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. 
Munro, B. A., Merenick, D. R., Gee, J. M. et al. 2023. Use of loss of righting reflex to assess susceptibility to carbon dioxide gas in three mouse strains. JAALAS 62(6), 553–558.

Exposure to CO2 gas is a common rodent euthanasia method. CO2 activates nociceptors in rats and is painful to humans at concentrations equal to or greater than 32.5% The concentration of CO2 at which rodents...

Hickman, D. L. 2023. Euthanasia of neonatal rats and mice using carbon monoxide. JAALAS 62(3), 274–278.

Minimization of potential pain and distress of rodents undergoing euthanasia is a touchstone of veterinary clinical medicine. Evaluation of this issue in postweanling rodents has supported revisions to the AVMA (American Veterinary Medical Association) Guidelines...

McNamara, A., Ballantine, A. R., Deuchande, R. et al. 2023. Comparison of fixed and rising displacement rates of CO2 for euthanasia of aged rats. JAALAS 62(5), 453–463.

This study compared euthanasia induced by rising concentrations of CO2 in aged rats (n = 59) using different gas displacement rates. Rats were preimplanted with cardiovascular telemetry devices and had been previously used for short...

Stuckey, J. E., Makhija, S. D., Reimer, D. C. et al. 2023. Effects of different grades of carbon dioxide on euthanasia of mice (Mus musculus). JAALAS 62(5), 430–437.

Carbon dioxide (CO2) is a conditionally acceptable method for mouse euthanasia, according to the American Veterinary Medical Association Guidelines for the Euthanasia of Animals. In a 2012 Office of Laboratory Animal Welfare (OLAW) webinar, representatives...

Hickman, D. L. 2022. Evaluation of carbon dioxide euthanasia of female Sprague Dawley rats alone or with unfamiliar conspecifics. JAALAS 61(2), 195-200.

Most studies evaluating methods of euthanasia to date have focused on the euthanasia of individual animals. However, larger chambers are commonly used to euthanize multiple cages of animals at once. This study evaluated the use...

Buckmaster, C. L., Levesque, D., LaFollette, M. et al. 2022. Five hot topics in refinement of nonhuman primate neuroscience research. Laboratory Animal Science Professional 10(1) (January/February), 24-26.

Members of the North American 3Rs Collaborative (NA3RsC) refinement initiative have chosen to summarize developments in five hot topics of interest: 1. Tips for welfare-friendly transport, chairing, and restraint; 2. Guidance on refining food and...

Berke, M. S., Fensholdt, L. K. D., Hestehave, S. et al. 2022. Effects of buprenorphine on model development in an adjuvant-induced monoarthritis rat model. PLOS ONE 17(1), e0260356.

Complete Freund’s adjuvant (CFA)-induced arthritis in rats is a common animal model for studying chronic inflammatory pain. However, modelling of the disease is associated with unnecessary pain and impaired animal wellbeing, particularly in the immediate...

Hirata, S. 2022. Sky after 30 years: A brief biography of three biomedical research chimpanzees in Japan. Primates 63(2), 105–108.

This article describes the strategies employed by Kumamoto Sanctuary in Japan to integrate 3 retired chimpanzees – who each spent 30 years singly housed in a biomedical facility – with the sanctuary’s other residents.

Guillaumin, A., Vlcek, B., Wallén-Mackenzie, Å. 2022. Improving well-being and survival in the 6-OHDA lesion model of Parkinson´s disease in mice: Literature review and step-by-step protocol. Scandinavian Journal of Animal Science 48(1), 1-21.

Parkinson’s disease (PD) is the most common neurodegenerative motor disorder and primarily affects movement control but also a range of non-motor functions. With unknown etiology and lack of cure, much research is dedicated to unravel...

Johansson, Ö, Kachel, S., Weckworth, B. 2022. Guidelines for telemetry studies on snow leopards. Animals 12(13), 1663.

Animal-borne tracking devices have generated a wealth of new knowledge, allowing us to better understand, manage and conserve species. Fitting such tracking devices requires that animals are captured and often chemically immobilized. Such procedures cause...

Davies, J. R., Purawijaya, D. A., Bartlett, J. M. et al. 2022. Impact of refinements to handling and restraint methods in mice. Animals 12(17), 2173.

There is increasing evidence that, compared to non-aversive handling methods (i.e., tunnel and cupping), tail handling has a negative impact on mouse welfare. Despite this evidence, there are still research organisations that continue to use...

Bethell, E. J., Khan, W., Hussain, A. 2022. A deep transfer learning model for head pose estimation in rhesus macaques during cognitive tasks: Towards a nonrestraint noninvasive 3Rs approach. Applied Animal Behaviour Science 255, 105708.

Head orientation is a measure of attention used in behavioral psychological research with non-human primates. It is used across a broad range of disciplines and settings, from the field to the laboratory. Field methods are...

Fehrenbach, L. A., Adekanye, A. A., Palillo, M. B. et al. 2022. Internal temperatures of packaging for overnight cross-country shipping of zebrafish (Danio rerio). Comparative Medicine 72(3), 195-203.

As the use of zebrafish (Danio rerio) as a research model continues to rise, so too will the shipping and sharing of zebrafish strains across collaborating institutions. If done incorrectly, shipping can result in significant...

Davis, A. K., Garner, J. P., Chu, D. K. et al. 2022. Propofol immersion as a euthanasia method for adult zebrafish (Danio rerio). Comparative Medicine 72(3), 204-209.

The exponential rise of the zebrafish (Danio rerio) as a model organism in biomedical research has far outstripped our un- derstanding of basic husbandry and welfare for this species. As a case in point, here...

Hickman, D. L. 2022. Minimal exposure times for irreversible euthanasia with carbon dioxide in mice and rats. JAALAS 61(3), 283-286.

When using an anesthetic overdose to euthanize laboratory rodents, a secondary method of euthanasia is recommended to ensure that the apparent death is irreversible. This secondary method usually is accomplished through the collection of tissues...

McKinney, M. M., Dupont, W. D., Corson, K. J. et al. 2022. Physiologic and behavioral effects in mice anesthetized with isoflurane in a red-tinted or a traditional translucent chamber. JAALAS 61(4), 322-332.

Isoflurane has been characterized as a distressing agent for rodents, causing both physiologic and behavioral effects. Using a "darkened home cage" has been recommended during CO2 administration for rodent euthanasia; this is arguably a similar...

Barkus, C., Bergmann, C., Branco, T. et al. 2022. Refinements to rodent head fixation and fluid/food control for neuroscience. Journal of Neuroscience Methods 381, 109705.

The use of head fixation in mice is increasingly common in research, its use having initially been restricted to the field of sensory neuroscience. Head restraint has often been combined with fluid control, rather than...

Van Assche, I. A., Padilla, M. S., Stupart, O. S. R. P. et al. 2022. Refinement of the stress-enhanced fear learning model of post-traumatic stress disorder: A behavioral and molecular analysis. Lab Animal 51(11), 293-300.

Post-traumatic stress disorder (PTSD) is a debilitating mental health condition for which current treatments have long-term efficacy in 50% of patients. There is a clear need for better understanding of the mechanisms underlying PTSD and...

Zevnik, B., Jerchow, B., Buch, T. 2022. 3R measures in facilities for the production of genetically modified rodents. Lab Animal 51(6), 162-177.

Sociocultural changes in the human–animal relationship have led to increasing demands for animal welfare in biomedical research. The 3R concept is the basis for bringing this demand into practice: Replace animal experiments with alternatives where...

Hughey, S., Campbell, D., Rapp-Santos, K. et al. 2022. Refining the rat sciatic nerve block: A novel ultrasound-guided technique. Laboratory Animals 56(2), 191-195.

Murine translational models are an important tool to understand pain pathophysiology. One procedure used frequently in murine research is the sciatic nerve block. This study sought to demonstrate the use of ultrasound-guided sciatic nerve block...

Jacob, G., Katti, H., Cherian, T. et al. 2021. A naturalistic environment to study visual cognition in unrestrained monkeys. eLife 10, e63816.

Macaque monkeys are widely used to study vision. In the traditional approach, monkeys are brought into a lab to perform visual tasks while they are restrained to obtain stable eye tracking and neural recordings. Here...

Clarkson, J. M., Martin, J. E., McKeegan, D. E. F. 2022. A review of methods used to kill laboratory rodents: Issues and opportunities. Laboratory Animals 56(5), 419-436.

Rodents are the most widely used species for scientific purposes. A critical pre-requisite of their use, based on utilitarian ethical reasoning, is the provision of a humane death when necessary for scientific or welfare grounds...

Allioux, C., Achaintre, L., Cheataini. F. et al. 2022. Animal welfare assessment after severe traumatic brain injury in rats. Laboratory Animals 56(6), 528-539.

Severe traumatic brain injury (TBI) is a multifactorial injury process involving respiratory, cardiovascular and immune functions in addition to the brain. Thus, live animal models are needed to study the molecular, cellular and systemic mechanisms...

Khalajzeyqami, Z., Grandi, A., Ferrini, E. et al. 2022. Pivotal role of micro-CT technology in setting up an optimized lung fibrosis mouse model for drug screening. PLOS ONE 17(6), e0270005.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with no curative pharmacological treatment. The most used animal model of IPF for anti-fibrotic drug screening is bleomycin (BLM)-induced lung fibrosis. However, several issues have been reported...

Ferreira, J. M., Félix, L., Jorge, S. et al. 2022. Anesthesia overdose versus rapid cooling for euthanasia of adult zebrafish. Zebrafish 19(4), 148-159.

The rapid increase in zebrafish use needs to be accompanied by research into the refinement of procedures. The European (EU) Directive lists three possible euthanasia methods for fish: anesthetic overdose, electrical stunning, and concussion. However...