Division 1.5.1 Number and sex animals

When the study is conducted as a separate study, at least 20 animals (10 females and 10 males) should be used in each dose and control group for the evaluation of detailed clinical and functional observations. At least five males and five females, selected from these 10 males and 10 females, should be perfused in situ and used for detailed neurohistopathology at the end of the study. In cases where only a limited number of animals in a given dose group are observed for signs of neurotoxic effects, consideration should be given to the inclusion of these animals in those selected for perfusion. When the study is conducted in combination with a repeated dose toxicity study, adequate numbers of animals should be used to meet the objectives of both studies. The minimum numbers of animals per group for various combinations of studies are given in Table 1. If interim kills or recovery groups for observation of reversibility, persistence or delayed occurrence of toxic effects post treatment are planned or when supplemental observations are considered, then the number of animals should be increased to ensure that the number of animals required for observation and histopathology are available.