Roberta F. White, Ph.D. - US grants

A computerized measure of behavioral function with known validity as a measure of brain behavior function, which can be used.in epidemiologic investigations of occupational and environmental exposures, has yet to be identified. The Neurobehavioral Evaluation System (NES) is a battery of computer-assisted behavioral tests developed for such epidemiologic settings. The sensitivity of some subtests of the NES to known neurotoxins has been shown in a number of studies; i.e., subjects with acute experimental or chronic occupational exposure to known neurotoxins show impaired performance relative to controls on certain NES subtests. However, it is difficult to interpret the meaning of these findings, because the brain-behavior relationships which may exist for the NES subtests have not yet been identified. Impaired performance on specific NES subtests or groups of subtests may not reflect cerebral damage at all: It may be due to peripheral sensory loss. If it does reflect cerebral dysfunction, it may do so because of damage to any of several parts of the brain. This lack of specificity regarding brain-behavior relationships is not true of many other behavioral tests used in occupational settings. Several of the tests included in the WHO/NIOSH core test battery , (Johnson, 1987) for example, have been used extensively in populations of patients with known brain damage and the neurobehavioral/neuropsychological meaning of these tests have been well described (Lezak, 1983; Grant and Adams, 1986). In order to begin to develop a similar level of knowledge concerning the cerebral correlates of impaired performance on the NES subtests, the battery will be validated on 3 groups of neurological patients and 2 control groups. This will allow us to determine the sensitivity of each NES subtest to known neuropathology, to determine if there are patterns of performance on the NES subtests which predict known neurologic disorders, and, ultimately, to validate the NES as a measure of CNS function. If the NES is shown to be a valid predictor of specific types of neuropathology, it will greatly enhance the battery's theoretical utility in epidemiologic studies of behavioral neurotoxicology and will provide a new clinical tool for the evaluation of patients with possible brain damage secondary to neurotoxic exposure.

DESCRIPTION (provided by applicant): Due to endemic contamination of the environment in areas of South Africa by pesticides used in agriculture and for disease prevention, the neurotoxicity of these substances is of major concern as a health hazard among inhabitants of rural areas. Several classes of pesticides are known to be neurotoxic in adult populations with occupational and environmental exposures to them and some pesticides are well established as endocrine disruptors, affecting sexual maturation during prenatal growth and in children. However, very little is known about the effects of these chemicals on central nervous system (CNS) development in utero and in early childhood. Knowledge concerning the neurodevelopmental effects of these substances is of critical importance because of the fragility of the brain in early development, the known structural and neurochemical effects of pesticides on the brain, and potential neurotoxicity during development secondary to endocrine disruption. Children in South Africa are particularly susceptible to the effects of environmental exposure to pesticides in utero because of maternal exposure to pesticides. This work has important public health implications in South Africa, including documentation of the severity and types of pesticide exposure identified through biological and environmental assessments and the acquisition of new knowledge concerning the neurodevelopmental effects of exposures to these chemicals. Such knowledge will be important for public health policy in South Africa, including development of primary prevention and educational programs designed to reduce exposure and adverse health effects. It was also be applicable to development of public health policy in other parts of the world, including the United States. Longitudinal investigation of the effects of prenatal pesticide exposure on neurodevelopment of children in South Africa is the long-range goal of the work proposed in this application for pilot funding. The procedures described in the proposal will be pursued in order to develop the collaborative mechanisms, pilot methods, and feasibility studies that will facilitate the design and completion of such an investigation. The communities of interest are rural areas in KwaZulu-Natal, where pesticide contamination is widespread. Collaboration between district health personnel, scientists at the University of Cape Town and the University of Natal in South Africa, and investigators at Boston University is key to the project.