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. 
Eeza, M. N. H., Singer, R., Ding, Y. et al. 2023. Probing microstructural changes in muscles of leptin-deficient zebrafish by non-invasive ex-vivo magnetic resonance microimaging. PLOS ONE 18(4), e0284215.

Leptin is a hormone that plays a key role in controlling food intake and energy homeostasis. Skeletal muscle is an important target for leptin and recent studies have shown that leptin deficiency may lead to...

Liu, P., Roberts, S., Shoemaker, J. T. et al. 2023. Validation of a 3D perfused cell culture platform as a tool for humanised preclinical drug testing in breast cancer using established cell lines and patient-derived tissues. PLOS ONE 18(3), e0283044.

3D cell culture models of cancer are currently being developed to recapitulate in vivo physiological conditions and to assess therapeutic responses. However, most models failed to incorporate the biochemical and biophysical stimuli from fluid flow...

Marks, C. A., Allen, L., Lindeberg, H. 2023. Non-lethal dose-response models replace lethal bioassays for predicting the hazard of para-animopropiophenone to Australian wildlife. Animals 13(3), 472.

Para-aminopropiophenone (PAPP) is a potent methaemoglobin (MetHb) forming agent used for the lethal control of exotic carnivores and mustelids. To assess the sensitivity of Australian wildlife to PAPP we developed an in vivo assay that...

Peruga, M., Kawala, B., Sarul, M. et al. 2023. Are currently selected laboratory animals useful in the research of how female hormones influence orthodontic biomechanics? Animals 13(4), 629.

Animal testing was and remains the only method of introducing a certain treatment and medical procedure on humans. On the other hand, animals have their rights resulting from applicable legal acts, including Directive 2010/63/EU and...

Martinez-Lopez, S., Angel-Gomis, E., Sanchez-Ardid, E. et al. 2023. The 3Rs in experimental liver disease. Animals 13(14), 2357.

Patients with cirrhosis present multiple physiological and immunological alterations that play a very important role in the development of clinically relevant secondary complications to the disease. Experimentation in animal models is essential to understand the...

Leyden, C., Brüggemann, T., Debinski, F. et al. 2022. Efficacy of tricaine (MS-222) and hypothermia as anesthetic agents for blocking sensorimotor responses in larval zebrafish. Frontiers in Veterinary Science 9, 864573.

Tricaine, or MS-222, is the most commonly used chemical anesthetic in zebrafish research. It is thought to act via blocking voltage-gated sodium channels, though its mechanism of action, particularly at the neuronal level, is not...

Knaebe, B., Weiss, C. C., Zimmermann, J. et al. 2022. The promise of behavioral tracking systems for advancing primate animal welfare. Animals 12(13), 1648.

Recent years have witnessed major advances in the ability of computerized systems to track the positions of animals as they move through large and unconstrained environments. These systems have so far been a great boon...

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...

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...

Chung, Y. H., Gulumian, M., Pleus, R. C. et al. 2022. Animal welfare considerations when conducting OECD test guideline inhalation and toxicokinetic studies for nanomaterials. Animals 12(23), 3305.

The OECD test guidelines for animal experiments play an important role in evaluating the chemical hazards. Animal tests performed using OECD guidelines, especially when the good laboratory practice (GLP) principle is applied, reduce the duplication...

Mason, G. J., Lavery, J. M. 2022. What is it like to be a bass? Red herrings, fish pain and the study of animal sentience. Frontiers in Veterinary Science 9, 788289.

Debates around fishes’ ability to feel pain concern sentience: do reactions to tissue damage indicate evaluative consciousness (conscious affect), or mere nociception? Thanks to Braithwaite’s research leadership, and concerns that current practices could compromise welfare...

Serrano, C., Antonio, J. 2022. Ultrasound guided surgery as a refinement tool in oncology research. Animals 12(23), 3445.

Refinement is one of the ethical pillars of the use of animals in research. Ultrasonography is currently used in human medicine as a surgical tool for guided biopsies and this idea can be applied to...

Hepps Keeney, C., Harrison, T. M. 2022. Euthanasia complications in non-domestic species. Journal of Zoological and Botanical Gardens 3(4), 616–623.

There are very few studies describing euthanasia complications in non-domestic species. The goal of this study was to survey veterinarians to determine what complications may commonly occur during the euthanasia of non-domestic species. An online...

Owen, J. P., Kelsh, R. N. 2021. A suitable anaesthetic protocol for metamorphic zebrafish. PLOS ONE 16(3), e0246504.

Zebrafish are frequently used as a means to investigate development. These studies increasingly require repeated anaesthesia of zebrafish during juvenile (i.e. metamorphic) stages. The effects of anaesthesia during this time remain poorly studied. The aim...

Leeds, A., Boyer, D., Ross, S. R. et al. 2021. Patterns of wounding in mixed-sex social groups of western lowland gorillas (Gorilla gorilla gorilla). Applied Animal Behaviour Science 236, 105226.

Long-term, multi-institutional assessments have become a reliable tool for evaluating patterns of wounding in zoo-living primates, with results informing on best practices for species-specific care protocols and population management strategies. For western lowland gorillas (Gorilla...

Archibald, W., Glynn, C. 2021. Refining cages for social housing of non-human primates on ADME studies. Animal Technology and Welfare 20(2), 172-174.

The assessment and understanding of Absorption, Distribution, Metabolism and Elimination (ADME) for new pharmaceuticals is required in regulatory submissions. Typically, ADME studies are conducted using metabolism cages designed for the single housing of animals to...

Kay, W. R., Mawson, P. R. 2021. An efficient method for the euthanasia of cane toads (Rhinella marina) under northern Australian field conditions. Animals 11(8), 2239.

The euthanasia of cane toads under field conditions presents a number of logistical and animal welfare challenges. One recommended method of control involves the use of carbon dioxide in plastic bags. This paper describes the...

Jorge, S., Ferreira, J. M., Olsson, I. A. S. et al. 2021. Efficacy and behavioral recovery of different anesthetics. Zebrafish 18(5), 330-337.

The use of proper anesthesia in zebrafish research is essential to ensure fish welfare and data reliability. However, anesthesia long-term side effects remain poorly understood. The purpose of this study was to assess anesthesia quality...

Persson, K., Selter, F., Neitzke, G. et al. 2020. Philosophy of a “good death” in small animals and consequences for euthanasia in animal law and veterinary practice. Animals 10(1), 124.

Moral stress is a major concern in veterinary practice. Often, it is associated with the challenges in end-of-life situations. Euthanasia, however, is also meant to bring relief to animal patients and their owners. The reasons...

Gades, N. M., Thompson, K. L., Mi, L. et al. 2020. Impact of euthanasia on compassion fatigue in personnel working in animal research. Laboratory Animal Science Professional 8(1) (January/February), 22-23.

We conducted a cross-sectional study to investigate the association between euthanasia and compassion fatigue among employees working in animal research at a large academic medical center. In summary, animal research workers who euthanize animals reported...

Larson, C. M., Wilcox, G. L., Fairbanks, C. A. 2019. Defining and managing pain in stroke and traumatic brain injury research. Comparative Medicine 69(6), 510–519.

Neurologic conditions such as stroke and traumatic brain injury are challenging conditions to study in humans. Animal models are necessary to uncover disease processes and develop novel therapies. When attempting to model these or other...

Galex, I. A., Gallant, C. M., D'Avignon, N. et al. 2020. Evaluation of effective and practical euthanasia methods for larval African clawed frogs (Xenopus laevis). JAALAS 59(3), 269–274.

Larval, or tadpole-stage Xenopus laevis frogs are a popular research model for developmental biology and disease studies. Existing euthanasia guidance documents offer recommendations for both eggs and adult stages, yet do not specifically address the...

Clutton, R. E. 2020. An Anglocentric history of anaesthetics and analgesics in the refinement of animal experiments. Animals 10(10), 1933.

Previous histories of animal experimentation, e.g., Franco (2013) have focused on ethics, the law and the personalities involved, but not on the involvement of anaesthetics or analgesics. Given that these were major subjects of (UK)...

Musk, G. C., Ezzy, B. J., Kenchington, L. M. et al. 2020. A comparison of buffered tricaine methanesulfonate (MS-222) and isoeugenol anesthesia for caudal fin clipping in zebrafish (Danio rerio). JAALAS 59(6), 732-736.

The purpose of this study was to compare the safety and efficacy of buffered tricaine methanesulfonate (MS-222) and isoeugenol for the anesthesia of zebrafish undergoing caudal fin clipping. Eighty 9 mo Danio rerio (AB strain)...

Sloman, K, A., Bouyoucos, I. A., Brooks, E. J. et al. 2019. Ethical considerations in fish research. Journal of Fish Biology 94(4), 556-577.

In this review, we focus primarily on the refinement of common methods used in fish research based on emerging knowledge with the aim of improving the welfare of fish used in scientific studies. We consider...