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COMPARISONS OF THE ACUTE EFFECTS OF CHOLINESTERASE INHIBITORS USING A NEUROBEHAVIORAL SCREENING BATTERY IN RATS
Citation:
Moser, V. COMPARISONS OF THE ACUTE EFFECTS OF CHOLINESTERASE INHIBITORS USING A NEUROBEHAVIORAL SCREENING BATTERY IN RATS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-96/052, 1995.
Description:
The clinical signs of intoxication produced by cholinesterase inhibitors, many of which are used as pesticides, are considered important information for regulatory purposes. e conducted acute studies of cholinesterase inhibitors in order to compare their effects as determined by a functional observational battery (FOB) and motor activity. he acute effects of two carbamates (carbaryl, aldicarb) and five organophosphates (OP; chlorpyrifos, diazinon, parathion, fenthion, and diisopropyl fluorophosphate, or DFP) were evaluated on the day of dosing at the time of peak effect, at one and three days, and one week after dosing (oral gavage, in corn oil). igh dose was selected that produced clear cholinergic signs, and lower doses were chosen to produce a range of affects. enerally all cholinesterase inhibitors produced autonomic signs of cholinergic over-stimulation (salivation, lacrimation, and miosis), hypothermia, mild tremors and mouth-smacking (chewing motions), lowered motor activity, decreased tail-pinch response, and altered neuromuscular function (gait changes and increased foot splay). he measures generally found to be most sensitive on the day of dosing were body temperature, motor activity, gait, and the and fine tremors. owever, no single measure was the most sensitive across all lowest dose of fenthion decreased motor activity by 86% but did not alter the tail-pinch dose of parathion did not lower activity but did decrease the tail-pinch response in the slopes of the dose-response curves were evident. any effects were still observed at 24 hours, but recovery was apparent for all compounds. nterestingly, residual effects at 72 hours were obtained with the carbamates (carbaryl, aldicarb) as well as with the OP fenthion, but not with the other compounds. hus, the overall clinical picture of toxicity was similar for these cholinesterase inhibitors, but compound-specific differences emerged in terms of the individual measures, dose-response, and time-course.