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GESTATIONAL EXPOSURE TO CHLORPYRIFOS: QUALITATIVE AND QUANTITATIVE NEUROPATHOLOGICAL CHANGES IN THE FETAL NEOCORTEX.
Citation:
Lassiter, T. L., L. D. White, S. Padilla, AND S Barone. GESTATIONAL EXPOSURE TO CHLORPYRIFOS: QUALITATIVE AND QUANTITATIVE NEUROPATHOLOGICAL CHANGES IN THE FETAL NEOCORTEX. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
This study investigated the qualitative and quantitative neuropathological changes that occur in the fetal brain following gestational exposure to chlorpyrifos [(O,O'diethyl O-3,5,6-trichloro-2-pyridyl) phosphorothionate], a commonly used organophosphorus insecticide. Two cohorts of pregnant rats were orally dosed daily with chlorpyrifos in corn oil on gestational days 14-18. Cohort A consisted of a time course study of fetuses collected at 2, 5, 10, and 24 hours after the last dose of chlorpyrifos (0 or 7 mg/kg/day). Cohort B is a replication of Cohort A and includes a dose response component at 5 hours (0, 1, 3, 5, and 7 mg/kg/day of chlorpyrifos). Fetal brain total cholinesterase, acetylcholinesterase, or butyrylcholinesterase activities were 70, 75, or 53 % of control activity 5 hours after the last 7 mg/kg dose of chlorpyrifos. Fetal brain sections stained with cresyl violet for neuropathological assessments showed overt pathology in the neocortex, consisting of vascular alterations, disorganized migratory waves, ectopic cells, neuropathological holes, and qualitative thinning of the ventricular zone and cortical plate. Neuropathological changes were evident at dosages as low as 1 mg/kg/day. Stereology used to quantify the volume of the ventricular zone, subventricular zone, and cortical plate in the fetal neocortex showed limited treatment-related changes in the volume of the subventricular zone at 7 mg/kg/day but no changes in other neocortical laminae. We conclude that repeated, gestational exposure to chlorpyrifos not only inhibits cholinesterase activity in the fetal brain, but also causes neuropathological changes in the fetal neocortex. This abstract does not reflect EPA policy.