The objective of these chronic toxicity studies is to characterize the profile of
a substance in a mammalian species (primarily rodents) following prolonged and repeated
The Test Guideline focuses on rodents and oral administration. Both sexes should be
used. For rodents, at least 20 animals per sex per group should normally be used at
each dose level, while for non-rodents a minimum of 4 per sex per group is recommended.
At least three dose levels should be used in addition to the concurrent control group.
Frequency of exposure normally is daily, but may vary according to the route chosen
(oral, dermal or inhalation) and should be adjusted according to the toxicokinetic
profile of the test substance. The duration of the exposure period should be 12 months.
The study report should include: measurements (weighing) and regular detailed observations
(haematological examination, urinalysis, clinical chemistry), as well as necropsy
procedures and histopathology.