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DIFFERENTIAL PROFILES OF CHOLINESTERASE INHIBITION AND NEUROBEHAVIORAL EFFECTS IN RATS EXPOSED TO FENAMIPHOS AND PROFENOPHOS.
Citation:
McDaniel, K. L., P. M. Phillips, AND V C. Moser. DIFFERENTIAL PROFILES OF CHOLINESTERASE INHIBITION AND NEUROBEHAVIORAL EFFECTS IN RATS EXPOSED TO FENAMIPHOS AND PROFENOPHOS. Presented at Society of Toxicology 42nd Annual Meeting, Salt Lake City, UT, March 9-13, 2003.
Description:
The relationship between cholinesterase (ChE) inhibition and neurobehavioral changes was examined using two ChE-inhibiting organophosphorus pesticides, fenamiphos and profenophos. Both pesticides inhibit blood ChE, yet brain ChE is relatively spared (little to no inhibition up to lethal doses). Interestingly, pronounced neurobehavioral signs were observed following fenamiphos but not profenophos. A direct comparison was then undertaken to evaluate the influence of brain ChE on the behavioral signs observed. After a single oral dose, both pesticides greatly inhibited blood ChE (87-98% inhibition), yet whole brain ChE was only inhibited by 9-14% at the highest doses. Fenamiphos produced dose-dependent lacrimation, salivation, tremors, gait abnormalities, and decreased motor activity and tail pinch response. Despite the similar ChE inhibition profile, profenophos produced no changes in any of these measures. Thus, the neurobehavioral effects of fenamiphos could not be explained based on brain ChE inhibition alone. Pretreatment with anticholinergic drugs was used to evaluate the contribution of peripheral vs central ChE inhibition. Scopolamine (SCO) and methylscopolamine (MSC) were used as central/peripheral and peripheral-only cholinergic receptor blockers, respectively, in combination with fenamiphos. Neither drug altered fenamiphos effects on ChE. Some effects of fenamiphos were blocked or attenuated only by SCO, whereas other effects were blocked by both drugs. These data indicate that some of the pronounced neurobehavioral changes observed following fenamiphos may be centrally mediated (blocked by SCO only), despite the relative sparing of brain ChE. Regionally specific ChE inhibition or direct cholinergic receptor activation may be responsible for these effects. Other behavioral changes may be mediated more peripherally (blocked by both MSC and SCO), yet the contrast between profenophos and fenamiphos indicates that these neurobehavioral effects cannot be predicted on the basis of blood ChE.
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