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. 
Peruga, M., Kawala, B., Sarul, M. et al. 2023. Are currently selected laboratory animals useful in the research of how female hormones influence orthodontic biomechanics? Animals 13(4), 629.

Animal testing was and remains the only method of introducing a certain treatment and medical procedure on humans. On the other hand, animals have their rights resulting from applicable legal acts, including Directive 2010/63/EU and...

Silva-Reis, R., Faustino-Rocha, A. I., Silva, J. et al. 2023. Studying and analyzing humane endpoints in the fructose-fed and streptozotocin-injected rat model of diabetes. Animals 13(8), 1397.

This work aimed to define a humane endpoint scoring system able to objectively identify signs of animal suffering in a rat model of type 2 diabetes. Sprague-Dawley male rats were divided into control and induced...

Lupfer, G., Brandenburger, A., Machado, M. et al. 2023. Ultrasonic vocalizations near 30 kHz may indicate excitement rather than distress in female Wistar rats. Applied Animal Behaviour Science 261, 105881.

Rats emit ultrasonic vocalizations (USVs), sometimes referred to as 50-kHz vocalizations, during activities such as play and lower-frequency USVs, sometimes referred to as 22-kHz vocalizations, when experiencing distress. Definitions of 22-kHz vocalizations vary in terms...

Broadfoot, C. K., Lenell, C., Kelm-Nelson, C. A. et al. 2023. Effects of social isolation on 50-kHz ultrasonic vocalizations, affective state, cognition, and neurotransmitter concentrations in the ventral tegmental and locus coeruleus of adult rats. Behavioural Brain Research 437, 114157.

Vocal communication, cognition, and affective state are key features of sustained health and wellness, and because vocalizations are often socially-motivated, social experience likely plays a role in these behaviors. The monoaminergic systems of the ventral...

Klabukov, I., Shestakova, V., Krasilnikova, O. et al. 2023. Refinement of animal experiments: Replacing traumatic methods of laboratory animal marking with non-invasive alternatives. Animals 13(22), 3452.

Reliable methods for identifying rodents play an important role in ensuring the success of preclinical studies. However, animal identification remains a trivial laboratory routine that is not often discussed, despite the fact that more than...

Van Loo, P. L. P., Janssens, M. R. E. 2023. Why all healthy laboratory animals should be rehomed, no matter how small. Animals 13(17), 2727.

This paper explores the ethical imperative of rehoming all healthy animals of sentient species after experiments have finished or when they have become otherwise redundant. We take into account disparate perspectives in animal ethics and...

Tivey, E. K. L., Martin, J. E., Brown, S. M. et al. 2022. Sex differences in 50 kHz call subtypes emitted during tickling-induced playful behaviour in rats. Scientific Reports 12(1), 15323.

‘Tickling’ induces positive affective states in laboratory rats as evidenced by the production of 50-kHz ultrasonic vocalisations (USVs), although this has mostly been investigated in males. Juvenile rats emit distinctive 50-kHz USV subtypes. Frequency-modulated (FM)...

Carbone, L. 2021. Estimating mouse and rat use in American laboratories by extrapolation from Animal Welfare Act-regulated species. Scientific Reports 11(1), 493.

Alone among Western nations, the United States has a two-tier system for welfare protections for vertebrate animals in research. Because its Animal Welfare Act (AWA) excludes laboratory rats and mice (RM), government veterinarians do not...

Silva-Reis, R., Faustino-Rocha, A. I., Gonçalves, M. et al. 2021. Refinement of animal model of colorectal carcinogenesis through the definition of novel humane endpoints. Animals 11(4), 985.

This study aimed to define appropriate humane endpoints (HEs) for an animal model of colorectal carcinogenesis (CRC). Twenty-nine male Wistar rats were divided into two control groups (CTRL1 and CTRL2) injected with ethylenediamine tetraacetic acid...

Seidisarouei, M., van Gurp, S., Pranic, N. M. et al. 2021. Distinct profiles of 50 kHz vocalizations differentiate between social versus non-social reward approach and consumption. Frontiers in Behavioral Neuroscience 15, 693698.

Social animals tend to possess an elaborate vocal communication repertoire, and rats are no exception. Rats utilize ultrasonic vocalizations (USVs) to communicate information about a wide range of socially relevant cues, as well as information...

Ellis, T., Katsiadaki, I. 2021. Clarification of early end-points for refinement of animal experiments, with specific reference to fish. Laboratory Animals 55(3), 244-253.

Appropriate end-points are integral to the refinement of laboratory animal experiments. Our recent experience has highlighted that ambiguity around end-points is hampering their adoption in experiments that cause severe suffering to fish. In toxicology, the...

Young, T., Whiteside, T., Locklear, J. 2020. What is your tattoo ink telling you? Laboratory Animal Science Professional 8(2) (March/April), 62-65.

Tattooing traumatizes the skin, which can result in microbial infections with the severity ranging from minor to life-threating septicemia. Additionally, the metals in colored tattoo ink are known to cause dermal inflammation in some people...

Talbot, S. R., Biernot, S., Bleich, A. et al. 2020. Defining body-weight reduction as a humane endpoint: A critical appraisal. Laboratory Animals 54(1), 99–110.

In many animal experiments scientists and local authorities define a body-weight reduction of 20% or more as severe suffering and thereby as a potential parameter for humane endpoint decisions. In this study, we evaluated distinct...

Zemanova, M. A. 2020. Towards more compassionate wildlife research through the 3Rs principles: Moving from invasive to noninvasive methods. Wildlife Biology 2020(1), no page numbers.

Research in ecology and wildlife biology remains crucial for increasing our knowledge and improving species management and conservation in the midst of the current biodiversity crisis. However, obtaining information on population status often involves invasive...

Helgers, S., Talbot, S. R., Riedesel, A. K. et al. 2020. Body weight algorithm predicts humane endpoint in an intracranial rat glioma model. Scientific Reports 10, 9020.

Humane endpoint determination is fundamental in animal experimentation. Despite commonly accepted endpoint criteria for intracranial tumour models (20% body weight loss and deteriorated clinical score) some animals still die before being euthanized in current research...

Kennedy, R. J., Evans, D., Allen, M. 2020. Long-term retention of dummy acoustic transmitters in adult brown trout. Journal of Fish Biology 97(4), 1281–1284.

A group of 36 1+ age class Salmo trutta were surgically implanted with dummy acoustic tags and monitored for 370 days. In total 13 tags were expelled throughout the experiment with an overall tag loss...

Do, J. P., Defensor, E. B., Ichim, C. V. et al. 2020. Automated and continuous monitoring of animal welfare through digital alerting. Comparative Medicine 70(4), 313-327.

A primary goal in preclinical animal research is respectful and responsible care aimed toward minimizing stress and discomfort while enhancing collection of accurate and reproducible scientific data. Researchers use hands-on clinical observations and measurements as...

Brudzynski, S. M. 2019. Emission of 22 kHz vocalizations in rats as an evolutionary equivalent of human crying: Relationship to depression. Behavioural Brain Research 363, 1-12.

There is no clear relationship between crying and depression based on human neuropsychiatric observations. This situation originates from lack of suitable animal models of human crying. In the present article, an attempt will be made...

Colby, L. A., Nowland, M. H., Kennedy, L. H. 2019. Clinical Laboratory Animal Medicine: An Introduction (5th ed). Wiley-Blackwell, Ames, IA.

The revised fifth edition of Clinical Laboratory Animal Medicine: An Introduction is an accessible guide to basic information for conducting animal research safely and responsibly. It includes a review of the unique anatomic and physiologic...

Wolfe, A. M., Rahman, M., McFadden, D. G. et al. 2018. Refinement and successful implementation of a scoring system for myxomatosis in a susceptible rabbit (Oryctolagus cuniculus) model. Comparative Medicine 68(4), 280–285.

Myxoma virus is a member of Leporipoxviridae whose tropism is tightly restricted to lagomorphs. In susceptible Oryctolagus rabbits, the virus causes a highly lethal disease known as myxomatosis, which begins as a localized infection but...

Burke, C. J., Kisko, T. M., Swiftwolfe, H. et al. 2017. Specific 50-kHz vocalizations are tightly linked to particular types of behavior in juvenile rats anticipating play. PLOS ONE 12(5), e0175841.

Rat ultrasonic vocalizations have been suggested to be either a byproduct of physical movement or, in the case of 50-kHz calls, a means to communicate positive affect. Yet there are up to 14 distinct types...

Wever, K. E., Geessink, f. J., Brouwer, M. A. E. et al. 2017. A systematic review of discomfort due to toe or ear clipping in laboratory rodents. Laboratory Animals 51(6), 583-600.

Toe clipping and ear clipping (also ear notching or ear punching) are frequently used methods for individual identification of laboratory rodents. These procedures potentially cause severe discomfort, which can reduce animal welfare and distort experimental...

Jones, T., Robinson, M., Leach, M. et al. 2017. Ultrasonic vocalisation as a measure of positive welfare in rats. Animal Technology and Welfare 16(2), 127-129.

Studies of animal welfare in laboratory animals have historically relied on the measurement of negative indicators rather than the assessment of positive indicators of welfare. Practical methods of welfare assessment are required to allow refinement...

National Health and Medical Research Council [NHMRC]. 2016. Principles and guidelines for the care and use of non-human primates for scientific purposes. National Health and Medical Research Council: Canberra, Australia, 25 pp.

The Principles and guidelines for the care and use of non-human primates for scientific purposes is a revision of NHMRC’s Policy on the care and use of non-human primates for scientific purposes 2003 (the Policy)...

Kisko, T. M., Himmler, B. T., Himmler, S. M. et al. 2015. Are 50-kHz calls used as play signals in the playful interactions of rats? II. Evidence from the effects of devocalization. Behavoural Processes 111, 25-33.

During playful interactions, juvenile rats emit many 50-kHz ultrasonic vocalizations, which are associated with a positive affective state. In addition, these calls may also serve a communicative role – as play signals that promote playful...