UFAW Rodent Welfare Group meeting. Lab Animal 37(5), 216-222.

The RSPCA/UFAW Rodent Welfare Group holds a one-day meeting every autumn to discuss current welfare research and to exchange views on rodent welfare issues. A key aim of the group is to encourage people to...