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...

Malik, A., Zavadil, J. A., Geusz, M. E. 2023. Using bioluminescence to image gene expression and spontaneous behavior in freely moving mice. PLOS ONE 18(1), e0279875.

Bioluminescence imaging (BLI) of gene expression in live animals is a powerful method for monitoring development, tumor growth, infections, healing, and other progressive, long-term biological processes. BLI remains an effective approach for reducing the number...

Morton, D. B. 2023. A model framework for the estimation of animal “suffering”: Its use in predicting and retrospectively assessing the impact of experiments on animals. Animals 13(5), 800.

This paper presents and illustrates, with a working example, a hypothesis for the assessment of ongoing severity before and during an experiment that will enable humane endpoints and intervention points to be applied accurately and...

Palumbo, G., Kunze, L. H., Oos, R. et al. 2023. Longitudinal studies on Alzheimer disease mouse models with multiple tracer PET/CT: Application of reduction and refinement principles in daily practice to safeguard animal welfare during progressive aging. Animals 13(11), 1812.

Longitudinal studies on mouse models related to Alzheimer disease (AD) pathology play an important role in the investigation of therapeutic targets to help pharmaceutical research in the development of new drugs and in the attempt...

Silva-Reis, R., Faustino-Rocha, A. I., Silva, J. et al. 2023. Studying and analyzing humane endpoints in the fructose-fed and streptozotocin-injected rat model of diabetes. Animals 13(8), 1397.

This work aimed to define a humane endpoint scoring system able to objectively identify signs of animal suffering in a rat model of type 2 diabetes. Sprague-Dawley male rats were divided into control and induced...

Ferguson, L. T., Rashied, A. A., Liang, Z. et al. 2023. A novel scoring system for humane endpoints in mice with cecal ligation and puncture-induced sepsis. Comparative Medicine 73(6), 446–460.

Animal-based research is essential to the study of sepsis pathophysiology, diagnostics, and therapeutics. However, animal models of sepsis are often associated with high mortality because of the difficulty in predicting imminent death based on premortem...

Froman, N., Genain, M.-A., Stevens, G. M. W. et al. 2023. Use of underwater contactless ultrasonography to elucidate the internal anatomy and reproductive activity of manta and devil rays (family: Mobulidae). Journal of Fish Biology 103(2), 305–323.

The ability to visualise the internal anatomical structures of fish provides important information on their reproductive status and body condition and has made important contributions to many areas of fish biology. Obtaining information on the...

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...

Williams, W. O., Baneux, P. 2022. Humane Intervention Points: Refining endpoint terminology to incorporate non-euthanasia intervention options to improve animal welfare and preserve experimental outcomes. Laboratory Animals 56(5), 482-489.

Consideration of The Three R’s (Replacement, Reduction, and Refinement) is essential when setting Humane Endpoints; however, a common interpretation assumes that Humane Endpoints are timepoints to perform euthanasia. This interpretation is not always consistent with...

Chen, T., Zhou, Z.-Y., Liu, J.-Y. et al. 2022. Impact of partial bile duct ligation with or without repeated magnetic resonance imaging examinations in mice. Scientific Reports 12(1), 21014.

Partial bile duct ligation (pBDL) is considered a well-tolerated cholestatic model. Magnetic resonance imaging (MRI) is one of the most widely used tools in noninvasive imaging. However, no systematic studies have reported the possible effects...

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...

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...

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...

Nunamaker, E. A., Davis, S., O’Malley, C. I. et al. 2021. Developing recommendations for cumulative endpoints and lifetime use for research animals. Animals 11(7), 2031.

Research animals are important for scientific advancement, and therefore, their long-term welfare needs to be monitored to not only minimize suffering, but to provide positive affective states and experiences. Currently, there is limited guidance 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...

Onozawa, E., Azakami, D., Seki, S. et al. 2021. Effect of an insulation device in preventing hypothermia during magnetic resonance imaging examinations for dogs and cats under general anesthesia. Animals 11(8), 2378.

Dogs and cats under general anesthesia may develop hypothermia. When performing a magnetic resonance imaging (MRI) examination, it is not possible to place a magnetic material in the MRI room, and MRI equipment requires a...

Tölgyesi, B., Bakker, J., Nagy, K. et al. 2021. Refined acquisition of high-resolution chest CTs in macaques by free breathing. Laboratory Animals 55(6), 551-559.

The use of medical imaging as a non-invasive or minimally invasive method to assess disease or treatment response continues to grow. A similar trend is observed in pre-clinical research, in general, and more specifically in...

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...

Bertho, J.-M., Ancelet, S., Denais-Laliève, D. et al. 2020. Humane endpoints in severe irradiation experiments using non-human primates: A retrospective analysis. Scandinavian Journal of Laboratory Animal Science 46(1).

A retrospective statistical study has been performed in order to identify the biological, clinical and behavioural variables that could potentially predict the survival status of irradiated non-human primates (NHP) and to refine the future use...

Talbot, S. R., Biernot, S., Bleich, A. et al. 2020. Defining body-weight reduction as a humane endpoint: A critical appraisal. Laboratory Animals 54(1), 99–110.

In many animal experiments scientists and local authorities define a body-weight reduction of 20% or more as severe suffering and thereby as a potential parameter for humane endpoint decisions. In this study, we evaluated distinct...

Nwagwu, C. D., Defensor, E., Jiang, M. Y. et al. 2020. Endpoint in ovarian cancer xenograft model predicted by nighttime motion metrics. Lab Animal 49(8), 227–232.

Despite several therapeutics showing promise in nonclinical studies, survival from ovarian cancer remains poor. New technologies are urgently needed to optimize the translation of nonclinical studies into clinical successes. While most nonclinical settings utilize subjective...

Wilkinson, M. J. A., Selman, C., McLaughlin, L. et al. 2020. Progressing the care, husbandry and management of ageing mice used in scientific studies. Laboratory Animals 54(3) 225–238.

Driven by the longer lifespans of humans, particularly in Westernised societies, and the need to know more about ‘healthy ageing’, ageing mice are being used increasingly in scientific research. Many departments and institutes involved with...

Kersemans, V., Wallington, S., Allen, P. D. et al. 2020. Manganese-free chow, a refined non-invasive solution to reduce gastrointestinal signal for T1-weighted magnetic resonance imaging of the mouse abdomen. Laboratory Animals 54(4), 353–364.

Commercial mouse chow is designed to provide a complete, nutrient-rich diet, and it can contain upwards of 100 mg/kg manganese, an essential mineral. Manganese acts as a relaxation time-shortening contrast agent for both T1 and T2...

Sharpe, S. A., Scott, S., Taylor, I. et al. 2020. Use of high frequency jet ventilation as a refinement for imaging macaques with respiratory disease. Laboratory Animals 54(4), 386–390.

Imaging is used in human medicine to diagnose disease and monitor treatment efficacy. Computed tomography (CT) positron emission tomography (PET) and magnetic resonance (MR) are applied to animal models of infectious diseases to increase data...