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. 
Kells, N. J., Beausoleil, N. J., Sutherland, M. A. et al. 2018. Electroencephalographic responses of anaesthetised pigs to intraperitoneal injection of sodium pentobarbital. Animal Welfare 27(3), 205-214.

Small laboratory animals are commonly euthanased via intraperitoneal (IP) injection of sodium pentobarbital. However, there is concern that animals may experience pain prior to loss of consciousness with this delivery route. The present study investigated...

Grist, A., Lines, J., Knowles, T. et al. 2018. The use of a non-penetrating captive bolt for the euthanasia of neonate piglets. Animals 8(4), 48.

The most common method for the on-farm euthanasia of neonate piglets is reported to be manual blunt force trauma. This paper presents the results of research to evaluate a mechanical non-penetrating captive bolt (the Accles...

Smith, R., Rault, J., Gates, R. et al. 2018. A two-step process of nitrous oxide before carbon dioxide for humanely euthanizing piglets: On-farm trials. Animals 8(4), 52.

Current methods of euthanizing piglets are raising animal welfare concerns. Our experiment used a novel two-step euthanasia method, using nitrous oxide (N2O) for six minutes and then carbon dioxide (CO2) on compromised 0- to 7-day-old...

Kells, N., Beausoleil, N., Johnson, C. et al. 2018. Evaluation of different gases and gas combinations for on-farm euthanasia of pre-weaned pigs. Animals 8(3), 40.

The aim of this research was to evaluate the welfare of pre-weaned piglets euthanised using three different gas treatments: 100% carbon dioxide (CO2), 100% argon (Ar) or a mixture of 60% Ar/40% carbon dioxide (Ar/CO2)...

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...

Grist, A., Knowles, T. G., Wotton, S. B. 2018. Humane euthanasia of neonates II: field study of the effectiveness of the Zephyr EXL non-penetrating captive-bolt system for euthanasia of newborn piglets. Animal Welfare 27(4), 319-326.

A previous study demonstrated the effectiveness of the Bock Industries Zephyr EXL non-penetrating captive bolt, using the abolition of visual-evoked potentials as a determination of brain death, in piglets in a laboratory. A second trial...

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...

Sutherland, M. A., Bryer, P. J., Backus, B. L. 2017. The effect of age and method of gas delivery on carbon dioxide euthanasia of pigs. Animal Welfare 26(3), 293-299.

The objectives of this research were to evaluate the effect of age and delivering method during carbon dioxide (CO2) euthanasia on the welfare of pigs (Sus scrofa). In Experiment 1, pigs aged 1, 2, 3...

Grist, A., Murrell, J. C., McKinstry, J. L. et al. 2017. Humane euthanasia of neonates I: validation of the effectiveness of the Zephyr EXL non-penetrating captive-bolt euthanasia system on neonate piglets up to 10.9 kg live-weight. Animal Welfare 26(1), 111-120.

To determine if mechanical blunt force trauma using a non-penetrating captive bolt was a viable method of producing an immediate stun/kill in neonate piglets (Sus scrofa domesticus) as an alternative to manual blunt force trauma...

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...

Grant, C., Marks, L., Prior, H. 2017. Provision of food and water in rodent whole body plethysmography safety pharmacology respiratory studies – Impact on animal welfare and data quality. Journal of Pharmacological and Toxicological Methods 88(Part 1), 79-84.

Introduction: We evaluated the feasibility of providing food and water to rodents during whole body plethysmography (WBP) studies as a welfare improvement to standard conditions. Methods: Male Han Wistar rats or CD1 mice (n=8) were...

Fiedler, K. J., Parsons, R. L., Sadler, L. J. et al. 2016. Effects of stocking rate on measures of efficacy and welfare during argon gas euthanasia of weaned pigs. Animal Welfare 25(1), 83-89.

The objective of this study was to evaluate the effects of chamber stocking rate on facets of animal welfare and efficacy during euthanasia of weaned pigs (Sus scrofa domesticus) with argon gas. Two hundred and...

Valentim, A. M., Guedes, S. R., Pereira, A. M. et al. 2016. Euthanasia using gaseous agents in laboratory rodents. Laboratory Animals 50(4), 241-253.

Several questions have been raised in recent years about the euthanasia of laboratory rodents. Euthanasia using inhaled agents is considered to be a suitable aesthetic method for use with a large number of animals simultaneously...

Powell, K., Ethun, K., Taylor, D. K. 2016. The effect of light level, CO2 flow rate, and anesthesia on the stress response of mice during CO2 euthanasia. Lab Animal 45(10), 386-395.

Euthanasia protocols are designed to mitigate the stress experienced by animals, and an environment that induces minimal stress helps achieve that goal. A protocol that is efficient and practical in a typical animal research facility...

Hawkins, P., Prescott, M., Carbone, L. et al. 2016. A good death? Report of the second Newcastle meeting on laboratory animal euthanasia. Animals 6(9), 50.

Millions of laboratory animals are killed each year worldwide. There is an ethical, and in many countries also a legal, imperative to ensure those deaths cause minimal suffering. However, there is a lack of consensus...

Prior, H., Bottomly, A., Champéroux, P. et al. 2016. Social housing of non-rodents during cardiovascular recordings in safety pharmacology and toxicology studies. Journal of Pharmacological and Toxicological Methods 81, 75-87.

Introduction: The Safety Pharmacology Society (SPS) and National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs) conducted a survey and workshop in 2015 to define current industry practices relating to housing...

Mietsch, M., Einspanier, A. 2015. Non-invasive blood pressure measurement: values, problems and applicability in the common marmoset (Callithrix jacchus). Laboratory Animals 49(3), 241-250.

The common marmoset (Callithrix jacchus, C. j.) is an established primate model in biomedical research and for human-related diseases. Monitoring of cardiovascular parameters including blood pressure (BP) is important for the health surveillance of these...

Moody, C. M., Makowska, I. J., Weary, D. M. 2015. Testing three measures of mouse insensibility following induction with isoflurane or carbon dioxide gas for a more humane euthanasia. Applied Animal Behaviour Science 163, 183-87.

Laboratory mice are commonly killed via exposure to gradually increasing concentrations of isoflurane and carbon dioxide (CO2) gas. Once rendered insensible using isoflurane or CO2, a high concentration of CO2 is used to decrease time...