Comments for: Implementation of the Updated AVMA Guidelines for the Euthanasia of Animals: 2013 Edition
Comment List: |
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For more information, see NIH Guide Notices (NOT-OD-13-048, NOT-OD-13-090) and Federal Register Notice, Doc# 2013-06661 (PDF).
Comment Period: March 1, 2013 - May 31, 2013
| Date: | Name of Organization | City and State | Comment 1: | Comment 2 | Comment 3 | Comment 4 | Comment 5 | Comment 6 | Comment 7 | Comment 8 | Attachments |
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| 05/31/2013 10:44 PM | People for the Ethical Treatment of Animals | Washington, DC | A central tenet of both the Guide for the Care and Use of Laboratory Animals (Eighth Edition) and the AVMA Guidelines for Euthanasia of Animals: 2013 Edition (Guidelines) is that euthanasia of animals be conducted in such a manner as "to induce the most rapid and painless and distress-free death possible." It is encouraging to read, in the Preface of the Guidelines, an acknowledgement of the rapidly evolving animal welfare science of euthanasia methods: "[T]he Panel on Euthanasia (POE) made every effort to identify and apply the best research and empirical information available. As new research is conducted and more practical experience gained, recommended methods of euthanasia may change. As such, the AVMA and its POE have made a commitment to ensure the Guidelines reflect an expectation and paradigm of continuous improvement that is consistent with the obligations of the Veterinarian's Oath." Indeed, even as the Guidelines were being discussed and prepared, multiple studies were published on welfare issues associated with the extent to which carbon dioxide is aversive to mice and rats in comparison to various inhaled anesthetics. Even as other countries have shifted their policies and practices away from using carbon dioxide alone as a method of euthanizing mice and rats, it is clear that the AVMA is not ready to take that position at this time. We hope that as more data is published on the issue, steps are taken to align policies with the science, to ensure that pain and distress to animals are minimized. In a similar vein, even as the Guidelines were being finalized, a research paper, authored by Dr. Larry Carbone (who, of course, served as a member of the Panel on Euthanasia) and focused on welfare considerations associated with the use of cervical dislocation to kill mice, was published. The paper shed new light on this issue, reporting startling data on the percentage of mice who continue breathing after attempted cervical and thoracic dislocation at the hands of experienced operators. The authors concluded: "If additional studies replicate our findings, recommended practices will need to change ..." In both of these examples, evolving science may challenge practices deemed "acceptable" or even "acceptable with conditions" in the 2013 Guidelines. It is imperative that the Office of Laboratory Animal Welfare (OLAW) monitor new studies in these and other areas and apply the information gleaned to ensure that euthanasia methods used at PHS-Assured facilities comply with the requirements outlined in the Guide that animals are euthanized in such a manner that pain and distress are minimized. | Considerable controversy surrounds the use of carbon dioxide as a sole agent to kill tens of millions of rats and mice in laboratories each year. While the Guidelines correctly note that "all inhaled methods have the potential to adversely affect animal welfare because onset of unconsciousness is not immediate," there is near scientific consensus that carbon dioxide is particularly aversive to mice and rats (please see Comment 5). Thus, while it not possible to eliminate pain and distress when using inhaled agents, it is possible to minimize pain and distress to animals by first rendering animals unconscious through a less aversive inhalant anesthetic, such as isoflurane, and then using carbon dioxide to kill the animals. While we appreciate that the POE has considered the challenges inherent in assessing pain in animals whose anatomic structures are so different from ours, we are disappointed that with regard to the killing of rats and mice-mammals about whom much is known-the panel's recommendations reflect political expedience, at the expense of scientific rigor. Four issues are listed in the Guidelines as "advantages" to using carbon dioxide as a method of euthanizing animals, none of which addresses the central concern that pain and distress to animals must be minimized: (1) The rapid depressant, analgesic, and anesthetic effects of CO2 are well established. (2) Carbon dioxide is readily available in compressed gas cylinders. (3) Carbon dioxide is inexpensive, nonflammable, and nonexplosive and poses minimal hazard to personnel when used with properly designed equipment. (4) Carbon dioxide does not result in accumulation of toxic tissue residues in animals from which food is produced. While the second and third points are transparently focused on economic considerations and operator convenience, the fourth point is not relevant to animals in laboratories. The first point pertains only peripherally to animal welfare, with the greater focus being on the historical knowledge of the functioning of carbon dioxide. Eight issues are listed in the Guidelines as "disadvantages" to using carbon dioxide, and three of these indicate welfare concerns. The Guidelines acknowledge that carbon dioxide "whether administered by prefill or gradual displacement methods, can be aversive to some species, and therefore potential exists to cause distress;" that because carbon dioxide "is heavier than air, layering of gas or incomplete filling of a chamber may permit animals to climb or raise their heads above the effective concentrations and avoid exposure," and that "[i]nduction of loss of consciousness at concentrations < 80% may produce postmortem pulmo-nary and upper respiratory tract lesions." In spite of this litany of welfare concerns, the Guidelines deem carbon dioxide to be "acceptable with conditions" for euthanasia of small rodents. | While acknowledging that "few scientific studies" have been conducted to confirm the assumption that killing animals using cervical dislocation is humane, the Guidelines offer as a general recommendations that "[m]anual cervical dislocation is acceptable with conditions for euthanasia of small birds, poultry, mice, rats weighing < 200 g, and rabbits when performed by individuals with a demonstrated high degree of technical proficiency." However, as noted in Comment 1, a paper authored by Dr. Larry Carbone and his colleagues and published in the May 2012 issue of the Journal of the American Association for Laboratory Animal Science: JAALAS reports startling data on this method of euthanasia. In the paper, "Assessing cervical dislocation as a humane euthanasia method in mice," the authors evaluated three methods of cervical dislocation (CD) - including manual cervical dislocation - and determined that all three methods "can result in unsuccessful euthanasia in which mice continue breathing after the attempted dislocation." The authors write: "If additional studies replicate our findings, recommended practices will need to change, whether to disallow CD of unanesthetized mice, identify a CD method with a higher success rate, or emphasize that mice must be watched closely after CD, and if still breathing (which can be difficult to ascertain given the motor discharge that often follows CD), immediately treated through the same or an alternate method of euthanasia." In the absence of "additional studies" at this time, we would suggest that the objective of the Guidelines and the Guide to minimize pain and distress to animals would be best served by applying the precautionary principle and requiring that all mice be anesthetized prior to CD. In the absence of this change in policy, the Office of Laboratory Animal Welfare (OLAW) should monitor studies in this area and apply information gleaned from these studies to ensure that euthanasia methods used at PHS-Assured facilities minimize pain and distress to animals. | There is near scientific consensus that carbon dioxide is particularly aversive to mice and rats: 1. The Newcastle Consensus Meeting on Carbon Dioxide Euthanasia of Laboratory Animals notes that "both pre-fill and rising concentrations [of CO2] can cause welfare problems." Studies indicate that if animals are placed into a chamber containing a high concentration of CO2 (above 50%), they will experience at least 10 to 15 seconds of noxious pain in the mucosa of the upper airways before losing consciousness; time to unconsciousness can extend as long as 90 seconds. If animals are placed into a chamber with a rising concentration of CO2, they will find it aversive at a certain level and may experience "respiratory distress and asphyxia (including some histological indications of a state similar to conscious drowning)." 2. The European Food Safety Authority's Scientific Panel on Animal Health and Welfare advises that "a considerable number of papers involving aversion tests, behavioural observations and physiological responses" have addressed "[t]he high risk of compromising animal welfare due to the inherent properties of CO2." The panel notes, "Animals given the choice do not enter or remain in high concentrations of CO2 (e.g. for rodents 100% of animals at concentrations above 16%), and indeed they make active attempts to escape lethal concentrations. Lung oedema, and lung haemorrhaging, may induce a sense of breathlessness or drowning, prior to loss of consciousness ..." 3. A report issued by a joint working group comprised of members of the Universities Federation for Animal Welfare and others corroborates the point: "There is ... evidence to indicate that exposure to carbon dioxide, even at low concentrations, may cause distress to mice and rats prior to their loss of consciousness. It has therefore been recommended that carbon dioxide should only be used for euthanasia once the rodents have first been rendered unconscious with an anaesthetic agent such as halothane." 4. In comparative studies of aversiveness of gaseous euthanasia agents, carbon dioxide was found to be "by far the most aversive anaesthetic for both rats and mice .... [T]he level of distress observed with carbon dioxide was so severe that any animal confined in an environment containing this gas is likely to suffer considerably. Moreover, carbon dioxide is aversive at concentrations below those deemed to produce humane induction." One study conducted by researchers at UBC noted: "Mice show aversion to CO2 concentrations as low as 13.5-18.2%, but concentrations of greater than 30% are needed to render them unconscious. Mice also showed aversion to argon, CO, and the two inhalant anaesthetics, so the search for a non-aversive agent should continue. Aversion to the inhalant anaesthetic isoflurane appears to be weaker than aversion to the other agents, so we recommend the use of this agent to render mice unconscious before euthanasia with any method." | |||||
| 05/31/2013 5:59 PM | The American Society of Mammalogists | Appendix A OC Fact Sheet- thoracic compression.pdf |
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| 05/31/2013 3:30 PM | The Humane Society of the United States | Washington, DC | HSUS Comments-all parts.pdf | ||||||||
| 05/31/2013 5:52 PM | Seattle Children's Research Institute | Seattle WA | S1.7 Fetuses and Neonates The conclusion that embryos and fetuses cannot experience pain and thus do not suffer while dying in utero is based in this section on the work and opinions of primarily one author (D Mellor). The primary reference (JVME 2010 37:94) focuses on farm animals, and the author equivocates regarding fetal consciousness and pain. He suggests that "... fetal removal should be delayed for at least 15-20 minutes after slaughter of the dam, as this would guarantee a substantial degree of anoxia-induced dysfunction of the fetal cerebral cortex. Preferably, however, the fetus should be left in the uterus until it is dead... to avoid ... the possibility of faulty judgments about the presence or absence of consciousness... if there is any doubt about consciousness, the fetus should be killed with a captive bolt..." The author seems to recommend this practice as a matter of convenience without complete confidence that the welfare of the fetus is protected. S2 Laboratory Animals S2.2.4 Fetuses and Neonates This paragraph seems to suggest that all genera of mice and rats have altricial young. However, some wild rodents have precocial young. The paragraph does not address developmental differences between fetuses of altricial and precocial species and how that might impact decisions regarding euthanasia. S2.2.4.1 Acceptable Methods The statement, "Rodent fetuses along with other mammals are unconscious in utero and hypoxia does not evoke a response," cites a single reference by the same author as above (D Mellor et al.). The work in this paper focuses on recordings from fetal sheep, and conclusions are extrapolated to other animals. In my opinion, this work is somewhat speculative and concludes that gasping and other movements of the fetus in utero do not indicate pain or distress in the absence of breathing. This statement is inconsistent with the assertion above that hypoxia does not evoke a response by the fetus. There is most certainly a fetal response when the dam is hypoxic, which is demonstrated by increased fetal movements in most species when the dam is euthanized. In my opinion, the conclusion that this response does not represent fetal pain or distress is not well substantiated in the literature. It is standard practice to anesthetize human fetuses for surgery due to presumed perception of noxious stimuli, and it seems the same presumption should be used for animal species unless proven otherwise. S2.2.4.2.2 Physical Methods Hypothermia The last sentence allows altricial neonates <5 days of age to be killed by rapid freezing in liquid N2 because they lack "sufficient nervous system development to perceive pain." This statement again cites the Mellor (2010) paper on farm animals, which does not appear to provide a specific timeline for development of pain responses in altricial rodent neonates. | My concern is that the assertions and operational guidance provided in the new Guidelines regarding euthanasia of fetuses and neonates of all species are based on limited scientific data in a few species. In my opinion, it would be prudent to err on the side of caution until more definitive evidence is available regarding the stage at which pain and distress is experienced by fetuses and neonates of different species. The thalamocortical connections needed to transmit noxious stimuli to the brain are present and become functional in many species during the fetal period. The ability to perceive pain is thought by some to depend on consciousness, which is likely absent before birth. It is well established that the adverse physiologic response to a noxious stimulus is not dependent on consciousness. The operational objective definition of "consciousness" using physiologic parameters is controversial and difficult to establish, even in adult humans. The embryo and fetus accommodate to an hypoxic environment, and assumptions about consciousness and pain perception during hypoxia at these stages are not well substantiated. In my opinion, there are still many unanswered questions about fetal pain and distress, and a conservative approach is the wisest and most humane option. | |||||||
| 05/30/2013 12:32 PM | Ornithological Council | BETHESDA, MD | Our comments are attached. As we have a number of appendices, we will also submit these comments and the appendices by e-mail to Dr. Brown and other members of the OLAW staff. | Our comments are attached. | Our comments are attached. | Our comments are attached. | Our comments are attached. | Appendix A OC Fact Sheet- thoracic compression.pdf Appendix B OC Position statement on the use of thoracic compression.pdf Appendix C Statement Heatley AVMA.pdf Appendix E Ludders-Thoracic-JAVMA-2001.pdf Appendix G AVMA backgrounder 2012.pdf |
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| 05/30/2013 3:24 PM | Cornell University | Ithaca, NY | The document as a whole is thorough, well-researched and has a much needed element of flexibility for circumstances such as working with wildlife in captivity and the field. When reviewing the document by section, the guidance provided is clear and practical. From the perspective of an institution with a complex animal care program which requires application of multiple sections of the document, the new AVMA Guidelines can be difficult to follow. There is a lack of consistency and cohesiveness in the way the information is presented thus creating a need to cross reference multiple sections to ensure compliance. | Since the venous access limitations in laboratory rodents are analogous to that of comparably sized birds, the condition of unconsciousness should not be required for IP injections in small avians as per section M2.2.1 (page 27) where it is stated that "When intravascular administration is considered impractical or impossible, IP or intracoelomic administration of a nonirritating barbiturate or other approved solution is acceptable." | In several sections, euthanasia of birds by thoracic compression is deemed as unacceptable practice. This causes practical limitations to the investigators at Cornell's Ithaca campus in general and to our field researchers in particular. We acknowledge the document prepared by the American Ornithologists' Union on this method of euthanasia (attached), and we are looking forward to continued dialogue as well as continued research on this subject. | In section S5.2.1.1, under noninhaled agents for avian euthanasia (page 66), it is stated that "When IV injection is impossible, injectable euthanasia agents can be administered via intracoelomic, intracardiac, or intraosseous routes only if a bird is unconscious or anesthetized." Such condition seems reasonable for intracardiac and intraosseous route. However, it is unclear why this condition (unconscious or anesthesia) is required for intracoelomic route. No supporting literature has been cited for this. | On page 71 under finfish, Section S6.2.2 Physical Methods (6), rapid chilling guidelines are provided for fry 4 to 7 dpf and for embyros < 3 dpf. The document does not address animals of 3 dpf. Perhaps referring to embryos < or = 3dpf would help to address animals that are precisely 3 dpf. | On page 77 under captive amphibians and reptiles Section S7.3.5.2 Physical Methods, rapid freezing with liquid nitrogen is allowed in animals < 4g. The fish section does not mention the liquid nitrogen for rapid freezing. It seems reasonable that if liquid nitrogen is acceptable with conditions for amphibians and reptiles, it would also be acceptable under similar conditions in fish. | Ornithological Council.pdf | ||
| 05/28/2013 8:53 AM | The Wildlife Society | Bethesda, MD | TWS general comments.doc | ||||||||
| 05/10/2013 9:58 AM | NIH Intramural Research Program | Bethesda, Maryland | M1.3 Inhaled Anesthetics 1) Carrier gas inconsistency between page 21 and page 26 "Advantages-(1) Inhaled anesthetics are particularly useful for euthanasia of smaller animals (< 7 kg [15.4 lb]) or for animals in which venipuncture maybe difficult. (2) Inhaled anesthetics can be administered by several different methods depending on the circumstances and equipment available (eg, face mask, open drop where the animal is not permitted to directly contact the anesthetic liquid, precision vaporizer, rigid or nonrigid containers). "Time to death may be prolonged as O2 is commonly used as the vapor carrier gas with precision anesthetic vaporizers." Requested change/clarification: clarify that the use of an open drop method produces significantly higher concentrations of anesthetics, results in almost immediate unconsciousness and rapid death and therefore is the preferred method for use of an inhalant as a sole means of euthanasia. Further clarify that is a vaporizer is used to deliver the inhalant, prolonged exposure will likely be needed and confirmation of death is essential. 2) Inhalant anesthetics versus CO2 On page 21 at the bottom "In those species where aversion or overt escape behaviors have not been noted, exposure to high concentrations resulting in rapid loss of consciousness is preferred." But on page 26 in the paragraph before Advantages, "Inhaled halocarbon anesthetics have been proposed as alternatives to CO2 for rodent euthanasia. However, inhaled anesthetics also produce varying degrees of aversion in rodents..." Requested change/clarification: both methods can be used in an acceptable manner with rodents in a research setting. M1.6 Carbon Dioxide, Page 26: "If animals need to be combined, they should be of the same species..." S2.2.2.1 Inhaled Agents, Page 48: "If euthanasia cannot be conducted in the home cage, chambers should be emptied and cleaned between uses." Requested change/clarification: clarify that an accepted and common practice is to group animals for euthanasia as long as this occurs immediately prior to euthanasia and each animal has the ability to make normal postural adjustments. Further clarify, when euthanizing successive groups of animals that have been combined into the same cage/container, a new/unused cage/container would be used with each group or the euthanizing cage/container should be cleaned between uses to remove the potential distress secondary to remaining pheromones, etc. | M2.18 Sodium Hypochlorite Use of Sodium Hypochlorite (Bleach); Inconsistency between M2.18 and M2.20 M2.18 says bleach is acceptable (with criteria) for early embryonic and larval stages of zebrafish. M2.20 says "cleaning agents" are unacceptable. Requested change/clarification: clarify to say "Cleaning agents, with the exception of bleach, are unacceptable. M2.19 Formaldehyde States "formaldehyde is unacceptable as a first step or adjunctive method of euthanasia." Section S2.1 (Laboratory Animals - General Considerations, page 48) states "Research needs may also require the use of an adjunctive method (e.g., bilateral thoracotomy, exsanguination, perfusion with fixatives, injection of potassium chloride). The application of such adjunctive methods is acceptable when the animal is fully anesthetized." Section S2.3.2 (Laboratory Dogs, Cats, NHPs, page 50) states "Research needs may also require the use of an adjunctive method (e.g., bilateral thoracotomy, exsanguination, perfusion with fixatives, injection of potassium chloride). The application of such adjunctive methods is acceptable when the animal is fully anesthetized Requested change/clarification: clarify that in a research setting the use of perfusion with fixatives as an adjunctive method of is acceptable. | S2.2.4.2.2 Physical Methods 1) Use of Freezing for Fetuses; Page 50 "The gradual cooling of fetuses and altricial neonates is acceptable with conditions. As cold surfaces can cause tissue damage and presumably pain, the animals should not come in direct contact with ice or precooled surfaces...Fetuses that are believed to be unconscious and altricial neonates < 5 days of age that do not have sufficient nervous system development to perceive pain may be quickly killed by rapidly freezing in liquid N2." Requested change/clarification: clarify that rodent fetuses and certain altricial neonates do not have sufficient nervous system development to perceive pain and therefore may be euthanized by rapid freezing with liquid nitrogen. 2) Cervical dislocation; pages 38 & 50 Page 50: "Cervical dislocation...is acceptable with conditions for fetal and neonatal mice and rats." Page 38 states: "manual cervical dislocation is acceptable with conditions for euthanasia of small birds, poultry, mice, rats weighing < 200 g, and rabbits". Requested change/clarification: clarify that cervical dislocation is acceptable for fetal, neonatal and certain adult research animals. S2.4.1 & S2.4.3.1 Laboratory Rabbits Inhaled Agents; page 50 "Rabbits will struggle and breath-hold when confronted with any unpleasant or unfamiliar odors. This makes most inhaled methods difficult to use in rabbits without premedication...Although rabbits breath-hold when confronted with unpleasant odors animals already under anesthesia may be euthanized by an overdose of [inhalant] anesthetic." Requested change/clarification: clarify that rabbits can be euthanized with an overdose of inhalant anesthetic regardless of how the animal was initially induced to reach general anesthesia. | ||||||
| 04/30/2013 9:11 PM | Comment 4 Part II - Methods of Euthanasia: M3. Physical Methods.pdf [not accessible: error in file upload] | ||||||||||
| 04/24/2013 4:31 PM | Euthanex Corporation | Bethlehem, PA 18015 | If managed properly, rabbits (of any size or breed) do not need to be sedated or anesthetized prior to being euthanized by CO2. Properly sized chambers and regulated flows of CO2 can humanely (without pain, stress or distress) euthanize rabbits. | ||||||||
| 04/22/2013 3:13 PM | Covance Laboratories, Inc | Madison, WI | M1.6 Carbon Dioxide: CO2 euthanasia of rodents. I have concerns for the slow-fill method of CO2 to rodents. I have compared the slow-fill method to a rapid fill-method in mice. It is my impression that there is much more distress at the 30% fill rate compared to the 80% fill rate tested by my technicians. The clinical signs are similar, however, the animals at 30% flow rate show these signs for 2.5 minutes as opposed to ~55 seconds with the faster fill rate of 80%. The animals clearly showed signs of distress such as tachypnea, labored respiration, open mouth breathing along with ataxia and sternal recumbency. These signs were prolonged in the slow-fill method as compared to the rapid-fill rate. With the 30% fill rate, mice exhibited clear nasal discharge likely due to pulmonary edema at death. Examination of the lung tissue for histological evaluation showed normal pink colored lungs in the rapid-fill method and reddened hemorrhagic lungs in the slow-fill method. I can understand the concern for nociceptor pain upon placing an animal in a charged chamber but comparing a death that occurs within one minute in an 80% fill rate to a prolonged death that lasted greater than 2.5 minutes in a chamber with a 30% fill rate seems far more humane. | ||||||||
| 04/13/2013 5:33 PM | Bat World Sanctuary | Mineral Wells, TX | M1.6 Carbon Dioxide Use of CO2 for Euthanasia of Insectivorous Bats The 2013 Guidelines for Humane Euthanasia address the use of CO2 in great detail, with a general recommendation indicating that "CO2 is acceptable with conditions for euthanasia in those species where aversion or distress can be minimized". This broadly implies that any species not specifically excluded may be euthanized in accordance with the techniques outlined in the Guidelines. It is Bat World Sanctuary's position that insectivorous bats must be specifically identified as a species for which the use of CO2 is unacceptable. Because most bat species live in areas with high concentrations of CO2, they are naturally resistant to CO2. They may not display aversive or distress reactions when exposed to high volumes of CO2; however, in these conditions they may enter a torpid state which, to the inexperienced operator, may be mistaken for cessation of life. As a result, animals may be necropsied or incinerated while still alive - which is clearly contradictory to the intent of the Guidelines. Bat World Sanctuary recommends the use of inhalant anesthetics such as Isoflurane, as described in the Guidelines, for the euthanasia of insectivorous bats. When properly induced, bats will quickly succumb to the CNS depressant effects of Isoflurane, and death typically ensues in less than two minutes. There is little or no distress if proper techniques are used. The bat is placed inside a padded pouch in a small container. The Isoflurane is applied to gauze or cotton inside a plastic cylinder, which is placed near the opening of the pouch. The top of the container is closed and the bat is left undisturbed for a minimum of 30 minutes. |
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