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PATTERN OF CHOLINESTERASE INHIBITION IN ADULT, MALE RATS CHRONICALLY EXPOSED TO DIETARY CHLORPYRIFOS.
Marshall, R S., D L. Hunter, AND S. Padilla. PATTERN OF CHOLINESTERASE INHIBITION IN ADULT, MALE RATS CHRONICALLY EXPOSED TO DIETARY CHLORPYRIFOS. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Very little is known about the effects of chronic exposure to relatively low levels of anticholinesterase insecticides or how the effects of chronic exposure compare to higher, intermittent exposure of the same compound for the same duration. To that end, we exposed adult male rats to the anticholinesterase insecticide, chlorpyrifos (CPF)for one year at three levels of dietary exposure: 0,1,or 5 mg/kg/day. In addition, those groups also received a bolus dosage of CPF (i.e., "spiked" animals; 60 mg/kg initially and 45 mg/kg thereafter) in corn oil every two months; therefore there were 6 dosage groups, n=5/group. Animal tissues were taken for analysis during dosing (at 6 or 12 months) and also 3 months after dosing ceased (i.e. "recovery" animals). Tissues analyzed were retina, whole blood and components, diaphragm, and central nervous system (pons). In general, the groups receiving dietary CPF exposure only produced substantial cholinesterase (ChE) inhibition (80%) in the blood at 1 mg/kg/day and no inhibition in retina, pons, or diaphragm; the higher dosage (5 mg/kg) produced more blood inhibition and approximately 50% or less inhibition in the other tissues. One day after receiving the oral, spike dose, all three feeding (i.e., 0,1 or 5 mg/kg/day) groups showed more than 70% inhibition in each tissue. In the dietary exposure groups (unspiked), the ChE inhibition at 6 months was, in general, not different from the inhibition at 12 months, indicating that a steady state had been reached prior to 6 months. Three months after CPF dosing ended, ChE levels had returned to control levels in all groups. These data indicate that although chronic feeding with or without intermittent spiked dosages of CPF produces substantial ChE inhibition in a dose- and tissue-related manner, ChE activity recovers to normal within 3 months after dosing is ceased.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
CELLULAR AND MOLECULAR TOXICOLOGY BRANCH