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. 
Lambert, H., Cornish, A., Waley, D. 2024. The value of regulating stocking densities in aquaculture must not be dismissed: A reply to Saraiva et al. 2022. Frontiers in Veterinary Science 10.

We would like to rebut the argument made by Saraiva et al. (1) in their paper “Finding the “golden stocking density”: a balance between fish welfare and farmers' perspectives,” that stocking densities should not be...

Bozzay, J. D., Walker, P. F., Atwood, R. E. et al. 2023. Development, refinement, and characterization of a nonhuman primate critical care environment. PLOS ONE 18(3), e0281548.

Systemic inflammatory response remains a poorly understood cause of morbidity and mortality after traumatic injury. Recent nonhuman primate (NHP) trauma models have been used to characterize the systemic response to trauma, but none have incorporated...

Diao, W., Jia, R., Hou, Y. et al. 2023. Effects of stocking density on the growth performance, physiological parameters, antioxidant status and lipid metabolism of Pelteobagrus fulvidraco in the integrated rice-fish farming system. Animals 13(11), 1721.

Pelteobagrus fulvidraco is a freshwater fish commonly raised in rice fields, yet the optimal stocking density for this species remains unknown. Therefore, this study aimed to investigate the appropriate stocking density of P. fulvidraco in...

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...

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...

Peruga, M., Kawala, B., Sarul, M. et al. 2023. Are currently selected laboratory animals useful in the research of how female hormones influence orthodontic biomechanics? Animals 13(4), 629.

Animal testing was and remains the only method of introducing a certain treatment and medical procedure on humans. On the other hand, animals have their rights resulting from applicable legal acts, including Directive 2010/63/EU and...

Sen Sarma, O., Frymus, N., Axling, F. et al. 2023. Optimizing zebrafish rearing−Effects of fish density and environmental enrichment. Frontiers in Behavioral Neuroscience 17, 1204021.

Despite its popularity in research, there is very little scientifically validated knowledge about the best practices on zebrafish (Danio rerio) husbandry, which has led to several facilities having their own husbandry protocols. This study was...

Attokaren, M. K., Jeong, N., Blanpain, L. et al. 2023. BrainWAVE: A flexible method for noninvasive stimulation of brain rhythms across species. ENeuro 10(2) ENEURO.0257-22.2022.

Rhythmic neural activity, which coordinates brain regions and neurons to achieve multiple brain functions, is impaired in many diseases. Despite the therapeutic potential of driving brain rhythms, methods to noninvasively target deep brain regions are...

Baßmann, B., Hahn, L., Rebl, A. et al. 2023. Effects of stocking density, size, and external stress on growth and welfare of African catfish (Clarias gariepinus Burchell, 1822) in a commercial RAS. Fishes 8(2), 74.

The effects of semi-intensive (100 kg m−3), intensive (200 kg m−3), and super-intensive (400 kg m−3) stocking densities on the growth and welfare of African catfish (Clarias gariepinus) were investigated under commercial production conditions. Plasma...

Gauy, A. C. dos S., Bolognesi, M. C., Gonçalves-de-Freitas, E. 2023. Body tactile stimulation reduces the effects of high stocking density on the welfare of Nile tilapia (Oreochromis niloticus). Fishes 8(6), 320.

High stocking density is used in aquaculture to optimize farming. However, such strategies can stress territorial fish by increasing aggression, thus harming the fish welfare and productive performance. Here, we tested the effect of long-term...

Van Loo, P. L. P., Janssens, M. R. E. 2023. Why all healthy laboratory animals should be rehomed, no matter how small. Animals 13(17), 2727.

This paper explores the ethical imperative of rehoming all healthy animals of sentient species after experiments have finished or when they have become otherwise redundant. We take into account disparate perspectives in animal ethics and...

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...

Cho, E., Walsh, C. A., D’Angelo-Gavrish, N. M. et al. 2023. Effects of housing density on reproductive performance, intracage ammonia, and welfare of mice continuously housed as breeders in standard mouse and rat caging. JAALAS 62(2), 116–122.

Maintaining compliance with cage density recommendations in The Guide for the Care and Use of Laboratory Animals precludes continuous trio breeding in standard-sized mouse cages. This study evaluated and compared several parameters of reproductive performance...

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...

Scariot, P. P., Gobatto, C. A., Polisel, E. E. et al. 2022. Early-life mice housed in standard stocking density reduce the spontaneous physical activity and increase visceral fat deposition before reaching adulthood. Laboratory Animals 56(4), 344-355.

Laboratory rodents spend the entire day housed in standard cages that provide a restricted area for movements and might, therefore, limit physical activity. However, it has not been tested in immature rodents of ages ranging...

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...

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...

Saraiva, J. L., Rachinas-Lopes, P., Arechavala-Lopez, P. 2022. Finding the “golden stocking density”: A balance between fish welfare and farmers’ perspectives. Frontiers in Veterinary Science 9, 930221.

The effects of stocking density on fish welfare are complex and involve many interacting parameters. This complex relationship between fish welfare, stocking density and influencing factors make it challenging to define a specific optimal (“golden”)...

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...

Anderson, M. G., Campbell, A. M., Kuhn, D. D. et al. 2022. Impact of environmental complexity and stocking density on affective states of rainbow trout (Oncorhynchus mykiss). Animal Cognition 25(5), 1331–1343.

Environmental condition, such as environmental complexity or stocking density, can directly or indirectly influence animal emotion and ultimately, affective state. Affective states of animals can be assessed through judgement bias tests, evaluating responses to ambiguous...

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...

Carbone, L. 2021. Estimating mouse and rat use in American laboratories by extrapolation from Animal Welfare Act-regulated species. Scientific Reports 11(1), 493.

Alone among Western nations, the United States has a two-tier system for welfare protections for vertebrate animals in research. Because its Animal Welfare Act (AWA) excludes laboratory rats and mice (RM), government veterinarians do not...

Kammertoens, T., Jeuthe, S., Baranzke, H. et al. 2021. Breeding and maintenance of immunodeficient mouse lines under SPF conditions—A call for individualized severity analyses and approval procedures. Animals 11(6), 1789.

In the EU, the breeding of genetically modified laboratory animals is, by definition, an animal experiment if the offspring may experience pain, suffering, or harm. In order to determine the actual burden of genetically modified...

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...