Neuropathologic Screening in Rodent and Other Species

In screening for neurotoxicity, the purpose of neuropathologic evaluation is to detect and characterize morphologic changes and to demonstrate their absence at low levels or in cases showing only functional effects. Attempts to identify the cellular targets of neurotoxicity are made in pattern-finding studies by thorough examination of selected individuals shortly after exposure to high levels of the suspected toxicants. When the target areas and suitable investigative techniques have been established, a screening for dose-effect relationship and no-effect level can be carried out. Methods of examination routinely used in toxicologic pathology are insufficient to detect subtle neural lesions; special techniques, including perfusion fixation, embedding in plastic, isolation of nerve fibers, and quantitation, are required. The areas of the nervous system to be examined are selected according to functional signs and mechanisms of action. Despite the presence of metabolic and anatomic interspecies differences, the occurrence of neurotoxicity in any animal model may be relevant to humans.