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...

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...

Kaiser, S., Korte, A., Wistuba, J. et al. 2023. Effects of castration and sterilization on baseline and response levels of cortisol—A case study in male guinea pigs. Frontiers in Veterinary Science 9, 1093157.

An uncontrolled reproduction of animals in human hands should be avoided. To meet this goal, animals are widely castrated, i.e., the gonads are completely removed. Since the gonads are the most important source of sex...

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...

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...

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...

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...

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...

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...

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...

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...

da Silva Medeiros Elidio, H., Coelho, J. W. R., Cavalcanti Pereira da Silva, L. C. et al. 2021. Housing density and aggression in Syrian hamsters. JAALAS 60(5), 506-509.

The Syrian hamster (Mesocricetus auratus) is a solitary and naturally territorial animal, with female hamsters being more aggressive than males. This behavior makes handling difficult because they are usually housed in groups, which can lead...

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...

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...

Helgers, S., Talbot, S. R., Riedesel, A. K. et al. 2020. Body weight algorithm predicts humane endpoint in an intracranial rat glioma model. Scientific Reports 10, 9020.

Humane endpoint determination is fundamental in animal experimentation. Despite commonly accepted endpoint criteria for intracranial tumour models (20% body weight loss and deteriorated clinical score) some animals still die before being euthanized in current research...

Zhang, X., Kumstel, S., Tang, G. et al. 2020. A rational approach of early humane endpoint determination in a murine model for cholestasis. ALTEX 37(2), 197-207.

Reduction of animal suffering during in vivo experiments is usually ensured by continuously monitoring the health status using a score sheet and by applying humane endpoints. However, most studies do not evaluate the plausibility of...