A humane endpointHumane 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. can be defined as:

‘the earliest indicator in an animal experiment of (potential) 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/or 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. that, within the context of moral justification and scientific endpoints to be met, can be used to avoid or limit pain and/or distress by taking actions such as humane killing or terminating or alleviating the pain and distress’ (Hendriksen and Morton, 1999).

Some elements of this definition can be further explained as follows:

• ‘….potential pain….’ (Hendriksen): indicates that also non-clinical endpoints might be used e.g. pre-clinical parameters such as hormone level changes, biochemical parameters or gene up/down regulations as an indicator for pain/distress later on in the disease process or even physiological parameters such as induction of antibody titres.
• ‘…within the context of the scientific endpoints….” (Wallace, Hendriksen): applying 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. should always be balanced against the scientific endpoint(s).
• ‘….taking actions such as…’ (CCAC, Hendriksen): alleviation of pain/distress or terminating the painful/stressful procedure are also considered to be a humane endpoint.

The following conclusions can be drawn from this definition. A humane endpoint:

• Not necessarily means the humane killing of the animal, but could also result in interventions to alleviate the stressful/painful experimental procedure (e.g. performing surgery) or providing 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)..
• Is not necessarily based on clinical signs but could also start from pre-clinical signs or from physiological or molecular biomarkers predictive of pain/distress later on in the disease process.
• Should be balanced against the scientific endpoints to be met. Thus, pain and distress might be intrinsic to a certain experimental model (e.g., arthritisArthritis An inflammation of the joint. For some arthritis research purposes, a similar condition can be induced artificially in laboratory animals by injecting Freund’s complete adjuvant into the base of the tail.). However, in this case the humane endpoint should never be beyond the scientific endpoint.
• Should never be beyond the level of moral justification.

A humane endpoint can be considered as a possible 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. alternative for those experiments that involve pain and discomfortDiscomfort A state of pain and distress in laboratory animals. to the animals.

Biomedical research areas with relatively high percentages of pain and distress are 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, toxicity studies, vaccine potency studies, infectious disease studies and autoimmune disease studies.

Applying humane endpoints should seriously be considered when animal experiments involve severe pain and 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..

Above the mentioned definition, several other definitions are being used to describe a humane endpoint, like for example the following definitions of the OECD, the CCAC and Wallace:

• The earliest indicator in an animal of pain, distress, suffering, or impending death on the basis of which an animal is killed (definition OECD);
• “The point at which an experimental animal’s pain and/or distress is terminated, minimized or reduced, by taking actions such as killing the animal humanely, terminating a painful procedure, or giving treatment to relieve pain and/or distress” (definition CCAC).
• ‘The limits placed on the amount of pain and distress any laboratory animal will be allowed to experience within the context of the scientific endpoints to be met’ (Wallace 2000)