OECD

The OECD (Organisation for Economic Co-operation and Development) defines a humane endpoint as follows: the earliest indicator in an animal 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., 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., sufferingSuffering A negative emotional state which derives from adverse physical, physiological and psychological circumstances, in accordance with the cognitive capacity of the species and of the individual being, and its life experience., or impending death on the basis of which an animal is killed.

The purpose of establishing 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. in toxicology studies is to accurately predict severe pain, intense stressStress An animal’s biologic response in trying to deal with a threat to its internal equilibrium (homeostasis) by internal and external stressors. A failure to do so may lead to ‘distress’ resulting in an inability to cope, leading to poor welfare., suffering, or an impending death, before the animal experiences these consequences.

The OECD published a report in the year 2000, called “OECD Guidance document on the recognition, assessment, and use of clinical signs as humane endpoints for experimental animals used in safety evaluation”. Its purpose is to limit distress in regulatory toxicity studies.

Among the conditions for correctly observing distress in experimental animals, the OECD requires:

  • awareness of potential clinical signs and conditions, and the ability to identify them;
  • careful and regular observation (clinical scoring);
  • frequent determining the discomfortDiscomfort A state of pain and distress in laboratory animals. (pain/distress);
  • awareness of indications for an irreversible condition likely to lead to further deterioration
  • involvement of all members of the study team and awareness of their roles and responsibilities

Observations/ inspection health condition:

  • observation frequency depends on the animal species, previously identified abnormalities, the nature and mechanism of toxic effects, and the intended study objectives (weighing at least weekly);
  • animals should preferably be observed during their active period;
  • increased observation in those experiments where direct effects are expected:
    • intensively the first half hour;
    • special attention during the first four hours;
    • periodically during the first 24 hours;
    • after 24 hours at least daily.

The following clinical signs may indicate that an animal is experiencing significant pain and distress:

  • abnormal vocalizationVocalisation Sounds produced by animals that may or may not (ultrasound, infrasound) be audible to humans. The rat associates 20 kHz sounds with fear or pain and 50 kHz sounds with pleasant situations.
  • abnormal aggressiveness
  • abnormal posture
  • abnormal reaction to handlingHandling Manipulating the animal, picking it up, holding it, and restraining it.
  • abnormal movements
  • self-induced traumaTrauma Tissue injury, damage.
  • open wounds or skin ulcerationUlceration Sore. Deep skin or mucous membrane tissue loss below the regenerating layer of skin cells. Can be caused by wound infection, poor local perfusion (e.g., tumor), local nutritional deficiencies. Ulcers tend to heal slowly, in which case the animal should be killed.
  • breathing difficulties
  • corneal ulceration (the corneaCornea The transparent part of the membrane (sclera) which surrounds the eyeball. is very sensitive to pain, and according to some, stages that precede ulceration are painful, but not the ulceration itself)
  • bone fractures
  • reluctance to move
  • abnormal external appearance
  • rapid weight loss or emaciationEmaciation Severe weight loss. or severe 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).
  • significant bleeding
  • or any other factors that suggests that the animal may be in pain or distress.

Guidelines for implementation of humane endpoints:

  • obvious enduring pain/distress;
  • recovery not likely;
  • health condition affect the study results;
  • definitions clinical signs;
  • instruction poster for an animal laboratory.