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. 
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...

Kloefkorn H, Aiani, L. M., Lakhani, A. et al. 2020. Noninvasive three-state sleep-wake staging in mice using electric field sensors. Journal of Neuroscience Methods 344, 108834.

Study Objective: Validate a novel method for sleep-wake staging in mice using noninvasive electric field (EF) sensors. Methods: Mice were implanted with electroencephalogram (EEG) and electromyogram (EMG) electrodes and housed individually. Noninvasive EF sensors were...

Murphy, A. M., Ross, C. N., Bliss‐Moreau, E. 2019. Noninvasive cardiac psychophysiology as a tool for translational science with marmosets. American Journal of Primatology 81(9), e23037.

The importance of marmosets for comparative and translational science has grown in recent years because of their relatively rapid development, birth cohorts of twins, family social structure, and genetic tractability. Despite this, they remain understudied...

Cowley, P. M., Roberts, C. R., Baker, A. J. 2019. Monitoring the health status of mice with bleomycin-induced lung injury by using body condition scoring. Comparative Medicine 69(2), 95–102.

Well-defined, humane endpoints aid in monitoring animal health status during disease development. Body condition scoring (BCS) is a method for assessing health status in mouse studies where wasting and death are potential endpoints. Whether BCS...

Franco, N. H., Gerós, A., Oliveira, L. et al. 2019. ThermoLabAnimal – A high-throughput analysis software for non-invasive thermal assessment of laboratory mice. Physiology & Behavior, 207, 113-121.

Body temperature changes in laboratory mice are often assessed by invasive and stressful methods, which may confound the measurement. Infrared thermography is a possible non-invasive alternative, but the cost of standard thermal cameras, lack of...

Redaelli, V., Papa, S., Marsella, G. et al. 2019. A refinement approach in a mouse model of rehabilitation research. Analgesia strategy, reduction approach and infrared thermography in spinal cord injury. PLOS ONE 14(10), e0224337.

The principles of Refinement, Replacement and Reduction (3R’s) should be taken into account when animals must be used for scientific purpose. Here, a Reduction / Refinement approach was applied to the procedure of spinal cord...

Broche Jr., N., Takeshita, R. S. C., Mouri, K. et al. 2019. Salivary alpha-amylase enzyme is a non-invasive biomarker of acute stress in Japanese macaques (Macaca fuscata). Primates volume 60(6), 547–558.

Salivary alpha-amylase (sAA) enzyme functions as a digestive enzyme in many species that consume starch in their diet. Human studies have also revealed that sAA enzyme activity levels are positively correlated with the release of...

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...

France, L. K., Vermillion, M. S., Garrett, C. M. 2018. Comparison of direct and indirect methods of measuring arterial blood pressure in healthy male rhesus macaques (Macaca mulatta). JAALAS 57(1), 64-69.

Blood pressure is a critical parameter for evaluating cardiovascular health, assessing effects of drugs and procedures, monitoring physiologic status during anesthesia, and making clinical decisions. The placement of an arterial catheter is the most direct...

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...

Ash, H., Smith, T. E., Knight, S. et al. 2018. Measuring physiological stress in the common marmoset (Callithrix jacchus): Validation of a salivary cortisol collection and assay technique. Physiology & Behavior 185, 14-22.

Cortisol levels are often used as a physiological measure of the stress response in captive primates, with noninvasive measures of this being an important step in welfare assessment. We report a method of collecting saliva...

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...

Toth, L. A. 2018. Identifying and implementing endpoints for geriatric mice. Comparative Medicine 68(6), 439–451.

The types of changes in physical appearance and behavior that occur in elderly people similarly develop in elderly animals. Signs and symptoms that might cause concern in younger people or mice may be normal in...

Fuller, G., Allard, S. 2018. Preliminary data showing potential for salivary C-reactive protein as an indicator of welfare in western lowland gorillas (Gorilla gorilla gorilla). Journal of Veterinary Behavior 28, 58-62.

C-reactive protein (CRP) is an acute phase protein often used as a biomarker for inflammation related to acute trauma or chronic illness. Animal studies showing elevations in CRP following events such as road transport and...

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...

Tan, A. W. Y., Dominy, N. J. 2018. Validation of a noninvasive hair trapping method for extractive-foraging primates. Folia Primatologica 89(6), 415–422.

Hair is a useful source of biological information. For example, the bulb can be a source of high-quality genetic material, whereas the shaft can be useful for measuring heavy metals and some hormones, such as...

Johnston, J. M., Wilson, J. M., Smith, A. L. et al. 2017. Using a cageside device for testing glycosylated hemoglobin in cynomolgus macaques (Macaca fascicularis). JAALAS 56(1), 90-94.

Recording an accurate body temperature is important to assess an animal's health status. We compared temperature data from sedated cynomolgus macaques (Macaca fascicularis) to evaluate differences between rectal, infrared (inguinal and chest), and implanted telemetry...

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...

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...

Xing, G., Lu, J., Hu, M. et al. 2015. Effects of group housing on ECG assessment in conscious cynomolgus monkeys. Journal of Pharmacological and Toxicological Methods 75, 44-51.

Assessing the cardiovascular safety of new chemical or biological entities is important during pre-clinical development. Electrocardiogram (ECG) assessments in non-human primate (NHP) toxicology studies are often made using non-invasive telemetry systems. We investigated whether ECG...

Pizzi, R., Dowling, A., Brown, D. et al. 2015. Facial thermography is not useful in assessing body temperature in common squirrel monkeys (Saimiri sciureus) in comparison to rectal temperatures. Journal of Zoo and Aquarium Research 3(3), 94-98.

A group of 39 captive common squirrel monkeys (Saimiri sciureus) had their body temperature measurements compared by rectal thermometry and facial infrared thermal imaging (Flir i3, Flir Systems Inc). Squirrel monkeys were caught up and...

Kaiser, R. A., Tichenor, S. D., Regalia, D. E. et al. 2015. Telemetric assessment of social and single housing: Evaluation of electrocardiographic intervals in jacketed cynomolgus monkeys. Journal of Pharmacological and Toxicological Methods 75, 38-43.

Introduction: Proactive efforts to socially house laboratory animals are a contemporary, important focus for enhancing animal welfare. Jacketing cynomolgus monkeys has been traditionally considered an exclusionary criterion for social housing based on unsubstantiated concerns that...

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...

Schnell, C. R., Gerber, P. 1997. Training and remote monitoring of cardiovascular parameters in non-human primates. Primate Report 49, 61-70.

The use of "pre-invasive" implantable radio telemetry has revolutionized the collection of physiological data under stress-free conditions. It is now possible to measure accurately 'normal' baseline data of haemodynamic and electrical parameters in conscious and...