Division 3 Severe:

toxicity testing where death is the end-point, or fatalities are to be expected and severe pathophysiological states are induced. For example, single dose acute toxicity testing (see OECD testing guidelines);

testing of device where failure may cause severe pain, distress or death of the animal (e.g. cardiac assist devices);

vaccine potency testing characterised by persistent impairment of the animal’s condition, progressive disease leading to death, associated with long-lasting moderate pain, distress or suffering;

irradiation or chemotherapy with a lethal dose without reconstitution of the immune system, or reconstitution with production of graft versus host disease;

models with induction of tumours, or with spontaneous tumours, that are expected to cause progressive lethal disease associated with long-lasting moderate pain, distress or suffering. For example tumours causing cachexia, invasive bone tumours, tumours resulting in metastatic spread, and tumours that are allowed to ulcerate;

surgical and other interventions in animals under general anaesthesia which are expected to result in severe or persistent moderate postoperative pain, suffering or distress or severe and persistent impairment of the general condition of the animals. Production of unstable fractures, thoracotomy without adequate analgesia, or trauma to produce multiple organ failure;

organ transplantation where organ rejection is likely to lead to severe distress or impairment of the general condition of the animals (e.g. xenotransplantation);

breeding animals with genetic disorders that are expected to experience severe and persistent impairment of general condition, for example Huntington’s disease, Muscular dystrophy, chronic relapsing neuritis models;

use of metabolic cages involving severe restriction of movement over a prolonged period;

inescapable electric shock (e.g. to produce learned helplessness);

complete isolation for prolonged periods of social species e.g. dogs and non-human primates;

immobilisation stress to induce gastric ulcers or cardiac failure in rats;

forced swim or exercise tests with exhaustion as the end-point.