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. 
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...

Tonachella, N., Martini, A., Martinoli, M. et al. 2022. An affordable and easy-to-use tool for automatic fish length and weight estimation in mariculture. Scientific Reports 12(1), 15642.

Common aquaculture practices involve measuring fish biometrics at different growth stages, which is crucial for feeding regime management and for improving farmed fish welfare. Fish measurements are usually carried out manually on individual fish. However...

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...

Nuber, M., Gonzalez-Uarquin, F., Neufurth, M. et al. 2022. Development of a 3D simulator for training the mouse in utero electroporation. PLOS ONE 17(12), e0279004.

In utero electroporation (IUE) requires high-level training in microinjection through the mouse uterine wall into the lateral ventricle of the mouse brain. Training for IUE is currently being performed in live mice as no artificial...

O’Malley, C. I., Hubley, R., Tambadou, H. et al. 2022. Refining restraint techniques for research pigs through habituation. Frontiers in Veterinary Science 9, 1016414.

Pigs are common research models and are strong animals that can be difficult to restrain. Improper restraint can put pigs and research personnel at risk for injury and induce stress, which can affect research outcomes...

Santymire, R. M., Young, M., Lenihan, E. et al. 2022. Preliminary investigation into developing the use of swabs for skin cortisol analysis for the ocean sunfish (Mola mola). Animals 12(20), 2868.

The ocean sunfish (mola; Mola mola) is the heaviest bony fish in the world. This slow-moving fish often is injured by fishing boats that use drift gillnets attributing to its listing as Vulnerable by the...

Brough, D. W., Murkin, J. T., Amos, H. E. et al. 2022. Comparing variability in measurement of subcutaneous tumors in mice using 3D thermal imaging and calipers. Comparative Medicine 72(6), 364–375.

Repeatable tumor measurements are key to accurately assessing tumor growth and treatment efficacy. A preliminary study that we conducted showed that a novel 3D and thermal imaging system (3D-TI) for measuring subcutaneous tumors in rodents...

Kishida, T., Motokawa, Y., Yokoi, R. et al. 2022. Less invasive, simultaneous, and continuous measurements of locomotor activity and body temperature using the nano tag® small accelerometer device in cynomolgus monkeys. Journal of Pharmacological and Toxicological Methods 118, 107224.

Locomotor activity and body temperature evaluations of cynomolgus monkeys are useful to understand the effects of drugs on the central nervous system. Here, we describe a simple, inexpensive, and less invasive evaluation method using the...

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...

Navarro-Castilla, A., Garrido, M., Hawlena, H. et al. 2021. Non-invasive monitoring of adrenocortical activity in three sympatric desert gerbil species. Animals 11(1), 75.

The study of the endocrine status can be useful to understand wildlife responses to the changing environment. Here, we validated an enzyme immunoassay (EIA) to non-invasively monitor adrenocortical activity by measuring fecal corticosterone metabolites (FCM)...

Wang, M., Youssef, Al., Larsen, M. et al. 2021. Contactless video-based heart rate monitoring of a resting and an anesthetized pig. Animals 11(2), 442.

Heart rate (HR) is a vital bio-signal that is relatively easy to monitor with contact sensors and is related to a living organism’s state of health, stress and well-being. The objective of this study was...

Wiechers, D.-H., Brunner, S., Herbrandt, S. et al. 2021. Analysis of hair cortisol as an indicator of chronic stress in pigs in two different farrowing systems. Frontiers in Veterinary Science 8, 605078.

Confinement to farrowing crates is known to prevent sows from performing natural behavior, impairing animal welfare and possibly causing chronic stress. Hair cortisol analyses are increasingly used to detect chronic stress in animals. In the...

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...

Schmid, S. M., Büscher, W., Steinhoff-Wagner, J. 2021. Suitability of different thermometers for measuring body core and skin temperatures in suckling piglets. Animals 11(4), 1004.

Monitoring the temperature of piglets after birth is critical to ensure their well-being. Rectal temperature measurement is time-consuming, requires fixation of the animal and is stressful for piglets. This study aims to evaluate the effectiveness...

Silva-Reis, R., Faustino-Rocha, A. I., Gonçalves, M. et al. 2021. Refinement of animal model of colorectal carcinogenesis through the definition of novel humane endpoints. Animals 11(4), 985.

This study aimed to define appropriate humane endpoints (HEs) for an animal model of colorectal carcinogenesis (CRC). Twenty-nine male Wistar rats were divided into two control groups (CTRL1 and CTRL2) injected with ethylenediamine tetraacetic acid...

Chmurska-Gąsowska, M., Sowińska, N., Pałka, S. et al. 2021. Non-invasive measurement of thyroid hormones in domestic rabbits. Animals 11(5), 1194.

Thyroid hormones are essential for metabolism, energy homeostasis and reproduction. Hormones can be measured in various biological source materials: blood, feces, urine, saliva and others. The aim of our study was to verify usefulness of...

Ordóñez-Grande, B., Guerreiro, P. M., Sanahuja, I. et al. 2021. Environmental salinity modifies mucus exudation and energy use in European sea bass juveniles. Animals 11(6), 1580.

Changes in skin mucus production and composition offer a new means to study how fish cope with changes in the environment. We explored the utility of skin mucus as an indicator of physiological responses and...

Labitt, R. N., Oxford, E. M., Davis, A. K. et al. 2021. A validated smartphone-based electrocardiogram reveals severe bradyarrhythmias during immobilizing restraint in mice of both sexes and four strains. JAALAS 60(2), 201-212.

Mouse handling and restraint affect behavior, physiology, and animal welfare, yet little information is available on how various mouse restraint methods affect cardiovascular parameters. We validated the use of a smartphone-based ECG sys- tem in...

Ellis, T., Katsiadaki, I. 2021. Clarification of early end-points for refinement of animal experiments, with specific reference to fish. Laboratory Animals 55(3), 244-253.

Appropriate end-points are integral to the refinement of laboratory animal experiments. Our recent experience has highlighted that ambiguity around end-points is hampering their adoption in experiments that cause severe suffering to fish. In toxicology, the...

Houser, L. A., Ramsey, C., de Carvalho, F. M. et al. 2021. Improved training and semen collection outcomes using the closed box chair for macaques. Animals 11(8), 2384.

Collaborative semen collection in monkeys is a valuable tool in research, animal collection management, and conservation efforts. To obtain samples, monkeys are often restrained in open restraint chairs (ORC) with the “pole and collar” technique...

Holdsworth, S. E., Kells, N. J., Chidgey, K. L. et al. 2021. Characterisation of the behavioural effects of a thoracic squeeze in healthy newborn piglets. Animals 11(8), 2465.

Firmly squeezing the chests of newborn foals and calves that are showing abnormal behaviours after birth causes them to enter a less-responsive state, characterised by lying down with eyes closed and no limb movements. Once...

Falendysz, E. A., Calhoun, D. M., Smith, C. A. et al. 2020. Outside the box: Working with wildlife in biocontainment. ILAR Journal 61(1), 72-85.

Research with captive wildlife in Animal Biosafety Level 2 (ABSL2) and 3 (ABSL3) facilities is becoming increasingly necessary as emerging and re-emerging diseases involving wildlife have increasing impacts on human, animal, and environmental health. Utilizing...

Redaelli, V., Bosi, A., Luzi, F. et al. 2021. Neuroinflammation, body temperature and behavioural changes in CD1 male mice undergoing acute restraint stress: An exploratory study. PLOS ONE 16(11), e0259938.

Background: Animal models used to study pathologies requiring rehabilitation therapy, such as cardiovascular and neurologic disorders or oncologic disease, must be as refined and translationally relevant as possible. Sometimes, however, experimental procedures such as those...

Winn, C. B., Hwang, S. K., Morin, J. et al. 2021. Automated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models. PLOS ONE 16(9), e0257694.

In oncology research, while xenograft tumor models are easily visualized and humane endpoints can be clearly defined, metastatic tumor models are often based on more subjective clinical observations as endpoints. This study aimed at identifying...

Miller, A. L., Roughan, J. V. 2021. Welfare assessment, end-point refinement and the effects of non-aversive handling in C57BL/6 mice with Lewis lung cancer. Animals 12(1), 23.

Cancer-bearing mice are at risk of developing anxiety, pain, or malaise. These conditions may not only harm welfare but could also undermine data quality and translational validity in studies to develop therapeutic interventions. We aimed...