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. 
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...

Lopes, V. M., Sampaio, E., Roumbedakis, K. et al. 2017. Cephalopod biology and care, a COST FA1301 (CephsInAction) training school: Anaesthesia and scientific procedures. Invertebrate Neuroscience 17, 8.

Cephalopods are the sole invertebrates included in the list of regulated species following the Directive 2010/63/EU. According to the Directive, achieving competence through adequate training is a requisite for people having a role in the...

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...

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...

McEntee, D., Borg, K., Markiewicz, V. 2016. Establishment of a home-cage in vivo method of New Zealand white rabbit urine collection. Laboratory Animal Science Professional 4(4) (December), 44-46.

The most common methods for rabbit urine collection are newborn stroking, cystocentesis, and transfer to a metabolism cage.2 None of these options allow for a significant, quality amount of urine to be collected in vivo...

Wickremsinhe, E. R., Perkins, E. J. 2015. Using dried blood spot sampling to improve data quality and reduce animal use in mouse pharmacokinetic studies. JAALAS. 54(2), 139-144.

Traditional pharmacokinetic analysis in nonclinical studies is based on the concentration of a test compound in plasma and requires approximately 100 to 200 μL blood collected per time point. However, the total blood volume of...

Caron, A., Lelong, C., Pascual, M. H. et al. 2015. Miniaturized blood sampling techniques to benefit reduction in mice and refinement in nonhuman primates: Application to bioanalysis in toxicity studies with antibody-drug conjugates. JAALAS 54(2), 145-152.

Minimizing the number of animals in regulatory toxicity studies while achieving study objectives to support the development of future medicines contributes to good scientific and ethical practices. Recent advances in technology have enabled the development...

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...

Allaire. A. C., Boule, S. 2014. Refining blood collection techniques to improve animal welfare and sample quality. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 605-606. (Abstract #P212).

An effort to refine rodent blood collection techniques resulted in an examination of alternative methodologies to improve animal welfare and sample quality. Disease model or repeated sample collection resulted in inadequate sample volume, occasional hemolysis...

Bratcher, N. A., Ebert, P. A., Buck, W. et al. 2014. Refinement and efficiency through serial microsampling: Cost:benefit analysis. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 580. (Abstract #P121).

Advances in bioanalytic methods allow for accurate plasma drug level measurement in small sample volumes. Decreased sample volumes enable serial blood sample collection from one rodent, rather than terminal or sparse sampling from multiple rodents...

Tupper, T., Manning, H., Turner, D. et al. 2014. An innovative restraint device for the placement of intravenous tail vein catheters in anesthetized mice. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 584. (Abstract #P136).

Consistently accurate intravenous tail vein administration of radiopharmaceuticals in anesthetized mice is a critical component of successful PET/CT imaging in the preclinical setting. Injectable anesthetics are often not suitable for PET imaging and commercially available...

Torres, M. 2014. Refining methods for mouse hepatic biopsy. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 557-558 (Abstract #P32).

The mouse is a commonly used species in liver research such as oncology, toxicology, and disease models. The ability to collect specimens of liver is vital to such research. Such studies require either a major...

Teilmann, A. C., Madsen, A. N., Holst, B. et al. 2014. Impact of blood sampling procedures on the welfare of laboratory mice. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 600-601. (Abstract #P195).

A previous study showed that blood sampling either automatically, through a catheter, or by puncture of the tail vein is less stressful than facial vein phlebotomy in mice. We decided to investigate how facial vein...

Lambeth, S. P., Schapiro, S. J., Bernacky, B. J. et al. 2013. Establishing 'quality of life' parameters using behavioural guidelines for humane euthanasia of captive non-human primates. Animal Welfare 22(4) 429-435.

Chronic pain and distress are universally accepted conditions that may adversely affect an animal’s quality of life (QOL) and lead to the humane euthanasia of an animal. At most research institutions and zoological parks in...

Voigt, C. C., Klockner, P., Touma, C. et al. 2013. Hormonal stress response of laboratory mice to conventional and minimally invasive bleeding techniques. Animal Welfare 22(4), 449-455.

Conventional bleeding of small laboratory animals is often associated with stress and injuries that can cause haematomas, inflammation and ultimately the death of animals under investigation. Here, we used faecal glucocorticoid metabolites as an indicator...

Sadler, A. M., Bailey, S. J. 2013. Validation of a refined technique for taking repeated blood samples from juvenile and adult mice. Laboratory Animals 47(4), 316-319.

Repeated blood sampling from laboratory animals is desirable in certain experimental designs and also for reducing the number of animals used in research. Biochemical methods for analysing blood samples require only small blood volumes to...

Buijs, S., Maertens, L., Tuyttens, F. A. M. et al. 2011. Glucocorticoid metabolites in rabbit faeces - Influence of environmental enrichment and cage size. Physiology & Behavior 104(3), 469-473.

The concentration of glucocorticoid metabolites (GCM) in rabbit faeces has been suggested as a non-invasive indicator of stress. In the present study, GCM concentrations were measured in faeces of fattening rabbits kept in groups of...

Zahorsky-Reeves, J. 2011. The choice of bedding substrate, route of blood collection, and method of glucose determination all affect fasting blood glucose levels in C57BL/6 mice. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 738 (Abstract #PS80).

This study compared 4 bedding substrates (corncob, paper, hardwood chip, and wire-bottomed cage inserts) and 2 routes of blood collection (lateral tail vein and retroorbital sinus) in 6 male C57BL/6NCrl mice. Mice were maintained with...

Aasland, K. E., Skjerve, E., Smith, A. J. 2010. Quality of blood samples from the saphenous vein compared with the tail vein during multiple blood sampling of mice. Laboratory Animals 44(1), 25-29.

A large number of methods for obtaining blood from mice have been published. In our facility, saphenous venepuncture is considered the method of choice for bleeding mice and is believed to have a number of...

Fernandez, I., Pena, A., Del Teso, N. et al. 2010. Clinical biochemistry parameters in C57BL/6J mice after blood collection from the submandibular vein and retroorbital plexus. JAALAS 49(2), 202-206.

Collection of blood from the submandibular vein allows simple and rapid processing of many animals without anesthesia and facilitates rapid recovery with no signs of pain and discomfort in the mice. Here we compared the...

Nelson, E. A., Keller, G. L., Mitchell, T. W. et al. 2010. A jugular bleeding technique in rabbits. Lab Animal 39(1), 17-22.

When studying pharmacokinetics in rabbits, researchers must often take multiple blood samples from conscious rabbits. Researchers usually collect these samples via the auricular vein, typically through a port or an indwelling catheter. The authors have...

Howard, B., Nevalainen, T., Perretta, G. (ed). 2010. The COST Manual of Laboratory Animal Care and Use: Refinement, Reduction, and Research (1st Ed). CRC Press, Boca Raton, FL.

COST Action B-24 established four working groups to research and discuss issues relevant to laboratory animal science. These included the housing of animals, environmental needs, refinement of procedures, genetically modified animals, and cost-benefit analysis. Based...

Christensen, S. D., Mikkelsen, L. F., Fels, J. J. et al. 2009. Quality of plasma sampled by different methods for multiple blood sampling in mice. Laboratory Animals 43, 65-71.

For oral glucose tolerance test (OGTT) in mice, multiple blood samples need to be taken within a few hours from conscious mice. Today, a number of essential parameters may be analysed on very small amounts...