Division 1.4.5 Administration of doses

The animals should be dosed with the test substance on a 7-days-a-week basis. The oral route of administration (diet, drinking water, or gavage) is preferred. If another route of administration is used, justification shall be provided, and appropriate modifications may be necessary. All animals shall be dosed by the same method during the appropriate experimental period. When the test substance is administered by gavage, this should be done using a stomach tube. The volume of liquid administered at one time should not exceed 1 ml/100 g body weight (0.4 ml/100 g body weight is the maximum for corn oil), except in the case of aqueous solutions where 2 ml/100 g body weight may be used. Except for irritant or corrosive substances, which will normally reveal exacerbated effects with higher concentrations, variability in test volume should be minimised by adjusting the concentration to ensure a constant volume at all dose levels. In gavage studies, the pups will normally only receive test substance indirectly through the milk, until direct dosing commences for them at weaning. In diet or drinking water studies, the pups will additionally receive test substance directly when they commence eating for themselves during the last week of the lactation period.

For substances administered via the diet or drinking water, it is important to ensure that the quantities of the test substance involved do not interfere with normal nutrition or water balance. When the test substance is administered in the diet either a constant dietary concentration (ppm) or a constant dose level in terms of the body weight of the animal may be used; the alternative used must be specified. For a substance administered by gavage, the dose should be given at similar times each day, and adjusted at least weekly to maintain a constant dose level in terms of animal body weight. Information regarding placental distribution should be considered when adjusting the gavage dose based on weight.