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. 
Améndola, L., Ratuski, A., Weary, D. M. 2019. Variation in the onset of CO2-induced anxiety in female Sprague Dawley rats. Scientific Reports 9, 19007.

Carbon dioxide (CO2) is commonly used to kill laboratory rats. Rats find CO2 aversive and aversion varies between individuals, indicating that rats vary in CO2 sensitivity. Healthy humans experience feelings of anxiety at concentrations similar...

Message, R., Greenhough, B. 2019. “But it’s just a fish”: Understanding the challenges of applying the 3Rs in laboratory aquariums in the UK. Animals 9(12), 1075.

Adopting a social science perspective and qualitative methodology on the problem of laboratory fish welfare, this paper examines some underlying social factors and drivers that influence thinking, priorities and implementation of fish welfare initiatives and...

Smith, B. J., Bruner, K., Kendall, L. V. 2019. Female- and intruder-induced ultrasonic vocalizations in C57BL/6J mice as proxy indicators for animal wellbeing. Comparative Medicine 69(5), 374–383.

Female urine-induced male mice ultrasonic vocalizations (FiUSV) are ultrasonic vocalizations produced by adult male mice after presentation of adult female urine, whereas intruder-induced ultrasonic vocalizations (IiUSV) are produced by resident adult female mice when interacting...

Jirkof, P., Rudeck, J., Lewejohann, L. 2019. Assessing affective state in laboratory rodents to promote animal welfare—What is the progress in applied refinement research? Animals 9(12), 1026.

In the past, there was a strong focus on avoiding or reducing negative animal welfare in animal experimentation. Recently, the importance of promoting positive animal welfare in laboratory animals has been highlighted. To ensure and...

Rowland, N. E., Toth, L. A. 2019. Analytic and interpretational pitfalls to measuring fecal corticosterone metabolites in laboratory rats and mice. Comparative Medicine 69(5), 337–349.

Minimization and alleviation of stress are generally viewed as desirable aspects of laboratory animal management and use. However, achieving that goal requires an unambiguous and valid measure of stress. Glucocorticoid concentrations are commonly used as...

McMillan, F. D. (ed). 2019. Mental Health and Well-being in Animals (2nd ed). CABI, Wallingford, UK.

This second edition is fully revised, expanded, and comprehensively updated with the most current knowledge about the full array of mental health issues seen in animals. Written by key opinion leaders, internationally-recognized experts and specialists...

Gent, T. C., Detotto, C., Vyssotski, A. L. et al. 2018. Epileptiform activity during inert gas euthanasia of mice. PLOS ONE 13(4), e0195872.

Carbon dioxide (CO2) is one of the most commonly used euthanasia agents for mice, yet it is highly aversive and nociceptive. Inert gases are a possible alternative, however there are qualitative reports of seizures resulting...

Kells, N. J., Beausoleil, N. J., Sutherland, M. A. et al. 2018. Electroencephalographic responses of anaesthetised rats to carbon dioxide inhalation. Animal Welfare 27(3), 215-223.

Exposure to high concentrations of CO2 is a common means of stunning and killing laboratory rodents. However, there is concern regarding the potential for animals to have aversive experiences, such as pain or breathlessness, prior...

Williams, E., Chadwick, C. L., Yon, L. et al. 2018. A review of current indicators of welfare in captive elephants (Loxodonta africana and Elephas maximus). Animal Welfare 27(3), 235-249.

Concerns over elephant welfare in UK zoos have implications for their future in captivity. To monitor improvements made to elephant welfare in UK zoos, non-invasive, valid and reliable indicators of welfare are needed. Using a...

Golledge, H., Carter, E. 2018. Welfare of fish farmed in the EU during transport and at slaughter. Animal Welfare 27(3), 287-288.

This Report, commissioned by the European Commission, summarises the current state of transport and slaughter practices in the aquaculture industry within eleven case-study countries in the European Economic Area (EAA). Comparisons are also made with...

Peric, T., Comin, A., Corazzin, M., et al. 2018. Hair cortisol concentrations in New Zealand white rabbits subjected to surgery. Animal Welfare 27(1), 13-20.

The aim of this study was to assess hair cortisol concentrations in New Zealand white rabbits (Oryctolagus cuniculus) that were subjected to relocation and surgery to evaluate HPA-axis activity; in addition, we used this marker...

Khoo, S. Y.-S., Lay, B. P. P., Joya, J. et al. 2018. Local anaesthetic refinement of pentobarbital euthanasia reduces abdominal writhing without affecting immunohistochemical endpoints in rats. Laboratory Animals 52(2), 152-162.

Sodium pentobarbital is a commonly used agent for euthanizing laboratory rats, however its high pH can cause abdominal discomfort after intraperitoneal injection. Previous studies suggest that the addition of a local anaesthetic may alleviate this...

Tuttle, A. H., Molinaro, M. J., Jethwa, J. F. et al. 2018. A deep neural network to assess spontaneous pain from mouse facial expressions. Molecular Pain 14, 1-9.

Grimace scales quantify characteristic facial expressions associated with spontaneous pain in rodents and other mammals. However, these scales have not been widely adopted largely because of the time and effort required for highly trained humans...

Clegg, I. 2018. Cognitive bias in zoo animals: An optimistic outlook for welfare assessment. Animals 8(7), 104.

Cognitive bias testing measures how emotional states can affect cognitive processes, often described using the “glass half-full/half-empty” paradigm. Classical or operant conditioning is used to measure responses to ambiguous cues, and it has been reported...

Wolfensohn, S., Shotton, J., Bowley, H. et al. 2018. Assessment of welfare in zoo animals: Towards optimum quality of life. Animals 8(7), 110.

Zoos are required to maintain a high standard of animal welfare, and this can be assessed using a combination of resource-based and animal-based indices usually divided into behavioural indicators, physiological indicators and clinical/pathological signs. Modern...

Oliver, V. L., Thurston, S. E., Lofgren, J. L. 2018. Using cageside measures to evaluate analgesic efficacy in mice (Mus musculus) after surgery. JAALAS 57(2), 186-201.

Recent studies have revealed some of the most frequently used analgesics in mice are not effectively treating postoperative pain. Our laboratory sought to compare and assess the validity and reliability of 2 cageside pain assessments...

Dudley, E. S., Boivin, G. P. 2018. Evaluation of a commercially available euthanasia solution as a voluntarily ingested euthanasia agent in laboratory mice. JAALAS 57(1), 30-34.

All currently accepted methods of euthanasia for laboratory mice involve some degree of stress, fear, anxiety, or pain. We evaluated the voluntary oral administration of a euthanasia drug in 99 male and 81 female mice...

Jones, S., Neville, V., Higgs, L. et al. 2018. Assessing animal affect: An automated and self-initiated judgement bias task based on natural investigative behaviour. Scientific Reports 8, 12400.

Scientific methods for assessing animal affect, especially affective valence (positivity or negativity), allow us to evaluate animal welfare and the effectiveness of 3Rs Refinements designed to improve wellbeing. Judgement bias tasks measure valence; however, task-training...

Mei, J., Riedel, N., Grittner, U. et al. 2018. Body temperature measurement in mice during acute illness: Implantable temperature transponder versus surface infrared thermometry. Scientific Reports 8, 3526.

Body temperature is a valuable parameter in determining the wellbeing of laboratory animals. However, using body temperature to refine humane endpoints during acute illness generally lacks comprehensiveness and exposes to inter-observer bias. Here we compared...

Chotard, H., Ioannou, S., Davila-Ross, M. 2018. Infrared thermal imaging: Positive and negative emotions modify the skin temperatures of monkey and ape faces. American Journal of Primatology 80(5), e22863.

Facial thermography has enabled researchers to noninvasively and continuously measure the changes of a range of emotional states in humans. The present work used this novel technology to study the effect of positive and negative...

Lahger, C., Laska, M. 2018. Behavioral responses of CD-1 mice to conspecific and heterospecific blood odors and to a blood odor component. Physiology & Behavior 184, 2015-210.

The odor of blood may have both aversive and attractive properties for mammals, depending on the species of the odor donor and the species perceiving the odor. To better understand the informational content of blood...

Balko, J. A., Oda, A., Posner, L. P. 2018. Use of tricaine methanesulfonate or propofol for immersion euthanasia of goldfish (Carassius auratus). Journal of the American Veterinary Medical Association 252(12), 1555-1561.

OBJECTIVE To substantiate current AVMA guidelines for immersion euthanasia of goldfish (Carassius auratus) with tricaine methanesulfonate (TMS), determine whether immersion in propofol at 5 times its immersion anesthesia concentration for 30 minutes is sufficient for...

MacRae, A. M., Makowska, I. J., Fraser, D. 2018. Initial evaluation of facial expressions and behaviours of harbour seal pups (Phoca vitulina) in response to tagging and microchipping. Applied Animal Behaviour Science 205, 167-174.

There are no proven species-specific indicators of pain in harbour seals (Phoca vitulina). The analysis of facial expressions has proven to be a repeatable, accurate and valid method of identifying pain in multiple species, but...

Creamer-Hente, M. A., Lao, F. K., Dragos, Z. P. et al. 2018. Sex- and strain-related differences in the stress response of mice to CO₂ euthanasia. JAALAS 57(5), 513–519.

The 2013 edition of the AVMA Guidelines for the Euthanasia of Animals recommends a 10% to 30% volume displacement rate (VDR) per minute for CO2 euthanasia of rodents. Here we sought to evaluate behavior and...

Fiebig, K., Jourdan, T., Kock, M. H. et al. 2018. Evaluation of infrared thermography for temperature measurement in adult male NMRI nude mice. JAALAS 57(6), 715–724.

Temperature monitoring during critical care provides important data required to guide treatment delivery. Body temperature is an easily quantified clinical parameter that can yield much information concerning the health of an animal. In research settings...