Carbamate Insecticides Research Articles

Effects of acute and chronic bendiocarb exposure during early life stages of the pond snail (Lymnaea stagnalis)

ABSTRACT Environmental pollution is a global concern, and anthropogenic activities have contaminated natural water sources. Pesticides are one of the most recognised pollutants worldwide. Carbamates are a widely used pesticide family, and bendiocarb is a broad-spectrum carbamate insecticide detected in surface and groundwater. In the present work, acute lethal and chronic effects of bendiocarb on the early life stages of freshwater snail Lymnaea stagnalis were investigated. 24-h LC50 of bendiocarb on L. stagnalis embryos and juveniles was estimated at 20.39 (18.30–22.71) mg/L and 38.35 (29.58–52.89) mg/L, respectively. Chronic tests were conducted for 21-d to evaluate the potential effects of the environmentally realistic concentrations of bendiocarb (5 and 100 µg/L) on the embryos. Mortality, development, growth (embryo: egg ratio and shell height), heart rate, and hatching success were investigated. The test results showed that mortality, developmental progression, embryo: egg ratio, shell height measurements and cumulative hatching rate were not significantly impaired by chronic bendiocarb exposure compared to the control. However, bendiocarb induced increased heart rate in the exposed snails.

Predicting the insecticide-driven mutations in a crop pest insect: Evidence for multiple polymorphisms of acetylcholinesterase gene with potential relevance for resistance to chemicals.

The silverleaf whitefly Bemisia tabaci (Gennadius, 1889) (Homoptera: Aleyrodidae) is a serious invasive herbivorous insect pest worldwide. The excessive use of pesticides has progressively selected B. tabaci specimens, reducing the effectiveness of the treatments, and ultimately ending in the selection of pesticide-resistant strains. The management of this crop pest has thus become challenging owing to the level of resistance to all major classes of recommended insecticides. Here, we used in silico techniques for detecting sequence polymorphisms in ace1 gene from naturally occurring B. tabaci variants, and monitor the presence and frequency of the detected putative mutations from 30 populations of the silverleaf whitefly from Egypt and Pakistan. We found several point mutations in ace1-type acetylcholinesterase (ace1) in the studied B. tabaci variants naturally occurring in the field. By comparing ace1 sequence data from an organophosphate-susceptible and an organophosphate-resistant strains of B. tabaci to ace1 sequence data retrieved from GenBank for that species and to nucleotide polymorphisms from other arthropods, we identified novel mutations that could potentially influence insecticide resistance. Homology modeling and molecular docking analyses were performed to determine if the mutation-induced changes in form 1 acetylcholinesterase (AChE1) structure could confer resistance to carbamate and organophosphate insecticides. Mutations had small effects on binding energy (ΔGb) interactions between mutant AChE1 and insecticides; they altered the conformation of the peripheral anionic site of AChE1, and modified the enzyme surface, and these changes have potential effects on the target-site sensitivity. Altogether, the results from this study provide information on genic variants of B. tabaci ace1 for future monitoring insecticide resistance development and report a potential case of environmentally driven gene variations.

EPA targets methomyl insecticide

The US Environmental Protection Agency is proposing measures to reduce runoff and drift of the carbamate insecticide methomyl to protect vulnerable endangered species. The changes would amend the agency’s registration review decision made in October 2020 under the administration of former president Donald J. Trump. Methomyl is used on field crops, vegetables, and orchards. It is also approved for use in a fly-bait product. The EPA is evaluating the risks of methomyl to human health and the environment as part of a registration review process that happens every 15 years. The agency completed an evaluation of the effects of methomyl on threatened and endangered species in March 2021, finding that the insecticide is likely to adversely affect more than 1,000 species. It is now consulting with the Fish and Wildlife Service and the National Marine Fisheries Service to determine what mitigation measures are needed to protect affected species. In the

Electrospun zeolitic imidazolate framework-8/poly(lactic acid) nanofibers for pipette-tip micro-solid phase extraction of carbamate insecticides from environmental samples

In the present study, electrospun zeolitic imidazolate framework-8/poly(lactic acid) nanofibers were successfully synthesized and characterized as a potential nanosorbent for the pipette-tip micro-solid phase extraction of chlorpropham, pirimicarb, carbaryl, and methiocarb carbamate insecticides from environmental water samples. The extraction procedure was followed by gas chromatography/mass spectrometry separation and determination of the target analytes. All the effective parameters of the extraction procedure were optimized through the one variable at-a-time method. Thanks to the very simple extraction procedure as well as the application of electrospun nanofibers with high surface area, the four analytes were efficiently extracted with as lowest extraction times as practicable. Under the optimal conditions, the calibration plots of the analytes were obtained within broad linear dynamic ranges of 0.5 – 150 ng mL −1 for chlorpropham and pirimicarb plus 1.0 – 175 ng mL −1 for carbaryl and methiocarb, respectively. Besides, limits of detection as low as 0.2 and 0.15 ng mL −1 for chlorpropham and pirimicarb, respectively, as well as 0.5 ng mL −1 for carbaryl and methiocarb indicate the favorable sensitivity of the analytical procedure. The applicability of the developed method was evaluated by quantitative determination of the target analytes in four different environmental water samples. Relative recoveries higher than 88.0% shows the acceptable accuracy of the method in the quantitative determination of the four carbamate insecticides.

Susceptibility status of Anopheles gambiae complex in NNEWI community, Anambra state

Insecticide resistance in Anopheles mosquito is a major concern for vector control interventions in Nigeria. The present base-line study was carried out in Nnewi community, Nnewi North L.G.A., Anambra State, South-east Nigeria to investigate the insecticide susceptibility status of wild Anopheles gambiae s.l. to the four classes of insecticide used in vector control interventions. Anopheles larvae collected from different breeding sites in the community were reared to adults in the insectary and were morphologically identified following standard protocols. Two to five-day old adult female mosquitoes were exposed to different doses of organochlorine (4% DDT), organophosphate (0.25% pirimiphos-methyl and 5.0% malathaion), carbamate (0.1% propoxur and 0.1% bendiocarb) and pyrethroid (0.05% deltamethrin, 0.75% permethrin) insecticides using WHO susceptibility assay protocol. Data generated were subjected to probit analysis and analysis of variance. The organochlorine insecticide (DDT) had the highest knockdown time KDT50 (113.8 minutes) and KDT95 (182.1 minutes) while the carbamate insecticide, bendiocarb had the least KDT50 (8.97 minutes) and KDT95 (28.78 minutes). The mosquitoes were totally susceptible to propoxur and bendiocarb. The two pyrethroid used (deltamethrin and permethrin) and organochlorine (DDT) recorded percentage mortalities of 17.5%, 43.75% and 11.25% respectively. The report of organochlorine and pyrethroid resistance in the study area calls for immediate implementation of management action in the study area. The study has also shown that carbamate insecticides may be a suitable alternative to mitigate pyrethroid resistance in mosquito population in the study area.

Hapten designs based on aldicarb for the development of a colloidal gold immunochromatographic quantitative test strip.

The common carbamate insecticide aldicarb is considered one of the most acutely toxic pesticides. Herein, rational design was used to synthesize two haptens with spacers of different carbon chain lengths. The haptens were then used to immunize mice. The antibodies obtained were evaluated systematically, and a colloidal gold immunochromatographic strip was developed based on an anti-aldicarb monoclonal antibody. The 50% inhibition concentration and linear range of anti-aldicarb monoclonal antibody immunized with Hapten 1 were 0.432 ng/mL and 0.106–1.757 ng/mL, respectively. The cross-reactivities for analogs of aldicarb were all <1%. The limit of detection of the colloidal gold immunochromatographic strip was 30 μg/kg, and the average recoveries of aldicarb ranged from 80.4 to 110.5% in spiked samples. In the analysis of spiked samples, the test strip could accurately identify positive samples detected by the instrumental method in the GB 23200.112-2018 standard but produced some false positives for negative samples. This assay provides a rapid and accurate preliminary screening method for the determination of aldicarb in agricultural products and environments.

Enzyme inhibition-based biosensors using Acetylcholinesterase from Monopterus albus for detection of carbamates contamination

Insecticides are an example of an environmental contaminant that can cause harmful effects on various types of organisms. Implementation of continuous monitoring program is needed to ensure the level of contamination can be controlled. In this present study, acetylcholinesterase (AChE) from the brain of Monopterus albus was elucidated to determine the potential alternative source of biosensor kit, which is sensitive towards various insecticides, especially carbamates. AChE from M. albus brain was extracted and purified through ammonium sulfate precipitation followed by procainamide-based affinity chromatography. Carbamate insecticides were used, such as bendiocarb, carbaryl, carbofuran, methomyl, and propoxur, to test their ability to inhibit AChE activity. Bendiocarb and methomyl show the capability to inhibit almost half of the enzyme activity at 51.05 and 51.20 %, respectively, while carbaryl, propoxur, and carbofuran inhibit 43.03, 42.80, and 15.06 %, respectively. Bendiocarb and methomyl were selected, and M. albus AChE was separately exposed with different concentrations of those carbamates and half maximal inhibitory concentration; IC50 was determined at 0.874 and 1.639 ppm, respectively. A field trial was conducted by testing the enzyme with various vegetable samples. All samples show no significant effect on AChE activity, meaning there was no existence of insecticides in each sample (p > 0.05). This study could be used as an alternative source for developing biosensor kits for the environmental monitoring program.

Functional characterization of CYP6G4 from the house fly in propoxur metabolism and resistance

The house fly (Musca domestica L.) (Diptera: Muscidae) is a global vector that can transmit >250 human and animal diseases. The control of house flies has heavily relied on the application of various chemical insecticides. The carbamate insecticide propoxur has been widely used for the control of house flies, and resistance to propoxur has been documented in many house fly populations worldwide. Previous studies have identified several propoxur resistance-conferring mutations in the target protein acetylcholinesterase; however, the molecular basis for metabolic resistance to propoxur remains unknown. In this study, we investigated the involvement of CYP6G4, a cytochrome P450 overexpressed in many insecticide resistant populations of Musca domestica, in propoxur metabolism and resistance by using combined approaches of recombinant protein-based insecticide metabolism and the Drosophila GAL4/UAS transgenic system. The recombinant CYP6G4 and its redox partners (NADPH-dependent cytochrome P450 reductase and cytochrome b5) were functionally expressed in Escherichia coli. Metabolism experiments showed that CYP6G4 was able to transform propoxur with a turnover rate of around 0.79 min−1. Six metabolites were putatively identified, suggesting that CYP6G4 could metabolize propoxur via hydroxylation, O-depropylation and N-demethylation. Moreover, bioassay results showed that ectopic overexpression of CYP6G4 in fruit flies significantly increased their tolerance to propoxur. Our in vivo and in vitro data convincingly demonstrate that CYP6G4 contributes to propoxur metabolism and resistance.

Isoprocarb causes neurotoxicity of zebrafish embryos through oxidative stress-induced apoptosis

Isoprocarb is a widely used carbamate insecticide in agriculture and aquaculture. Overuse of isoprocarb always leaves toxic residues in soil and water, however, the potential ecotoxicity of isoprocarb to organisms is still confusing. In this study, zebrafish embryo was used as a model to evaluate the toxicity of isoprocarb. Zebrafish embryos (96 hpf) were separately exposed at different concentrations of isoprocarb. The mortality rate, hatchability rate, average heart beat of the zebrafish embryo were separately calculated. Our results suggested that exposure to isoprocarb induced developmental toxicity in zebrafish embryos. HE staining showed that exposure to isoprocarb caused developmental defect in the hindbrain of zebrafish embryos. As expected, the behavioral analysis also showed that the motor ability of zebrafish embryos were significantly inhibited following exposure to isoprocarb. In terms of mechanism, The expressions of genes involved in neurodevelopment signaling pathways, such as foxo3a, gfap, syn2a, elavl3 and sox19b, were inhibited in zebrafish embryos after exposure to isoprocarb. The acetylcholinesterase (AChE) activity was also reduced in isoprocarb-treated zebrafish embryos. Moreover, oxidative stress was induced by increasing the reactive oxygen species (ROS) level and decreasing the activity of antioxidant enzyme (SOD) after exposure to isoprocarb. Expectedly, acridine orange (AO) staining and the detection of some apoptosis-related genes revealed that oxidative stress resulted in apoptosis. In short, the expressions of genes associated with the neurodevelopmental signaling pathway are inhibited, and oxidative stress is also induced in zebrafish embryos after exposure to isoprocarb, which may be the molecular basics of isoprocarb-induced neurotoxicity in zebrafish embryos.

Organophosphate Insecticide Exposure Impacts Reproductive Success in Insensitive Acetylcholinesterase Anopheles gambiae Mosquitoes

Extensive use of insecticides has led to the selection of resistance alleles in malaria vectors threatening the control programs. Even if mosquitoes are not killed directly in the contact of insecticide-treated bed nets, their capacity to transmit malaria parasite could be decreased because of the consequences on their life-history traits after repeated exposure. The current work investigated the effects of organochlorine, carbamate, organophosphate, and pyrethroid insecticide exposure on the reproductive success in Anopheles gambiae s.s. Two Anopheles gambiae strains, AcerKis, KisKdr, were used. According to WHO recommendations, female mosquitoes of these resistant strains were exposed to discriminant doses of DDT, chlorpyriphos-methyl, bendiocarb, and permethrin insecticides. Surviving mosquitoes were then fed and allowed to lay eggs. Fecundity was assessed by examining the number of eggs per mosquito, the number of larvae per egg batch and larval hatching rates were used to evaluate the fertility. The data showed that AcerKis females surviving chlorpyriphos-methyl exposure significantly laid few eggs. No significant difference in the hatching rate was noticed in AcerKis females exposed to bendiocarb compared to their control. No significant effect on the fecundity and fertility was observed in KisKdr females exposed to permethrin. Our finding showed that organophosphate insecticides represented here by chlorpyriphos-methyl could hamper egg-laying in insensitive acetylcholinesterase An. gambiae female mosquitoes. This knowledge could help design alternative vector control strategies targeting fecundity and fertility in resistant malaria vectors.

Methyl benzoate derivatives: in vitro Paraoxonase 1 inhibition and in silico studies.

Paraoxonase 1 (PON1) can metabolize some compounds such as aromatic carboxylic acid and unsaturated aliphatic esters, arylesters, cyclic carbonate, plucuronide drugs, some carbamate insecticide classes, nerve gases, and lactone compounds. Methyl benzoate has recently been shown to display potent toxicity against several insect species. In the current study, we aimed to investigate the effect of the methyl benzoate compounds (1-17) on PON1 activity. Methyl benzoate compounds inhibited PON1 with KI values ranging from 25.10 ± 4.73 to 502.10 ± 64.72 μM. Compound 10 (methyl 4-amino-2-bromo benzoate) showed the best inhibition (KI = 25.10 ± 4.73 μM). Furthermore, using the ADME-Tox, Glide XP, and MM-GBSA tools of the Schrödinger Suite 2021-4, a complete ligand-receptor interaction prediction was performed to characterize the methyl benzoates (1-17), probable binding modalities versus the PON1.

Characterization of molecular and kinetic properties of two acetylcholinesterases from the Colorado potato beetle, Leptinotarsa decemlineata

The molecular and biochemical properties of two acetylcholinesterases (LdAChE1 and LdAChE2) from the Colorado potato beetle, Leptinotarsa decemlineata, were investigated in this study. Polyacrylamide gel electrophoresis in conjunction with western blotting with LdAChE1- or LdAChE2-specific antibodies suggested that LdAChE1 exists in a soluble form, whereas LdAChE2 exists in both soluble and amphiphilic forms with a glycophosphatidylinositol anchor. Both LdAChEs exist as homodimers with each monomer connected with a disulfide bond. LdAChE1 was the most highly expressed in the thorax followed by the head, leg, and abdomen, whereas LdAChE2 was the most highly expressed in the head, followed by the thorax, leg, and abdomen. The overall expression levels of LdAChE1, however, were higher than those of LdAChE2 in all examined tissues. Kinetic analysis using recombinant LdAChE1 and LdAChE2 showed that LdAChE2 has a 4.8-fold higher catalytic efficiency toward acetylthiocholine iodide compared to LdAChE1. LdAChE2 was more sensitive to organophosphorus and carbamate insecticides than LdAChE1. The addition of irreversibly phosphorylated LdAChE1 via paraoxon titration significantly reduced LdAChE2 inhibition by insecticides and glycoalkaloids, suggesting a sequestration role of soluble LdAChE1 in the chemical defense against xenobiotics. Taken together, LdAChE2 may be the main enzyme for synaptic transmission, thus serving as a toxicologically more relevant target, whereas the soluble LdAChE1 may function as a bioscavenger.

Carbosulfan Induced Reproductive Toxicity in Male Albino Rats (&lt;i&gt;Rattus norvegicus&lt;/i&gt;) and Protective effect of &lt;i&gt;Cissus quadrangularis&lt;/i&gt;

Carbosulfan is the most commonly used carbamate insecticide in the agriculture industry and is known to cause diverse toxicological effects on non-target organisms. Farmers are more susceptible to accidental consumption of insecticides owing to their unscientific use and ease of access. The present investigation was carried out to evaluate reproductive toxicity induced by carbosulfan and its amelioration using traditional Cissus quadrangularis plant extract. The rats were divided into six groups; (E1) control treated with 1% DMSO/kg bw, (E2) plant extract alone (1000 mg/kg bw), (E3) low dose of carbosulfan (3.4 mg/kg bw), (E4) high dose of carbosulfan (6.37 mg/kg bw), (E5) low dose (3.4 mg/kg bw) and (E6) high dose (6.37 mg/kg bw) carbosulfan co-treatment with Cissus quadrangularis extract (1000 mg/kg bw) for 60 days. The reproductive parameters including histology of testes, sperm count, motility, morphology, and hormonal assay (FSH, T, LH) were performed. Carbosulfan treated groups (E3 &amp; E4) were manifested histopathological alterations including tubular degeneration, disorganisation of cells, vacuolisation, and sloughing of germ cells into the tubular lumen. The hormonal level, sperm count, and motility were significantly decreased and the sperm abnormality rate was increased in the E4 group compared to the control group. The groups (E5 &amp; E6) co-treated with plant extract were significantly recovered compared to insecticide-treated groups (E3 &amp; E4). The histological and hormonal changes were attributed to the reprotoxic effects of the insecticide. However, co-treatment of plant extract significantly recovered the toxic effects caused by low concentration (E5) than the high concentration (E6) of carbosulfan.

Association between pesticide exposure and obesity: A cross-sectional study of 20,295 farmers in Thailand.

Background: Obesity isaseriousconditionbecause it is associated with other chronic diseaseswhichaffect the quality of life. In addition to problems associated with diet and exercise, recent research has foundthatpesticide exposure might be another important risk factor.The objective of this study was to determine the association between pesticide exposure and obesityamong farmers in Nakhon Sawan andPhitsanulokprovince, Thailand. Methods: This study was a population-based cross-sectional study. Data on pesticide use and obesity prevalence from 20,295 farmers aged 20 yearsandolder were collected usingan in-person interviewquestionnaire. The associationwas analysed using multivariable logistic regression, adjusted for its potential confounding factors. Results:Obesity was found to be associated with pesticide use in the past. The risk of obesity was significantly predicted by types of pesticides, including insecticides(OR=2.10, 95% CI 1.00-4.38), herbicides (OR=4.56, 95% CI 1.11-18.62), fungicides (OR=2.12, 95% CI 1.34-3.36), rodenticides (OR=2.55, 95% CI 1.61-4.05),and molluscicides(OR=3.40, 95% CI 2.15-5.40).Among 35 surveyed individual pesticides, 22 were significantly associated with higher obesity prevalence (OR = 1.78, 95% CI 1.10-2.88 to OR = 8.30, 95% CI 2.54-27.19),including herbicide butachlor, 15 insecticides (two carbamate insecticides,fiveorganochlorine insecticides, and eight organophosphate insecticides), andsixfungicides. Conclusion:This study found obesity in farmers in Nakhon Sawan andPhitsanulokprovince,Thailand,to be associated withthelong-termuse of several types of pesticides. The issue should receive more public attention, and pesticide use should be strictly controlled.

Pesticide use, agricultural outputs, and pesticide poisoning deaths in Japan

Objective Although pesticide poisonings occur worldwide, most high-income countries have not been severely affected. Japan is a key exception, with pesticide suicides becoming a major public health concern in the 1980s. We here report the epidemiology of lethal pesticide poisoning in Japan in relation to its pesticide regulation and agricultural output. Methods We obtained data on pesticide registration and sales from the Japan Plant Protection Association’s annual Pesticide Handbook, National Food and Agricultural Materials Inspection Center, and Food and Agriculture Organization of the United Nations. Data on deaths due to pesticide poisoning and population were obtained from Vital Statistics of Japan. We reviewed the registration status and hazard classification of pesticides in Japan and analysed the relationships between the use/sales, pesticides fatalities, and agricultural output. Results Five hundred and twenty-nine pesticide active ingredients are currently registered in Japan, including four WHO hazard class IB organophosphorus and carbamate insecticides. Paraquat was registered in 1962 as a liquid SL20 formulation. In 1986, restrictions were imposed on its sale/use and a 4.3% paraquat ion/4.1% diquat ion combination product registered by ICI. There were 221 pesticide poisoning fatalities in 2019, down from 2648 in 1986, a 92% reduction over 33 years. Self-poisoning was responsible for most pesticide deaths in both 1985 (2013/2476, 81.3%) and 2019 (146/221, 66.1%). Pesticide poisoning made up 8.6% of all suicides in 1985, down to 0.7% in 2019. Unintentional pesticide poisoning deaths also all fell by 83.8%, from 463 to 75. These reductions were associated with reduced sales of both OP/carbamate insecticides and paraquat/diquat but no apparent change in agricultural output across a broad range of crops. Conclusions Reduced use of highly hazardous pesticides and lowered concentration formulations in Japan were associated with major decreases in all deaths from pesticide poisoning and the proportion of all suicides due to pesticide ingestion.

Baseline susceptibility of Australian Myzus persicae (Hemiptera: Aphididae) to novel insecticides flonicamid and afidopyropen

The green peach aphid, Myzus persicae (Sulzer) is a significant global pest of a broad range of horticultural and grain crops. Control of M. persicae is primarily dependent on insecticides, however, this species has a high propensity to evolve insecticide resistance and has evolved resistance to over 80 insecticides from various chemical groups worldwide. In Australia, widespread resistance to carbamates, organophosphates, pyrethroids and neonicotinoids in M. persicae populations is commonplace. Given the ability of M. persicae to establish resistance to new chemistries quickly, programs are needed to monitor susceptibility to new insecticides before their widespread use. In this study, we used leaf-dip bioassays to generate sensitivity data and investigate potential cross-resistance in multiple field-collected populations of Australian M. persicae to two recently registered insecticides, flonicamid and afidopyropen. After 144 and 168 h exposure, we found little variation in the susceptibility of M. persicae populations to either flonicamid or afidopyropen, and no evidence of sensitivity shifts in the field. Additionally, there was no evidence of cross-resistance between flonicamid or afidopyropen and multiple known resistance mechanisms for carbamate, pyrethroid, organophosphate and neonicotinoid insecticides. The sensitivity data generated in this study prior to the evolution of field resistance provides a useful starting point for future resistance monitoring, and allows for the development and implementation of insecticide resistance management strategies which should prolong the long-term efficacy of flonicamid and afidopyropen against M. persicae.

Temperature affects the toxicity of pesticides to cercariae of the trematode Echinostoma trivolvis.

Global climate change is predicted to have significant impacts on ecological interactions such as host-parasite relationships. Increased temperatures may also interact with other anthropogenic stressors, such as chemical contaminants, to exacerbate or reduce parasite transmission. However, studies on the effects of pesticides on non-target species are typically conducted at one standard temperature, despite the toxicity of many agrochemicals being temperature-dependent. Furthermore, most studies assessing the effects of temperature on pesticide toxicity have been conducted on host organisms, limiting our understanding of how temperature affects the toxicity of pesticides to free-living parasite stages as they move through the environment in search of a host. Using the free-swimming cercariae stage of the trematode Echinostoma trivolvis, we examined how the toxicities of three different pesticides (a carbamate insecticide, strobilurin fungicide, and triazine herbicide) vary by temperature by monitoring cercarial swimming activity over time. Our three main findings were: 1) a strong main effect of temperature across all pesticide trials - higher temperatures caused cercariae to cease swimming activity earlier, likely due to an increased rate of energy expenditure, 2) atrazine, azoxystrobin, and carbaryl were directly toxic to cercariae to some degree, but not in a predictable dose-dependent manner, and 3) the temperature at which pesticide exposure occurs could affect its toxicity to cercariae. The interaction between pesticide and temperature was most evident in the azoxystrobin exposure; azoxystrobin caused cercariae to cease swimming activity earlier at 30°C but caused cercariae to maintain swimming activity longer at 18°C relative to their respective pesticide-free control treatments. These findings highlight the importance of conducting toxicity assays at multiple temperatures and suggest that the combined effects of pesticides and temperature on host-parasite interactions may be difficult to generalize.

Environmental Substances Associated with Chronic Obstructive Pulmonary Disease-A Scoping Review.

Chronic obstructive pulmonary disease (COPD) is a slowly developing non-communicable disease (NCD), causing non-reversible obstruction and leading to marked morbidity and mortality. Besides traditional risk factors such as smoking, some environmental substances can augment the risk of COPD. The European Human Biomonitoring Initiative (HBM4EU) is a program evaluating citizens’ exposure to various environmental substances and their possible health impacts. Within the HBM4EU, eighteen priority substances or substance groups were chosen. In this scoping review, seven of these substances or substance groups are reported to have an association or a possible association with COPD. Main exposure routes, vulnerable and high-exposure risk groups, and matrices where these substances are measured are described. Pesticides in general and especially organophosphate and carbamate insecticides, and some herbicides, lead (Pb), and polycyclic aromatic hydrocarbons (PAHs) showed an association, and cadmium (Cd), chromium (Cr and CrVI), arsenic (As), and diisocyanates, a possible association with COPD and/or decreased lung function. Due to long latency in COPD’s disease process, the role of chemical exposure as a risk factor for COPD is probably underestimated. More research is needed to support evidence-based conclusions. Generally, chemical exposure is a growing issue of concern, and prompt action is needed to safeguard public health.

Ligandability Assessment of Human Glutathione Transferase M1-1 Using Pesticides as Chemical Probes.

Glutathione transferases (GSTs; EC 2.5.1.18) form a group of multifunctional enzymes that are involved in phase II of the cellular detoxification mechanism and are associated with increased susceptibility to cancer development and resistance to anticancer drugs. The present study aims to evaluate the ligandability of the human GSTM1-1 isoenzyme (hGSTM1-1) using a broad range of structurally diverse pesticides as probes. The results revealed that hGSTM1-1, compared to other classes of GSTs, displays limited ligandability and ligand-binding promiscuity, as revealed by kinetic inhibition studies. Among all tested pesticides, the carbamate insecticide pirimicarb was identified as the strongest inhibitor towards hGSTM1-1. Kinetic inhibition analysis showed that pirimicarb behaved as a mixed-type inhibitor toward glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB). To shine a light on the restricted hGSTM1-1 ligand-binding promiscuity, the ligand-free crystal structure of hGSTM1-1 was determined by X-ray crystallography at 1.59 Å-resolution. Comparative analysis of ligand-free structure with the available ligand-bound structures allowed for the study of the enzyme’s plasticity and the induced-fit mechanism operated by hGSTM1-1. The results revealed important structural features of the H-site that contribute to xenobiotic-ligand binding and specificity. It was concluded that hGSTM1-1 interacts preferentially with one-ring aromatic compounds that bind at a discrete site which partially overlaps with the xenobiotic substrate binding site (H-site). The results of the study form a basis for the rational design of new drugs targeting hGSTM1-1.

Assessment of Five Pesticides as Endocrine-Disrupting Chemicals: Effects on Estrogen Receptors and Aromatase.

Pesticides are widely applied all over the world, and pesticide exposure can induce different biological effects posing a possible threat to human health. Due to their effects on the endocrine system, some pesticides are classified as endocrine disruptors. The aim of the study is to assess the interference of five pesticides on estrogen biosynthesis and estrogen signaling. Three neonicotinoid insecticides (Acetamiprid, Clothianidin, and Thiamethoxam), a carbamate insecticide (Methiocarb) and a herbicide (Oxadiazon) were tested. The effect of pesticides on estrogen biosynthesis was studied through an ELISA assay using a recombinant form of human aromatase, the enzyme that catalyzes the transformation of androgens to estrogens. Moreover, the effect of pesticides on estrogen signaling was assessed using a gene reporter assay on MELN cells, which measures estrogen receptor-mediated estrogenic activity. The results of the ELISA assay showed that the pesticides did not alter aromatase activity (no interference with estrogen biosynthesis), while the results of the gene reporter assay showed that only Methiocarb was able to alter estrogen signaling at high doses. The estrogenic activity of Methiocarb, expressed as 17β-estradiol equivalency factor (EEF), was equal to 8.0 × 10−8. In conclusion, this study suggested that Methiocarb should be considered a potential endocrine disruptor.