The test substance is administered in graduated doses to several groups of males and females. Males should be dosed for a minimum of four weeks; females should be dosed throughout the study (approximately 54 days). Normally, matings “one male to one female” should be used in this study.
This Test Guideline is designed for use with the rat. It is recommended that the test substance be administered orally by gavage. This should be done in a single dose daily to the animals using a stomach tube or a suitable intubation cannula. Each group should be started with at least 10 animals of each sex. Generally, at least three test groups and a control group should be used. Dose levels should be selected taking into account any existing toxicity and (toxico-) kinetic data available. The limit test corresponds to one dose level of at least 1000 mg/kg body weight. The results of this study include measurements (weighing, food/water consumption) and daily detailed observations (including sensory reactivity to stimuli), preferably each day at the same time, as well as gross necropsy and histopathology. The findings of this toxicity study should be evaluated in terms of the observed effects, necropsy and microscopic findings. The evaluation will include the relationship between the dose of the test substance and the presence or absence of observations. Because of the short period of treatment of the male, the histopathology of the testis and epididymus must be considered along with the fertility data, when assessing male reproduction effects.
