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. 
Laferriere, C. A., Leung, V. S., Pang, D. S. 2020. Evaluating intrahepatic and intraperitoneal sodium pentobarbital or ethanol for mouse euthanasia. JAALAS 59(3), 264–268.

Intraperitoneal (IP) injection of sodium pentobarbital (PB) is an accepted method of euthanasia for mice. However, this method has important drawbacks, including the potential for pain or misinjection. The objective of this prospective, randomized, blinded...

Cloutier Barbour, C., Danforth, M. D., Murphy, H. et al. 2020. Monitoring great ape heart health through innovative electrocardiogram technology: Training methodologies and welfare implications. Zoo Biology 39(6), 443-447.

Assessing and treating cardiovascular disease (or heart disease) is a growing concern for institutions housing great apes, as it is a major cause of mortality in all four taxa managed in human care. As part...

van der Vinne, V., Pothecary, C. A., Wilcox, S. L. et al. 2020. Continuous and non-invasive thermography of mouse skin accurately describes core body temperature patterns, but not absolute core temperature. Scientific Reports 10(1), 20680.

Body temperature is an important physiological parameter in many studies of laboratory mice. Continuous assessment of body temperature has traditionally required surgical implantation of a telemeter, but this invasive procedure adversely impacts animal welfare. Near-infrared...

Elmi, A., Galligioni, V., Govoni, N. et al. 2020. Quantification of hair corticosterone, DHEA and testosterone as a potential tool for welfare assessment in male laboratory mice. Animals 10(12), 2408.

Steroids, providing information regarding several biological patterns including stress and sexual behavior, have been investigated in different matrices in laboratory mice. Data regarding hair quantification, indicative of longer timespans when compared to blood and saliva...

Kloefkorn H, Aiani, L. M., Lakhani, A. et al. 2020. Noninvasive three-state sleep-wake staging in mice using electric field sensors. Journal of Neuroscience Methods 344, 108834.

Study Objective: Validate a novel method for sleep-wake staging in mice using noninvasive electric field (EF) sensors. Methods: Mice were implanted with electroencephalogram (EEG) and electromyogram (EMG) electrodes and housed individually. Noninvasive EF sensors were...

Axiak Flammer, S., Eskes, C., Kohler, I. et al. 2019. Alternatives to carbon dioxide—Taking responsibility for humanely ending the life of animals. Animals 9(8), 482.

Carbon dioxide (CO2) is commonly used to kill rodents. However, a large body of research has now established that CO2 is aversive to them. A multidisciplinary symposium organized by the Swiss Federal Food Safety and...

Steiner, A. R., Axiak Flammer, S., Beausoleil, N. J. et al. 2019. Humanely ending the life of animals: Research priorities to identify alternatives to carbon dioxide. Animals 9(11), 911.

The use of carbon dioxide (CO2) for stunning and killing animals is considered to compromise welfare due to air hunger, anxiety, fear, and pain. Despite decades of research, no alternatives have so far been found...

Dutton III, J. W., Artwohl, J. E., Huang, X. et al. 2019. Assessment of pain associated with the injection of sodium pentobarbital in laboratory mice (Mus musculus). JAALAS 58(3), 373-379.

The AVMA Guidelines for the Euthanasia of Animals considers injection of barbiturates to be an acceptable method of euthanasia in rodents but states there is a potential for pain when administered intraperitoneally. This study examined...

Moffitt, A. D., Brignolo, L. L., Ardeshir, A. et al. 2019. The role of emotional contagion in the distress exhibited by grouped mice exposed to CO2. JAALAS 58(4), 430-437.

The 2013 AVMA Guidelines for the Euthanasia of Animals recommends a chamber volume displacement rate of 10% to 30% per minute (v/min) when euthanizing small laboratory rodents with CO2. Group euthanasia of mice is a...

Franco, N. H., Gerós, A., Oliveira, L. et al. 2019. ThermoLabAnimal – A high-throughput analysis software for non-invasive thermal assessment of laboratory mice. Physiology & Behavior, 207, 113-121.

Body temperature changes in laboratory mice are often assessed by invasive and stressful methods, which may confound the measurement. Infrared thermography is a possible non-invasive alternative, but the cost of standard thermal cameras, lack of...

Redaelli, V., Papa, S., Marsella, G. et al. 2019. A refinement approach in a mouse model of rehabilitation research. Analgesia strategy, reduction approach and infrared thermography in spinal cord injury. PLOS ONE 14(10), e0224337.

The principles of Refinement, Replacement and Reduction (3R’s) should be taken into account when animals must be used for scientific purpose. Here, a Reduction / Refinement approach was applied to the procedure of spinal cord...

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...

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...

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...

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...

Fuller, G., Allard, S. 2018. Preliminary data showing potential for salivary C-reactive protein as an indicator of welfare in western lowland gorillas (Gorilla gorilla gorilla). Journal of Veterinary Behavior 28, 58-62.

C-reactive protein (CRP) is an acute phase protein often used as a biomarker for inflammation related to acute trauma or chronic illness. Animal studies showing elevations in CRP following events such as road transport and...

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...

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...

Guedes, S. R., Valentim, A. M., Antunes, L. M. 2017. Mice aversion to sevoflurane, isoflurane and carbon dioxide using an approach-avoidance task. Applied Animal Behaviour Science 189, 91-97.

Euthanasia of laboratory animals is one of the main concerns for animal welfare, especially the use of carbon dioxide (CO2) which has been described to induce aversive-like behaviours. In order to refine mass euthanasia in...