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. 
Abdelrahman, A., Kumstel, S., Zhang, X. et al. 2019. A novel multi-parametric analysis of non-invasive methods to assess animal distress during chronic pancreatitis. Scientific Reports 9, 14084.

Ethical responsibility, legal requirements and the need to improve the quality of research create a growing interest in the welfare of laboratory animals. Judging the welfare of animals requires readout parameters, which are valid 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...

Gott, A., Andrews, C., Bedford, T. et al. 2019. Developmental history and stress responsiveness are related to response inhibition, but not judgement bias, in a cohort of European starlings (Sturnus vulgaris). Animal Cognition 22(1), 99–111.

Judgement bias tasks are designed to provide markers of affective states. A recent study of European starlings (Sturnus vulgaris) demonstrated modest familial effects on judgement bias performance, and found that adverse early experience and developmental...

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...

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...

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...

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...

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...

Häger, C., Keubler, L. M., Talbot, S. R. et al. 2018. Running in the wheel: Defining individual severity levels in mice. PLOS Biology 16(10), e2006159.

The fine-scale grading of the severity experienced by animals used in research constitutes a key element of the 3Rs (replace, reduce, and refine) principles and a legal requirement in the European Union Directive 2010/63/EU. Particularly...

Marquardt, N., Feja, M., Hünigen, H. et al. 2018. Euthanasia of laboratory mice: Are isoflurane and sevoflurane real alternatives to carbon dioxide? PLOS ONE 13(9), e0203793.

In the European Union (EU) millions of laboratory mice are used and killed for experimental and other scientific purposes each year. Although controversially discussed, the use of carbon dioxide (CO2) is still permitted for killing...

Unakafov, A. M., Möller, S., Kagan, I. et al. 2018. Using imaging photoplethysmography for heart rate estimation in non-human primates. PLOS ONE 13(8), e0202581.

For humans and for non-human primates heart rate is a reliable indicator of an individual’s current physiological state, with applications ranging from health checks to experimental studies of cognitive and emotional state. In humans, changes...

Miranda, A., Pego, J. M., Correia-Pinto, J. 2017. Animal facility videoendoscopic intubation station: Tips and tricks from mice to rabbits. Laboratory Animals 51(2), 204-207.

Endotracheal intubation of laboratory animals is a common procedure shared by several research fields for different purposes, such as mechanical ventilation of anaesthetized animals, instillation of cytotoxic nanoparticles, infectious agents or tumour cells for induction...

Walsh, J., Percival, A., Turner, P. 2017. Efficacy of blunt force trauma, a novel mechanical cervical dislocation device, and a non-penetrating captive bolt device for on-farm euthanasia of pre-weaned kits, growers, and adult commercial meat rabbits. Animals 7(12), 100.

The commercial meat rabbit industry is without validated on-farm euthanasia methods, potentially resulting in inadequate euthanasia protocols. We evaluated blunt force trauma (BFT), a mechanical cervical dislocation device (MCD), and a non-penetrating captive bolt device...

Boivin, G. P., Hickman, D. L., Creamer-Hente, M. A. et al. 2017. Review of CO2 as a euthanasia agent for laboratory rats and mice. JAALAS 56(5), 491-499.

Selecting an appropriate, effective euthanasia agent is controversial. Several recent publications provide clarity on the use of CO2 in laboratory rats and mice. This review examines previous studies on CO2 euthanasia and presents the current...

de Souza Dyer, C., Brice, A. K., Marx, J. O. 2017. Intraperitoneal administration of ethanol as a means of euthanasia for neonatal mice (Mus musculus). JAALAS 56(3), 299-306.

The humane euthanasia of animals in research is of paramount importance. Neonatal mice frequently respond differently to euthanasia agents when compared with adults. The AVMA's Guidelines for the Euthanasia of Animals includes intraperitoneal injection of...

Boivin, G. P., Bottomley, M. A., Schiml, P. A. et al. 2017. Physiologic, behavioral, and histologic responses to various euthanasia methods in C57BL/6NTac male mice. JAALAS 56(1), 69-78.

Rodent euthanasia using exposure to increasing concentrations of CO2 has come under scrutiny due to concerns of potential pain during the euthanasia process. Alternatives to CO2, such as isoflurane and barbiturates, have been proposed as...

Hawkins, P., McNeilly, A., Watson, J. et al. 2017. Report of the 2016 RSPCA/UFAW Rodent and Rabbit Welfare Group meeting. Animal Technology and Welfare 16(2), 77-86.

The RSPCA/UFAW Rodent (and now Rabbit) Welfare Group held a one-day meeting on 1 November 2016 at the University of Edinburgh and was attended by 70 delegates. Presentation topics included refinements in blood sampling rodents...

Ferguson, R. 3Rs improvements in the Bexsero® (Meningitis B) vaccine. Animal Technology and Welfare 16(2), 150-152.

Bexsero® is a new vaccine in the UK which since September 2015 has been added to the childhood immunisation programme for the prevention of Meningitis B. The in-vivo test as performed in Biological Services Division...