The OECD (Organisation for Economic Co-operation and Development) defines a humane endpoint as follows: the earliest indicator in an animal of pain, distress, suffering, or impending death on the basis of which an animal is killed.

The purpose of establishing humane endpoints in toxicology studies is to accurately predict severe pain, intense stress, 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 determing the discomfort (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: 

  • frequency of observation depends on the animal species, previous diagnosed  deviations, the toxic effects and the objectives;
  • animals should preferably be observed during their active period;
  • increased observation by experiments with signs expected immediately:
    • 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 vocalization
  • abnormal aggressiveness
  • abnormal posture
  • abnormal reaction to handling
  • abnormal movements
  • self-induced trauma
  • open wounds or skin ulceration
  • difficulties in respiration
  • corneal ulceration (the cornea 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 emaciation or severe dehydration
  • significant bleeding
  • or any other factor 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.