Neurotoxicity study in rodents

This Test Guideline has been designed to obtain the information necessary to confirm or to further characterise the potential neurotoxicity of chemicals in adult animals. This Test Guideline is designed for use with the rat. It specifically addresses the daily oral administration, by gavage, (in the diet, in drinking water or by capsules) of the test substance. When the study is conducted as a separate study, at least 20 animals (10 females and 10 males) should be used in each dose. At least three dose groups and a control group should generally be used. Dose levels should be selected by taking into account any previously observed toxicity and kinetic data available for the test compound or related materials. The dosing regimen may be 28 days, subchronic (90 days) or chronic (1 year or longer). The procedures set out in this Test Guideline may also be used for an acute neurotoxicity study. 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), functional tests, and, at least, daily detailed observations (Ophthalmology, haematology, clinical biochemistry and histopathology). At least five males and five females, selected from test group, should be perfused in situ and used for detailed neurohistopathology at the end of the study. The findings of the study should be evaluated in terms of the incidence, severity and correlation of neurobehavioural and neuropathological effects (neurochemical or electrophysiological effects as well if supplementary examinations are included) and any other adverse effects observed.  Read more...