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OLS Field Name OLS Field Data
Main Title Repeated Inhibition of Cholinesterase by Chlorpyrifos in Rats: Behavioral, Neurochemical and Pharmacological Indices of Tolerance.
Author Bushnell, P. J. ; Kelly, K. L. ; Ward, T. R. ;
CORP Author Health Effects Research Lab., Research Triangle Park, NC. Neurotoxicology Div. ;ManTech Environmental Technology, Inc., Research Triangle Park, NC.
Publisher cJul 94
Year Published 1994
Report Number EPA/600/J-94/535;
Stock Number PB95-148979
Additional Subjects Dursban ; Cholinesterase inhibitors ; Drug tolerance ; Organophosphate insecticides ; Neurochemistry ; Animal behavior ; Dose-response relationships ; Rats ; Muscarinic receptors ; Cholinergic receptors ; Dopamine agents ; Cholinergic agents ; Conditioned responses ; Hypothermia ; Oxotremorine ; Visual performance ; Brain ; Quinuclidinyl benzilate ; Reprints ;
Holdings
Library Call Number Additional Info Location Last
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Status
NTIS  PB95-148979 Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy. NTIS 03/06/1995
Collation 13p
Abstract
Daily subcutaneous (s.c) injections of the organophosphate diisopropylfluorophosphate caused prolonged inhibition of cholinesterase (ChE) activity in whole blood and brain and downregulation of muscarinic receptors in the central nervous system; these changes were accompanied by progressive, persistent deterioration of working memory and motor function. Further, a single s.c. injection of the organophosphate insecticide chlorpyrifos (O,O',-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothionate, CPF), caused neurochemical changes of the same magnitude and duration, but transient impairment of working memory and motor slowing. In the present study, weekly injections of CPF (0, 15, 30 or 60 mg/kg s.c.) inhibited ChE activity in whole blood of rats by 60% to 90% after 5 weeks; the highest dose also induced tremor, working memory impairment and motor slowing in daily delayed matching-to-position/visual discrimination tests. Reducing the CPF injection frequency to every other week relieved the inhibition of whole blood ChE activity (to 50%-75% of control) and ameliorated all the behavioral deficits. These studies indicate that inhibition of ChE activity by repeated injection of CPF produces a constellation of behavioral effects not evident after a single CPF treatment, even though both treatment regimens caused prolonged inhibition of ChE activity and downregulation of central muscarinic receptors.