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. 
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...

Perea, C., Vázquez-Ágredos, A., Ruiz-Leyva, L. et al. 2021. Caloric restriction in group-housed mice: Littermate and sex influence on behavioral and hormonal data. Frontiers in Veterinary Science 8, 639187.

Much of the research done on aging, oxidative stress, anxiety, and cognitive and social behavior in rodents has focused on caloric restriction (CR). This often involves several days of single housing, which can cause numerous...

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...

Xu, J. J., Thurston, S. E., Robinson, T. J. et al. 2021. Effects of analgesics on tumor growth in mouse models of prostate cancer bone metastasis. JAALAS 60(3), 341-348.

Murine models of tumor development often require invasive procedures for tumor implantation, potentially causing pain or distress. However, analgesics are often withheld during implantation because of concerns that they may adversely affect tumor development. Previous...

Martini, A., Huysseune, A., Witten, P. E. et al. 2021. Plasticity of the skeleton and skeletal deformities in zebrafish (Danio rerio) linked to rearing density. Journal of Fish Biology 98(4), 971-986.

The teleost zebrafish (Danio rerio), an established model for human skeletal diseases, is reared under controlled conditions with defined parameters for temperature and photoperiod. Studies aimed at defining the proper rearing density have been performed...

Koch, A. L., Rusnak, M., Peachee, K. et al. 2021. Comparison of the effects of osmotic pump implantation with subcutaneous injection for administration of drugs after total body irradiation in mice. Laboratory Animals 55(2), 142-149.

The increasing potential for radiation exposure from nuclear accidents or terrorist activities has intensified the need to develop pharmacologic countermeasures against injury from total body irradiation (TBI). Many initial experiments to develop and test these...

Huber, N., Mahr, K., Tóth, Z. et al. 2021. The stressed bird in the hand: Influence of sampling design on the physiological stress response in a free-living songbird. Physiology & Behavior 238, 113488.

Despite the widely used application of standardized capture-handling protocols to collect blood and assess the physiological stress response, the actual sampling design (e.g., timing and the number of blood samples) often differs between studies, and...

Kittelsen, K. E., Gretarsson, P., Jensen, P. et al. 2021. Keel bone fractures are more prevalent in White Leghorn hens than in Red Jungle fowl hens—A pilot study. PLOS ONE 16(7), e0255234.

Fractures and deviations to the keel bone are common in commercial laying hens, with reported variations in occurrence across strains and breeds. The aetiology is not fully understood, however, modern genetics and selection for efficient...

Xie, W., Kordt, M., Palme, R. et al. 2021. Diagnostic ability of methods depicting distress of tumor-bearing mice. Animals 11(8), 2155.

Subcutaneous tumor models in mice are the most commonly used experimental animal models in cancer research. To improve animal welfare and the quality of scientific studies, the distress of experimental animals needs to be minimized...

Anderson, M. G., Campbell, A. M., Crump, A. et al. 2021. Effect of environmental complexity and stocking density on fear and anxiety in broiler chickens. Animals 11(8), 2383.

Barren housing and high stocking densities may contribute to negative affective states in broiler chickens, reducing their welfare. We investigated the effects of environmental complexity and stocking density on broilers’ attention bias (measure of anxiety)...

Kolarevic, J., Calduch-Giner, J., Espmark, Å. M. et al. 2021. A novel miniaturized biosensor for monitoring Atlantic salmon swimming activity and respiratory frequency. Animals 11(8), 2403.

The advanced development of sensor technologies has led to the emergence of fish biosensors that are currently used for research and commercial purposes. AEFishBIT is a miniaturized biosensor attached to fish operculum that measures physical...

Xie, W., Palme, R., Schafmayer, C. et al. 2021. Distress analysis of mice with cervical arteriovenous fistulas. Animals 11(11), 3051.

The welfare of laboratory animals is a consistent concern for researchers. Its evaluation not only fosters ethical responsibility and addresses legal requirements, but also provides a solid basis for a high quality of research. Recently...

Forslind, S., Blokhuis, H. J., Riber, A. B. 2021. Disturbance of resting behaviour of broilers under different environmental conditions. Applied Animal Behaviour Science 242, 105425.

Resting behaviours make up a large part of the daily time budget of broilers. However, in intensive broiler production systems disruptions of resting behaviours occur, where resting individuals get disturbed by active individuals. Such interruptions...

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...

Andersson, M., Kettunen, P. 2021. Effects of holding density on the welfare of zebrafish: A systematic review. Zebrafish 18(5), 297-306.

The zebrafish is becoming an increasingly popular research animal around the world. Its welfare is affected by an array of environmental factors, such as food access and water quality. Holding density is an important welfare...

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...

Weegh, N., Zentrich, E., Zechner, D. et al. 2021. Voluntary wheel running behaviour as a tool to assess the severity in a mouse pancreatic cancer model. PLOS ONE 16(12), e0261662.

Laboratory animals frequently undergo routine experimental procedures such as handling, restraining and injections. However, as a known source of stress, these procedures potentially impact study outcome and data quality. In the present study, we, therefore...

Wolfoviz-Zilberman, A., Houri-Haddad, Y., Beyth, N. 2021. A novel dental caries model replacing, refining, and reducing animal sacrifice. Applied Sciences 11(15), 7141.

In vitro and in vivo models simulating the dental caries process enable the evaluation of anti-caries modalities for prevention and treatment. Animal experimentation remains important for improving human and animal health. Nonetheless, reducing animal sacrifice...

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...

Piller, A., Bergmann, S., Schwarzer, A. et al. 2020. Validation of histological and visual scoring systems for foot-pad dermatitis in broiler chickens. Animal Welfare 29(2), 185-196.

In this study, an appropriate visual scoring system for foot-pad dermatitis was validated, considering the histologically measured depth of the inflammation zone and the histopathological grade (no lesion, mild lesion, ulcer). The aim being to...

Jones, P., Tahamtani, F., Pedersen, I. et al. 2020. The productivity and financial impacts of eight types of environmental enrichment for broiler chickens. Animals 10(3), 378.

Reduced mobility in broilers can contribute to leg health problems. Environmental enrichment has been suggested as one approach to combat this through stimulating increased physical activity. Past studies have tested the effect of environmental enrichments...

Baker, S. L., Robison, C. I., Karcher, D. M. et al. 2020. Keel impacts and associated behaviors in laying hens. Applied Animal Behaviour Science 222, 104886.

Factors contributing to the development of keel bone damage are not well understood. This study aimed to identify behaviors and cage structures associated with acceleration events experienced by individual hens at their keels as the...

Thøfner, I., Hougen, H. P., Villa, C. et al. 2020. Pathological characterization of keel bone fractures in laying hens does not support external trauma as the underlying cause. PLOS ONE 15(3), e0229735.

Keel bone fractures in laying hens have been described with increasing prevalence from several countries over the last twenty years and are considered one of the greatest welfare problems to the layer industry. In Denmark...

Armstrong, E. A., Rufener, C., Toscano, M. J. et al. 2020. Keel bone fractures induce a depressive-like state in laying hens. Scientific Reports 10(1), 3007.

In commercial flocks of laying hens, keel bone fractures (KBFs) are prevalent and associated with behavioural indicators of pain. However, whether their impact is severe enough to induce a depressive-like state of chronic stress is...