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. 
Manteca Vilanova, X., De Briyne, N., Beaver, B. et al. 2019. Horse welfare during equine chorionic gonadotropin (eCG) production. Animals 9(12), 1053.

Collection of blood from pregnant mares for extraction of equine chorionic gonadotropin (eCG) is a critical but relatively unknown and poorly regulated practice in the countries in which it occurs. Equine chorionic gonadotropin is a...

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...

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...

Santurtun, E., Broom, D. M., Phillips, C. J. C. 2018. A review of factors affecting the welfare of Atlantic salmon (Salmo salar). Animal Welfare 27(3), 193-204.

In the expanding salmon industry, many farmers use production methods that could result in poor welfare of the fish at various points of their lifecycle. We have reviewed methods used for producing salmon for food...

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...

McGreevy, P., Berger, J., de Brauwere, N. et al. 2018. Using the five domains model to assess the adverse impacts of husbandry, veterinary, and equitation interventions on horse welfare. Animals 8(3), 41.

The aim of this study was to conduct a series of paper-based exercises in order to assess the negative (adverse) welfare impacts, if any, of common interventions on domestic horses across a broad range of...

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...

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...

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...

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...

Deckers, N., Ruigrok, C. A., Verhoeve, H. P. et al. 2018. Comparison of pain response after subcutaneous injection of two maropitant formulations to beagle dogs. Veterinary Record Open 5(1), e000262.

The antiemetic maropitant, with metacresol as preservative (Cerenia, Zoetis), has been associated with pain after subcutaneous injection in dogs and cats. Recently, a generic formulation containing benzyl alcohol was authorised (Prevomax, Le Vet). Benzyl alcohol...

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...

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...

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...

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...

McMillan, J. L., Bloomsmith, M. A., Prescott, M. J. 2017. An international survey of approaches to chair restraint of nonhuman primates. Comparative Medicine 67(5), 442–451.

Specifically designed restraint chairs are the preferred method of restraint for research studies that require NHP to sit in place for sustained periods of time. In light of increasing emphasis on refinement of restraint to...

Ali, A. B. A., Gutwein, K. L., Heleski, C. R. 2017. Assessing the influence of upper lip twitching in naive horses during an aversive husbandry procedure (ear clipping). Journal of Veterinary Behavior 21, 20-25.

When engaging in procedures that horses may find aversive, restraint methods are often used to help ensure safety of both horse and handler. Twitching is a common restraint method, but its use is sometimes considered...