The animals are kept under the experimental housing and feeding conditions for at least five days prior to the test. Before the test healthy young animals are randomised and assigned to the treated and control groups.
1.6.1.
Experimental animals
Based upon the results of previously conducted studies other species (rodent or non-rodent) may be used. Commonly used laboratory strains of young healthy animals should be employed and dosing should begin as soon as possible after weaning.
At the commencement of the study the weight variation in the animals used should not exceed ± 20 % of the mean value. Where a sub-chronic oral study is conducted as a preliminary to a long-term study, the same species/breed and strain should be used in both studies.
1.6.2.
Number and sex
For rodents at least 100 animals (50 female and 50 male) should be used at each dose level and concurrent control group. The females should be nulliparous and non-pregnant. If interim sacrifices are planned the number should be increased by the number of animals scheduled to be sacrificed before the completion of the study.
1.6.3.
Dose levels and frequency of exposure
At least three dose levels should be used in addition to the concurrent control group. The highest dose level should elicit signs of minimal toxicity, such as a slight depression of bodyweight gain (less than 10 %), without substantially altering the normallifespan due to effects other than tumours.
The lowest dose level should not interfere with normal growth, development and longevity of the animal or produce any indication of toxicity. In general, this should not be lower than 10 % of the high dose.
The intermediate dose(s) should be established in a mid-range between the high and low doses.
The selection of dose levels should take into account data from preceding toxicity tests and studies.
Frequency of exposure is normally daily.
If the chemical is administered in the drinking water or mixed in the diet it should be continuously available.
1.6.4.
Controls
A concurrent control group which is identical in every respect to the treated groups, except for exposure to the test substance, should be used.
In special circumstances, such as in inhalation studies involving aerosols or the use of an emulsifier of uncharacterised biological activity in oral studies, an additional control group which is not exposed to the vehicle should be used.
1.6.5.
Route of administration
The three main routes of administration are oral, dermal and inhalation. The choice of the route of administration depends upon the physical and chemical characteristics of the test substance and the likely route of exposure in humans.
1.6.5.1. Oral studies
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