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. 
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...

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...

Young, T., Whiteside, T., Locklear, J. 2020. What is your tattoo ink telling you? Laboratory Animal Science Professional 8(2) (March/April), 62-65.

Tattooing traumatizes the skin, which can result in microbial infections with the severity ranging from minor to life-threating septicemia. Additionally, the metals in colored tattoo ink are known to cause dermal inflammation in some people...

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...

Składanowska-Baryza, J., Ludwiczak, A., Pruszyńska-Oszmałek, E. et al. 2020. Effect of two different stunning methods on the quality traits of rabbit meat. Animals 10(4), 700.

The aim of the study was to assess the effect of two different stunning methods on the level of blood stress indicators (cortisol, insulin, glucose) and rabbit meat quality. The experiment was conducted on crossbreds...

Frost, K., Shah, M., Leung , V. S. Y. et al. 2020. Aversion to desflurane and isoflurane in Sprague-Dawley rats (Rattus norvegicus). Animals 10(6), 950.

Carbon dioxide and isoflurane are widely used for killing rats, yet may not truly achieve “euthanasia”, because they elicit aversion. The inhalant anesthetic desflurane is faster acting than isoflurane, representing a potential refinement. Using an...

Ballantine, A., Rodgers, D., Watts, C. et al. 2020. The cotton rat – a new challenge. Animal Technology and Welfare 19(1), 92-95.

This poster describes how the Animal Technologists at Envigo adapted their current practices and procedures for a new species at their laboratory: the cotton rat. The paper describes cotton rat biology and behaviour; housing; environmental...

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...

Améndola, L., Weary, D. M. 2020. Understanding rat emotional responses to CO2. Translational Psychiatry 10, 253.

The aim of this review is to summarize evidence regarding rat emotional experiences during carbon dioxide (CO2) exposure. The studies reviewed show that CO2 exposure is aversive to rats, and that rats respond to CO2...

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...

Turner, P. V., Hickman, D. L., van Luijk, J. et al. 2020. Welfare impact of carbon dioxide euthanasia on laboratory mice and rats: A systematic review. Frontiers in Veterinary Science 7, 411.

Background: There has been increased concern about the suitability of CO2 as a method for euthanasia of laboratory mice and rats, including the potential discomfort, pain or distress that animals may experience prior to loss...

Tang, W., Zillmann, U., Sprengel, R. 2020. Alternative anesthesia of neonatal mice for global rAAV delivery in the brain with non-detectable behavioral interference in adults. Frontiers in Behavioral Neuroscience 14, 115.

Viral-transduced gene expression is the current standard for cell-type-specific labeling and cell tacking in experimental neuroscience. To achieve widespread gene expression, a viral delivery method to neonatal rodents was introduced more than two decades ago...