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. 
Wong, C.-H., Tsai, M.-A., Ko, F.-C. et al. 2023. Skin cortisol and acoustic activity: Potential tools to evaluate stress and welfare in captive cetaceans. Animals 13(9), 1521.

As people’s focus broadens from animals on farms to zoos and aquaria, the field of welfare science and the public’s concern for animal welfare continue to grow. In captive animals, stress and its causes are...

Higham, J. P., Cooper, E. B., Whalen, C. et al. 2023. Urinary cytokine measurements do not reflect surgery-induced inflammation in rhesus macaques. American Journal of Primatology 85(8), e23506.

Measurement of the health and disease status of free-ranging primates is often limited by a lack of available biomarkers of immune activation and inflammation that can be applied noninvasively via the measurement of urine or...

Chakravarty, S., Donoghue, J., Waite, A. S. et al. 2023. Closed-loop control of anesthetic state in nonhuman primates. PNAS Nexus 2(10), 293.

Research in human volunteers and surgical patients has shown that unconsciousness under general anesthesia can be reliably tracked using real-time electroencephalogram processing. Hence, a closed-loop anesthesia delivery (CLAD) system that maintains precisely specified levels of...

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...

Broche, N., Mouri, K., Suzumura, T. et al. 2023. Measuring short-term changes in stress-associated salivary analytes in free-ranging Japanese macaques (Macaca fuscata). Primates 64(4), 439–449.

Monitoring short-term changes of endocrine responses in non-human primates living in wild populations is a challenge. Saliva contains enzymes, steroids, and various analytes that can be broadly useful for helping us understand physiological responses to...

Paterson, E. A., Turner, P. V. 2022. Challenges with assessing and treating pain in research primates: A focused survey and literature review. Animals 12(17), 2304.

Research primates may undergo surgical procedures making effective pain management essential to ensure good animal welfare and unbiased scientific data. Adequate pain mitigation is dependent on whether veterinarians, technicians, researchers, and caregivers can recognize and...

Böswald, L. F., Matzek, D., Mohr, H. et al. 2022. Morphometrics of Xenopus laevis kept as laboratory animals. Animals 12(21), 2986.

Morphometric data that provide information on body conditions can be used to monitor the health and well-being of animals. In laboratory animals, they can help to evaluate the stress due to experiments or treatments, following...

Kishida, T., Motokawa, Y., Yokoi, R. et al. 2022. Less invasive, simultaneous, and continuous measurements of locomotor activity and body temperature using the nano tag® small accelerometer device in cynomolgus monkeys. Journal of Pharmacological and Toxicological Methods 118, 107224.

Locomotor activity and body temperature evaluations of cynomolgus monkeys are useful to understand the effects of drugs on the central nervous system. Here, we describe a simple, inexpensive, and less invasive evaluation method using the...

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...

Hausmann, J. C., Krisp, A. R., Mans, C. et al. 2021. Analgesic efficacy of tramadol and morphine in White's tree frogs (Litoria caerulea). JAALAS 60(6), 681-686.

Published data are sparse regarding the recognition of clinically relevant pain and appropriate analgesia in amphibians. The amphibian analgesia literature has primarily focused on nociceptive pathways in a single species, the northern leopard frog (Rana...

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...

Engel, R. M., Thomas III, M. L., Banks, R. E. 2019. Regional anesthesia for dentistry and orofacial surgery in rhesus macaques (Macaca mulatta). JAALAS 58(2), 223-230.

Regional anesthesia is a commonly used adjunct to orofacial dental and surgical procedures in companion animals and humans. However, appropriate techniques for anesthetizing branches of the mandibular and maxillary nerves have not been described for...

Smith, A. A., Halliday, L. C., Lindeblad, M. O. et al. 2019. Evaluation of analgesic patches in cynomolgus macaques (Macaca fascicularis). JAALAS 58(3), 356-361.

Opioids are widely used in veterinary and human medicine to manage pain. However, there is a paucity of information in the literature regarding the pharmacokinetics of opioid transdermal patches (TDP) in NHP. Therefore, to determine...

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...

Smith, B. D., Vail, K. J., Carroll, G. L. et al. 2018. Comparison of etomidate, benzocaine, and MS222 anesthesia with and without subsequent flunixin meglumine analgesia in African clawed frogs (Xenopus laevis). JAALAS 57(2), 202-209.

Often few alternative anesthetics for exotic species are available, due to the small numbers of these animals used in research. In this study, we evaluated the depth and duration of anesthesia in Xenopus laevis after...

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...

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...

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...

Salyards, G. W., Lemoy, M.-J., Knych, H. K. et al. 2017. Pharmacokinetics of a novel, transdermal fentanyl solution in rhesus macaques (Macaca mulatta). JAALAS 56(4), 443-451.

Rhesus macaques (Macaca mulatta) are the most commonly used NHP biomedical model and experience both research and clinical procedures requiring analgesia. Opioids are a mainstay of analgesic therapy. A novel, transdermal fentanyl solution (TFS) has...

Chatigny, F., Kamunde, C., Creighton, C. M. et al. 2017. Uses and doses of local anesthetics in fish, amphibians, and reptiles. JAALAS 56(3), 244-253.

Local anesthetics are an integral part of routine pain management in mammals, yet their use is relatively limited in fish, amphibians and reptiles. These animals frequently undergo potentially painful surgical procedures and therefore could possibly...

Chinnadurai, S. K., Johnson III, J. G., Langan, J. N. 2017. Comparison of 3 methods for preventing perianesthetic hypothermia in callimicos (Callimico goeldii). JAALAS 56(3), 318-321.

Perianesthetic hypothermia is one of the most common complications in veterinary anesthesia, especially in small patients with a large body surface area to mass ratio. During anesthesia, body heat can be lost through 4 mechanisms—radiation...

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...

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...

Morrison, K.E., Strahl-Heldreth, D. Clark-Price, S.C. 2016. Isoflurane, sevoflurane and desflurane use in cane toads (Rhinella marina). Veterinary Record Open 3(1), e000185.

Anaesthetic chamber concentrations of isoflurane, sevoflurane and desflurane that resulted in loss of righting reflex within 15 minutes in 50 per cent of toads (Rhinella marina) exposed (ED50-LRR