Inhibition Of Brain Acetylcholinesterase Research Articles

The relationships between brain, serum, and whole blood ChE activity in the wood mouse (Apodemus sylvaticus) and the common shrew (Sorex araneus) after acute sublethal exposure to dimethoate

Abstract Inhibition of cholinesterase (ChE) activity produced by a single acute intraperitoneal administration of dimethoate was studied in the wood mouse, Apodemus sylvaticus, and the common shrew, Sorex araneus, under laboratory conditions. ChE values from serum and whole blood were compared with those obtained from brain in order to obtain a non-destructive tool for predicting the severity of brain acetylcholinesterase (AChE) inhibition. In addition, serum and brain inhibition following oral exposure to dimethoate was also measured in the wood mouse. Normal ChE activity was higher in the brain and whole blood of the shrews than in wood mice. There was no difference between species in serum ChE activity. Exposure to dimethoate caused a dose-dependent reduction in ChE activity and there was a significant recovery in activity with increasing time after administration. In both species, serum and whole blood were more sensitive than brain for revealing organophosphate-induced ChE inhibition and serum was more sensitive than whole blood. Statistically significant relationships were defined between whole blood and brain ChE activity and between serum and brain ChE activity. Compared with serum, whole blood ChE activity was the more accurate predictor of brain AChE levels. The relationships between brain and serum ChE activity did not appear to be affected by the route of administration of the pesticide.

Comparative studies of two organophosphorus compounds in the mouse

A rodent model, the albino mouse, was used to investigate the in vitro and in vivo capacity of 2 organophosphate (OP) compounds, mipafox and ecothiopate, to inhibit enzymes considered to be involved in the mechanisms of OP toxicity. Mipafox and ecothiopate were chosen as model compounds because the former can produce a delayed neuropathy whereas the latter does not. Mipafox (110 μmol/kg s.c.) inhibited brain acetylcholinesterase (AChE), neuropathy target esterase (NTE) and phenylvalerate hydrolases by 58, 64 and 65%, while diaphragm AChE and phenylvalerate hydrolases were inhibited by 66 and 80%, respectively. In contrast, ecothiopate (0.5 μmol/kg) had no effect on brain NTE or on brain or diaphragm phenylvalerate hydrolases. At the same time, diaphragm AChE was inhibited by 60% while brain AChE activity had increased by 15% of control. Mipafox was a potent inhibitor of AChE and NTE in vitro. Although ecothiopate was a highly potent anti-ChE in vitro, it had no inhibitory effect on NTE.

Inhibition of acetylcholinesterase and aliesterases of fingerling channel catfish by chlorpyrifos, parathion, and S, S, S-tributyl phosphorotrithioate (DEF)

Serine esterases can be inhibited by organophosphorus compounds. The in vitro potency of the organophosphorus pesticide DEF and oxons of the phosphorothionate insecticides chlorpyrifos (chlorpyrifos-oxon, Cpxn) and parathion (paraoxon, Pxn) were determined for brain, gill, liver, muscle, and plasma for acetylcholinesterase (AChE) and gill, liver, and plasma aliesterases (ALiE). AChE activity was inhibited less than 15% in all tissues in the presence of 1 mM DEF ®. AChE I 50 values for Cpxn were 28–33 nM, and for Pxn were 446–578 nM. ALiE I 50 values for Cpxn were 0.1–0.2 nM, for DEF were 24–163 nM, and for Pxn were 6–46 nM. Fish were exposed to chlorpyrifos (Cp), parathion (Pth), DEF, and combinations of the phosphorothionates with DEF for 4 h followed by a 384-h recovery period. AChE inhibition following Cp and Pth exposures was rapid. Cp led to more persistent inhibition than Pth. DEF treatments yielded low levels of AChE inhibition in brain and muscle, and high levels of inhibition in gill, liver, and plasma. In vitro and in vivo results suggest that DEF's disposition and/or mode of action are different than those of Cp or Pth. Exposure to DEF resulted in persistent, high level inhibition of ALiE activity. Greater AChE inhibition in DEF plus Cp or Pth treatments was not evident, suggesting that ALiEs do not serve to appreciably protect AChE in channel catfish, even though ALiEs are inherently more sensitive to inhibition.

The study of interactive effects of pollutants: a biomarker approach

Biochemical biomarkers, such as inhibition of serum butyryl cholinesterase (BuChE) and brain acetyl cholinesterase (AChE), have been useful in studies of interactive effects of pesticides in birds. Examples of interactions due to increased activation or decreased detoxication are reviewed. Studies have shown that hybrid red-legged partridges ( Alectoris rufa cross) pretreated with the inducing ergosterol biosynthesis inhibiting (EBI) fungicide, prochloraz, were more sensitive to the toxic effects of the organophosphorous (OP) insecticide, malathion, than controls. A dose of 90 mg/kg prochloraz produced greater inhibition at 1, 4 and 24 h following oral administration of 50 mg/kg malathion, compared to corn oil controls. Pigeons ( Columba livia) given 180 or 90 mg/kg prochloraz showed greater inhibition of BuChE activity following malathion administration than did control birds. Starlings ( Sturnus vulgaris), however, appeared not to be induced by 180 or 300 mg/kg prochloraz, and no difference in BuChE activity following dosing with malathion was apparent in comparison with controls. Other EBIs and OP combinations have been investigated in the partridge. Birds pretreated with prochloraz showed a trend towards greater inhibition of serum BuChE activity at most time points following dosing with the OPs dimethoate and chlorpyriphos. Birds pretreated with the EBI penconazole showed significantly greater inhibition of serum BuChE activity at 1, 4 and 24 h after malathion administration than did controls. The mechanism of increased activation of malathion due to induction of cytochrome P-450 by prochloraz is reviewed. In the case of interactions due to inhibition of detoxication, inhibition of brain AChE activity was a useful biochemical biomarker. An increased sensitivity of partridges to the carbamate pesticide, carbaryl, following pretreatment with malathion was attributed mainly to suicide inhibition (by malathion) of cytochrome P-450, resulting in an inhibition of carbaryl metabolism. The enhancement (or potentiation) of toxicity found in these studies was the consequence of modulations of cytochrome P-450-induction (by EBIs) or inhibition (by malathion). More generally, interactions of this kind may also occur between other environmental chemicals, for example, as the consequence of inductions caused by persistent compounds such as PCBs. The biomarker assays for monooxygenases based upon cytochrome P-450 employed in the present study (measurement of enzyme activies and Western blotting) can be used to measure these changes in vertebrates in the field.

Comparison of efficacy of two oximes (HI-6 and obidoxime) in soman poisoning in rats

The action of HI-6 (1-[[[(4-aminocarbonyl)pyridiniol]methoxy]methyl]-2-[(hydroxyimino)methyl]pyridinium dichloride monohydrate) and obidoxime on soman-induced anticholinesterase and stressogenic effects was studied in rats. HI-6 significantly affected acetylcholinesterase inhibition in erythrocytes, brain and diaphragm and practically eliminated the stressogenic effects of soman, i.e. an increase in plasma corticosterone level and liver tyrosine aminotransferase activity, while obidoxime, on the other hand, had very little influence on soman-induced inhibition of acetylcholinesterase activity and the stressogenic effects of soman. These findings support a hypothesis that the effects of HI-6 are not solely due to reactivation of the enzyme. They also demonstrate its importance in the treatment of soman poisoning in rats.

Inhibition and aging of channel catfish brain acetylcholinesterase following exposure to two phosphorothionate insecticides and their active metabolites.

The inhibition and aging of acetylcholinesterase (AChE) in fingerling channel catfish (lctalurus punctatus) brain tissue was studied after single in vivo exposures to high levels of chlorpyrifos (0.25 mg/L), chlorpyrifos-oxon (7 micrograms/L), parathion (2.5 mg/L), or paraoxon (30 micrograms/L). Exposure to both parent compounds produced identical initial inhibition (95%), but in the later sampling times there was significantly more inhibited AChE in the chlorpyrifos-treated fish than in the parathion-treated fish (47% and 28%, respectively, on d 16). There were higher levels of aged AChE following chlorpyrifos exposure than following parathion exposure, but differences were not significant. Exposure to both oxons produced initial inhibition greater than 90%, and patterns of recovery and aging were statistically similar between both compounds; no significant inhibition was observed after d 11. The similar patterns of inhibition, recovery, and aging between the two oxon treatments, which have similar lipophilicities, suggest that the greater amount of AChE inhibition and aging observed in the chlorpyrifos-treated fish compared with the parathion-treated fish probably results from the higher lipophilicity of chlorpyrifos than of parathion. Overall, the prolonged brain AChE inhibition exhibited in catfish exposed to phosphorothionates is not the result of aging of the inhibited enzyme but is the result of either a slow rate or a lack of spontaneous reactivation.

Evaluation of P450 1A1 immunohistochemistry as a biomarker in field studies with marine fish

The mummichog, Fundulus heteroclitus, is a common inhabitant of eastern seaboard estuaries. As such, it can be affected by coastal agricultural and other nonpoint source runoff. We examined the effects of short-term episodic exposures to an agricultural pesticide, chlorpyrifos, on brain acetylcholinesterase (AChE) activity and vertebral yield strength in lab-reared and wild-caught fish. Brain AChE activity was chosen as an indicator because it is the target system for organophosphate action. Vertebral yield strength was chosen as an indicator because previous research warranted further investigation (Karen et al., 1998). Four daily or weekly 6 h exposures (2.5, 5.0, and 10.0 μg/l chlorpyrifos) in decreased salinity seawater (5 g/kg) significantly reduced brain AChE activity. The lowest concentration was within the range of reported environmental chlorpyrifos concentrations; thus inhibition of brain AChE from environmental chlorpyrifos exposures may pose a hazard to estuarine organisms. Yield strength measured in lab-reared fish appeared to be more sensitive to episodic chlorpyrifos exposures, because chlorpyrifos was a significant factor in 75% (3 out of 4) of tests performed with lab-reared fish. Chlorpyrifos exposure was a significant factor in only 25% (1 out of 4) tests performed with wild fish. These results suggested that changes in the responses of bone to load testing, following several short exposures to an organophosphate, could be sensitive indicators in lab-reared organisms.

PD 142676 (CI 1002), a novel anticholinesterase and muscarinic antagonist.

Inhibition of brain acetylcholinesterase (AChE) can provide relief from the cognitive loss associated with Alzheimer's disease (AD). However, unwanted peripheral side effects often limit the usefulness of the available anticholinesterases. Recently, we identified a dihydroquinazoline compound, PD 142676 (CI 1002) that is a potent anticholinesterase and a functional muscarinic antagonist at higher concentrations. Peripherally, PD 142676, unlike other anticholinesterases, inhibits gastrointestinal motility in rats, an effect consistent with its muscarinic antagonist properties. Centrally, the compound acts as a cholinomimetic. In rats, PD 142676 decreases core body temperature. It also increases neocortical arousal, as measured by quantitative electroencephalography, and cortical acetylcholine levels, measured by in vivo microdialysis. The compound improves the performance of C57/B10j mice in a water maze task and of aged rhesus monkeys in a delayed match-to-sample task involving short-term memory. The combined effect of AChE inhibition and muscarinic antagonism distinguishes PD 142676 from other anticholinesterases, and may be useful in treating the cognitive dysfunction of AD and produce fewer peripheral side effects.

Chromodacryorrhea in Rats: Absence Following Soman Poisoning

Chromodacryorrhea is the secretion of so-called "bloody tears" from the harderian gland which nearly circumscribes the eye within the bony orbit. Direct-acting cholinergic agonists such as oxotremorine, carbachol, and pilocarpine caused chromodacryorrhea but nicotine did not. Atropine blocked chromodacryorrhea induced by systemic administration of direct-acting cholinergic agonists. Thus, chromodacryorrhea appears to be a muscarinic receptor-related event. Soman (pinacolyl methylphosphonofluoridate), a potent irreversible inhibitor of acetylcholinesterase which increases the synaptic concentration of the neurotransmitter acetylcholine, did not induce chromodacryorrhea in rats. Similarly, physostigmine, a tertiary, carbamate acetylcholinesterase inhibitor, did not induce chromodacryorrhea. In vivo soman-induced inhibition of harderian gland acetylcholinesterase was independent of the soman dose and the inhibition was significantly less than brain acetylcholinesterase. In vitro soman-induced inhibition of harderian gland acetylcholinesterase was not significantly different from that of diaphragm acetylcholinesterase. The lack of inhibition of acetylcholinesterase in the harderian gland does not appear to be due to a difference in sensitivity to inhibition by soman. The distribution of the various molecular forms of acetylcholinesterase between the diaphragm and harderian gland was different. There was a great deal more of the 4S form of acetylcholinesterase in the harderian gland than in the diaphragm. The lack of the following, inhibition of harderian gland acetylcholinesterase and elevation of the synaptic concentration of acetylcholine, could explain the absence of chromodacryorrhea following soman poisoning. The discrepancy between the significant soman induced inhibition of brain acetylcholinesterase and the lack of inhibition of harderian gland acetylcholinesterase allows one to speculate that there may be a very efficient scavenger of soman present in the rat harderian gland.

SR 46559A: a novel and potent muscarinic compound with no cholinergic syndrome.

The cholinergic activities of SR 46559A, 3-[N-(2 diethyl-amino-2-methylpropyl)-6-phenyl-5-propyl] pyridazinamine sesquifumarate, have been investigated in vitro and in vivo, in rodents. Using rat brain cortical membranes, SR 46559A was a competitive ligand (Ki = 112 nM) at muscarinic M1 receptors, its affinity for muscarinic M2 (cardiac) and M3 (glandular) receptors being 6-7 times lower. SR 46559A did not interact with brain nicotinic receptors and high affinity choline uptake sites nor did it inhibit brain acetylcholinesterase activity. In contrast to reference muscarinic agonists, SR 46559A (1 mM) did not inhibit the forskolin-induced activation of cAMP synthesis nor did it stimulate phosphoinositides breakdown in various brain preparations. However, this compound enhanced (+67% at 1 mM) diacylglycerol formation in rat striatal miniprisms, an effect fully reversed by atropine. As shown with reference agonists, SR 46559A inhibited (IC50 = 10 microM) the K(+)-evoked release of [3H]GABA from rat striatal slices and reduced at 0.5 and 1 microM, the population spike amplitude of the CA1 pyramidal cells induced by stimulation of the Schaffer's collateral commissural pathway in rat hippocampal slices. In mice, SR 46559A at a near lethal dose (200 mg/kg PO) did not induce the typical cholinergic syndrome nor did it modify at 30 mg/kg PO the oxotremorine-induced hypothermia. Like muscarinic agonists, SR 46559A (1 mg/kg PO) potentiated haloperidol-induced catalepsy in rats and inhibited (ED50 = 0.12 mg/kg PO) rotations induced in mice by intrastriatal injection of pirenzepine.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of hen brain acetylcholinesterase and neurotoxic esterase by chlorpyrifos in vivo and kinetics of inhibition by chlorpyrifos oxon in vitro: Application to assessment of neuropathic risk

Chlorpyrifos (CPS; O,O-diethyl 3,5,6-trichloro-2-pyridyl phosphorothionate; Dursban) is a widely used broad-spectrum organophosphorus (OP) insecticide. Because some OP compounds can cause a sensory-motor distal axonopathy called OP compound-induced delayed neurotoxicity (OPIDN), CPS has been evaluated for this paralytic effect. Early studies of the neurotoxicity of CPS in young and adult hens reported reversible leg weakness but failed to detect OPIDN. More recently, a human case of mild OPIDN was reported to result from ingestion of a massive dose (about 300 mg/kg) in a suicide attempt. Subsequent experiments in adult hens (the currently accepted animal model of choice for studies of OPIDN) showed that doses of CPS in excess of the LD50 in atropine-treated animals inhibited brain neurotoxic esterase (NTE) and produced mild to moderate ataxia. Considering the extensive use of CPS and its demonstrated potential for causing OPIDN at supralethal doses, additional data are needed to enable quantitative estimates to be made of the neuropathic risk of this compound. Previous work has shown that the ability of OP insecticides to cause acute cholinergic toxicity versus OPIDN can be predicted from their relative tendency to inhibit the intended target, acetylcholinesterase (AChE), versus the putative neuropathic target, NTE, in brain tissue. The present study was designed to clarify the magnitude of neuropathic risk associated with CPS exposures by measuring hen brain AChE and NTE inhibition following dosing in vivo and determining the bimolecular rate constant of inhibition (ki) for each enzyme by the active metabolite, CPS oxon (CPO), in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationships between behavior and the inhibition of acetylcholinesterase in birds exposed to organophosphorus pesticides

AbstractEffects of sublethal acute doses of the organophosphate chlorfenvinphos on the behavior of captive starlings (Sturnus vulgaris) were investigated in four experiments. Effects were more complex and occurred at lower levels of exposure than in previous avian studies. Altered posture was associated with inhibition of brain acetylcholinesterase (AChE) activity to less than about 88% of the normal level. Reductions in flying and singing, and increased resting, were associated with inhibition of AChE to below 61 % normal. Substantial recovery of normal behavior occurred within 5 h of treatment. Feeding activity was reduced for over 8 h in birds with AChE inhibited to less than about 73% normal, accompanied by a proportionate loss of body weight. Flying activity was initially depressed for 1 to 2 h but then increased above normal levels. Singing of isolated males in response to the playback of recorded song decreased in proportion to the inhibition of AChE. Performance of a foraging task was unaffected by inhibition of AChE to as little as 57% normal. A review of relevant studies suggests that only broad generalizations, of limited practical value, can be made about the relationship between AChE inhibition and behavioral effects.

RELATIONSHIPS BETWEEN BEHAVIOR AND THE INHIBITION OF ACETYLCHOLINESTERASE IN BIRDS EXPOSED TO ORGANOPHOSPHORUS PESTICIDES

Effects of sublethal acute doses of the organophosphate chlorfenvinphos on the behavior of captive starlings (Sturnus vulgaris) were investigated in four experiments. Effects were more complex and occurred at lower levels of exposure than in previous avian studies. Altered posture was associated with inhibition of brain acetylcholinesterase (AChE) activity to less than about 88% of the normal level. Reductions in flying and singing, and increased resting, were associated with inhibition of AChE to below 61 % normal. Substantial recovery of normal behavior occurred within 5 h of treatment. Feeding activity was reduced for over 8 h in birds with AChE inhibited to less than about 73% normal, accompanied by a proportionate loss of body weight. Flying activity was initially depressed for 1 to 2 h but then increased above normal levels. Singing of isolated males in response to the playback of recorded song decreased in proportion to the inhibition of AChE. Performance of a foraging task was unaffected by inhibition of AChE to as little as 57% normal. A review of relevant studies suggests that only broad generalizations, of limited practical value, can be made about the relationship between AChE inhibition and behavioral effects.

Inhibition of Hen Brain Acetylcholinesterase and Neurotoxic Esterase by Chlorpyrifos in Vivo and Kinetics of Inhibition by Chlorpyrifos Oxon in Vitro: Application to Assessment of Neuropathic Risk

Inhibition of Hen Brain Acetylcholinesterase and Neurotoxic Esterase by Chlorpyrifos in Vivo and Kinetics of Inhibition by Chlorpyrifos Oxon in Vitro: Application to Assessment of Neuropathic Risk

Bioavailability and toxicity to rats of bound residues of 14C-pirimiphos-methyl in stored wheat.

Wheat grains were treated with 14C-pirimiphos-methyl to generate bound residues for testing their bioavailability to rats. Bound residues accounted for 25% of the applied dose (50 ppm) at the end of one year. When the grain bound residues were fed to rats for 48 hours the animals eliminated 30 and 40% of the administered dose in urine and feces respectively, after 5 days. Radioactivity in some selected organs and blood accounted for 37% of the administered dose after 2 days, which gradually declined to 1% after 5 days. These data indicate that wheat-bound pirimiphos-methyl residues are moderately bioavailable to rats. In a 90-day feeding study, inhibition of plasma cholinesterase and brain acetylcholinesterase strongly suggest that the bound residues possess a toxicological potential.

Pharmacokinetic analysis of protection by an organophosphorus insecticide, chlorfenvinphos, against the toxicity of its succeeding dosage in rats

We have previously reported that the acute oral toxicity of chlorfenvinphos (CVP) is reduced by the oral pretreatment of rats with the same compound. In this report, the mechanism of this protection was clarified mainly through the physiologically based pharmacokinetic analysis. The CVP pretreatment (15 mg/kg, po, 24 hr before) reduced the lethality of po CVP greatly, and that of iv CVP to a lesser extent. Brain acetylcholinesterase inhibition by po and iv CVP was also decreased by the pretreatment. The magnitude of reduction of the inhibition caused by the po CVP was greater than that of the iv CVP. The ratio of CVP concentration between the brain and plasma was the same, regardless of the route of administration or the pretreatment. The pretreatment greatly reduced the plasma concentration and the area under the plasma concentration versus time curve (AUC) of the po CVP, but did not change appreciably that of the iv CVP. The unbound fraction of CVP in the blood or the liver was not changed by the pretreatment. According to physiologically based pharmacokinetic analysis, the decrease in AUC of the po CVP may be mainly caused by an increase in intrinsic clearance of the liver and a decrease in the partition coefficient of CVP between the emergent blood and the liver. The increase in the intrinsic clearance may be related to the metabolic induction observed in vitro. The pretreatment decreased the absorption rate constant of the po CVP. This change in combination with the above two factors which reduce AUC might be the reason for the decrease in the plasma concentration after the po CVP, and the protection against the CVP toxicity of the succeeding dosage.

In vitro brain acetylcholinesterase response among three inbred strains of mice to monocrotophos

The strain differences in the neurotoxic potential of monocrotophos (MCP) were assessed by determining the inhibition of brain acetylcholinesterase (AChE) in BALB/cAnN, DBA/2J and C57BL/6J in vitro. MCP being a competitive inhibitor for AChE, alters the Km values widely among these inbred strains. Comparatively least alterations in Km were found in BALB/cAnN and maximum in DBA/2J. Based on the Ki values DBA/2J was found to be the most sensitive strain to MCP inhibition followed by C57BL/6J and BALB/cAnN.

A comparative study of blood changes and brain acetylcholinesterase inhibition by monocrotophos and its analogues in rats

The effects of monocrotophos and its newly synthesized analogues, RPR-II and RPR-V, on hematology and blood chemistry 24 hr post-treatment were studied in rats given doses of 0.96, 1.23, and 3.0 mg/kg po, respectively. It was found that monocrotophos caused a significant increase in the mean WBC count, RPR-V, a significant decrease in hematocrit and RBC count, whereas RPR-II did not alter any hematological parameter. The activities of membrane-bound enzymes in serum were not significantly changed by all three compounds except for a statistically significant increase of 38% in SGOT activity by RPR-II. Only monocrotophos caused a significant inhibition of the brain acetylcholinesterase activity. In vitro studies with partially purified preparations of rat brain cholinesterase revealed that monocrotophos was the most potent anticholinesterase agent, followed by RPR-II and RPR-V. All three compounds caused inhibition of rat brain cholinesterase by decreasing the V max and increasing the K m values, indicating a mixed type of inhibition. The two analogues appeared to be less neurotoxic than monocrotophos.

A novel tertiary pyridostigmine derivative [3-( N, N-dimethylcarbamyloxy)-1-methyl-Δ 3-tetrahydropyridine]: Anticholinesterase properties and efficacy against soman

In an effort to develop an effective centrally acting pretreatment compound against organophosphorus poisons, the tertiary pyridostigmine (Pyr) derivative 3-( N, N-dimethylcarbamyloxy)-1-methyl-Δ 3-tetrahydropyridine (THP) was synthesized and studied for its anticholinesterase properties, as well as its efficacy against soman intoxication in guinea pigs. Injection of THP (262 μg/kg, im) into adult male guinea pigs caused inhibition of blood (30%) and brain (25%) acetylcholinesterase (AChE), showing that THP penetrates the blood-brain barrier. Pyr (131 μg/kg, im) caused AChE inhibition in the blood (59%), but not in the brain. The inhibitory potencies of THP and Pyr were compared by determining their IC50 values for in vitro inhibition of both AChE (brain, erythrocyte) and pseudo-cholinesterase (plasma) in three mammalian species (guinea pig, rat, rabbit). THP, although effective in inhibiting both types of cholinesterase, was in general less potent than Pyr. Pretreatment of guinea pigs with THP 9262 μg/kg, im) plus Pyr (131 μg/kg, im), 30 min prior to subcutaneous soman challenge, with no antimuscarinic or oxime treatment, protected 60% of the animals against 2 × LD50 of soman. Neither THP nor Pyr alone was effective. The protective pretreatment regimen did not prevent convulsions, but shortened the recovery time in surviving animals (median recovery time 1.6 hr, compared to 24 hr in control and other groups of animals pretreated with THP or Pyr alone). A combination of THP and Pyr thus appears to provide a means of evaluating the relative importance of selective peripheral plus central vs peripheral AChE protection against soman.

Brain acetylcholinesterase activity in forest songbirds exposed to a new method of UULV fenitrothion spraying

Brain acetylcholinesterase (AChE) activity was measured in forest songbirds exposed to Ultra Ultra Low Volume (UULV) aerial spraying of fenitrothion in New Brunswick for spruce budworm control. Brain AChE activity was determined in 324 songbirds from the sprayed blocks and 47 from an unsprayed control area, and represented four species. In most cases, more than half of the individuals of any species sampled were diagnosed as "exposed" (greater than or equal to 20% inhibition) to the fenitrothion sprays and had a mean percent level of inhibition of 40% or greater, relative to mean control values. The proportion of birds with life-threatening levels of inhibition (greater than or equal to 50%) was usually less than 20%. The largest proportion of birds with life-threatening inhibition was found after the first 210 g AI/ha spray. The White-throated Sparrow had the highest proportion (25-55%) of individuals with life-threatening inhibition after all sprays. Brain AChE inhibition was greater in exposed birds collected after the first 210 g AI/ha spray than after the second one. Variation among species' responses to the sprays is discussed in relation to habitat and foraging preferences. Several sampling biases which may contribute to underestimation of the impact of fenitrothion spraying on birds are identified.