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. 
Zeng, Y., Jin, H., Wang, J. et al. 2022. An optimized method for intratracheal instillation in mice. Journal of Pharmacological and Toxicological Methods 118, 107230.

Non-invasive intratracheal instillation is an important method for direct exposure of the respiratory tract which is commonly used in toxicology, environmental science, and other research fields. However, there is no standard operating process for non-invasive...

Hickman, D. L. 2021. Wellbeing of mice euthanized with carbon dioxide in their home cage as compared with an induction chamber. JAALAS 60(1), 72-76.

The AVMA Guidelines on Euthanasia state that, to decrease potential distress of animals, the home cage should be used for the euthanasia of mice. The current study evaluated this recommendation by comparing behavioral and physiologic...

Améndola, L., Ratuski, A., Weary, D. M. 2021. Individual differences in rat sensitivity to CO2. PLOS ONE 16(1), e0245347.

Feelings of fear, anxiety, dyspnea and panic when inhaling carbon dioxide (CO2) are variable among humans, in part due to differences in CO2 sensitivity. Rat aversion to CO2 consistently varies between individuals; this variation in...

Krueger, L. D., Chang, S. E., Motoc, M. et al. 2021. Effects of pair housing on patency of jugular catheters in rats (Rattus norvegicus). JAALAS 60(3), 357-364.

Chronic vascular access devices are widely used in a variety of species for repeated blood sampling or substance administration. Jugular catheters are commonly used for studying addiction-related behaviors in rats. Rats with catheters have historically...

Windsor, Z. 2021. Refinements in head plate mouse nesting: Using composite nests to enhance welfare. Animal Technology and Welfare 20(2), 135-141.

When given the opportunity, mice will choose to build nests using multiple different materials. Studies indicate that providing mice with choices which mimic the natural environment allows laboratory mice to build the best quality nests...

Rodriguez-Sanchez, R., Barnaby, E., Améndola, L. et al. 2021. Voluntary oral ingestion of a sedative prior to euthanasia with CO2: Behavioural responses of mice. Animals 11(10), 2879.

Laboratory mice are commonly euthanised with carbon dioxide (CO2); however, there is ample evidence that this gas is aversive. Previous work suggests that sedation achieved via injection with benzodiazepines prior to CO2 administration could reduce...

Brunt, M. W., Améndola, L., Weary, D. M. 2021. Attitudes of laboratory animal professionals and researchers towards carbon dioxide euthanasia for rodents and perceived barriers to change. Laboratory Animals 55(6), 531-539.

Evidence indicates that carbon dioxide (CO2) induces negative affective states (including anxiety, fear and distress) in laboratory rodents, but many countries still accept it for euthanasia. Alternative methods (e.g. inhalant anaesthetic) may represent a refinement...

Verjat, A., Devienne, P., Rödel, H. G. et al. 2021. More exploratory house mice judge an ambiguous situation more negatively. Animal Cognition 24(1), 53–64.

Exploration tendency, one of the most investigated animal personality traits, may be driven by either positive (when seeking interesting information) or negative (to reduce the uncertainty of the environment) affective/emotional profiles. To disentangle the valence...

Składanowska-Baryza, J., Ludwiczak, A., Pruszyńska-Oszmałek, E. et al. 2020. Effect of two different stunning methods on the quality traits of rabbit meat. Animals 10(4), 700.

The aim of the study was to assess the effect of two different stunning methods on the level of blood stress indicators (cortisol, insulin, glucose) and rabbit meat quality. The experiment was conducted on crossbreds...

Frost, K., Shah, M., Leung , V. S. Y. et al. 2020. Aversion to desflurane and isoflurane in Sprague-Dawley rats (Rattus norvegicus). Animals 10(6), 950.

Carbon dioxide and isoflurane are widely used for killing rats, yet may not truly achieve “euthanasia”, because they elicit aversion. The inhalant anesthetic desflurane is faster acting than isoflurane, representing a potential refinement. Using an...

Ballantine, A., Rodgers, D., Watts, C. et al. 2020. The cotton rat – a new challenge. Animal Technology and Welfare 19(1), 92-95.

This poster describes how the Animal Technologists at Envigo adapted their current practices and procedures for a new species at their laboratory: the cotton rat. The paper describes cotton rat biology and behaviour; housing; environmental...

Améndola, L., Weary, D. M. 2020. Understanding rat emotional responses to CO2. Translational Psychiatry 10, 253.

The aim of this review is to summarize evidence regarding rat emotional experiences during carbon dioxide (CO2) exposure. The studies reviewed show that CO2 exposure is aversive to rats, and that rats respond to CO2...

Turner, P. V., Hickman, D. L., van Luijk, J. et al. 2020. Welfare impact of carbon dioxide euthanasia on laboratory mice and rats: A systematic review. Frontiers in Veterinary Science 7, 411.

Background: There has been increased concern about the suitability of CO2 as a method for euthanasia of laboratory mice and rats, including the potential discomfort, pain or distress that animals may experience prior to loss...

Reinhardt, V. (ed.) 2020. It’s Okay to Cry - Discussions by the Laboratory Animal Refinement & Enrichment Forum [LAREF], Volume V. Animal Welfare Institute, Washington, DC.

This is the 5th volume of selected discussions that took place on the electronic Laboratory Animal Refinement & Enrichment Forum between February 2016 and December 2019. The forum was created in October 2002; it allows...

Shomer, N. H., Allen-Worthington, K. H., Hickman, D. L. et al. 2020. Review of rodent euthanasia methods. JAALAS 59(3), 242–253.

The optimal choice of euthanasia method for laboratory rodents depends on a number of factors, including the scientific goals of the study, the need to minimize animal pain and/or distress, applicable guidelines and laws, the...

Laferriere, C. A., Pang, D. S. 2020. Review of intraperitoneal injection of sodium pentobarbital as a method of euthanasia in laboratory rodents. JAALAS 59(3), 254–263.

Euthanasia is one of the most commonly performed procedures in biomedical research, involving tens of millions of animals in North America and Europe every year. The use of sodium pentobarbital, injected intraperitoneally, for killing rodents...

Laferriere, C. A., Leung, V. S., Pang, D. S. 2020. Evaluating intrahepatic and intraperitoneal sodium pentobarbital or ethanol for mouse euthanasia. JAALAS 59(3), 264–268.

Intraperitoneal (IP) injection of sodium pentobarbital (PB) is an accepted method of euthanasia for mice. However, this method has important drawbacks, including the potential for pain or misinjection. The objective of this prospective, randomized, blinded...

Cohen, S., Kwok, M., Huang, J. 2020. Humane euthanasia of guinea pigs (Cavia porcellus) with a penetrating spring-loaded captive bolt. Animals 10(8), 1356.

Guinea pigs (Cavia porcellus) have been used in research since the 19th century to collect data due to their physiological similarities to humans. Today, animals perform a vital role in experiments and concerns for laboratory...

Kulkarni, S., Hickman, D. 2020. Isoflurane and carbon dioxide elicit similar behavioral responses in rats. Animals 10(8), 1431.

Euthanasia in rodents is an ongoing topic of debate due to concerns regarding the aversive nature of gases with anesthetic properties such as carbon dioxide (CO2) and isoflurane. The aim of this study was to...

Stanger, K. J., Kells, N. J., Fisher, A. D. et al. 2019. Evaluation of euthanasia of sheep with intravenous saturated salt solutions to enable the collection of whole, intact brains. Animal Welfare 28(4), 397-406.

Captive bolts or firearms are unsuitable for euthanasia of livestock when an intact brain is required for diagnostics. Injectable barbiturates can be used, but this method carries risk of poisoning animals eating the carcase. Intravenous...

Fogarty, E. S., Swain, D. L., Cronin, G. M. et al. 2019. A systematic review of the potential uses of on-animal sensors to monitor the welfare of sheep evaluated using the Five Domains Model as a framework. Animal Welfare 28(4), 407-420.

This systematic review explores the use of on-animal sensors in sheep and their potential application in objective welfare monitoring. The key questions posed were: To what extent can current scientific knowledge inform a sensor-based approach...

Axiak Flammer, S., Eskes, C., Kohler, I. et al. 2019. Alternatives to carbon dioxide—Taking responsibility for humanely ending the life of animals. Animals 9(8), 482.

Carbon dioxide (CO2) is commonly used to kill rodents. However, a large body of research has now established that CO2 is aversive to them. A multidisciplinary symposium organized by the Swiss Federal Food Safety and...

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...

Finkemeier, M.-A., Oesterwind, S., Nürnberg, G. et al. 2019. Assessment of personality types in Nigerian dwarf goats (Capra hircus) and cross-context correlations to behavioural and physiological responses. Applied Animal Behaviour Science 217, 28-35.

The assessment of personality in farm animals and its relation to other behavioural and physiological traits is of growing scientific and practical interest. Therefore, the aims of the present study were first to assess the...

Williams, E., Carter, A., Hall, C. et al. 2019. Exploring the relationship between personality and social interactions in zoo-housed elephants: Incorporation of keeper expertise. Applied Animal Behaviour Science 221, 104876.

Individual animal personalities affect experiences of zoo environments, and thus potentially welfare. Incorporating keeper knowledge of animal personality in a reliable way has great value in optimising welfare in zoo-housed animals. Assessment of animal personality...