The widely used insecticide chlorpyrifos (CP) is known to inhibit acetylcholinesterase (AChE) activity attributed to result in various neurological disorders and acetylcholine-dependent organ functions including heart, skeletal muscle, lung, gastrointestinal tract, and central nervous systems. Enzyme reactivators, such as oximes, are known to restore AChE activity and mitigate adverse effects. The identification of compounds that reactivate AChE constitute agents with important therapeutic beneficial effects in cases of pesticide poisoning. However, the screening of novel drugs using traditional models may raise ethical concerns. This study aimed to investigate the potential of Drosophila melanogaster as a model organism for screening AChE reactivators, with a focus on organophosphate poisoning. The efficacy of several oximes, including pralidoxime, trimedoxime, obidoxime, methoxime, HI-6, K027, and K048, against CP-induced AChE activity inhibition in D. melanogaster was determined in silico, in vitro, and in vivo experiments. Molecular docking studies indicated a strong interaction between studied oximes and the active-site gorge of AChE. Data showed that selected oximes (100 μM) are effective in the reactivation of AChE inhibited by CP (10 μM) in vitro. Finally, in vivo investigations demonstrated that selected oximes, pralidoxime and K048 (1.5 ppm), reversed the locomotor deficits, inhibition of AChE activity as well as lowered the mortality rates induced by CP (0.75 ppm). Our findings contribute to utilization of D. melanogaster as a robust model for determination of actions of identified new AChE inhibitory agents with more effective therapeutic properties that those currently in use in the clinical practice in treatment of AChE associated disorders.

• Klíčová slova
• Drosophila melanogaster, Insecticides, acetylcholinesterase inhibition, locomotor, molecular docking, organophosphates, oximes, risk assessment, screening,
• MeSH
• acetylcholinesterasa * metabolismus   MeSH
• cholinesterasové inhibitory toxicita   MeSH
• Drosophila melanogaster * účinky léků   enzymologie   MeSH
• dursban * toxicita   MeSH
• insekticidy toxicita   MeSH
• modely u zvířat MeSH
• oximy * farmakologie   MeSH
• reaktivátory cholinesterázy * farmakologie   MeSH
• simulace molekulového dockingu * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylcholinesterasa * MeSH
• cholinesterasové inhibitory MeSH
• dursban * MeSH
• insekticidy MeSH
• oximy * MeSH
• reaktivátory cholinesterázy * MeSH

The Colorado potato beetle (CPB; Leptinotarsa decemlineata) is an important potato pest with known resistance to pyrethroids and organophosphates in Czechia. Decreased efficacy of neonicotinoids has been observed in last decade. After the restriction of using chlorpyrifos, thiacloprid and thiamethoxam by EU regulation, growers seek for information about the resistance of CPB to used insecticides and recommended antiresistant strategies. The development of CPB resistance to selected insecticides was evaluated in bioassays in 69 local populations from Czechia in 2017-2022 and in 2007-2022 in small plot experiments in Zabcice in South Moravia. The mortality in each subpopulation in the bioassays was evaluated at the field-recommended rates of insecticides to estimate the 50% and 90% lethal concentrations (LC50 and LC90, respectively). High levels of CPB resistance to lambda-cyhalothrin and chlorpyrifos were demonstrated throughout Czechia, without significant changes between years and regions. The average mortality after application of the field-recommended rate of lambda-cyhalothrin was influenced by temperature before larvae were sampled for bioassays and decreased with increasing temperature in June. Downwards trends in the LC90 values of chlorpyrifos and the average mortality after application of the field-recommended rate of acetamiprid in the bioassay were recorded over a 6-year period. The baseline LC50 value (with 95% confidence limit) of 0.04 mg/L of chlorantraniliprole was established for Czech populations of CPBs for the purpose of resistance monitoring in the next years. Widespread resistance to pyrethroids, organophosphates and neonicotinoids was demonstrated, and changes in anti-resistant strategies to control CPBs were discussed.

• MeSH
• brouci * účinky léků   MeSH
• dursban * farmakologie   MeSH
• insekticidy * farmakologie   MeSH
• larva účinky léků   MeSH
• neonikotinoidy * farmakologie   MeSH
• nitrily farmakologie   MeSH
• pyrethriny farmakologie   MeSH
• rezistence k insekticidům * MeSH
• Solanum tuberosum parazitologie   MeSH
• thiamethoxam MeSH
• thiaziny * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• cyhalothrin MeSH Prohlížeč
• dursban * MeSH
• insekticidy * MeSH
• neonikotinoidy * MeSH
• nitrily MeSH
• pyrethriny MeSH
• thiacloprid MeSH Prohlížeč
• thiamethoxam MeSH
• thiaziny * MeSH

Currently used pesticides (CUPs) were introduced to have lower persistence and bioaccumulation, and lesser bioavailability towards non-target species. Nevertheless, CUPs still represent a concern for both human health and the environment. India is an important agricultural country experiencing a conversion from the use of obsolete organochlorine pesticides to a newer generation of phytosanitary products. As for other developing countries, very little is known about the transfer of CUPs to the human diet in India, where systematic monitoring is not in place. In this study, we analyzed ninety four CUPs and detected thirty CUPs in several food products belonging to five types: cereals and pulses, vegetables, fruits, animal-based foods, and water. Samples were taken from markets in Delhi (aggregating food produced all over India) and in the periurban area of Dehradun (northern India) (representing food produced locally and through more traditional practices). Overall, chlorpyrifos and chlorpropham were the most detected CUPs with a detection frequency of 33% and 25%, respectively. Except for vegetables and fruits, the levels of CUPs in all other food types were significantly higher in samples from Delhi (p < 0.05). Exposure dosage of CUPs through different food matrices was calculated, and chlorpropham detected in potatoes had the maximum exposure dosage to humans (2.46 × 10-6 mg/kg/day). Risk analysis based on the hazard quotient technique indicated that chlorpyrifos in rice (2.76 × 10-2) can be a concern.

• Klíčová slova
• Currently used pesticides, Exposure dosage, Food samples, Health-risk analysis, Metropolitan and non-metropolitan city,
• MeSH
• chlorprofam analýza   MeSH
• dietární expozice analýza   MeSH
• dursban * MeSH
• kontaminace potravin analýza   MeSH
• lidé MeSH
• pesticidy * analýza   MeSH
• zelenina MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Indie MeSH
• Názvy látek
• chlorprofam MeSH
• dursban * MeSH
• pesticidy * MeSH

BACKGROUND: The microbiomes of some arthropods are believed to eliminate pesticides by chemical degradation or stimulation of the host immune system. The Colorado potato beetle (CPB; Leptinotarsa decemlineata) is an important agricultural pest with known resistance to used pesticides. We sought to analyze microbiome composition in CPB larvae from different sites and to identify the effect of pesticides on the microbiome of surviving and dead larvae after chlorpyrifos treatment in laboratory. Changes in the Lactococcus lactis community in larvae treated with chlorpyrifos and fed by potato leaves with L. lactis cover were studied by manipulative experiment. The microbiome was characterized by sequencing the 16S RNA gene. RESULTS: The microbiome of L. decemlineata larvae is composed of a few operational taxonomic units (OTUs) (Enterobacteriaceae, Pseudocitrobacter, Acinetobacter, Pseudomonas, L. lactis, Enterococcus, Burkholderia and Spiroplasma leptinotarsae). The microbiome varied among the samples from eight sites and showed differences in profiles between surviving and dead larvae. The survival of larvae after chlorpyrifos treatment was correlated with a higher proportion of L. lactis sequences in the microbiome. The S. leptinotarsa profile also increased in the surviving larvae, but this OTU was not present in all sampling sites. In manipulative experiments, larvae treated with L. lactis had five-fold lower mortality rates than untreated larvae. CONCLUSION: These results indicate that the microbiome of larvae is formed from a few bacterial taxa depending on the sampling site. A member of the gut microbiome, L. lactis, is believed to help overcome the toxic effects of chlorpyrifos in the larval gut. © 2023 Society of Chemical Industry.

• Klíčová slova
• Lactococcus lactis, larvae, microbiome, pesticide, resistance,
• MeSH
• brouci * MeSH
• dursban * farmakologie   MeSH
• larva MeSH
• pesticidy * farmakologie   MeSH
• Solanum tuberosum * genetika   MeSH
• střevní mikroflóra * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dursban * MeSH
• pesticidy * MeSH

Human exposure to organic contaminants is widespread. Many of these contaminants show adverse health effects on human population. Human biomonitoring (HBM) follows the levels and the distribution of biomarkers of exposure (BoE), but it is usually done in a targeted manner. Suspect and non-targeted screening (SS/NTS) tend to find BoE in an agnostic way, without preselection of compounds, and include finding evidence of exposure to predicted, unpredicted known and unknown chemicals. This study describes the application of high-resolution mass spectrometry (HRMS)-based SS/NTS workflow for revealing organic contaminants in urine of a cohort of 200 children from Slovenia, aged 6-9 years. The children originated from two regions, urban and rural, and the latter were sampled in two time periods, summer and winter. We tentatively identified 74 BoE at the confidence levels of 2 and 3. These BoE belong to several classes of pharmaceuticals, personal care products, plasticizers and plastic related products, volatile organic compounds, nicotine, caffeine and pesticides. The risk of three pesticides, atrazine, amitraz and diazinon is of particular concern since their use was limited in the EU. Among BoE we tentatively identified compounds that have not yet been monitored in HBM schemes and demonstrate limited exposure data, such as bisphenol G, polyethylene glycols and their ethers. Furthermore, 7 compounds with unknown use and sources of exposure were tentatively identified, either indicating the entry of new chemicals into the market, or their metabolites and transformation products. Interestingly, several BoE showed location and time dependency. Globally, this study presents high-throughput approach to SS/NTS for HBM. The results shed a light on the exposure of Slovenian children and raise questions on potential adverse health effects of such mixtures on this vulnerable population.

• Klíčová slova
• Biomarker, Exposome, Exposure, HBM4EU, High resolution mass spectrometry, Non-targeted,
• MeSH
• atrazin * analýza   MeSH
• biologické markery MeSH
• biologický monitoring MeSH
• diazinon MeSH
• dítě MeSH
• ethery MeSH
• kofein analýza   MeSH
• léčivé přípravky MeSH
• lidé MeSH
• monitorování životního prostředí metody   MeSH
• nikotin analýza   MeSH
• pesticidy * analýza   MeSH
• plastické hmoty MeSH
• polyethylenglykoly MeSH
• těkavé organické sloučeniny * MeSH
• vystavení vlivu životního prostředí analýza   MeSH
• zvláčňovadla analýza   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• atrazin * MeSH
• biologické markery MeSH
• diazinon MeSH
• ethery MeSH
• kofein MeSH
• léčivé přípravky MeSH
• nikotin MeSH
• pesticidy * MeSH
• plastické hmoty MeSH
• polyethylenglykoly MeSH
• těkavé organické sloučeniny * MeSH
• zvláčňovadla MeSH

Current-use pesticides (CUP) are extensively applied in both agricultural and urban settings. Exposure occurs mainly via the dietary pathway; however, other pathways such as inhalation or skin contact are also important. In this study, urinary levels of 12 CUP metabolites were investigated among 110 parent-child pairs during two seasons of 2020. Metabolites of pyrethroids (3-PBA, t/c-DCCA), chlorpyrifos (TCPY), and tebuconazole (TEB-OH) were detected in more than 60% of the samples. Chlorpyrifos metabolite was found at the highest concentration and tebuconazole was detected in almost all samples. CUP urinary metabolite levels were significantly higher in children in comparison to adults, except for tebuconazole, which was similar in both groups. In children, winter samples had significantly higher concentrations of pyrethroid and chlorpyrifos metabolites in comparison to the summer samples, but in adults, only chlorpyrifos metabolite concentrations were higher in the winter. No association between CUP urinary metabolite levels and proximity/surface of agricultural areas around residences was observed. Based on our findings, we suspect that CUP exposure is mainly driven by diet and that the effect of environmental exposure is less significant. Daily Intakes were estimated with three possible scenarios considering the amount of the metabolite excreted in urine and were compared to Acceptable Daily Intake values. Using a realistic scenario, exposure to chlorpyrifos exhibited the highest health risk, but still within a safe level. The Acceptable Daily Intake was exceeded only in one child in the case of cypermethrin. The cumulative risk assessment of pesticide mixtures having an effect on the nervous system, based on the total margin of exposure calculations, did not indicate any risk. The overall risk associated with pesticide exposure in the observed population was low. However, the risk observed using the worst-case scenario suggests the need for continuous evaluation of human exposure to such compounds, especially in children.

• Klíčová slova
• Chlorpyrifos, Cumulative risk assessment, HBM4EU, Pyrethroids, Tebuconazole, Urine,
• MeSH
• biologické markery moč   MeSH
• dospělí MeSH
• dursban * moč   MeSH
• insekticidy * moč   MeSH
• lidé MeSH
• pesticidy * moč   MeSH
• pyrethriny * moč   MeSH
• vystavení vlivu životního prostředí analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• biologické markery MeSH
• dursban * MeSH
• insekticidy * MeSH
• pesticidy * MeSH
• pyrethriny * MeSH

Escherichia coli phage SU10 belongs to the genus Kuravirus from the class Caudoviricetes of phages with short non-contractile tails. In contrast to other short-tailed phages, the tails of Kuraviruses elongate upon cell attachment. Here we show that the virion of SU10 has a prolate head, containing genome and ejection proteins, and a tail, which is formed of portal, adaptor, nozzle, and tail needle proteins and decorated with long and short fibers. The binding of the long tail fibers to the receptors in the outer bacterial membrane induces the straightening of nozzle proteins and rotation of short tail fibers. After the re-arrangement, the nozzle proteins and short tail fibers alternate to form a nozzle that extends the tail by 28 nm. Subsequently, the tail needle detaches from the nozzle proteins and five types of ejection proteins are released from the SU10 head. The nozzle with the putative extension formed by the ejection proteins enables the delivery of the SU10 genome into the bacterial cytoplasm. It is likely that this mechanism of genome delivery, involving the formation of the tail nozzle, is employed by all Kuraviruses.

• MeSH
• bakteriofágy * genetika   metabolismus   MeSH
• DNA virů genetika   MeSH
• fosmet * MeSH
• genom virový genetika   MeSH
• Podoviridae * genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA virů MeSH
• fosmet * MeSH

Concerns about the possible negative impacts of current use pesticides (CUPs) for both the environment and human health have increased worldwide. However, the knowledge on the occurrence of CUPs in soil and air and the related human exposure in Africa is limited. This study investigated the presence of 30 CUPs in soil and air at two distinct agricultural sites in South Africa and estimated the human exposure and related risks to rural residents via soil ingestion and inhalation (using hazard quotients, hazard index and relative potency factors). We collected 12 soil and 14 air samples over seven days during the main pesticide application season in 2018. All samples were extracted, purified and analyzed by high-performance liquid chromatography coupled with tandem mass spectrometry. In soils, nine CUPs were found, with chlorpyrifos, carbaryl and tebuconazole having the highest concentrations (up to 63.6, 1.10 and 0.212 ng g-1, respectively). In air, 16 CUPs were found, with carbaryl, tebuconazole and terbuthylazine having the highest levels (up to 25.0, 22.2 and 1.94 pg m-3, respectively). Spatial differences were observed between the two sites for seven CUPs in air and two in soils. A large dominance towards the particulate phase was found for almost all CUPs, which could be related to mass transport kinetics limitations (non-equilibrium) following pesticide application. The estimated daily intake via soil ingestion and inhalation of individual pesticides ranged from 0.126 fg kg-1 day-1 (isoproturon) to 14.7 ng kg-1 day-1 (chlorpyrifos). Except for chlorpyrifos, soil ingestion generally represented a minor exposure pathway compared to inhalation (i.e. <5%). The pesticide environmental exposure largely differed between the residents of the two distinct agricultural sites in terms of levels and composition. The estimated human health risks due to soil ingestion and inhalation of pesticides were negligible although future studies should explore other relevant pathways.

• Klíčová slova
• Africa, Air, Current use pesticides, Human exposure, Inhalation, Soil,
• MeSH
• dursban * MeSH
• lidé MeSH
• monitorování životního prostředí MeSH
• pesticidy * analýza   MeSH
• půda MeSH
• vystavení vlivu životního prostředí MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Jihoafrická republika MeSH
• Názvy látek
• dursban * MeSH
• pesticidy * MeSH
• půda MeSH

Poisoning with organophosphorus compounds (OPCs) represents an ongoing threat to civilians and rescue personal. We have previously shown that oximes, when administered prophylactically before exposure to the OPC paraoxon, are able to protect from its toxic effects. In the present study, we have assessed to what degree experimental (K-27; K-48; K-53; K-74; K-75) or established oximes (pralidoxime, obidoxime), when given as pretreatment at an equitoxic dosage of 25% of LD01, are able to reduce mortality induced by the OPC azinphos-methyl. Their efficacy was compared with that of pyridostigmine, the only FDA-approved substance for such prophylaxis. Efficacy was quantified in rats by Cox analysis, calculating the relative risk of death (RR), with RR=1 for the reference group given only azinphos-methyl, but no prophylaxis. All tested compounds significantly (p ≤ 0.05) reduced azinphos-methyl-induced mortality. In addition, the efficacy of all tested experimental and established oximes except K-53 was significantly superior to the FDA-approved compound pyridostigmine. Best protection was observed for the oximes K-48 (RR = 0.20), K-27 (RR = 0.23), and obidoxime (RR = 0.21), which were significantly more efficacious than pralidoxime and pyridostigmine. The second-best group of prophylactic compounds consisted of K-74 (RR = 0.26), K-75 (RR = 0.35) and pralidoxime (RR = 0.37), which were significantly more efficacious than pyridostigmine. Pretreatment with K-53 (RR = 0.37) and pyridostigmine (RR = 0.52) was the least efficacious. Our present data, together with previous results on other OPCs, indicate that the experimental oximes K-27 and K-48 are very promising pretreatment compounds. When penetration into the brain is undesirable, obidoxime is the most efficacious prophylactic agent already approved for clinical use.

• Klíčová slova
• Cox analysis, acetylcholine, azinphos-methyl, carbamates, cholinesterase, obidoxime, organophosphate, pesticide, pralidoxime, prophylaxis, rat,
• MeSH
• analýza přežití MeSH
• azinfos-methyl chemie   toxicita   MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• inhibiční koncentrace 50 MeSH
• krysa rodu Rattus MeSH
• molekulová hmotnost MeSH
• organofosforové sloučeniny chemie   toxicita   MeSH
• oximy farmakologie   MeSH
• pesticidy chemie   toxicita   MeSH
• potkani Wistar MeSH
• proporcionální rizikové modely MeSH
• riziko MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• azinfos-methyl MeSH
• cholinesterasové inhibitory MeSH
• organofosforové sloučeniny MeSH
• oximy MeSH
• pesticidy MeSH

Acute intoxication incidents due to neurotoxic organophosphate (OP) insecticides are occasionally reported, related either to suicidal attempts or occupational exposure due to the misuse of protective equipment. Among them, chlorpyrifos is a compound related to great controversy, which is still authorized and easily accessible in many countries around the world. However, to screen for its exposure markers, instrumental methods are commonly applied, which cannot enable rapid monitoring at an early stage of an intoxication. Therefore, in this study, a microfluidic paper-based analytical device (μPAD) able to rapidly screen for chlorpyrifos-oxon, the toxic chlorpyrifos metabolite, in human serum was developed and fully validated. The μPAD combines wax-printed butyrylcholinesterase (BChE) paper sensors, a lab-on-a-chip (LOC) prototype injector and a smartphone as the analytical detector. In principle, the wax-printed strips with adsorbed BChE are embedded into LOC injectors able to deliver samples and reagents on-demand. A smartphone reader was used to monitor the color development on the strips providing binary qualitative results. μPAD method performance characteristics were thoroughly evaluated in terms of specificity, detection capability (CCβ) and ruggedness. The developed analytical platform is rapid (results within 10 min), cost-efficient (0.70 €), potentially applicable at the point-of-need and attained a low CCβ (10 μg L-1 in human serum). Finally, μPAD characteristics were critically compared to well-established methods, namely an in-house BChE microplate assay and liquid chromatography tandem mass spectrometry.

• Klíčová slova
• Chlorpyrifos, Chlorpyrifos-oxon, Lab-on-a-chip, Microfluidic paper-based analytical device, Smartphone readout, Wax-printing,
• MeSH
• chytrý telefon MeSH
• dursban * MeSH
• laboratoř na čipu MeSH
• lidé MeSH
• mikrofluidika MeSH
• mikrofluidní analytické techniky * MeSH
• papír MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dursban * MeSH