UKCCCR

The Guidelines for the WelfareWelfare A complex and dynamic internal state that includes: successful biologic functioning, positive experiences, and absence of negative conditions. The animal adapts effectively to internal needs and external stimuli and maintains a good mental state. of Animals in Experimental NeoplasiaNeoplasia New growth; uncontrolled growth of cells to form a benign or (harmful) malignant tumor. have been developed by the United Kingdom Coordinating Committee of CancerCancer A general term for a collection of diseases characterized by abnormal, uncontrolled growth of tissue cells or blood cells. Cancer may develop in specific tissues or cells, or it may spread from the original tumor to other parts of the body, where it can cause growth of secondary tumors (metastases). Research (UKCCCR).

This ad hoc committee was convened in 1988 by the major organisations in the United Kingdom involved in funding cancer research, with the aim of developing guidelines for laboratory animal researchers in experimental neoplasia. The second, revised version of these guidelines was published in 1997 and can be found here.

Below are sections of the guideline that are relevant to the application of humane endpointsHumane endpoint The moment in the experiment at which pain and/or distress experienced by the investigational animal is ended or alleviated by either killing the animal humanely or by discontinuing the procedure..

UKCCCR Guidelines for the Welfare of animals in Experimental Neoplasia

General recommendations:

  1. All involved staff should be aware of their individual legal and ethical responsibilities  and a clear chain of responsibility and consultation should be established.
  2. Determine possible disadvantageous (welfare) effects which can occur.
  3. The degree of painPain The negative sensory or emotional experience that indicates awareness in the animal of injury or the threat of injury to the body. This negative experience induces changes in an animal’s behavior and physiology, intended to limit the effect of, or avoid the injury, to reduce the chances of repeated injury and to promote recovery. and distressDistress It indicates a disadvantageous environment in which the animal is no longer able to adapt in a biologically successful manner to the stressors to which it is exposed. One speaks of distress when the level or the duration of stress are such that significant changes in biological function are required to survive. must be minimised by judicious use of anaesthetics and analgesicsAnalgesics Medication administrated in order to suppress pain (analgesia). There are several classes of analgesics, such as opiates (e.g., buprenorphine), local analgesics (e.g., lidocaine), and NSAIDs (e.g., ketoprofen)., the refinementRefinement The principle of limiting or reducing the severity of scientific procedures by treating laboratory animals in such a way that potential pain, distress and other deleterious effects inflicted on the animals are avoided, alleviated, or minimized. It may also be a way in which their welfare can be improved e.g., through enrichment of their husbandry. In laboratory animal care, Refinement is known as one of the 3Rs in the Three Rs ethical framework. of experimental techniques, and the early implementation of humane end points.
  4. Where certain procedures cause particular concern, these must be addressed  specifically in the Project Licence application.
  5. Execute pilot experiments.
  6. Stimulate researchers to publish improvements in humane endpoints.
  7. The design of all experiments should meet the highest scientific standards.

APPENDIX 3 – Humane endpoints and limiting clinical signs

Experimental protocols and severity limits in project licences should specify early experimental or humane end points requiring appropriate intervention. Criteria for such endpoints should be determined before the study commences. The following clinical signs may be useful:

  1. Persistent anorexiaAnorexia Loss of appetite. This is usually a consequence of a serious disease process, such as late-stage cancer or infection. Anorexia will cause (further) weight loss. or dehydrationDehydration “Drying out” because of reduced fluid intake or excessive fluid loss. The degree of dehydration can be determined by gently pinching and twisting the skin and releasing it, allowing the skin to fold and flatten (the turgor test)..
  2. Consistent or rapid body weight loss of 20% maintained for 72 hours.
  3. Unable to maintain an upright position or to move.
  4. Muscle atrophyAtrophy A decline in the nutritional state of an organ, causing it to wither or shrink. or emaciationEmaciation Severe weight loss..
  5. MoribundMoribund The state of extreme weakness of an animal when death is imminent. This phase is irreversible and is characterized by signs such as superficial, slowed or irregular breathing, muscle weakness or tremor, absence of a response to external stimuli, cyanosis, and coma., lethargicLethargy 1. somnolence; 2. state of disinterest and inactivity. or failure to respond to gentle stimuli.
  6. HypothermiaHypothermia A decreased in body temperature (mouse <36.5 °C/97.7 °F; rat <37.5 °C/99.5 °F). The extremities (ears and paws) may be white and are cold to the touch..
  7. Unconscious or comatose.
  8. Bloodstained or mucopurulent discharge from any orifice.
  9. Laboured respiration – particularly if accompanied by nasal discharge and/or cyanosisCyanosis Bluish discoloration of the skin and mucous membranes due to a lack of oxygen in the blood (reduced oxygenation)..
  10. Enlarged lymph nodes or spleen.
  11. Anaemia
  12. Ulcerated tumoursTumor Neoplasm, new growth. Is predicated upon autonomous growth of cells or tissues into benign or malignant tumors. or large tumours that interfere with normal movement.
  13. Significant abdominal distension or where the ascitesAscites An accumulation of fluid in the abdominal cavity, for instance as a result of a tumor mass. By injecting cells that produce antibodies (hybridoma cells) into the abdominal cavity, monoclonal antibodies can be harvested from the ascites thus induced, but this method is prohibited or discouraged in several European countries because in vitro antibody production is a good alternative. burden exceeds 10% of the baseline bodyweight.
  14. IncontinenceIncontinence The inability to retain feces and/or urine, e.g., caused by a spinal cord lesion. or prolonged diarrhoea.

Where any one of these signs is present in a single animal then the animal should be killed immediately and any remaining animals observed closely for changes in their condition.