Division 2 Moderate:

frequent application of test substances which produce moderate clinical effects, and withdrawal of blood samples (> 10 % of circulating volume) in a conscious animal within a few days without volume replacement;

acute dose-range finding studies, chronic toxicity/carcinogenicity tests, with non-lethal end-points;

surgery under general anaesthesia and appropriate analgesia, associated with post surgical pain, suffering or impairment of general condition. Examples include: thoracotomy, craniotomy, laparotomy, orchidectomy, lymphadenectomy, thyroidectomy, orthopaedic surgery with effective stabilisation and wound management, organ transplantation with effective management of rejection, surgical implantation of catheters, or biomedical devices (e.g. telemetry transmitters, minipumps etc.);

models of induction of tumours, or spontaneous tumours, that are expected to cause moderate pain or distress or moderate interference with normal behaviour;

irradiation or chemotherapy with a sublethal dose, or with an otherwise lethal dose but with reconstitution of the immune system. Adverse effects would be expected to be mild or moderate and would be short-lived (< 5 days);

breeding of genetically altered animals which are expected to result in a phenotype with moderate effects;

creation of genetically altered animals through surgical procedures;

use of metabolic cages involving moderate restriction of movement over a prolonged period (up to 5 days);

studies with modified diets that do not meet all of the animals’ nutritional needs and are expected to cause moderate clinical abnormality within the time-scale of the study;

withdrawal of food for 48 hours in adult rats;

evoking escape and avoidance reactions where the animal is unable to escape or avoid the stimulus, and are expected to result in moderate distress.