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. 
Morton, D. B. 2023. A model framework for the estimation of animal “suffering”: Its use in predicting and retrospectively assessing the impact of experiments on animals. Animals 13(5), 800.

This paper presents and illustrates, with a working example, a hypothesis for the assessment of ongoing severity before and during an experiment that will enable humane endpoints and intervention points to be applied accurately and...

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...

Webb, J. K., Keller, K. A., Chinnadurai, S. K. et al. 2023. Use of alfaxalone in bearded dragons (Pogona vitticeps): Optimizing pharmacodynamics and evaluating cardiogenic effects via echocardiography. Journal of the American Veterinary Medical Association 261(1), 126–131.

OBJECTIVE Bearded dragons (Pogona vitticeps), a popular zoological companion species, frequently require sedation for procedures. A novel formulation of alfaxalone with preservatives was FDA approved for 28-day use after the vial is breached. Research has...

Williams, W. O., Baneux, P. 2022. Humane Intervention Points: Refining endpoint terminology to incorporate non-euthanasia intervention options to improve animal welfare and preserve experimental outcomes. Laboratory Animals 56(5), 482-489.

Consideration of The Three R’s (Replacement, Reduction, and Refinement) is essential when setting Humane Endpoints; however, a common interpretation assumes that Humane Endpoints are timepoints to perform euthanasia. This interpretation is not always consistent with...

Wahltinez, S. J., Stacy, N. I., Hadfield, C. A. et al. 2022. Perspective: Opportunities for advancing aquatic invertebrate welfare. Frontiers in Veterinary Science 9, 973376.

Welfare considerations and regulations for invertebrates have lagged behind those for vertebrates, despite invertebrates comprising more than 95% of earth’s species. Humans interact with and use aquatic invertebrates for exhibition in zoos and aquaria, as...

Álvarez, E. R., Solé, L. V., Mateo, A. G. de C. 2022. Comparison of subcutaneous sedation with alfaxalone or alfaxalone-midazolam in pet guinea pigs (Cavia porcellus) of three different age groups. Journal of the American Veterinary Medical Association 260(9), 1024–1030.

OBJECTIVE To compare the cardiorespiratory effects, quality and duration of sedation of 2 subcutaneous sedation protocols for noninvasive procedures in guinea pigs (GPs). ANIMALS 24 pet GPs (15 females, 9 males) of 3 different age...

Nunamaker, E. A., Davis, S., O’Malley, C. I. et al. 2021. Developing recommendations for cumulative endpoints and lifetime use for research animals. Animals 11(7), 2031.

Research animals are important for scientific advancement, and therefore, their long-term welfare needs to be monitored to not only minimize suffering, but to provide positive affective states and experiences. Currently, there is limited guidance in...

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...

Argüelles, J., Echaniz, M., Bowen, J. et al. 2021. The impact of a stress-reducing protocol on the quality of pre-anaesthesia in cats. Veterinary Record 188(12), e138.

Introduction: Transport to the clinic is a major source of stress for cats. The process involves being put into a carrier, driven in a car and handled. Cats are therefore removed from the safe-haven of...

Abbo, L. A., Himebaugh, N. E., DeMelo, L. M. et al. 2021. Anesthetic efficacy of magnesium chloride and ethyl alcohol in temperate octopus and cuttlefish species. JAALAS 60(5), 556-567.

Cephalopods are important in biologic and biomedical research, yet relatively little objective information is available to guide researchers and veterinarians regarding the best methods for anesthetizing these animals for various experimental procedures. Recent studies demonstrate...

Bertho, J.-M., Ancelet, S., Denais-Laliève, D. et al. 2020. Humane endpoints in severe irradiation experiments using non-human primates: A retrospective analysis. Scandinavian Journal of Laboratory Animal Science 46(1).

A retrospective statistical study has been performed in order to identify the biological, clinical and behavioural variables that could potentially predict the survival status of irradiated non-human primates (NHP) and to refine the future use...

Yaw, T. J., Mans, C., Johnson,S. et al. 2020. Evaluation of subcutaneous administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius). Journal of the American Veterinary Medical Association 256(5), 573-579.

OBJECTIVE: To evaluate SC administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius). ANIMALS: 12 healthy juvenile ball pythons. PROCEDURES: In a randomized crossover study, each snake was administered a combination of...

Larson, C. M., Wilcox, G. L., Fairbanks, C. A. 2019. Defining and managing pain in stroke and traumatic brain injury research. Comparative Medicine 69(6), 510–519.

Neurologic conditions such as stroke and traumatic brain injury are challenging conditions to study in humans. Animal models are necessary to uncover disease processes and develop novel therapies. When attempting to model these or other...

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...

Kane, L. P., Chinnadurai, S. K., Vivirito, K. et al. 2020. Comparison of isoflurane, sevoflurane, and desflurane as inhalant anesthetics in prairie rattlesnakes (Crotalus viridis). Journal of the American Veterinary Medical Association 257(9), 945-949.

OBJECTIVE: To characterize induction and recovery characteristics of 3 commonly used inhalant anesthetics in prairie rattlesnakes (Crotalus viridis): isoflurane, sevoflurane, and desflurane. ANIMALS: 12 healthy adult prairie rattlesnakes. PROCEDURES: In a randomized crossover design, snakes...

Clutton, R. E. 2020. An Anglocentric history of anaesthetics and analgesics in the refinement of animal experiments. Animals 10(10), 1933.

Previous histories of animal experimentation, e.g., Franco (2013) have focused on ethics, the law and the personalities involved, but not on the involvement of anaesthetics or analgesics. Given that these were major subjects of (UK)...

Kane, L. P., Chinnadurai, S. K., Vivirito, K. et al. 2020. Comparison of isoflurane, sevoflurane, and desflurane as inhalant anesthetics in prairie rattlesnakes (Crotalus viridis). Journal of the American Veterinary Medical Association 257(9), 945-949.

OBJECTIVE: To characterize induction and recovery characteristics of 3 commonly used inhalant anesthetics in prairie rattlesnakes (Crotalus viridis): isoflurane, sevoflurane, and desflurane. ANIMALS: 12 healthy adult prairie rattlesnakes. PROCEDURES: In a randomized crossover design, snakes...

Darbyshire, A. K., Oliver, K. H., Dupont, W. D. et al. 2019. Anesthesia and euthanasia of brine shrimp (Artemia franciscana). JAALAS 58(1), 58-63.

Invertebrates are often overlooked as laboratory animals, yet they are commonly used in toxicology, developmental, cellular and molecular biology, and radiation studies with euthanasia as an endpoint. Little is known regarding appropriate euthanasia methods for...

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...

Sloman, K, A., Bouyoucos, I. A., Brooks, E. J. et al. 2019. Ethical considerations in fish research. Journal of Fish Biology 94(4), 556-577.

In this review, we focus primarily on the refinement of common methods used in fish research based on emerging knowledge with the aim of improving the welfare of fish used in scientific studies. We consider...

Jacobsen, J. V., Steen, K., Nilssen, K. J. 2019. Anaesthetic efficacy of Aqui-S, Benzoak, and MS-222 on lumpfish (Cyclopterus lumpus) fries. Impact from temperature, salinity, and fasting. PLOS ONE 14(1), e0211080.

Large numbers of lumpfish are produced for the Norwegian salmon industry and are used to combat sea lice infestations. Periodically high mortality of farmed lumpfish demonstrates the need to improve farming conditions and animal welfare...

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...

Dholakia, U., Seddighi, R., Odunayo, A. et al. 2019. Prolonged anesthetic recovery after continuous infusion of midazolam in 2 domestic cats (Felis catus). Comparative Medicine 69(4), 321–326.

Two healthy research cats involved in a randomized, blinded prospective pharmacodynamics study evaluating midazolam continuous-rate infusion as a means to decrease sevoflurane concentrations experienced unexpectedly prolonged recoveries. Midazolam loading doses, infusion rates, and the targeted...

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...

Lin, C.-H., Lo, P.-Y. 2018. Simple technique for aiding thoracic CT scanning of cats without general anaesthesia. Veterinary Record 182(7), 1-3.

Thoracic CT can provide additional diagnostic information in comparison to thoracic radiography for animals with respiratory diseases; however, the requirement of general anaesthesia can be of risk and may not be possible in cats with...