Landslide assessment through integrated geoelectrical and seismic methods: A case study in Thungsong site, southern Thailand.

Many landslides can cause significant damage to infrastructure, property, and human life. To study landslide structure and processes, geophysical techniques are most productive when employed in combination with other survey and monitoring tools, such as intrusive sampling. Here, the integration of electrical resistivity tomography (ERT) and seismic refraction tomography (SRT) methods is used to assess landslides in Thungsong district, Nakhon Si Thammarat, the south of Thailand, where is a hilly and seasons of prolonged rainfall region. The 2D cross-plot analysis of P-wave velocity and resistivity values obtained by these two methods is introduced to identify potential landslide-prone zones in this region. The results of the 2D cross-plot model reveal detailed image of the subsurface conditions, highlighting areas of low P-wave velocity (lower than 600 m/s) and low resistivity (lower than 600 Ωm). These areas are indicative of weak zone and are potential to be sliding materials. Moreover, an intrusive sampling data from boreholes is also used for the calibration and validation geophysical data with geological data. This can improve the accuracy of landslide assessment and develop effective mitigation strategies to reduce the risk of landslides in this area. In addition of the 2D cross-plot, the volume of sliding material is also determined from the difference of the surface and slipping plane elevations. The volume calculation of sliding material is roughly 33447.76 m3. This approach provides a preliminary tool for landslide studies and monitoring landslides in this region, thus enabling an improved understanding of slope failure processes in this context, and the basis of a landslide mitigation strategy in the future.

Hydrogeophysical imaging of deposit heterogeneity and groundwater chemistry changes during DNAPL source zone bioremediation.

Robust characterization and monitoring of dense nonaqueous phase liquid (DNAPL) source zones is essential for designing effective remediation strategies, and for assessing the efficacy of treatment. In this study high-resolution cross-hole electrical resistivity tomography (ERT) was evaluated as a means of monitoring a field-scale in-situ bioremediation experiment, in which emulsified vegetable oil (EVO) electron donor was injected into a trichloroethene source zone. Baseline ERT scans delineated the geometry of the interface between the contaminated alluvial aquifer and the underlying mudstone bedrock, and also the extent of drilling-induced physical heterogeneity. Time-lapse ERT images revealed major preferential flow pathways in the source and plume zones, which were corroborated by multiple lines of evidence, including geochemical monitoring and hydraulic testing using high density multilevel sampler arrays within the geophysical imaging planes. These pathways were shown to control the spatial distribution of the injected EVO, and a bicarbonate buffer introduced into the cell for pH control. Resistivity signatures were observed within the preferential flow pathways that were consistent with elevated chloride levels, providing tentative evidence from ERT of the biodegradation of chlorinated solvents.

Noninvasive monitoring of DNAPL migration through a saturated porous medium using electrical impedance tomography.

Electrical impedance tomography (EIT) was used to monitor the movement of a fluorinated hydrocarbon dense nonaqueous phase liquid (DNAPL) through a saturated porous medium within a laboratory column. Impedance measurements were made using a horizontal plane of 12 electrodes positioned at regular intervals around the centre of the column. A 2D inversion algorithm, which incorporated the cylindrical geometry of the column, was used to reconstruct resistivity and phase images from the measured data. Differential time-lapse images of DNAPL movement past the plane of electrodes were generated by the cell-by-cell subtraction of resistivity and phase baseline models from those associated with the DNAPL release stage of the experiment. The DNAPL pulse was clearly delineated as resistive anomalies in the differential time-lapse resistivity images. The spatial extent of the resistive anomalies indicated that in addition to vertical migration, some lateral spreading of the DNAPL had occurred. Residual contamination could be detected after quasi-static conditions were reestablished. Residual DNAPL saturation was estimated from the resistivity model data by applying Archie's second equation.Despite significant measured phase changes due to DNAPL contamination, the differential phase images revealed only weak anomalies associated with DNAPL flow; these anomalies could be seen only in the initial stages of the experiment during peak flow through the plane of electrodes.

Transferable residues from dog fur and plasma cholinesterase inhibition in dogs treated with a flea control dip containing chlorpyrifos.

We studied chlorpyrifos, an insecticide present in a commercial dip for treating ectoparasites in dogs, to estimate the amount of transferable residues that children could obtain from their treated pets. Although the chlorpyrifos dip is no longer supported by the manufacturer, the methodology described herein can help determine transferable residues from other flea control insecticide formulations. Twelve dogs of different breeds and weights were dipped using the recommended guidelines with a commercial, nonprescription chlorpyrifos flea dip for 4 consecutive treatments at 3-week intervals (nonshampoo protocol) and another 12 dogs were dipped with shampooing between dips (shampoo protocol). The samples collected at 4 hr and 7, 14, and 21 days after treatment in the nonshampoo protocol averaged 971, 157, 70, and 26 microg chlorpyrifos, respectively; in the shampoo protocol the samples averaged 459, 49, 15, and 10 microg, respectively. The highest single sample was about 7,000 microg collected at 4 hr. The pretreatment specific activities in the plasma of the dogs were about 75 nmol/min/mg protein for butyrylcholinesterase (BChE), and 9 nmol/min/mg protein for acetylcholinesterase (AChE). BChE was inhibited 50-75% throughout the study, and AChE was inhibited 11-18% in the nonshampoo protocol; inhibition was not as great in the shampoo protocol. There was no correlation (p

Analysis of the additivity of in vitro inhibition of cholinesterase by mixtures of chlorpyrifos-oxon and azinphos-methyl-oxon.

Organophosphorus (OP) insecticides or their active metabolites act through a common mechanism of toxicity, the inhibition of cholinesterase (ChE). The effects of in vitro exposure of brain (target) and serum (biomarker) ChE to chlorpyrifos-oxon (C horizontal lineO) and azinphos-methyl-oxon (AZM horizontal lineO), the active metabolites of the insecticides chlorpyrifos and azinphos-methyl, respectively, were investigated to determine if simultaneous or sequential exposure to these two OP compounds results in purely additive effects. Additive was defined by the theoretical calculated percent inhibition (dose additivity), which takes into account the fraction of ChE molecules assumed to be available for inhibition by the second compound following inhibition by the first compound, not simple mathematical summation of percent inhibition (response additivity). Brain ChE simultaneously exposed to the two compounds resulted in additive effects, which were less than the simple mathematical summation of percent inhibition. However, serum ChE simultaneously exposed to the two compounds resulted in a nonlinear response, presumably due in part to the presence of detoxifying enzymes in the serum. Sequential exposure of both brain and serum ChE to the two compounds resulted in greater than additive effects at the higher concentrations of each compound. There was no departure from additivity at the lower concentrations of the two compounds. These data suggest that simple mathematical summation of percent inhibitions, i.e., response additivity, is not the appropriate method for describing the combined effects of C horizontal lineO and AZM horizontal lineO on ChE in vitro. In addition, there are other mechanisms involved, such as the presence of detoxication enzymes, that must be taken into account when analyzing the effects of combined exposure of ChE to these two compounds.

Effects of repeated oral postnatal exposure to chlorpyrifos on open-field behavior in juvenile rats.

Organophosphorus (OP) insecticides have the potential to cause behavioral effects in children. This study was designed to determine if repeated oral exposure of preweanling rats to chlorpyrifos would produce behavioral changes at both pre- and postweanling ages. Treatment occurred every second day beginning on post-natal day (PND) 1, and continued through PND 21. The rats received one of the following regimens: a low-dosage (3 mg/kg) from PND 1-21; a medium dosage (mg/kg from PND 1-5, and then 6 mg/kg from PND 7-21; or a high-dosage schedule of 3 mg/kg on PND 1-5, then 6 mg/kg from PND 7-13, and 12 mg/kg from PND 15-21. There were no differences in body weights among the control-, low-, and medium-dosage groups but the high-dosage group had significantly lower body weights on PND 13-21. An open field was used to measure locomotor activity on PND 10, 12, 14, 16, 18, 20, 25, and 30. There were no differences in locomotor activity levels or treatment effects between males and females. On PND 10, 12, 14, 16, 18, and 20 there was no effect on locomotor activity with any dosage. On days 25 and 30, locomotor activity was significantly decreased with the medium- and high-dosage groups. Brain cholinesterase (ChE) inhibition was about 25-38% on PND 25 and 14-34% on PND 30. On PND 25 but not 30, lung and diaphragm ChE and serum butyrylcholinesterase (BChE), with the high-dosage animals, and heart ChE with the medium- and high-dosage groups were significantly inhibited. There was no significant inhibition of skeletal muscle ChE or serum acetylcholinesterase (AChE) on PND 25 and 30. These data suggest that early postnatal chlorpyrifos exposures will depress locomotor activity in juvenile rats, with the effects most pronounced after brain ChE activity has substantially recovered.

Changes in rat brain cholinesterase activity and muscarinic receptor density during and after repeated oral exposure to chlorpyrifos in early postnatal development.

The effects of repeated oral exposures to the organophosphorus insecticide chlorpyrifos (CPS) on brain muscarinic receptor densities, together with cholinesterase (ChE) activity, were studied in early postnatal rats. Initially, the effects on esterases from lactational exposure to CPS were investigated in young rats by administering CPS (100, 150, or 200 mg/kg subcutaneously in corn oil) to dams 1 day postpartum, yielding a significant body burden of CPS in the dams for possible excretion in the milk. Brain ChE inhibition in pups was less severe than in dams, whereas liver carboxylesterase (CbxE) inhibition in pups was at the same level as in dams. Because of the limited brain ChE inhibition obtained following lactation, pups were exposed to CPS directly by gavage, using 3 dosing regimens to yield a dose response. The rats were gavaged with CPS in corn oil on alternate days from postnatal day (PND) 1 through PND 21. Rats in the low-dosage group received 11 treatments at 3 mg/kg, those in the medium-dosage group received 3 treatments at 3 mg/kg and 8 at 6 mg/kg, and those in the high dosage group received 3 treatments at 3 mg/kg, 4 at 6 mg/kg, and 4 at 12 mg/kg. ChE activity in brain homogenates were inhibited significantly by 29% and 63% in the low- and high-dosage groups, respectively, on PND 22 and by 17% in the high dosage group on PND 40. Muscarinic receptor densities in brain synaptosomes were reduced using 3H-N-methylscopolamine (NMS) and 3H-quinuclidinyl benzilate (QNB) as ligands, with the effects more prominent from 3H-NMS. Densities of both ligands recovered to the control level several days after terminating treatment. The results indicate that pups are apparently exposed to only limited amounts of chlorpyrifos and/or its oxon through the milk when dams are exposed to extremely high chlorpyrifos levels. In addition, repeated direct oral exposures of early postnatal rats to CPS will result in persistent brain ChE inhibition and will transiently reduce muscarinic receptor density.

Detoxication of paraoxon by rat liver homogenate and serum carboxylesterases and A-esterases.

Paraoxon, the active metabolite of parathion, can be detoxified through a noncatalytic pathway by carboxylesterases and a catalytic pathway by calcium-dependent A-esterases, producing p-nitrophenol as a common metabolite. The detoxication patterns of carboxylesterases and A-esterases were investigated in vitro in the present study with a high tissue concentration (75 mg/mL rat liver homogenate or 50% rat serum solution) to more closely reflect enzyme concentrations in intact tissues. A final paraoxon concentration of 3.75 microM was used to incubate with liver homogenates or serum solutions for 5 seconds or 3, 5, 15, or 25 minutes; also 0.625, 1.25, 2.5, 3.125, 3.75, or 5.0 microM paraoxon (final concentration) was incubated with liver homogenates or serum solutions for 15 minutes. Phenyl saligenin cyclic phosphate and EDTA were used to inhibit carboxylesterases and A-esterases, respectively. Significant amounts of p-nitrophenol were generated with or without either inhibitor during a 15 minute incubation with paraoxon from low (0.625 microM) to high (5.0 microM) concentrations. The amount of p-nitrophenol generated via carboxylesterase phosphorylation was greater than via A-esterase-mediated hydrolysis in the initial period of incubation or when incubating with a low concentration of paraoxon. Plateau shape curves of p-nitrophenol concentration versus time or paraoxon concentration indicated that carboxylesterase phosphorylation was saturable. When incubated for long time intervals or with high concentrations of paraoxon, more p-nitrophenol was generated via A-esterase-mediated hydrolysis than from carboxylesterase phosphorylation. The ratio of paraoxon concentration to tissue amount used in in vitro assays of this study was equivalent to dosing a rat with toxicologically relevant dosages. These in vitro data suggest that both carboxylesterases and A-esterases detoxify paraoxon in vivo; carboxylesterases may be an important mode of paraoxon detoxication in initial exposures to paraoxon or parathion before they become saturated, whereas A-esterases may contribute to paraoxon detoxication in repeated exposures to paraoxon or parathion because they will not become inhibited and will remain catalytically active unlike the carboxylesterases. The importance of carboxylesterases in detoxication of paraoxon was verified by an in vivo study. In rats pretreated with tri-o-tolyl phosphate, an in vivo carboxylesterase inhibitor, brain acetylcholinesterase was significantly inhibited after intravenous exposure to parathion. No significant inhibition of brain acetylcholinesterase was observed in rats pretreated with corn oil.

The interaction of chlorinated alicyclic insecticides with brain GABA(A) receptors in channel catfish (Ictalurus punctatus).

Chlorinated alicyclic insecticides are believed to antagonize the action of the neurotransmitter gamma-aminobutyric acid (GABA) at its receptor in vertebrates. Binding of the specific GABA(A) receptor ligand [35S]-t-butylbicyclophosphorothionate (TBPS) to channel catfish brain P2 membranes suggested a single population of receptors with a Kd (56.6+/-2.6 nM) and Bmax (2435+/-276 fmol/mg protein) that are similar to published values for other fish species. The competition of several chlorinated compounds for TBPS binding was investigated. The most potent inhibitors of TBPS binding were 12-ketoendrin, photoheptachlor epoxide, photoheptachlor, telodrin, and endrin, respectively, with IC50s of 20-90 nM. Photooxychlordane, photo alpha-chlordane, and oxychlordane were intermediate in potency (122-219 nM), as were isodrin, dihydroisodrin, heptachlor epoxide, and alpha-chlordane, which were similar in potency (311-397 nM). Dieldrin, lindane, and dihydroaldrin were much less potent (592-1103 nM). Heptachlor, aldrin, and gamma-chlordane were weak inhibitors of TBPS binding (2073-2738 nM). Chlordene and chlordecone had the lowest potency of all compounds studied (10,201-21,178 nM) with the exception of mirex, which did not inhibit binding at a concentration of 50 microM. There is a good correlation between binding potency and the available toxicity data for several of these compounds in channel catfish. There is also a good correlation between the inhibitory potency in channel catfish by these types of compounds with that in rats.

Purification of two rat hepatic proteins with A-esterase activity toward chlorpyrifos-oxon and paraoxon.

A-esterases are calcium-dependent hydrolases that can detoxify the active metabolites (oxons) of organophosphorus insecticides such as chlorpyrifos and parathion. A-esterases from rat liver have previously been shown to hydrolyze chlorpyrifos-oxon but not paraoxon at low substrate concentrations. Two A-esterases were extracted by ammonium sulfate fractionation from solubilized rat liver microsomes followed by gel filtration chromatography and preparative scale isoelectric focusing. The proteins displayed similar characteristics and were difficult to separate; both had similar high molecular mass and isoelectric point range and exhibited A-esterase activity toward high and low concentrations of chlorpyrifos-oxon and high concentrations of paraoxon. Sufficient amounts of the higher molecular mass protein were obtained for kinetic studies, which yielded a Km of 0.93 mM toward high concentrations of chlorpyrifos-oxon and a Vmax of 369 nmoles product formed/mg protein-min. The protein hydrolyzed phenyl acetate, chlorpyrifos-oxon and paraoxon, suggesting that arylesterase and A-esterase activities are attributable to the same liver protein(s). Assays of purified protein and kinetic studies of microsomes suggested that the activity toward high (320 microM) and low (

Common mechanism of toxicity: a case study of organophosphorus pesticides.

The Food Quality Protection Act of 1996 (FQPA) requires the EPA to consider "available information concerning the cumulative effects of such residues and other substances that have a common mechanism of toxicity ... in establishing, modifying, leaving in effect, or revoking a tolerance for a pesticide chemical residue." This directive raises a number of scientific questions to be answered before the FQPA can be implemented. Among these questions is: What constitutes a common mechanism of toxicity? The ILSI Risk Science Institute (RSI) convened a group of experts to examine this and other scientific questions using the organophosphorus (OP) pesticides as the case study. OP pesticides share some characteristics attributed to compounds that act by a common mechanism, but produce a variety of clinical signs of toxicity not identical for all OP pesticides. The Working Group generated a testable hypothesis, anticholinesterase OP pesticides act by a common mechanism of toxicity, and generated alternative hypotheses that, if true, would cause rejection of the initial hypothesis and provide criteria for subgrouping OP compounds. Some of the alternative hypotheses were rejected outright and the rest were not supported by adequate data. The Working Group concluded that OP pesticides act by a common mechanism of toxicity if they inhibit acetylcholinesterase by phosphorylation and elicit any spectrum of cholinergic effects. An approach similar to that developed for OP pesticides could be used to determine if other classes or groups of pesticides that share structural and toxicological characteristics act by a common mechanism of toxicity or by distinct mechanisms.

Age-related differences in parathion and chlorpyrifos toxicity in male rats: target and nontarget esterase sensitivity and cytochrome P450-mediated metabolism.

Juvenile rats are more susceptible to the acute toxicity of the phosphorothionate insecticides parathion and chlorpyrifos than are adult rats. Developmental changes in brain acetylcholinesterase and hepatic aliesterase (carboxylesterase), cytochrome P450, and the P450-mediated metabolism of these two phosphorothionate insecticides were investigated in male Sprague-Dawley rats. Specific activities of acetylcholinesterase in cerebral cortex, but not medulla oblongata, and of liver aliesterases increased with age, indicating the presence of both more target esterases and more protective esterases, respectively, in the adult compared to the juvenile animal. Sensitivity of the brain acetylcholinesterase to inhibition by paraoxon and chlorpyrifosoxon, as measured by IC50 values, did not change significantly with age, whereas the hepatic aliesterase sensitivity to inhibition decreased with age. Progressive increases in activities of P450-mediated activation (desulfuration) (6- to 14-fold) and detoxication (dearylation) (2- to 4-fold), as well as concentrations of P450 (7-fold) and protein (2-fold), were observed between neonate and adult hepatic microsomes. Microsomal pentoxyresorufin O-dealkylase activity followed a developmental pattern similar to desulfuration and dearylation, displaying a 16-fold increase between neonates and adults. However, microsomal ethoxyresorufin O-deethylase activity increased until 21 days of age, displaying a 16-fold increase, then decreased in adulthood to a level 10-fold higher than neonates. These results indicate that target enzyme sensitivity is not responsible for age-related toxicity differences, nor is the potential for hepatic bioactivation, whereas lower levels of hepatic aliesterase-mediated protection and P450-mediated dearylation probably contribute significantly to the greater sensitivity of juveniles to phosphorothionate toxicity.

Kinetic analysis of the in vitro inhibition, aging, and reactivation of brain acetylcholinesterase from rat and channel catfish by paraoxon and chlorpyrifos-oxon.

In rats, the phosphorothionate insecticide parathion exhibits greater toxicity than chlorpyrifos, while in catfish the toxicities are reversed. The in vitro inhibition of brain acetylcholinesterase (AChE) by the active metabolites of the insecticides and the rates at which these inhibitor-enzyme complexes undergo reactivation/ aging were investigated in both species. Rat AChE was more sensitive to inhibition than catfish AChE as demonstrated by greater bimolecular rate constants (ki) in rats than in catfish. In both species, chlorpyrifos-oxon yielded higher ki's than paraoxon. The higher association constant (KA) of chlorpyrifos-oxon than paraoxon in both species and the lack of significant differences in the phosphorylation constants (kp) suggest that association of the inhibitor with AChE is the principal factor in the different potencies between these two inhibitors. In catfish, the ki of chlorpyrifos-oxon was 22-fold greater than that of paraoxon, while in rats it was 9-fold greater, suggesting that target site sensitivity is an important factor in the higher toxicity of chlorpyrifos to catfish but not in the higher toxicity of parathion to rats. No spontaneous reactivation of phosphorylated catfish AChE occurred and there were no differences in the first oder aging constants (ka) between compounds. For phosphorylated rat AChE, there were no differences in the first order reactivation constants (kr) but the ka for chlorpyrifos-oxon was significantly greater than that for paraoxon. This difference suggests that the steric positioning of the diethyl phosphate in the esteratic site is not the same between the two compounds, leading to differences in aging.

Identification and isolation of two rat serum proteins with A-esterase activity toward paraoxon and chlorpyrifos-oxon.

The active metabolites (oxons) of phosphorothionate insecticides can be detoxified via A-esterase hydrolysis. Two enzymes with A-esterase activity have been isolated from rat serum. Whole serum was applied to anion exchange gel (DEAE Sepharose Fast Flow) and incubated (1 hr). Tris-HCl buffer (0.05 M; pH 7.7, at 5 degrees) containing 0.25 M NaCl was added to the slurry and incubated. The decant, containing low A-esterase activity but a high protein concentration, was discarded. Further displacement of A-esterase from DEAE gel was achieved with 1.0 M NaCl in 0.05 M Tris-HCl buffer (Ph 7.7 at 5 degrees). Following desalting and concentration, further separation was achieved by gel filtration (Sephacryl S-100 HR) and two sequential preparative scale isoelectric focusings. Final fractions contained two proteins of high molecular mass (one about 200 kDa and one between 137 and 200 kDa). The apparent range of isoelectric points for the two enzymes was 4.5 to 5.6. Following native-PAGE analysis, activity stains with beta-naphthyl acetate and Fast Garnet GBC in the presence of paraoxon (10-5 M) verified that A-esterase activity was associated with both proteins. Spectropho-tometric assay detected A-esterase activity toward paraoxon, chlorpyrifos-oxon, and phenyl acetate in the final preparation.

Time course of inhibition of cholinesterase and aliesterase activities, and nonprotein sulfhydryl levels following exposure to organophosphorus insecticides in mosquitofish (Gambusia affinis).

Cholinesterase (ChE) in brain and muscle was quickly inhibited during a 48-hr in vivo exposure to chlorpyrifos (0.1 ppm), parathion (0.15 ppm), and methyl parathion (8 ppm) in mosquitofish (Gambusia affinis). ChE remained inhibited during a 96-hr nonexposure period. Brain ChE reached peak inhibition by 12 hr after exposure to parathion and chlorpyrifos and by 4 hr after exposure to methyl parathion. All insecticides caused greater than 70% ChE inhibition by 4 hr in muscle. There was no recovery of ChE after 4 days of nonexposure in either brain or muscle. Hepatic aliesterases (AliE) were quickly and greatly inhibited (> 70% by 4 hr) after exposure to parathion and chlorpyrifos but not after exposure to methyl parathion. Exposure to methyl parathion required 24-36 hr to inhibit hepatic AliE to the same level as that following parathion and chlorpyrifos exposures at 4 hr. Exposure to all insecticides eventually resulted in greater than 80% inhibition of AliE. None of the test groups treated with insecticides showed any signs of significant recovery of AliE during the 4 days of nonexposure. Nonprotein sulfhydryl (NPSH) concentrations were lower than controls after 24 hr of exposure and 96 hr after recovery for all compounds. Exposure to methyl parathion lowered NPSH concentrations greater than the other compounds. Hepatic AliE appear capable of affording some protection of ChE from inhibition following parathion or chlorpyrifos exposures, but considerably less protection against methyl parathion.

The effect of high and low dosages of paraoxon in beta-naphthoflavone-treated rats.

Aliesterases (carboxylesterases) are serine esterases that can serve a protective role for the target acetylcholinesterase (AChE) during organophosphorus insecticide intoxication because the former esterases are alternate phosphorylation sites. The levels of aliesterase activity in liver and plasma and AChE activity in brain regions were investigated after the intravenous administration of paraoxon (P = O) into female rats. The rats were pretreated intraperitoneally with beta-napthoflavone (BNF), which decreases hepatic aliesterase activity following a 3 day in vivo treatment, and/or tri-o-tolyl phosphate (TOTP) to inhibit aliesterases. The liver aliesterases were inhibited less by P = O in BNF-treated rats than in control rats, which suggests that either BNF exposure may have resulted in aliesterases that are less sensitive to P = O inhibition or BNF may have altered P = O's availability. The BNF treatment did not seem to alter the degree of inhibition of the brain AChE activity following the low dosage of paraoxon (0.04 mg/kg). However, the brain AChE activity in the P = O/TOTP/BNF-treated rats was lower than that in the P = O/TOTP-treated rats, suggesting that BNF also caused changes in systems affecting the disposition of P = O in addition to the changes in the hepatic aliesterases. At the high dosage of paraoxon (0.12 mg/kg), the AChE and aliesterase activities showed a pattern similar to that of the low dosage. This suggests that the aliesterases, as altered by BNF exposure, even when nearly completely inhibited, did not alter the response of the target enzyme, AChE, and, therefore, the magnitude of the toxic response.

Biochemical mechanisms contributing to species differences in insecticidal toxicity.

Comparison of published LD50 or LC50 levels for a variety of insecticides in several vertebrate species indicate that a wide range of toxicity levels exist, and these cannot be easily predicted within either a chemical group or within a species. There is a relatively limited data base documenting interactions between insecticides and other chemicals, either agricultural or non-agricultural; however, the fact that all major insecticide groups perturb nervous system function as their primary mechanism of acute toxicity suggests the potential for interactions. Studies in our laboratories on a select group of phosphorothionate insecticides in rats indicated that brain acetylcholinesterase sensitivity to inhibition by the oxons, the active metabolites of the phosphorothionates, does not correlate with acute toxicity levels. The activities and properties of hepatic cytochrome P450-mediated activation (desulfuration) and detoxication (dearylation) of the phosphorothionates as well as of A-esterase-mediated hydrolysis of oxons contribute substantially to understanding the acute toxicity levels in rats, as does the sensitivity of the protective aliesterases to phosphorylation. However, in the channel catfish, the acetylcholinesterase sensitivity to oxon inhibition reflects the acute toxicity level of these same insecticides, and may be largely responsible for determining the acute toxicity level in this species. Thus, metabolism of insecticides appears to be far more influential in some species than others in determining the toxicity elicited.

Organophosphate detoxication potential of various rat tissues via A-esterase and aliesterase activities.

Paraoxon and chlorpyrifos-oxon, active metabolites of the organophosphorus insecticides parathion and chlorpyrifos, can be detoxified via A-esterases and aliesterases. These enzyme activities were measured in various tissues of Sprague-Dawley rats. High A-esterase activities were detected in liver, serum and liver mitochondrial/microsomal fractions. Low or no A-esterase activities were detected in other tissues and tissue fractions. A-Esterase substrate:substrate activity ratios suggest that the substrates are probably not degraded by the same enzyme. Highest aliesterase activities were observed in the small intestine and liver with moderate activity in kidney, serum and lungs. Low activities were noted in brain, spleen and skeletal muscle.

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.