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. 
Mauthe von Degerfeld, M., Serpieri, M., Bonaffini, G. et al. 2023. Intranasal atomization of ketamine, medetomidine and butorphanol in pet rabbits using a mucosal atomization device. Animals 13(13), 2076.

A non-invasive method of drug delivery, intranasal atomization, has shown positive results in human medicine and in some animal species. The objective of this study was to evaluate the effects of intranasal atomization, compared to...

Imboden, T. J., Pownall, W. R., Rubin, S. et al. 2023. Determination of a safe sedative combination of dexmedetomidine, ketamine and butorphanol for minor procedures in dogs by use of a stepwise optimization method. Acta Veterinaria Scandinavica 65(1), 41.

In veterinary practice, most minor procedures such as radiographs, skin biopsies, and wound treatments require sedation. The combination of butorphanol, ketamine, and dexmedetomidine is commonly used, but the ideal dosages for this combination have not...

Alizadeh, E. A., Graf, K., Schiwon, J. et al. 2023. Thirty years of telemetry-based data acquisition for cardiovascular drug safety evaluation: Applications and optimization. Journal of Pharmacological and Toxicological Methods 122, 107279.

Conducting safety evaluations of new drugs using conscious animals has been a specialty of our working group for thirty years. In this article, we review the various technical challenges and solutions dealt with over the...

van der Laan, J. E., Vinke, C. M., Arndt, S. S. 2022. Evaluation of hair cortisol as an indicator of long-term stress responses in dogs in an animal shelter and after subsequent adoption. Scientific Reports 12(1), 5117.

Shelter dogs are exposed to a variety of stressors. Among non-invasive techniques, hair cortisol concentration (HCC) is suggested an easy to collect biomarker for giving insight into long-term stress responses. We evaluated HCC as an...

van der Laan, J. E., Vinke, C. M., Arndt, S. S. 2022. Evaluation of hair cortisol as an indicator of long-term stress responses in dogs in an animal shelter and after subsequent adoption. Scientific Reports 12(1), 5117.

Shelter dogs are exposed to a variety of stressors. Among non-invasive techniques, hair cortisol concentration (HCC) is suggested an easy to collect biomarker for giving insight into long-term stress responses. We evaluated HCC as an...

Reicher, V., Bálint, A., Újváry, D. et al.2022. Non-invasive sleep EEG measurement in hand raised wolves. Scientific Reports 12(1), 9792.

Sleep research greatly benefits from comparative studies to understand the underlying physiological and environmental factors affecting the different features of sleep, also informing us about the possible evolutionary changes shaping them. Recently, the domestic dog...

Mason, G. J., Lavery, J. M. 2022. What is it like to be a bass? Red herrings, fish pain and the study of animal sentience. Frontiers in Veterinary Science 9, 788289.

Debates around fishes’ ability to feel pain concern sentience: do reactions to tissue damage indicate evaluative consciousness (conscious affect), or mere nociception? Thanks to Braithwaite’s research leadership, and concerns that current practices could compromise welfare...

Santymire, R. M., Young, M., Lenihan, E. et al. 2022. Preliminary investigation into developing the use of swabs for skin cortisol analysis for the ocean sunfish (Mola mola). Animals 12(20), 2868.

The ocean sunfish (mola; Mola mola) is the heaviest bony fish in the world. This slow-moving fish often is injured by fishing boats that use drift gillnets attributing to its listing as Vulnerable by the...

Saraiva, J. L., Rachinas-Lopes, P., Arechavala-Lopez, P. 2022. Finding the “golden stocking density”: A balance between fish welfare and farmers’ perspectives. Frontiers in Veterinary Science 9, 930221.

The effects of stocking density on fish welfare are complex and involve many interacting parameters. This complex relationship between fish welfare, stocking density and influencing factors make it challenging to define a specific optimal (“golden”)...

Prior, H., Holbrook, M. 2021. Strategies to encourage the adoption of social housing during cardiovascular telemetry recordings in non-rodents. Journal of Pharmacological and Toxicological Methods 108, 106959.

The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) is working with industry to promote social housing during cardiovascular telemetry recordings within non-rodent safety pharmacology and toxicology studies. Following surveys...

Chmurska-Gąsowska, M., Sowińska, N., Pałka, S. et al. 2021. Non-invasive measurement of thyroid hormones in domestic rabbits. Animals 11(5), 1194.

Thyroid hormones are essential for metabolism, energy homeostasis and reproduction. Hormones can be measured in various biological source materials: blood, feces, urine, saliva and others. The aim of our study was to verify usefulness of...

Ordóñez-Grande, B., Guerreiro, P. M., Sanahuja, I. et al. 2021. Environmental salinity modifies mucus exudation and energy use in European sea bass juveniles. Animals 11(6), 1580.

Changes in skin mucus production and composition offer a new means to study how fish cope with changes in the environment. We explored the utility of skin mucus as an indicator of physiological responses and...

Koshman, Y. E., Wilsey, A. S., Bird, B. M. et al. 2021. Automated blood sampling in canine telemetry studies: Enabling enhanced assessments of cardiovascular liabilities and safety margins. Journal of Pharmacological and Toxicological Methods 109, 107066.

Introduction: A successful integration of automated blood sampling (ABS) into the telemetry instrumented canine cardiovascular model is presented in this study. This combined model provides an efficient means to quickly gain understanding of potential effects...

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...

Wang, P., Ma, Y., Liang, F. et al. 2020. Non-contact vital signs monitoring of dog and cat using a UWB radar. Animals 10(2), 205.

As pets are considered members of the family, their health has received widespread attention. Since pets cannot talk and complain when they feel uncomfortable, monitoring vital signs becomes very helpful in disease detection, as well...

Botman, J., Hontoir, F., Gustin, P. et al. 2020. Postanaesthetic effects of ketamine–midazolam and ketamine–medetomidine on gastrointestinal transit time in rabbits anaesthetised with isoflurane. Veterinary Record 186(8), 249.

Gastrointestinal stasis is a common perianaesthetic complication in rabbits. The objective of this study was to assess the impact on gastrointestinal transit time of ketamine–midazolam (KMZ) versus ketamine–medetomidine (later antagonised by atipamezole) (KMT-A) in rabbits...

Rasys, A. M., Divers, S. J., Lauderdale, J. D. et al. 2020. A systematic study of injectable anesthetic agents in the brown anole lizard (Anolis sagrei). Laboratory Animals 54(3), 281–292.

Anolis lizards have served as important research models in fields ranging from evolution and ecology to physiology and biomechanics. However, anoles are also emerging as important models for studies of embryo development and tissue regeneration...

Thoré, E. S. J., Brendonck, L., Pinceel, T. 2020. Conspecific density and environmental complexity impact behaviour of turquoise killifish (Nothobranchius furzeri). Fish Biology 97(5), 1448–1461.

Fish models are essential for research in many biological and medical disciplines. With a typical lifespan of only 6 months, the turquoise killifish (Nothobranchius furzeri) was recently established as a time- and cost-efficient model to...

Ordóñez-Grande, B., Guerreiro, P. M., Sanahuja, I. et al. 2020. Evaluation of an acute osmotic stress in European sea bass via skin mucus biomarkers. Animals 10(9), 1546.

European sea bass is a marine teleost which can inhabit a broad range of environmental salinities. So far, no research has studied the physiological response of this fish to salinity challenges using modifications in skin...

Lensen, C. M. M., Moons, C. P. H., Diederich, C. 2015. Saliva sampling in dogs: How to select the most appropriate procedure for your study. Journal of Veterinary Behavior 10(6), 504-512.

Saliva sampling is an easy, noninvasive method to assess short-term physiological changes, and as such is a valuable addition to behavioral studies in dogs. Different methods for collecting saliva samples in dogs have been reported...

Glover, C. N., Newton, D., Bajwa, J. et al. 2019. Behavioural responses of the hagfish Eptatretus stoutii to nutrient and noxious stimuli. Scientific Reports 9, 13369.

The suitability of a traditional testing paradigm (e.g. choice chamber) for assessing chemosensory behaviour in the Pacific hagfish, Eptatretus stoutii, was examined. Actively-swimming hagfish, tested at night, showed no preference for any region of a...

Bressan, T. F., Sobreira, T., Carregaro, A. B. 2019. Use of rodent sedation tests to evaluate midazolam and flumazenil in green iguanas (Iguana iguana). JAALAS 58(6), 810–816.

This study aimed to evaluate the applicability of rodent behavioral tests to assess the effects of midazolam and flumazenil in green iguanas. Four tests commonly used to assess sedation in rodents—the open field test, forced...

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...

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...

Sadekova, N., Boudreau, G., Jalbert, B. et al. 2016. The effects of housing conditions on baseline cardiovascular parameters and the sensitivity to detect changes in contractility in telemetry-implanted dogs. Journal of Pharmacological and Toxicological Methods 81, 60-74.

Introduction: There is a growing weight of evidence to suggest that myocardial contractility is an important parameter to assess as part of IND enabling studies in addition to standard assessments as per the ICH S7A...