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. 
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...

Sandgren, R., Grims, C., Waters, J. et al. 2021. Using cage ladders as a handling device reduces aversion and anxiety in laboratory mice, similar to tunnel handling. Scandinavian Journal of Laboratory Animal Science 47(5), 31-41.

Handling laboratory animals for husbandry and other procedures can be an important source of anxiety and stress, compromising animal welfare as well as the reliability of research that is sensitive to background stressors. Studies have...

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...

Kalafut, K. L., Kinley, R. 2020. Using radio frequency identification for behavioral monitoring in little blue penguins. Journal of Applied Animal Welfare Science 23(1), 62-73.

A common goal of captive animal institutions is to create environments that allow for the most naturalistic behavior from their animals. Behavioral data is often used as a measure of how an animal is thriving...

Muvhali, P. T., Bonato, M., Engelbrecht, A. et al. 2020. Extensive human presence and regular gentle handling improve growth, survival and immune competence in ostrich chicks. Journal of Applied Animal Welfare Science 23(1), 95-107.

A total of 416 day-old ostrich chicks were randomly allocated to one of the three different husbandry practices for 3 months after hatch; HP1 (extensive human presence with gentle human voice, visual and gentle physical...

Reese, L., Ladwig-Wiegard, M., von Fersen, L. et al. 2020. Deflighting zoo birds and its welfare considerations. Animal Welfare 29(1), 69-80.

For over a century, the practice of deflighting has taken place in zoological collections in order to ensure birds remain in open-topped enclosures. Over time, efforts have been made to improve or develop new (surgical)...

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...

Chartier, L. C., Hebart, M. L., Howarth, G. S. et al. 2020. Affective state determination in a mouse model of colitis-associated colorectal cancer. PLOS ONE 15(1), e0228413.

Behavioural indicators of affective state, including burrowing, clinical scores and the Mouse Grimace Score have not yet been validated in mouse models of chronic gastrointestinal disease. Additionally, a comparison of these methods has not been...

Henderson, L. J., Smulders, T. V., Roughan, J. V. 2020. Identifying obstacles preventing the uptake of tunnel handling methods for laboratory mice: An international thematic survey. PLOS ONE 15(4), e0231454.

Handling of laboratory mice is essential for experiments and husbandry, but handling can increase anxiety in mice, compromising their welfare and potentially reducing replicability between studies. The use of non-aversive handling (e.g., tunnel handling or...

Ueno, H., Takahashi, Y., Suemitsu, S. et al. 2020. Effects of repetitive gentle handling of male C57BL/6NCrl mice on comparative behavioural test results. Scientific Reports 10(1), 3509.

Mice are the most commonly used laboratory animals for studying diseases, behaviour, and pharmacology. Behavioural experiment battery aids in evaluating abnormal behaviour in mice. During behavioural experiments, mice frequently experience human contact. However, the effects...

Costa, R., Leite Tamascia, M., Sanches, A. et al. 2020. Tactile stimulation of adult rats modulates hormonal responses, depression-like behaviors, and memory impairment induced by chronic mild stress: Role of angiotensin II. Behavioural Brain Research 379, 112250.

Physical touch can help to decrease the effects of stress. The aim of this study was to evaluate the influence of tactile stimulation on the hormonal and behavioral responses of young adult rats submitted to...

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...

Thorpe, E. 2020. Alternative handling techniques to reduce anxiety in laboratory mice. Animal Technology and Welfare 19(1), 76-78.

Recent studies at Liverpool University have indicated that handling mice by their tails during routine cleaning and procedures induced aversion and high anxiety in many commonly used strains. The evidence from the Liverpool study suggests...

Unwin, S. L., Saunders, R. A., Blackwell, E.-J., et al. 2020. A double-blind, placebo-controlled trial investigating the value of Pet Remedy in ameliorating fear of handling of companion rabbits. Journal of Veterinary Behavior 36, 54-64.

Rabbits are popular companion animals. There are numerous welfare issues affecting the majority of the population, including the fact that most rabbits are fearful when handled. Pet Remedy ™ (Unex Designs) is an herbal product...

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...

Nørgaard, S. A., Søndergaard, H., Sørensen, D. B. et al. 2020. Optimising streptozotocin dosing to minimise renal toxicity and impairment of stomach emptying in male 129/Sv mice. Laboratory Animals 54(4), 341–352.

The streptozotocin (STZ)-induced diabetic mouse model has been extensively used as a model for diabetes and diabetic nephropathy, but it is still influenced by many off-target toxic effects and large variation in diabetes induction. Therefore...

van Dijk, R. M., Koska, I., Bleich, A. et al. 2020. Design of composite measure schemes for comparative severity assessment in animal-based neuroscience research: A case study focussed on rat epilepsy models. PLOS ONE 15(5): e0230141.

Comparative severity assessment of animal models and experimental interventions is of utmost relevance for harm-benefit analysis during ethical evaluation, an animal welfare-based model prioritization as well as the validation of refinement measures. Unfortunately, there is...

Hedenqvist, P., Trbakovic, A., Mellgren, T. et al. 2020. The effect of housing environment on bone healing in a critical radius defect in New Zealand white rabbits. PLOS ONE 15(5), e0233530.

In animal studies on bone healing, the effect of housing space and physical activity are seldom taken into account. Bone formation was evaluated in New Zealand White rabbits (mean ± SEM BW: 3.9 ± 0.11...

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...