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Journal of Toxicologic Pathology Jan 2017The aim of this study was to investigate the lethal and sublethal toxicity of a methomyl-based insecticide in , as methomyl-based insecticides are applied in massive...
The aim of this study was to investigate the lethal and sublethal toxicity of a methomyl-based insecticide in , as methomyl-based insecticides are applied in massive amounts and agrochemicals have effects on the decline in amphibian populations. To evaluate the toxic effects of methomyl from agricultural application, a methomyl-based insecticide containing 40% methomyl was selected. The median lethal concentration of 96 hours of methomyl exposure was 8.69 ppm for tadpoles. The lethal concentration also produced severe histological damage in the livers and kidneys of the exposed tadpoles. The sublethal concentration used for methomyl was 144 ppb during the metamorphosis period. It was found that the sublethal concentration of the methomyl compound could decrease growth, metamorphosis time, and size, disturb biochemical parameters, and produce histological damage. In livers, methomyl effects increased oxidative stress and dramatically decreased the glycogen level of the treated froglets. Mononuclear infiltration, blood congestion, amorphous substances, and hepatocytes vacuolization were observed throughout liver tissue. The methomyl-based insecticide also increased oxidative stress and decreased nitric oxide levels in the kidneys of the exposed froglets. Renal tissue damage including blood congestion, amorphous substances, and Bowman's capsule spaces reduction were found in the methomyl exposure group. The methomyl compound also produced vacuoles in various stages of oocytes, but no histological damage was found in testicular tissue. Our results indicated strong toxic effects of the methomyl-based insecticide on s, a broadly tolerant anuran.
PubMed: 28190921
DOI: 10.1293/tox.2016-0039 -
International Journal of Molecular... Dec 2022Methomyl is one of the most important carbamates that has caused potential hazardous effects on both human beings and the environment. Here, we systematically...
Methomyl is one of the most important carbamates that has caused potential hazardous effects on both human beings and the environment. Here, we systematically investigated the hydrolysis mechanism of methomyl catalyzed by esterase PestE using molecular dynamics simulations (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations. The hydrolysis mechanism involves two elementary steps: (Ⅰ) serine-initiated nucleophilic attack and (Ⅱ) C-O bond cleavage. Our work elicits the atomic level details of the hydrolysis mechanism and free energy profiles along the reaction pathway. The Boltzmann-weighted average potential barriers are 19.1 kcal/mol and 7.5 kcal/mol for steps Ⅰ and Ⅱ, respectively. We identified serine-initiated nucleophilic attack as the rate determining-step. The deep learning-based prediction model indicated that the barrier of the rate-determining step is 15.4 kcal/mol, which is in good agreement with the calculated results using Boltzmann-weighted average method. We have elucidated the importance of the protein-substrate interactions and the roles of the key active site residues during the hydrolysis process through noncovalent interactions analysis and electrostatic potential (ESP) analysis. The results provide practical value for achieving efficient degradation of carbamates by hydrolases.
Topics: Humans; Hydrolysis; Esterases; Molecular Dynamics Simulation; Methomyl; Carbamates; Quantum Theory
PubMed: 36613879
DOI: 10.3390/ijms24010433 -
Veterinary Medicine and Science Mar 2021Veterinary biocides used in animal husbandry have the potential to cause human health concerns. Biocidal products for veterinary use, which contain pesticides approved...
Veterinary biocides used in animal husbandry have the potential to cause human health concerns. Biocidal products for veterinary use, which contain pesticides approved in Korea, comprise 49 active ingredients within 234 products. Within 17 of these products there are 3 ingredients which are highly hazardous pesticides: coumaphos, dichlorvos and methomyl. In this study, the content of the active ingredients of 160 products sold domestically was investigated. Samples were collected for 119 biocidal products for veterinary use. These were analysed by high-performance liquid chromatography (HPLC) and gas chromatography (GC). Seventeen products were noncompliant (insufficient or excess quantity of active ingredients). The ingredients that were below the stated concentrations were amitraz, chlorpyrifos-methyl, cypermethrin, cyromazine, dichlorvos, fipronil, muscamone and trichlorfon. The ingredients that exceeded the stated concentrations were abamectin, fluvalinate and pyriproxyfen. The noncompliance rate in biocidal products for veterinary use was 9.19%. The results of this study show that three highly hazardous pesticides (coumaphos, dichlorvos and methomyl) and 10 active ingredients (abamectin, amitraz, chlorpyrifos-methyl, cypermethrin, cyromazine, fipronil, fluvalinate, muscamone, pyriproxyfen and trichlorfon) deviated from the stated concentrations. Thus, management plans should be established to ensure compliant veterinary drugs by post-distribution quality control, such as planning for regular inspection.
Topics: Chromatography, High Pressure Liquid; Pesticides; Republic of Korea; Veterinary Medicine
PubMed: 33107216
DOI: 10.1002/vms3.385 -
Journal For Immunotherapy of Cancer Apr 2024Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard treatment for patients with non-small cell lung cancer (NSCLC) lacking driver gene...
BACKGROUND
Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard treatment for patients with non-small cell lung cancer (NSCLC) lacking driver gene mutations. Reliable biomarkers are essential for predicting treatment outcomes. Emerging evidence from various cancers suggests that early assessment of serum metabolites could serve as valuable biomarkers for predicting outcomes. This study aims to identify metabolites linked to treatment outcomes in patients with advanced NSCLC undergoing first-line or second-line therapy with programmed cell death 1 (PD-1) inhibitors plus chemotherapy.
METHOD
200 patients with advanced NSCLC receiving either first-line or second-line PD-1 inhibitor plus chemotherapy, and 50 patients undergoing first-line chemotherapy were enrolled in this study. The 200 patients receiving combination therapy were divided into a Discovery set (n=50) and a Validation set (n=150). These sets were further categorized into respond and non-respond groups based on progression-free survival PFS criteria (PFS≥12 and PFS<12 months). Serum samples were collected from all patients before treatment initiation for untargeted metabolomics analysis, with the goal of identifying and validating biomarkers that can predict the efficacy of immunotherapy plus chemotherapy. Additionally, the validated metabolites were grouped into high and low categories based on their medians, and their relationship with PFS was analyzed using Cox regression models in patients receiving combination therapy.
RESULTS
After the impact of chemotherapy was accounted for, two significant differential metabolites were identified in both the Discovery and Validation sets: N-(3-Indolylacetyl)-L-alanine and methomyl (VIP>1 and p<0.05). Notably, upregulation of both metabolites was observed in the group with a poorer prognosis. In the univariate analysis of PFS, lower levels of N-(3-Indolylacetyl)-L-alanine were associated with longer PFS (HR=0.59, 95% CI, 0.41 to 0.84, p=0.003), and a prolonged PFS was also indicated by lower levels of methomyl (HR=0.67, 95% CI, 0.47 to 0.96, p=0.029). In multivariate analyses of PFS, lower levels of N-(3-Indolylacetyl)-L-alanine were significantly associated with a longer PFS (HR=0.60, 95% CI, 0.37 to 0.98, p=0.041).
CONCLUSION
Improved outcomes were associated with lower levels of N-(3-Indolylacetyl)-L-alanine in patients with stage IIIB-IV NSCLC lacking driver gene mutations, who underwent first-line or second-line therapy with PD-1 inhibitors combined with chemotherapy. Further exploration of the potential predictive value of pretreatment detection of N-(3-Indolylacetyl)-L-alanine in peripheral blood for the efficacy of combination therapy is warranted.
STATEMENT
The combination of ICIs and chemotherapy has established itself as the new standard of care for first-line or second-line treatment in patients with advanced NSCLC lacking oncogenic driver alterations. Therefore, identifying biomarkers that can predict the efficacy and prognosis of immunotherapy plus chemotherapy is of paramount importance. Currently, the only validated predictive biomarker is programmed cell death ligand-1 (PD-L1), but its predictive value is not absolute. Our study suggests that the detection of N-(3-Indolylacetyl)-L-alanine in patient serum with untargeted metabolomics prior to combined therapy may predict the efficacy of treatment. Compared with detecting PD-L1 expression, the advantage of our biomarker is that it is more convenient, more dynamic, and seems to work synergistically with PD-L1 expression.
Topics: Humans; B7-H1 Antigen; Biomarkers; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Metabolomics; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38641349
DOI: 10.1136/jitc-2023-008190 -
International Journal of Environmental... Sep 2021The present study was performed to fabricate a titanium dioxide (TiO) nanocatalyst with proper characteristics for the removal of some insecticides (dimethoate and...
The present study was performed to fabricate a titanium dioxide (TiO) nanocatalyst with proper characteristics for the removal of some insecticides (dimethoate and methomyl) from aqueous media. A TiO catalyst of regular (TiO-commercial-/HO/UV) or nano (TiO-synthesized-/HO/UV) size was employed as an advanced oxidation process by combining it with HO under light. Moreover, the total detoxification of insecticides after treatment with the most effective system (TiO(s)/HO/UV) was also investigated through exploring the biochemical alterations and histopathological changes in the liver and kidneys of the treated rats. Interestingly, the present study reported that degradation rates of the examined insecticides were faster using the TiO catalyst of nano size. Complete degradation of the tested insecticides (100%) was achieved under the TiO(s)/HO/UV system after 320 min of irradiation. The half-life values of the tested insecticides under HO/TiO(c)/UV were 43.86 and 36.28 for dimethoate and methomyl, respectively, whereas under the HO/TiO(c)/UV system, the half-life values were 27.72 and 19.52 min for dimethoate and methomyl, respectively. On the other hand, no significant changes were observed in the biochemical and histopathological parameters of rats administrated with water treated with TiO(s)/HO/UV compared to the control, indicating low toxicity of the TiO nanocatalyst-. Altogether, the advanced oxidation processes using TiO nanocatalyst can be considered as a promising and effective remediation technology for the complete detoxification of methomyl and dimethoate in water. However, further future research is needed to identify the possible breakdown products and to verify the safety of the used nanomaterials.
Topics: Animals; Catalysis; Hydrogen Peroxide; Insecticides; Oxidation-Reduction; Rats; Titanium; Ultraviolet Rays; Water; Water Pollutants, Chemical
PubMed: 34501865
DOI: 10.3390/ijerph18179278 -
Environmental Science & Technology Jan 2022Process wastewaters from food, beverage, and feedstock facilities, although regulated, are an under-investigated environmental contaminant source. Food process...
Process wastewaters from food, beverage, and feedstock facilities, although regulated, are an under-investigated environmental contaminant source. Food process wastewaters (FPWWs) from 23 facilities in 17 U.S. states were sampled and documented for a plethora of chemical and microbial contaminants. Of the 576 analyzed organics, 184 (32%) were detected at least once, with concentrations as large as 143 μg L (6:2 fluorotelomer sulfonic acid), and as many as 47 were detected in a single FPWW sample. Cumulative per/polyfluoroalkyl substance concentrations up to 185 μg L and large pesticide transformation product concentrations (e.g., methomyl oxime, 40 μg L; clothianidin TMG, 2.02 μg L) were observed. Despite 48% of FPWW undergoing disinfection treatment prior to discharge, bacteria resistant to third-generation antibiotics were found in each facility type, and multiple bacterial groups were detected in all samples, including total coliforms. The exposure-activity ratios and toxicity quotients exceeded 1.0 in 13 and 22% of samples, respectively, indicating potential biological effects and toxicity to vertebrates and invertebrates associated with the discharge of FPWW. Organic contaminant profiles of FPWW differed from previously reported contaminant profiles of municipal effluents and urban storm water, indicating that FPWW is another important source of chemical and microbial contaminant mixtures discharged into receiving surface waters.
Topics: Animals; Beverages; Environmental Monitoring; Rivers; Wastewater; Water Pollutants, Chemical
PubMed: 34967600
DOI: 10.1021/acs.est.1c06821 -
PloS One 2017Methomyl is currently used as a toxicant for the attracticide BioAttract in cotton and vegetables in China. However, methomyl is highly toxic to non-target organisms and...
Methomyl is currently used as a toxicant for the attracticide BioAttract in cotton and vegetables in China. However, methomyl is highly toxic to non-target organisms and a more environmental friendly acceptable alternative is required. Larvae of three lepidopteran insects Helicoverpa armigera, Agrotis ipsilon and Spodoptera litura are important pests of these crops in China. In the present study, the toxicity of 23 commonly used insecticides were tested on H. armigera, then tested the susceptibility of A. ipsilon and S. litura moths to the insecticides which were the most toxic to H. armigera, and the acute toxicity of the most efficacious insecticides were further investigated under laboratory conditions. Chlorantraniliprole, emamectin benzoate, spinetoram, spinosad and methomyl exhibited high levels of toxicity to H. armigera moths with a mortality of 86.67%, 91.11%, 73.33%, 57.78% and 80.00%, respectively, during 24 h period at the concentration of 1 mg a.i. L-1. Among these five insecticides, A. ipsilon and S. litura moths were more sensitive to chlorantraniliprole, emamectin benzoate and methomyl. The lethal time (LT50) values of chlorantraniliprole and methomyl were shorter than emamectin benzoate for all three lepidopteran moth species at 1000 mg a.i. L-1 compared to concentrations of 500, 100 and 1 mg a.i L-1. Chlorantraniliprole was found to have similar levels of toxicity and lethal time on the three lepidopteran moths tested to the standard methomyl, and therefore, can be used as an alternative insecticide to methomyl in the attracticide for controlling these pest species.
Topics: Animals; Biological Assay; Crop Protection; Drug Combinations; Female; Insect Control; Ivermectin; Larva; Macrolides; Male; Methomyl; Moths; Pesticides; ortho-Aminobenzoates
PubMed: 28658277
DOI: 10.1371/journal.pone.0180255 -
Ecotoxicology and Environmental Safety Dec 2023The extensive use of carbamate pesticides has led to a range of environmental and health problems, such as surface and groundwater contamination, and endocrine disorders...
The extensive use of carbamate pesticides has led to a range of environmental and health problems, such as surface and groundwater contamination, and endocrine disorders in organisms. In this study, we focused on examining the effects of toxic exposure to the carbamate pesticide methomyl on the hatching, morphology, immunity and developmental gene expression levels in zebrafish embryos. Four concentrations of methomyl (0, 2, 20, and 200 μg/L) were administered to zebrafish embryos for a period of 96 h. The study found that exposure to methomyl accelerated the hatching process of zebrafish embryos, with the strongest effect recorded at the concentration of 2 μg/L. Methomyl exposure also trigged significantly reductions in heart rate and caused abnormalities in larvae morphology, and it also stimulated the synthesis and release of several inflammatory factors such as IL-1β, IL-6, TNF-α and INF-α, lowered the IgM contents, ultimately enhancing inflammatory response and interfering with immune function. All of these showed the significant effects on exposure time, concentration and their interaction (Time × Concentration). Furthermore, the body length of zebrafish exposed to methomyl for 96 h was significantly shorter, particularly at higher concentrations (200 μg/L). Methomyl also affected the expression levels of genes associated with development (down-regulated igf1, bmp2b, vasa, dazl and piwi genes), demonstrating strong developmental toxicity and disruption of the endocrine system, with the most observed at the concentration of 200 μg/L and 96 h exposure to methomyl. The results of this study provide valuable reference information on the potential damage of methomyl concentrations in the environment on fish embryo development, while also supplementing present research on the immunotoxicity of methomyl.
Topics: Animals; Zebrafish; Methomyl; Embryo, Nonmammalian; Endocrine System; Pesticides; Carbamates; Larva; Water Pollutants, Chemical
PubMed: 37976935
DOI: 10.1016/j.ecoenv.2023.115684 -
Toxins Aug 2022The locusts (Bey-Bienko) and (Zubovski) (Orthoptera Acrididae) and the leaf beetle (Joannis) (Coleoptera, Chrysomelidae) are economically devastating insect species...
The locusts (Bey-Bienko) and (Zubovski) (Orthoptera Acrididae) and the leaf beetle (Joannis) (Coleoptera, Chrysomelidae) are economically devastating insect species in the desert steppes of Northern China. Control is mainly and frequently dependent on highly toxic chemicals. To date, there have been no complete and comprehensive reports of insecticide applications to these key pests. In this study, laboratory bioassays were carried out to determine and compare the toxicity of twelve insecticides to three outbreaking insects, , , and from three typical desert steppe regions, SZWQ, XHQ and WLTQQ, respectively. The responses of the two locust species and the leaf beetle were evaluated by topical application and leaf dip bioassay techniques across a range of concentrations to develop dosage-mortality regressions. The insecticides tested included six chemical insecticides (β-cypermethrin, imidacloprid, phoxim, λ-cyhalothrin, methomyl, chlorantraniliprole) and six biogenic insecticides (spinosad, avermectin, rotenone, matrine, azadiracthin, and methoxyfenozide). The results showed that phoxim, λ-cyhalothrin, β-cypermethrin and spinosad showed highly toxic activity to , , and , while methonyl, chlorantraniliprole, and rotenone were moderately toxic to both locust species and the leaf beetle. The LC values of matrine, azadiractin, and avermectin were more than 1 μg a.i./adult for and , the LC values of which were higher 2 g/L for . Our findings complement information from previous similar studies and will inform future studies relating to the control of outbreaking insects, such as , , and in desert steppes of northern China. This study is also expected to provide basic data on the use of chemical and biogenic insecticides for application in desert steppes.
Topics: Animals; China; Coleoptera; Insecta; Insecticides; Rotenone
PubMed: 36006208
DOI: 10.3390/toxins14080546 -
Metabolites Aug 2023Many pesticides have been identified as endocrine and metabolism-disrupting chemicals with hepatotoxic effects. However, data are limited for insecticides in the...
Many pesticides have been identified as endocrine and metabolism-disrupting chemicals with hepatotoxic effects. However, data are limited for insecticides in the n-methyl carbamate class, including methomyl. Here, we investigate the liver and systemic metabolic effects of methomyl in a mouse model. We hypothesize that methomyl exposure will disrupt xenobiotic and intermediary metabolism and promote hepatic steatosis in mice. Male C57BL/6 mice were exposed daily to 0-5 mg/kg methomyl for 18 days. Mice were fed water and regular chow diet ad libitum. Metabolic phenotyping was performed, and tissue samples were collected. Effects were generally greatest at the highest methomyl dose, which induced . Methomyl decreased whole body weight while the liver:body weight and testes:body weight ratios were increased. Hepatic steatosis increased while plasma LDL decreased. Fasting blood glucose and the glucose tolerance test area under the curve decreased along with hepatic glycogen stores. Methomyl, however, did not increase liver oxidative stress or injury. Collectively, these data demonstrate that methomyl disrupts hepatic xenobiotic and intermediary metabolism while increasing the testes:body weight ratio, suggesting that it may be an endocrine disrupting chemical. Besides methomyl's known action in cholinesterase inhibition, it may be involved in aryl hydrocarbon receptor activation. The potential impact of n-methyl carbamate insecticides on metabolic health and diseases, including toxicant-associated steatotic liver disease (TASLD), warrants further investigation.
PubMed: 37623845
DOI: 10.3390/metabo13080901