ToxSci Advance Access published online on August 4, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi274
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1 Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
* To whom correspondence should be addressed. 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. To that end, adult, male rats were fed an anticholinesterase insecticide, chlorpyrifos (CPF), for one year at three levels of dietary exposure: 0, 1, or 5 mg/kg/day (0+oil, 1+oil and 5+oil). In addition, half of each of these groups also received a bolus dosage of CPF ("spiked" animals; 60 mg/kg initially and 45 mg/kg thereafter) in corn oil every two months (0+CPF, 1+CPF, 5+CPF). Animals were analyzed after 6 or 12 months of dosing, and also three months after cessation of dosing (i.e. "recovery" animals) (six experimental groups with n=4-6/group/time point). Cholinesterase (ChE) activity was measured in retina, whole blood, plasma, red blood cells, diaphragm, and brain [pons, striatum and the rest-of-brain (referred to as "brain")]. Muscarinic receptor density was assessed in retina, pons, and brain, whereas dopamine transporter density, as well as the levels of dopamine and its metabolites, were assessed in striatum. ChE activity at 6 and 12 months was not different in any of the tissues, indicating that a steady state had been reached prior to 6 months. The 1+oil group showed ChE inhibition only in the blood, whereas the 5+oil group exhibited
Neurotoxicology
Neurochemical Effects of Chronic Dietary and Repeated High-Level Acute Exposure to Chlorpyrifos in Rats
2 Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711; Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
3 Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
4 Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Departments of Pharmacology, Neurology, and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
Stephanie Padilla, E-mail: Padilla.Stephanie{at}epa.gov
Abstract 
50% ChE inhibition in all tissues tested. One day after the bolus dose, all three groups (0+CPF, 1+CPF or 5+CPF) showed 70% ChE inhibition in all tissues. Muscarinic receptor density decreased only in the brain of the 5+oil and 5+CPF groups, whereas dopamine transporter density increased only at 6 months in all three spiked groups. Striatal dopamine or dopamine metabolite levels did not change at any time. Three months after CPF dosing ended, all endpoints had returned to control levels. These data indicate that although chronic feeding with or without intermittent spiked dosages with CPF produces substantial biochemical changes in a dose- and tissue-related manner, there are no persistent biochemical changes.
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