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BEHAVIORAL AND NEUROCHEMICAL OUTCOMES OF REPEATED ORAL ADMINISTRATION OF CHLORPYRIFOS IN POSTNATAL/JUVENILE RATS.
Citation:
Moser, V C., D L. Hunter, R S. Marshall, K. L. McDaniel, AND P. M. Phillips. BEHAVIORAL AND NEUROCHEMICAL OUTCOMES OF REPEATED ORAL ADMINISTRATION OF CHLORPYRIFOS IN POSTNATAL/JUVENILE RATS. Presented at Society of Toxicology, San Francisco, CA, March 25-29, 2000.
Description:
Concern has been raised regarding potential adverse effects on the nervous system following childhood exposure to chlorpyrifos (O,O-diethyl-O-3,5,6-trichloro-2-pyridyl-phosphorothioate). This study examined the outcomes of daily oral dosing with chlorpyrifos, from early postnatal life to adolescence. Male and female Long-Evans rats were dosed with chlorpyrifos 0, 2, or 6 mg/kg/day, 5 days per week, beginning on postnatal day 11 (PND11) and ending PND46 (total, 26 doses). Brains were collected from a subset of rats on PND18 and PND41 (23 hours after the previous dose), and cholinesterase (ChE) activity, muscarinic receptor binding (QNB as ligand), and brain weights were evaluated. The remaining rats were tested using a functional observational battery and motor activity on PND17, 27, 40, 81, and 123; thus, tests were conducted both during and after the dosing period. At the end of dosing, a step-through passive avoidance task was used to evaluate learning and memory, and oxotremorine was administered to determine the functional status of the cholinergic system. Body and brain weights were not altered. ChE was inhibited in a dose-dependent manner in both blood (35-73% inhibition) and brain (7-55% inhibition). Somewhat less inhibition was detected on PND41, in spite of ongoing dosing. Receptor downregulation was suggested by decreased QNB binding (12% lower) in the high-dose groups (both sexes), and an attenuation of oxotremorine-induced hypothermia (females). Passive avoidance performance was not altered. Increased activity (females) and excitability/reactivity (males) were observed at PND17. On PND27, only depressed responses to sensory stimuli were evident. Most effects were obtained only in the high-dose group, and gender differences were observed; the low dose produced behavioral effects only in females. Persistent neurobehavioral alterations, up to PND123, were not detected in these rats. (This abstract does not necessarily reflect EPA policy)