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. 
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...

Woody, S. M., Santymire, R. M., Cronin, K. A. 2021. Posture as a non-invasive indicator of arousal in American toads (Anaxyrus americanus). Journal of Zoological and Botanical Gardens 2(1), 1–9.

Animal welfare has become a priority for modern zoos and aquariums. However, amphibians have not yet been the focus of much welfare research, perhaps in part because they do not tend to display many quantifiable...

Harvey, A., Beausoleil, N., Ramp, D. et al. 2020. A ten-stage protocol for assessing the welfare of individual non-captive wild animals: Free-roaming horses (Equus ferus caballus) as an example. Animals 10(1), 148.

Knowledge of the welfare status of wild animals is vital for informing debates about the ways in which we interact with wild animals and their habitats. Currently, there is no published information about how to...

Botman, J., Hontoir, F., Gustin, P. et al. 2020. Postanaesthetic effects of ketamine–midazolam and ketamine–medetomidine on gastrointestinal transit time in rabbits anaesthetised with isoflurane. Veterinary Record 186(8), 249.

Gastrointestinal stasis is a common perianaesthetic complication in rabbits. The objective of this study was to assess the impact on gastrointestinal transit time of ketamine–midazolam (KMZ) versus ketamine–medetomidine (later antagonised by atipamezole) (KMT-A) in rabbits...

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...

Jirkof, P., Abdelrahman, A., Bleich, A. et al. 2020. A safe bet? Inter-laboratory variability in behaviour-based severity assessment. Laboratory Animals 54(1), 73–82.

Evidence-based severity assessment is essential as a basis for ethical evaluation in animal experimentation to ensure animal welfare, legal compliance and scientific quality. To fulfil these tasks scientists, animal care and veterinary personnel need assessment...

Ernst, L., Kopaczka, M., Schulz, M. et al. 2020. Improvement of the Mouse Grimace Scale set-up for implementing a semi-automated Mouse Grimace Scale scoring (Part 1). Laboratory Animals 54(1), 83–91.

The Mouse Grimace Scale (MGS) has been widely used for the noninvasive examination of distress/pain in mice. The aim of this study was to further improve its performance to generate repeatable, faster, blinded and reliable...

Ernst, L., Kopaczka, M., Schulz, M. et al. 2020. Semi-automated generation of pictures for the Mouse Grimace Scale: A multi-laboratory analysis (Part 2). Laboratory Animals 54(1), 92–98.

The Mouse Grimace Scale (MGS) is an established method for estimating pain in mice during animal studies. Recently, an improved and standardized MGS set-up and an algorithm for automated and blinded output of images for...

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...

Andresen, N., Wöllhaf, M., Hohlbaum, K. et al. 2020. Towards a fully automated surveillance of well-being status in laboratory mice using deep learning: Starting with facial expression analysis. PLOS ONE 15(4), e0228059.

Assessing the well-being of an animal is hindered by the limitations of efficient communication between humans and animals. Instead of direct communication, a variety of parameters are employed to evaluate the well-being of an animal...

Alemán-Laporte, J., Bandini, L. A., Garcia-Gomes, M. S. et al. 2020. Combination of ketamine and xylazine with opioids and acepromazine in rats: Physiological changes and their analgesic effect analysed by ultrasonic vocalization. Laboratory Animals 54(2), 171–182.

In this study, the effect of four anaesthetic protocols that included the combination of xylazine (X) and ketamine (K) with acepromazine (A) and opioids (methadone (Me), morphine (Mo) or tramadol (T)) was evaluated in laboratory...

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...

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...

Alfonso, S., Sadoul, B., Cousin, X. et al. 2020. Spatial distribution and activity patterns as welfare indicators in response to water quality changes in European sea bass, Dicentrarchus labrax. Applied Animal Behaviour Science 226, 104974.

In aquaculture, fish are exposed to unavoidable stressors that can be detrimental for their health and welfare. However, welfare in farmed fish can be difficult to assess, and, so far, no standardized test has been...

Turner, P. V., Pang, D. S., Lofgren, J. L. 2019. A review of pain assessment methods in laboratory rodents. Comparative Medicine 69(6), 451–467.

Ensuring that laboratory rodent pain is well managed underpins the ethical acceptability of working with these animals in research. Appropriate treatment of pain in laboratory rodents requires accurate assessments of the presence or absence of...

Smith J. C. 2019. A review of strain and sex differences in response to pain and analgesia in mice. Comparative Medicine 69(6), 490–500.

Pain and its alleviation are currently a highly studied issue in human health. Research on pain and response to analgesia has evolved to include the effects of genetics, heritability, and sex as important components in...

Gjendal, K., Ottesen, J. L., Olsson, I. et al. 2020. Effect of repeated exposure to isoflurane on nest building and burrowing in mice. JAALAS 59(1), 30–36.

Nest building and burrowing are highly motivated natural behaviors in rodents, and changes in these behaviors can serve as welfare assessment tools. In this study, we investigated: 1) the limits of agreement between 2 observers...

Gallo, M. S., Karas, A. Z., Pritchett-Corning, K. et al. 2020. Tell-tale TINT: Does the time to incorporate into nest test evaluate postsurgical pain or welfare in mice? JAALAS 59(1), 37–45.

Identifying early indicators of distress in mice is difficult using either periodic monitoring or current technology. Likewise, poor pain identification remains a barrier to providing appropriate pain relief in many mouse models. The Time to...

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...

Rasys, A. M., Divers, S. J., Lauderdale, J. D. et al. 2020. A systematic study of injectable anesthetic agents in the brown anole lizard (Anolis sagrei). Laboratory Animals 54(3), 281–292.

Anolis lizards have served as important research models in fields ranging from evolution and ecology to physiology and biomechanics. However, anoles are also emerging as important models for studies of embryo development and tissue regeneration...

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...