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. 
Jorge, S., Félix, L., Costas, B. et al. 2023. Housing conditions affect adult zebrafish (Danio rerio) behavior but not their physiological status. Animals 13(6), 1120.

Zebrafish is a valuable model for neuroscience research, but the housing conditions to which it is exposed daily may be impairing its welfare status. The use of environmental enrichment and the refinement of methodology for...

Danforth, M. D., Clyde, V. L., Jourdan, B. et al. 2023. Blood pressure monitoring in zoologically managed bonobos (Pan paniscus). American Journal of Primatology 85(3), e23474.

In response to the growing evidence that hypertension may play a significant role in the development of cardiovascular disease (CVD) in bonobos, the Great Ape Heart Project established a finger blood pressure (BP) monitoring protocol...

Alejandro, J., Yamanashi, Y., Nemoto, K. et al. 2023. Reducing stress and stereotypic behaviors in captive female pygmy slow lorises (Nycticebus pygmeaus). American Journal of Primatology 85(7), e23495.

Improving captive conditions of pygmy slow lorises (Nekaris and Nijman have recently suggested that the pygmy slow loris should be called the pygmy loris and is distinctive enough to warrant a new genus, Xanthonycticebu) (Nycticebus...

Higham, J. P., Cooper, E. B., Whalen, C. et al. 2023. Urinary cytokine measurements do not reflect surgery-induced inflammation in rhesus macaques. American Journal of Primatology 85(8), e23506.

Measurement of the health and disease status of free-ranging primates is often limited by a lack of available biomarkers of immune activation and inflammation that can be applied noninvasively via the measurement of urine or...

Chakravarty, S., Donoghue, J., Waite, A. S. et al. 2023. Closed-loop control of anesthetic state in nonhuman primates. PNAS Nexus 2(10), 293.

Research in human volunteers and surgical patients has shown that unconsciousness under general anesthesia can be reliably tracked using real-time electroencephalogram processing. Hence, a closed-loop anesthesia delivery (CLAD) system that maintains precisely specified levels of...

Turcu, M.-C., Paștiu, A. I., Bel, L.-V. et al. 2023. Minimally invasive sampling methods for molecular sexing of wild and companion birds. Animals 13(21), 3417.

Birds are highly social and must be paired in order to increase their welfare. Most bird species are monomorphic; therefore, molecular sexing helps provide appropriate welfare for birds. Moreover, early sex determination can be of...

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...

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...

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.

Midttun, H., Øverli, Ø., Tudorache, C. et al. 2022. Non-invasive sampling of water-borne hormones demonstrates individual consistency of the cortisol response to stress in laboratory zebrafish (Danio rerio). Scientific Reports 12(1) 6278.

Glucocorticoid (GC) stress hormones are well-known for their impact on phenotypic traits ranging from immune function to behaviour and cognition. For that reason, consistent aspects of an individual’s physiological stress response (i.e. GC responsiveness) can...

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...

Edes, A. N., Zimmerman, D., Jourdan, B. et al. 2022. Value ranges and clinical comparisons of serum DHEA-S, IL-6, and TNF-α in western lowland gorillas. Animals 12(19), 2705.

Physiological data can provide valuable information about the health and welfare of animals. Unfortunately, few validated assays and a lack of information on species-typical levels of circulating biomarkers for wildlife make the measurement, interpretation, and...

Fink, L. B., Mukobi, A., Gruber, L. et al. 2022. Longitudinal analysis of variability in fecal glucocorticoid metabolite concentrations in three orangutans (Pongo pygmaeus pygmaeus and Pongo pygmaeus abelii) before, during, and after transition from a regular habitat environment to temporary housing in indoor holding facilities. Animals 12(23), 3303.

Considerable research has been conducted on the effects of inter-institutional transfers, but far less consideration has been given to intra-institutional transfers and extended housing in off-habitat holding. On 15 May 2018, The Oregon Zoo’s orangutans...

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...

Wahltinez, S. J., Stacy, N. I., Hadfield, C. A. et al. 2022. Perspective: Opportunities for advancing aquatic invertebrate welfare. Frontiers in Veterinary Science 9, 973376.

Welfare considerations and regulations for invertebrates have lagged behind those for vertebrates, despite invertebrates comprising more than 95% of earth’s species. Humans interact with and use aquatic invertebrates for exhibition in zoos and aquaria, as...

Ramos, J., Balasch, J. C., Tort, L. 2021. About welfare and stress in the early stages of fish. Frontiers in Veterinary Science 8, 634434.

In conclusion, the investigations carried out up to now demonstrate that during the early stages fish show high sensitivity to many types of stressors involving an array of responses to overcome alterations that could affect...

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...

Prior, H., Holbrook, M. 2021. Strategies to encourage the adoption of social housing during cardiovascular telemetry recordings in non-rodents. Journal of Pharmacological and Toxicological Methods 108, 106959.

The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) is working with industry to promote social housing during cardiovascular telemetry recordings within non-rodent safety pharmacology and toxicology studies. Following surveys...

Yolles, J. N., Lee-Stubbs, R. B. 2021. Comparison of direct and indirect methods of measuring arterial blood pressure in healthy, anesthetized African green monkeys (Chlorocebus aethiops). JAALAS 60(2), 229-237.

Quantitative blood pressure measurement is a critical parameter for assessing cardiovascular health, monitoring physiologic status under anesthesia, and making clinical decisions. The placement of an arterial catheter is the most accurate way to measure blood...

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...

Ross, S. R., Lake, B. R., Fultz, A. et al. 2021. An evaluation of thermal imaging as a welfare monitoring tool for captive chimpanzees. Primates 62(6), 919-927.

Among the growing list of novel tools with which to assess animal welfare is the use of thermal (infrared) imaging. The technology has already been utilized to identify emotional arousal in several nonhuman primate species...

Edes, A. N., Brand, C. M. 2021. Age, sex, and inflammatory markers predict chronic conditions, cardiac disease, and mortality among captive western lowland gorillas (Gorilla gorilla gorilla). Primates 62(6), 931-943.

In humans, inflammatory markers predict health risks. As great apes experience many similar conditions, measuring inflammation may provide valuable health information. We examined four serum inflammatory markers in zoo-housed gorillas (n = 48): albumin, CRP, IL-6, and...

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...

Anderson, J., Kaplan-Stein, S., Adolph, S. et al. 2020. Assessment of non-contact infrared thermometer measurement sites in birds. Journal of Applied Animal Welfare Science 23(2), 131-139.

The standard method of obtaining body temperature in a bird can be a stressful event, making routine evaluations challenging. Twenty-eight privately owned birds in good health were enrolled in the study to compare digital and...

Byrnes, E. E., Lear, K. O., Morgan, D. L. et al. 2020. Respirometer in a box: Development and use of a portable field respirometer for estimating oxygen consumption of large‐bodied fishes. Journal of Fish Biology 96(4), 1045-1050.

Respirometry has become the standard method for measuring the metabolic rate of fishes. Traditionally, respirometry has required the fish to be kept in captivity and tested under controlled conditions; however, many species do not readily...