Methods to identify and characterize developmental neurotoxicity for humanhealth risk assessment. II: Neuropathology

Neuropathologic assessment of chemically induced developmental alterations in the nervous system for regulatory purposes is a multifactorial, complex process. This calls for careful qualitative and quantitative morphologic st udy of numerous brains at several developmental stages in rats. Quantitativ e evaluation may include such basic methods as determination of brain weigh t and dimensions as well as the progressively more complex approaches of li near, areal, or stereologic measurement of brain sections. Histologic evalu ation employs routine stains (such as hematoxylin and eosin), which can be complemented by a variety of special and immunohistochemical procedures. Th ese brain studies are augmented by morphologic assessment of selected perip heral nervous system structures. Studies of this nature require a high leve l of technical skill as well as special training on the pari of the patholo gist. The pathologist should have knowledge of normal microscopic neuroanat omy/neuronal circuitry and an understanding of basic principles of developm ental neurobiology, such as familiarity with the patterns of physiologic or programmed cell death (apoptosis) expected at those developmental stages t o be examined.