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. 
Mertens, S., Vogt, M. A., Gass, P. et al. 2019. Effect of three different forms of handling on the variation of aggression-associated parameters in individually and group-housed male C57BL/6NCrl mice. PLOS ONE 14(4), e0215367.

Mice are social animals hence group-housing of mice is preferred over individual housing. However, aggression in group-housed male mice under laboratory housing conditions is a well-known problem leading to serious health issues, including injury or...

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...

Gouveia, K., Hurst, J. L. 2019. Improving the practicality of using non-aversive handling methods to reduce background stress and anxiety in laboratory mice. Scientific Reports 9, 20305.

Handling can stimulate stress and anxiety in laboratory animals that negatively impacts welfare and introduces a confounding factor in many areas of research. Picking up mice by the tail is a major source of handling...

Ritchie, A., Collier, P., Clare, P. et al. 2019. Food for thought: The development of drug loaded diets improve both science and welfare. Animal Technology and Welfare 18(3), 222-224.

In our facility, we use several hormone dependent tumour models with supplementation delivered via slow release subcutaneously implanted pellets, implanted via trochar. For example, breast tumours which rely on 17-β-Estradiol. Administration of E2 supplementation can...

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...

Doerning, C. M., Thurston, S. E., Villano, J. S. et al. 2019. Assessment of mouse handling techniques during cage changing. JAALAS 58(6), 767–773.

Mouse handling during cage changing and health evaluation has traditionally been performed by using forceps. This method was adopted as a biosecurity measure but can adversely affect employee ergonomics and rodent behavior. In this study...

Makowska, I. J., Weary, D. M. 2019. A good life for laboratory rodents? ILAR Journal 60(3), 373-388.

Most would agree that animals in research should be spared “unnecessary” harm, pain, or distress, and there is also growing interest in providing animals with some form of environmental enrichment. But is this the standard...

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...

Clarkson, J. M., Dwyer, D. M., Flecknell, P. A. et al. 2019. Handling method alters the hedonic value of reward in laboratory mice. Scientific Reports 8, 2448.

Mice are the most widely used model species for drug discovery and scientific research. Consequently, it is important to refine laboratory procedures and practices to ensure high standards of welfare and scientific data quality. Recent...

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...

Galvin, M., Lallo, A., Brown, S. et al. 2018. Refinement of tumour passage by optimisation of the tissue disaggregation protocol. Animal Technology and Welfare 17(2), 101-103.

Surgical implantation of tumour pieces has been used regularly in the passage of tumour models. This involves an invasive surgical procedure, carried out under anaesthesia, ensuring mice have adequate pain relief and peri-operative care. The...

Swan, A. 2018. Refining mouse handling - do we or don't we? An animal technologist's perspective. Animal Technology and Welfare 17(2), 130-131.

Recent research in the industry identified that picking up mice in a tunnel or cupping them in the hand significantly reduces their stress levels. As Animal Tecgnologists, we could see advantages and disadvantages with this...

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...

Neely, C., Lane, C., Torres, J. et al. 2018. The effect of gentle handling on depressive-like behavior in adult male mice: Considerations for human and rodent interactions in the laboratory. Behavioural Neurology 2018, 2976014.

Environmental factors play a significant role in well-being of laboratory animals. Regulations and guidelines recommend, if not require, that stressors such as bright lighting, smells, and noises are eliminated or reduced to maximize animal well-being...

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...

Tavera-Mendoza, L. E., Brown, M. 2017. A less invasive method for orthotopic injection of breast cancer cells into the mouse mammary gland. Laboratory Animals 51(1), 85-88.

Breast cancer is the most common type of cancer diagnosed in women, and the second most common cause of cancer-related deaths in women in North America. The use of laboratory mice in research is an...

Larsen, R. A., Peveler, J. L., Klutzke, J. B. et al. 2017. Effects of daily restraint with and without injections on skeletal properties in C57BL/6NHsd mice. Lab Animal 46(7), 299-301.

Studies typically involve groups of animals that are injected with placebo compounds. As there are studies that demonstrate that restraint and injection can affect behavior and corticosteroid levels in rodents, the basis of such placebo...

Hubbard, J. S., Chen, P. H., Boyd, K. L. 2017. Effects of repeated intraperitoneal injection of pharmaceutical-grade and nonpharmaceutical-grade corn oil in female C57BL/6J mice. JAALAS 56(6), 779-785.

Due to potential adverse effects on animal wellbeing, the use of nonpharmaceutical-grade substances in animal research must be scientifically justified in cases where a pharmaceutical-grade version of the substance exists. This requirement applies to all...

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...