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. 
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...

Manthey, T., Nagel-Riedasch, S., Dülsner, A. 2021. The interactive stress assessment in basic animal science training. Animals 11(7), 2145.

In order to assess the extent to which the legally prescribed training for the acquisition of animal experimentation expertise provides scientific personnel with the necessary competence and expertise to carry out a correct harm-benefit analysis...

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...

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...

Yatkin, E., Kulmala, N., Saukkonen, A. et al. 2021. A real-time health notification system aimed at enhancing the interaction between animal care staff and researchers promotes animal welfare. Laboratory Animals 55(3), 281-289.

Regardless of the microbiological status of an animal facility, research animals may experience health problems, leading to pain, suffering and distress. Simple and efficient tools are needed to collect data systematically, allowing researchers to react...

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...

Benato, L., Murrell, J., Knowles, T. G. et al. 2021. Development of the Bristol Rabbit Pain Scale (BRPS): A multidimensional composite pain scale specific to rabbits (Oryctolagus cuniculus). PLOS ONE 16(6), e0252417.

A species-specific composite pain scale is a prerequisite for adequate pain assessment. The aim of this study was to develop a multidimensional pain scale specific to rabbits (Oryctolagus cuniculus) called the Bristol Rabbit Pain Scale...

Zieglowski, L., Kümmecke, A. M., Ernst, L. et al. 2021. Assessing the severity of laparotomy and partial hepatectomy in male rats—A multimodal approach. PLOS ONE 16(8), e0255175.

This study assessed the postoperative severity after three different visceral surgical interventions in rats by using objective parameters pertaining to various disciplines. The objective was to evaluate whether the degree of severity increases with the...

Komatsu, T., Ohta, H., Motegi, H. et al. 2021. A novel model of ischemia in rats with middle cerebral artery occlusion using a microcatheter and zirconia ball under fluoroscopy. Scientific Reports 11(1), 12806.

Here, we present a highly selective rat MCAO model by percutaneous caudal arterial puncture using a microcatheter and zirconia ball under fluoroscopic guidance. The model is predictable and reproducible, which is well confined within the...

Silva, A. V., Norinder, U., Liiv, E. et al. 2021. Associations between clinical signs and pathological findings in toxicity testing. ALTEX 38(2), 198-214.

Animal testing for toxicity assessment of chemicals and pharmaceuticals must take the 3R principles into consideration. During toxicity testing in vivo, clinical signs are used to monitor animal welfare and to inform about potential toxicity...

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...

Travain, T., Valsecchi, P. 2021. Infrared thermography in the study of animals’ emotional responses: A critical review. Animals 11(9), 2510.

Whether animals have emotions was historically a long-lasting question but, today, nobody disputes that they do. However, how to assess them and how to guarantee animals their welfare have become important research topics in the...

Rodriguez-Sanchez, R., Barnaby, E., Améndola, L. et al. 2021. Voluntary oral ingestion of a sedative prior to euthanasia with CO2: Behavioural responses of mice. Animals 11(10), 2879.

Laboratory mice are commonly euthanised with carbon dioxide (CO2); however, there is ample evidence that this gas is aversive. Previous work suggests that sedation achieved via injection with benzodiazepines prior to CO2 administration could reduce...

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...

Diana, A., Salas, M., Pereboom, Z. et al. 2021. A systematic review of the use of technology to monitor welfare in zoo animals: Is there space for improvement? Animals 11(11), 3048.

A top priority of modern zoos is to ensure good animal welfare (AW), thus, efforts towards improving AW monitoring are increasing. Welfare assessments are performed through more traditional approaches by employing direct observations and time-consuming...

Bennett, T. E., Pavek, T. J., Schwark, W. S. et al. 2021. Comparison of nociceptive effects of buprenorphine, firocoxib, and meloxicam in a plantar incision model in Sprague–Dawley rats. JAALAS 60(5), 539-548.

Due to their reduced frequency of dosing and ease of availability, NSAIDs are generally preferred over opioids for rodent analgesia. We evaluated the efficacy of the highly COX2-selective NSAID firocoxib as compared with meloxicam and...

Brunt, M. W., Améndola, L., Weary, D. M. 2021. Attitudes of laboratory animal professionals and researchers towards carbon dioxide euthanasia for rodents and perceived barriers to change. Laboratory Animals 55(6), 531-539.

Evidence indicates that carbon dioxide (CO2) induces negative affective states (including anxiety, fear and distress) in laboratory rodents, but many countries still accept it for euthanasia. Alternative methods (e.g. inhalant anaesthetic) may represent a refinement...

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...

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...

Nøgaard, S. A., Sand, F. W., Sørensen, D. B. et al. 2020. Four- and six-hour urinary albumin excretion is a valuable alternative to 24-h urinary albumin excretion in male db/db mice. Animal Welfare 29(2), 143-149.

In mouse (Mus musculus) models of diabetic nephropathy (DN), one of the most important read-outs is the 24-h urinary albumin excretion (UAE). The 24-h urine collection is usually performed by single housing mice in metabolic...

Mallien, A. S., Häger, C., Palme, R. et al. 2020. Systematic analysis of severity in a widely used cognitive depression model for mice. Laboratory Animals 54(1), 40–49.

Animal models in psychiatric research are indispensable for insights into mechanisms of behaviour and mental disorders. Distress is an important aetiological factor in psychiatric diseases, especially depression, and is often used to mimic the human...

Weegh, N., Füner, J., Janke, O. et al. 2020. Wheel running behaviour in group-housed female mice indicates disturbed wellbeing due to DSS colitis. Laboratory Animals 54(1), 63–72.

Voluntary wheel running (VWR) behaviour is a sensitive indicator of disturbed wellbeing and used for the assessment of individual experimental severity levels in laboratory mice. However, monitoring individual VWR performance usually requires single housing, which...

Jirkof, P., Abdelrahman, A., Bleich, A. et al. 2020. A safe bet? Inter-laboratory variability in behaviour-based severity assessment. Laboratory Animals 54(1), 73–82.

Evidence-based severity assessment is essential as a basis for ethical evaluation in animal experimentation to ensure animal welfare, legal compliance and scientific quality. To fulfil these tasks scientists, animal care and veterinary personnel need assessment...