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...

Kumar, P., Abubakar, A. A., Ahmed, M. A. et al. 2023. Electroencephalogram and physiological responses as affected by slaughter empathy in goats. Animals 13(6), 1100.

Recent advances in emotions and cognitive science make it imperative to assess the emotional stress in goats at the time of slaughter. The present study was envisaged to study the electroencephalogram and physiological responses as...

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...

Mauthe von Degerfeld, M., Serpieri, M., Bonaffini, G. et al. 2023. Intranasal atomization of ketamine, medetomidine and butorphanol in pet rabbits using a mucosal atomization device. Animals 13(13), 2076.

A non-invasive method of drug delivery, intranasal atomization, has shown positive results in human medicine and in some animal species. The objective of this study was to evaluate the effects of intranasal atomization, compared to...

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...

Rucinque, D. S., van de Vis, H., Reimert, H. et al. 2023. Pre-slaughter stunning of farmed Atlantic halibut in CO2-saturated seawater: Assessment of unconsciousness by electroencephalography (EEG). Animals 13(12), 1993.

As fish welfare becomes a growing concern, it is important to ensure humane treatment during slaughter. This study aimed to assess the onset of unconsciousness in Atlantic halibut immersed in CO2-saturated seawater through electroencephalography (EEG)...

Clemente, G. A., Tolini, C., Boscarino, A. et al. 2023. Farmed fish welfare during slaughter in Italy: Survey on stunning and killing methods and indicators of unconsciousness. Frontiers in Veterinary Science 10.

Information on slaughter procedures for farmed fish in aquaculture is limited, both in Europe and in Italy, due to a general lack of field data. The aim of this study was to gather information on...

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...

Trujanovic, R., Rohrbach, H. 2023. Ultrasound-guided block of the sciatic and the femoral nerves in rabbits—A descriptive anatomical study. Animals 13(14), 2393.

The rabbit is a popular animal model for human biomechanical research involving surgery on the hind limb. Mortality is higher in rabbits when undergoing general anesthesia compared to dogs and cats. Moreover, due to their...

Miller, A. L., Clarkson, J. M., Quigley, C. et al. 2022. Evaluating pain and analgesia effectiveness following routine castration in rabbits using behavior and facial expressions. Frontiers in Veterinary Science 9, 782486.

Prevention of pain in rabbits is a priority for both welfare and validity of scientific data. We aimed to determine if the rabbit grimace scale (RbtGS) could be used as a viable, rapid assessment tool...

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...

Perret-Thiry, C., Raulic, J., Vergneau-Grosset, C. 2022. Evaluation of prolonged immersion in tricaine methanesulfonate for juvenile goldfish (Carassius auratus) euthanasia. Journal of the American Veterinary Medical Association 260(8), 911-915.

OBJECTIVE: Doses of buffered tricaine methanesulfonate (MS-222) up to 1000 mg/L for 15 minutes are reported inefficient to produce euthanasia in goldfish. The goal of this study was to determine if goldfish can be euthanized...

Windsor, P. A. 2022. Role of topical anaesthesia in pain management of farm animals, a changing paradigm. Animals 12(18), 2459.

Field evidence indicates that livestock producers are motivated by access to products that readily deliver pain management during husbandry interventions and, more recently, viral epidermal infectious diseases, including FMD. There has been impressive adoption in...

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...

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...

Casey, K. M., Gore, F., Vilches-Moure, J. G. et al. 2021. Management of morbidity and mortality in a New Zealand white rabbit model of steroidinduced osteonecrosis of the femoral head. Comparative Medicine 71(1), 86-98.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a condition documented in humans and animals exposed to chronic steroid administration. The rabbit has become a preferred animal model for investigating the pathogenesis and treatment of...

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...

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...

Camargo-dos-Santos, B., Carlos, C. L., Favero-Neto, J. et al. 2021. Welfare in Nile tilapia production: Dorsal fin erection as a visual indicator for insensibility. Animals 11(10), 3007.

In aquaculture, to ensure animal welfare in pre-slaughter and slaughter stages, it is fundamental that fish are insensible. A method for evaluating fish insensibility is based on visual sensibility indicators (VSI) assessment (i.e., self-initiated behavior...

Hausmann, J. C., Krisp, A. R., Mans, C. et al. 2021. Analgesic efficacy of tramadol and morphine in White's tree frogs (Litoria caerulea). JAALAS 60(6), 681-686.

Published data are sparse regarding the recognition of clinically relevant pain and appropriate analgesia in amphibians. The amphibian analgesia literature has primarily focused on nociceptive pathways in a single species, the northern leopard frog (Rana...