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Journal of Applied Toxicology : JAT Jan 2019Organophosphorus compounds (OPCs), inhibitors of acetylcholinesterase (AChE), are useful agents as pesticides, but also represent a serious health hazard. Standard... (Review)
Review
Organophosphorus compounds (OPCs), inhibitors of acetylcholinesterase (AChE), are useful agents as pesticides, but also represent a serious health hazard. Standard therapy with atropine and established oxime-type enzyme reactivators (pralidoxime, obidoxime) is unsatisfactory. Better therapeutic results are obtained, when reversible AChE inhibitors are administered before OPC exposure. This review summarizes the history of such a pretreatment approach and sums up a set of experiments undertaken in search of compounds that are efficacious when given before a broad range of OPCs. The prophylactic efficacy of 10 known AChE inhibitors, either already used clinically for different indications (physostigmine, pyridostigmine, ranitidine, tiapride, tacrine, amiloride, metoclopramide, methylene blue) or developed for possible therapeutic use in the future (7-methoxytacrine, K-27) was compared, when administered before exposure to six chemically diverse OPCs in the same experimental setting: ethyl-paraoxon, methyl-paraoxon, diisopropylfluorophosphate, terbufos sulfone, azinphos-methyl and dicrotophos. The experimental oxime K-27 was the most efficacious compound, affording best protection, when administered before terbufos sulfone, azinphos-methyl and dicrotophos, second best before ethyl- and methyl-paraoxon exposure and third best before diisopropylfluorophosphate administration. This ranking was similar to that of physostigmine, which was superior to the Food and Drug Administration-approved pretreatment for soman with pyridostigmine. Tiapride, amiloride, metoclopramide, methylene blue and 7-methoxytacrine did not achieve protection. No correlation was observed between the IC of the reversible AChE inhibitors and their protective efficacy. These studies indicate that K-27 can be considered a very promising broad-spectrum prophylactic agent in case of imminent organophosphate exposure, which may be related to its AChE reactivating activity rather than its AChE inhibition.
Topics: Animals; Cholinesterase Inhibitors; Humans; Models, Animal; Organophosphate Poisoning; Organophosphates; Pre-Exposure Prophylaxis
PubMed: 30027640
DOI: 10.1002/jat.3662 -
Journal of Economic Entomology Apr 2018To assess the toxicity of bifenthrin and four mixtures of insecticides to tarnished plant bug, we used an insecticide dip method of green bean to treat adults of a...
To assess the toxicity of bifenthrin and four mixtures of insecticides to tarnished plant bug, we used an insecticide dip method of green bean to treat adults of a laboratory colony; mortality was assessed after 48 h. LC50s for imidacloprid, bifenthrin, acephate, thiamethoxam, and dicrotophos were 0.12, 0.39, 0.62, 0.67, and 3.96 ppm, respectively. LC75s for imidacloprid, bifenthrin, acephate, thiamethoxam, and dicrotophos were 0.61, 4.22, 5.10, 2.65, and 7.86 ppm, respectively. Based on the LC50s and LC75s, dicrotophos was much less toxic than the other chemicals tested. PoloMix software was used to determine syngerism, antagonism, or addition effects of the mixtures. Three out of four analyses of the joint action of bifenthrin plus imidacloprid or acephate or dicrotophos showed that toxicity was not independent and not correlated. For bifenthrin plus dicrotophos, observed mortality was greater than expected mortality at most concentrations suggesting synergism. Mixtures of bifenthrin plus imidacloprid and bifenthrin plus acephate showed observed mortality significantly less than expected, suggesting antagonism. LC50s for bifenthrin plus dicrotophos, acephate, imidacloprid, and thiamethoxam were 0.38, 1.06, 0.17, and 0.26 ppm, respectively. LC75s for bifenthrin plus dicrotophos, acephate, imidacloprid, and thiamethoxam were 13.61, 13.18, 0.67, and 0.80 ppm, respectively. Based on the LC50s and LC75s, bifenthrin plus acephate was 3- to 10-fold less toxic than the other chemicals tested. Bifenthrin plus acephate is frequently used in tank mixes to control tarnished plant bug and other cotton pests, and the effectiveness of each individual chemical appears to be reduced in one to one ratio mixtures.
Topics: Animals; Heteroptera; Insecticide Resistance; Insecticides; Neonicotinoids; Nitro Compounds; Organophosphorus Compounds; Organothiophosphorus Compounds; Oxazines; Phosphoramides; Pyrethrins; Thiamethoxam; Thiazoles
PubMed: 29361174
DOI: 10.1093/jee/tox341 -
Protein and Peptide Letters 2015Organophosphorus (OP) pesticides and nerve agents have been designed to inhibit the hydrolysis of the neurotransmitter acetylcholine by covalently binding to the active...
Organophosphorus (OP) pesticides and nerve agents have been designed to inhibit the hydrolysis of the neurotransmitter acetylcholine by covalently binding to the active site serine of acetylcholinesterase while Alzheimer drugs and prophylactics, such as tacrine, are characterized by reversible binding. Historically, the guinea pig has been believed to be the best non-primate model for OP toxicology and medical countermeasure development because, similarly to humans, guinea pigs have low amounts of circulating OP metabolizing carboxylesterase. To explore the hypothesis that guinea pigs are the appropriate responder species for OP toxicology and medical countermeasure development, guinea pig acetylcholinesterase (gpAChE) was cloned into pENTR/D-TOPO, recombined into pT-Rex-DEST30 and expressed in Human Embryonic Kidney 293 cells. Recombinant gpAChE was purified to a specific activity of 800 U/mg using size exclusion and immobilized nickel affinity chromatography, with purity confirmed by gel electrophoresis. Ellman's assay was used to enzymatically characterize gpAChE, identifying a K(M) of 154±18.7 µmol L(-1) and a k(cat) of 4.79x10(4)±5.26x10(2) /sec. Apparent gpAChE IC50's for diisopropylfluorophosphate, dicrotophos, paraoxon, and an Alzheimer's drug, tacrine, were found to be 10.1±1.98, 337±108, 1.02±0.29 and 0.30±0.01 µmol L(-1), respectively. Apparent gpAChE inhibition constants for diisopropylfluorophosphate, dicrotophos, paraoxon, and tacrine were found to be 8.40±0.60, 4.50±0.30, 0.29±0.01 and 0.42±0.07 µmol L(-1), respectively. Lineweaver-Burk plots confirmed tacrine as a mixed inhibitor and paraoxon, dicrotophos and diisopropylfluorophosphate as irreversible non-competitive inhibitors. gpAChE bimolecular rate constants for diisopropylfluorophosphate, dicrotophos and paraoxon were found to be 1.44±0.33x10(4), 1.56±0.12x10(3) and 4.57± 0.23x10(5) L µmol(-1) min(-1), respectively. Although the blood levels of OP metabolizing carboxylesterases in the guinea pig are similar to the low levels in human blood, the gpAChE is different in its enzymology. Therefore, medical countermeasures against OP intoxication should be tested for efficacy with the recombinant form of gpAChE prior to initiating animal studies.
Topics: Acetylcholinesterase; Animals; Cholinesterase Inhibitors; Guinea Pigs; Humans; Organophosphorus Compounds; Recombinant Proteins
PubMed: 26216268
DOI: 10.2174/0929866522666150728114754 -
Chemosphere Sep 2016Insecticide resistance is usually associated with pests, but may also evolve in natural enemies. In this study, adult beetles of three distinct North American...
Insecticide resistance is usually associated with pests, but may also evolve in natural enemies. In this study, adult beetles of three distinct North American populations of Hippodamia convergens Guérin-Méneville, and the progeny of reciprocal crosses between the resistant and most susceptible population, were treated topically with varying concentrations of lambda-cyhalothrin and dicrotophos. In addition, the LD50s of both insecticides were applied in combination to resistant individuals. The developmental and reproductive performance of each population was assessed in the absence of insecticide exposure to compare baseline fitness. California and Kansas populations were susceptible to both materials, whereas Georgia (GA) beetles exhibited a resistance ratio (RR50) of 158 to lambda-cyhalothrin and 530 to dicrotophos. Inheritance of lambda-cyhalothrin resistance was X-linked, whereas inheritance of dicrotophos resistance was autosomal. Mortality of resistant beetles treated with a mixture of LD50s of both materials was twice that of those treated with lambda-cyhalothrin alone, but not significantly different from those receiving dicrotophos alone. Life history parameters were largely similar among populations, except that Georgia beetles had higher egg fertility relative to susceptible populations. We conclude that the high levels of resistance to lambda-cyhalothrin and dicrotophos in Georgia beetles reflect heavy loads of these insecticides in local environments, most likely the large acreage under intensive cotton cultivation.
Topics: Animals; California; Coleoptera; Female; Fertility; Georgia; Insecticide Resistance; Insecticides; Kansas; Male; Nitriles; Organophosphorus Compounds; Pyrethrins
PubMed: 27266835
DOI: 10.1016/j.chemosphere.2016.05.075 -
Journal of Economic Entomology Apr 2017Application of insecticides for stink bug management through overhead irrigation, also called chemigation, could reduce application costs, soil compaction, and...
Application of insecticides for stink bug management through overhead irrigation, also called chemigation, could reduce application costs, soil compaction, and applicator exposure, while enabling growers to treat multiple fields simultaneously. The objective of these laboratory experiments was to compare knockdown, survival, and efficacy of insecticides when appropriately diluted for ground sprayer and chemigation applications. Treatments included water, bifenthrin [0.11 kg (AI)/ha] and dicrotophos [0.56 kg (AI)/ha] diluted for a ground sprayer (93.5 liters/ha), bifenthrin and dicrotophos diluted for chemigation (25,396 liters/ha), and bifenthrin and dicrotophos plus adjuvants diluted for ground sprayer or chemigation. Two- to 14-day-old adults of Nezara viridula (L.), Euschistus servus (Say), and Halyomorpha halys (Stål) were briefly submerged in appropriately diluted insecticides and then introduced into a disposable petri dish with or without food. Dishes were placed in a growth chamber provisioned with digital video cameras to monitor knockdown and feeding after insecticide exposure. Knockdown was visually assessed at 24 h after treatment followed by mortality and recovery from knockdown at 48 h after treatment. All stink bugs were knocked down within 1 h and never recovered when exposed at ground sprayer dilutions. However, many bugs survived chemigation dilutions. Less than half of the stink bugs were knocked down when exposed to dicrotophos (with or without adjuvants) and survival ranged from 17 to 77%, compared to 7-90% survival when exposed to bifenthrin at chemigation dilutions. These results strongly suggest that chemigation applications for stink bug management need to be closely examined.
Topics: Animals; Heteroptera; Insect Control; Insecticides; Organophosphorus Compounds; Pyrethrins; Species Specificity
PubMed: 28334122
DOI: 10.1093/jee/tow315 -
International Journal of Clinical and... 2015Organophosphorus compound poisoning (OPC) is a global issue. The problem is aggravated with the threats of terrorist use, unintentional use and irresponsible practice as...
Organophosphorus compound poisoning (OPC) is a global issue. The problem is aggravated with the threats of terrorist use, unintentional use and irresponsible practice as happened recently in turmoil countries. The purpose of the current study was to investigate the old-generation antihistamine promethazine (PROM), a drug with multi pharmacological actions, as an antidote to extremely and highly toxic (WHO's class IA and IB) OPC poisoning in experimental animal models conducted on adult male wistar rats. Experimental groups were treated intraperitoneal (i.p.) with LD70 of methyl paraoxon (MPOX), class IA and dicrotophos (DCP), class IB alone and a combination of simultaneously i.p. injection of PROM. Mortality was recorded at 30 minutes, 1, 2, 3, 4, 24, 48 hours post injections. RBC-AChE was measured in survivals. MPOX was chosen for further studies with atropine (ATR) and pralidoxime (PAM). In addition to Kaplan-Meir survival analysis, serum lactate dehydrogenase (LDH) and creatinine kinase (CK) from serum were measured in all experimental groups with MPOX. The results revealed significant protection by PROM in both MPOX and DCP intoxicated rats, though the inhibition of RBC-AChE was high. The observed results show that groups treated with a combination of MPOX and PROM or MPOX, PROM, and PAM were protected higher than those treated with MPOX and ATR or MPOX, ATR, and PAM though statistically not significantly different (P ≤ 0.05). No effect was observed on the activity of LDH and CK. The study concludes that PROM may be effectively used in OPC poisoning. However, risk/benefits trials and further studies with different doses and other OPC groups are warranted.
PubMed: 26770383
DOI: No ID Found -
Current Pharmaceutical Design 2017Reversible cholinesterase inhibitors, when given prophylactically before exposure to organophosphates, are able to decrease organophosphate-induced mortality. However,...
BACKGROUND
Reversible cholinesterase inhibitors, when given prophylactically before exposure to organophosphates, are able to decrease organophosphate-induced mortality. However, the efficacy of pyridostigmine, the only pre-treatment substance approved by the US Federal Drug Administration, is unsatisfactory.
METHODS
In search of a better prophylactic compound, we determined in vivo the protection conferred by five cholinesterase inhibitors (ranitidine, physostigmine, tacrine, K-27 and pyridostigmine), which were administered in equitoxic dosage (1/4 of LD01) 30 minutes before exposure to the organophosphate dicrotophos. Efficacy was measured in rats by Cox analysis calculating the relative risk of death (RR), RR being 1 for the reference group which received dicrotophos and no prophylaxis.
RESULTS
K-27 (RR=0.06), physostigmine (RR=0.15), pyridostigmine (RR=0.22) and tacrine (RR=0.28) significantly (p ≤ 0.05) reduced dicrotophos-induced mortality in comparison to the reference group (dicrotophos without pre-treatment), whereas ranitidine (RR=0.86) had no significant influence. The experimental oxime K-27, when given before dicrotophos exposure, conferred the best in vivo protection. This was significantly (p ≤ 0.05) more efficacious than pre-treatment with any other tested compound. The differences in efficacy between the second best compound, physostigmine, and the less efficacious substances (tacrine and pyridostigmine) were also statistically significant.
CONCLUSION
These data indicate that K-27 can be considered a very efficacious prophylactic agent for organophosphate exposure.
Topics: Animals; Cholinesterase Inhibitors; Female; Humans; Male; Organophosphates; Organophosphorus Compounds; Oximes; Pre-Exposure Prophylaxis; Pyridinium Compounds; Rats; Rats, Wistar; Survival Rate; Treatment Outcome
PubMed: 27799040
DOI: 10.2174/1381612822666161027154303 -
Analytical Sciences : the International... 2017The overuse of organophosphorus pesticides on cotton production is a big concern in China today. Therefore, developing methods for the rapid screening and confirming of...
The overuse of organophosphorus pesticides on cotton production is a big concern in China today. Therefore, developing methods for the rapid screening and confirming of pesticide residues in textiles has become a top public health security priority. Here, a method was established for the rapid screening and quantifying of 11 kinds of organophosphorus pesticides (ethoprophos, coumaphos, profenofos, diazinon, ethion, parathion, phosalone, quinalphos, dicrotophos, azinphos methyl, and tribuphos) in textiles by high-performance liquid chromatography high-resolution mass spectrometry (HPLC-HRMS). Rapid screening and quantifying could be completed by using software of Peakview and MultiQuant. Samples were extracted by the method of modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) and analyzed in the positive mode with MS detection. The results showed that the limits of detection were between 0.1 and 5.0 ng g, with correlation coefficients above 0.9990. The recoveries were in the range of 70.3 - 109.8%, with relative standard deviations from 5.1 to 16.4%. This method is accurate and simple, which can be used in the rapid screening and quantitative analysis of 11 kinds of organophosphorus pesticides in textiles.
PubMed: 28890486
DOI: 10.2116/analsci.33.1027 -
The Science of the Total Environment Nov 2020During water years (WY) 2013-2017, the U.S. Geological Survey, National Water-Quality Assessment (NAWQA) Project, sampled the National Water Quality Network - Rivers and...
During water years (WY) 2013-2017, the U.S. Geological Survey, National Water-Quality Assessment (NAWQA) Project, sampled the National Water Quality Network - Rivers and Streams (NWQN) year-round and reported on 221 pesticides at 72 sites across the United States in agricultural, developed, and mixed land use watersheds. The Pesticide Toxicity Index (PTI) was used to estimate the potential chronic and acute toxicity to three taxonomic groups - fish, cladocerans, and benthic invertebrates. For invertebrates (either cladocerans, benthic invertebrates, or both), the maximum PTI score exceeded the predicted acute toxicity screening level at 18 of the 72 sites (25%) at some point during WY 2013-2017. The predicted toxicity of a single pesticide compound was found to overwhelm the toxicity of other pesticides in the mixtures after concentrations were toxicity weighted. For this study, about 71%, 72%, and 92% of the Fish-, Cladoceran-, and Benthic Invertebrate-PTI scores, respectively, had one pesticide compound primarily contributing to sample potential toxicity (>50%). There were 17 (13 insecticides, 2 herbicides, 1 fungicide, and 1 synergist) of the 221 pesticide compounds analyzed that were the primary drivers of potential toxicity in each water sample in which the PTI and TUmax (toxic unit score for the pesticide that makes the single largest contribution to the PTI) scores were above predicted chronic (>0.1) or acute (>1) toxicity levels for one of the three taxa. For cladocerans and benthic invertebrates, the drivers of predicted chronic (>0.1) and acute (>1) PTIs were mostly insecticides. For cladocerans, the pesticide compounds driving the PTI scores were bifenthrin, carbaryl, chlorpyrifos, diazinon, dichlorvos, dicrotophos, diflubenzuron, flubendiamide, and tebupirimfos. For benthic invertebrates, atrazine (an herbicide), as well as the insecticides - bifenthrin, carbaryl, carbofuran, chlorpyrifos, diazinon, dichlorvos, fipronil, imidacloprid, and methamidophos - were the drivers of predicted toxicity. For fish, there were three pesticide types that contributed the most to predicted chronic (>0.1) PTIs - acetochlor, an herbicide; carbendazim, a fungicide degradate; and piperonylbutoxide, a synergist.
Topics: Animals; Environmental Monitoring; Pesticides; Rivers; United States; Water; Water Pollutants, Chemical
PubMed: 32943215
DOI: 10.1016/j.scitotenv.2020.141285 -
Chemosphere Apr 2023Pesticides are a large group of pristine organic contaminants, which are widely discharged into environmental water due to agricultural activities. Hence, extraction,...
Pesticides are a large group of pristine organic contaminants, which are widely discharged into environmental water due to agricultural activities. Hence, extraction, determination, and removal of pesticides from water resources are necessary for human health. In this study, novel adsorbent was developed based on three-dimensional magnetic graphene coated with gold nanoparticles (3D-MG@AuNPs) for extraction of chlorpyrifos, dicrotophos, fenitrothion, and piperophos as four specific organophosphorus pesticides (OPPs) from wastewater and tap water samples. The proposed nanocomposite was characterized; FTIR and EDX are performed for the expected functional groups and elemental analysis, SEM showed the unique and spherical AuNPs are well dispersed over graphene sheets. In this investigation, the important parameters that have effect on the extraction efficiency, including the desorbing solvent, desorbing solvent volume, vortex time, the extraction time, adsorbent dosage, pH of sample solutions, and salt effect were evaluated. In conclusion, the measured amounts of the chosen OPPs were determined using the gas chromatography microelectron capture (μECD-GC) method. Limits of quantification (S/N ratio of 10) and detection (S/N ratio of 3) were attained at concentrations of 0.26-0.43 μg.L and 0.08-0.14 μg.L, respectively. According to the results of the investigations, the synthesized 3D-MG@AuNPs did not require any complicated sample preparation methods; therefore, it is a very good choice for solid magnetic phase extraction studies.
Topics: Humans; Water; Pesticides; Graphite; Gold; Organophosphorus Compounds; Metal Nanoparticles; Insecticides; Chlorpyrifos; Solvents; Solid Phase Extraction; Magnetic Phenomena; Limit of Detection
PubMed: 36754307
DOI: 10.1016/j.chemosphere.2023.138065