Natural pyrethrins induced developmental toxicity of zebrafish swim bladder in vivo and genotoxicity of lung cells in vitro.

Natural pyrethrins (NPs) are insecticidal compounds isolated and extracted from pyrethrum flowers and are primarily use to control sanitary pests. The lungs become the main target after exposure, and its use may pose potential hazards to respiratory health. Therefore, in this paper, the toxic effects of NPs on human lung cells A549 were investigated and the risk of respiratory toxicity of NPs was studied using zebrafish swim bladder as a model. The results showed that NPs induced cytotoxicity, caused oxidative DNA damage and triggered mitochondria-mediated apoptosis. In addition, exposure to NPs decreased zebrafish embryo survival, hatchability, and heartbeat, and may inhibit normal swim bladder development by disrupting Wnt and Hedgehog signaling pathways. In conclusion, our results suggest that NPs can induce cytotoxicity in A549 in vitro and developmental toxicity in zebrafish in vivo. This study provides a conceptual basis for understanding the mechanisms of toxicity of NPs and assessing respiratory health risks in humans.

Cardiotoxicity risk induced by sanitary insecticide Dimefluthrin.

Dimefluthrin (DIM) is a commonly utilized sanitary insecticide, predominantly employed for indoor pest management within residential and public environments directly interacting with human habitation. However, the usage of DIM is escalating with increasing mosquito resistance, prompting concerns about its health risks. Here, using zebrafish as a research model, we systematically evaluated DIM's impact on human health. Findings revealed significant health hazards during embryonic development, including reduced hatching rates, shortened body lengths, and organ malformations, notably affecting the heart. It was explored the mechanism of DIM-induced cardiotoxicity in zebrafish, and histopathological analyses revealed that DIM resulted in ventricular linearization in zebrafish embryos. Antioxidant enzyme activities were reduced and cardiac reactive oxygen species (ROS) accumulated after DIM exposure, suggesting clear signs of oxidative stress. Additionally, acridine orange (AO) staining and caspase-3 immunofluorescence demonstrated cardiac apoptosis in Tg (kdrl: EGFP) zebrafish. qPCR analysis implied that DIM induced apoptosis via the p53/Caspase pathway by up-regulating the expression levels of p53, cytochrome C (cyto-C), caspase-9, and caspase-3. Together, our work provided a systematic perspective on the cardiotoxicity of sanitary pesticides, which could offer opportunities for future risk management.

3D-QSAR model-oriented optimization of Pyrazole ß-Ketonitrile derivatives with diphenyl ether moiety as novel potent succinate dehydrogenase inhibitors.

BACKGROUND: Succinate dehydrogenase inhibitor (SDHI) fungicides play important roles in the control of plant fungal diseases. However, they are facing serious challenges from issues with resistance and cross-resistance, primarily attributed to their frequent application and structural similarities. There is an urgent need to design and develop SDHI fungicides with novel structures. RESULTS: Aiming to discover novel potent SDHI fungicides, 31 innovative pyrazole ß-ketonitrile derivatives with diphenyl ether moiety were rationally designed and synthesized, which were guided by a 3D-QSAR model from our previous study. The optimal target compound A23 exhibited not only outstanding in vitro inhibitory activities against Rhizoctonia solani with a half-maximal effective concentration (EC50) value of 0.0398 µg mL-1 comparable to that for fluxapyroxad (EC50 = 0.0375 µg mL-1), but also a moderate protective efficacy in vivo against rice sheath blight. Porcine succinate dehydrogenase (SDH) enzymatic inhibitory assay revealed that A23 is a potent inhibitor of SDH, with a half-maximal inhibitory concentration of 0.0425 µm. Docking study within R. solani SDH indicated that A23 effectively binds into the ubiquinone site mainly through hydrogen-bonds, and cation-π and π-π interactions. CONCLUSION: The identified ß-ketonitrile compound A23 containing diphenyl ether moiety is a potent SDH inhibitor, which might be a good lead for novel fungicide research and optimization. © 2024 Society of Chemical Industry.

Design, Synthesis, and Bioactivity of Trifluoroethylthio-Substituted Phenylpyrazole Derivatives.

As the first marketed phenylpyrazole insecticide, fipronil exhibited remarkable broad-spectrum insecticidal activity. However, it poses a significant threat to aquatic organisms and bees due to its high toxicity. Herein, 35 phenylpyrazole derivatives containing a trifluoroethylthio group on the 4 position of the pyrazole ring were designed and synthesized. The predicted physicochemical properties of all of the compounds were within a reasonable range. The biological assay results revealed that compound 7 showed 69.7% lethality against Aedes albopictus (A. albopictus) at the concentration of 0.125 mg/L. Compounds 7, 7g, 8d, and 10j showed superior insecticidal activity for the control of Plutella xylostella (P. xylostella). Notably, compound 7 showed similar insecticidal activity against Aphis craccivora (A. craccivora) compared with fipronil. Potential surface calculation and molecular docking suggested that different lipophilicity and binding models to the Musca domestica (M. domestica) gamma-aminobutyric acid receptors may be responsible for the decreased activity of the tested derivatives. Toxicity tests indicated that compound 8d (LC50 = 14.28 mg/L) induced obviously 14-fold lower toxicity than fipronil (LC50 = 1.05 mg/L) on embryonic-juvenile zebrafish development.

Computational Modeling Oriented Substructure Splicing Application in the Identification of Thiazolidine Derivatives as Potential Low Honeybee Toxic Neonicotinoids.

With the aim of identifying novel neonicotinoid insecticides with low bee toxicity, a series of compounds bearing thiazolidine moiety, which has been shown to be low bee toxic, were rationally designed through substructure splicing strategy and evaluated insecticidal activities. The optimal compounds A24 and A29 exhibited LC50 values of 30.01 and 17.08 mg/L against Aphis craccivora, respectively. Electrophysiological studies performed on Xenopus oocytes indicated that compound A29 acted on insect nAChR, with EC50 value of 50.11 µM. Docking binding mode analysis demonstrated that A29 bound to Lymnaea stagnalis acetylcholine binding protein through H-bonds with the residues of D_Arg55, D_Leu102, and D_Val114. Quantum mechanics calculation showed that A29 had a higher highest occupied molecular orbit (HOMO) energy and lower vertical ionization potential (IP) value compared to the high bee toxic imidacloprid, showing potentially low bee toxicity. Bee toxicity predictive model also indicated that A29 was nontoxic to honeybees. Our present work identified an innovative insecticidal scaffold and might facilitate the further exploration of low bee toxic neonicotinoid insecticides.

Discovery of Potential Neonicotinoid Insecticides by an Artificial Intelligence Generative Model and Structure-Based Virtual Screening.

The identification of neonicotinoid insecticides bearing novel scaffolds is of great importance for pesticide discovery. Here, artificial intelligence-based tools and virtual screening strategy were integrated to discover potential leads of neonicotinoid insecticides. A deep generative model was successfully constructed using a recurrent neural network combined with transfer learning. The model evaluation showed that the pretrained model could accurately grasp the SMILES grammar of drug-like molecules and generate potential neonicotinoid compounds after transfer learning. The generated molecules were evaluated by hierarchical virtual screening, hits were subjected to a similarity search, and the most similar structures were purchased for the bioassay. Compounds A2 and A5 displayed 52.5 and 50.3% mortality rates against Aphis craccivora at 100 mg/L, respectively. The docking study indicated that these two compounds have similar binding modes to neonicotinoids, which were verified by further molecular dynamics simulations.

Hepatic effects of acetochlor chiral isomers in zebrafish and L02 cells.

The pesticide acetochlor (ACT) is a chiral isomer commonly detected in the global environment, yet its specific impacts on liver function remain poorly understood. We utilized zebrafish and L02 cells as research models to comprehensively investigate how ACT and its chiral isomers affect the liver. Our investigations unveiled that the R, Rac, and S isomers of ACT disrupt hepatic lipid transport, catabolism, and synthesis, leading to delayed yolk sac absorption and the accumulation of lipids in zebrafish embryos. These isomers induce oxidative stress in the liver of zebrafish embryos, reducing antioxidant levels and enzyme activity. The accumulated lipids in the liver render it susceptible to oxidative stress, further exacerbating hepatocyte damage. Hepatocyte damage manifests as extensive vacuolization of liver cells and alterations in liver morphology, which are induced by R, Rac, and S. Furthermore, we elucidated the molecular mechanisms underpinning the disturbance of hepatic lipid metabolism by R, Rac, and S in L02 cells. These compounds stimulate lipid synthesis through the upregulation of the AMPK/SREBP-1c/FAS pathway while inhibiting lipolysis via downregulation of the PPAR-α/CPT-1a pathway. Remarkably, our results highlight that S exhibits significantly higher hepatotoxicity in comparison to R. This study provides valuable insights into the hepatic effects of ACT chiral isomers.

Enhanced fungicidal efficacy and improved interfacial properties with the co-delivery of prothioconazole and tebuconazole using polylactic acid microspheres.

BACKGROUND: Prothioconazole (PTC) is one of the leading fungicide products worldwide. However, excessive use of PTC facilitates the development of resistance. Pesticide compounding technology plays an important role in reducing pesticide resistance. Microspherization technology for the construction of pesticide dual-loaded systems has recently provided a new direction for researching novel and efficient pesticide formulations. In this study, prothioconazole-tebuconazole@polylactic acid microspheres (PTC-TBA@PLA MS) were constructed by combining these two technologies. RESULTS: The final PTC-TBA@PLA MS were selected by an orthogonal method, which were uniformly spherical with smooth surface. The resultant drug loading (DL) and average particle size of PTC-TBA@PLA MS were 31.34% and 22.3 µm, respectively. A PTC-TBA@PLA MS suspending agent (SC) with a high suspension rate of 94.3% was prepared according to the suspension rate, dumping ability and stability. Compared with a commercial SC, the PTC-TBA@PLA MS SC had a larger cumulative release and better interfacial properties. Biological experiments showed that PTC-TBA@PLA MS SC had an obviously improved bactericidal effect than the commercial SC. CONCLUSION: The constructed PTC-TBA@PLA MS system detailed here is expected to reduce the risk of resistance and the frequency of pesticide use while enhancing fungal control. © 2023 Society of Chemical Industry.

Stereoselective toxicity of acetochlor chiral isomers on the nervous system of zebrafish larvae.

Acetochlor (ACT) is a widely detected pesticide globally, and the neurotoxic effects of its chiral isomers on humans and environmental organisms remain uncertain. Zebrafish were used to study the neurotoxicity of ACT and its chiral isomers. Our study reveals that the R-ACT, Rac-ACT, and S-ACT induce neurotoxicity in zebrafish larvae by impairing vascular development and disrupting the blood-brain barrier. These detrimental effects lead to apoptosis in brain cells, hindered development of the central nervous system, and manifest as altered swimming behavior and social interactions in the larvae. Importantly, the neurotoxicity caused by the S-ACT exhibits the most pronounced impact and significantly diverges from the effects induced by the R-ACT. The neurotoxicity associated with the Rac-ACT falls intermediate between that of the R-ACT and S-ACT. Fascinatingly, we observed a remarkable recovery in the S-ACT-induced abnormalities in BBB, neurodevelopment, and behavior in zebrafish larvae upon supplementation of the Wnt/ß-catenin signaling pathway. This observation strongly suggests that the Wnt/ß-catenin signaling pathway serves as a major target of S-ACT-induced neurotoxicity in zebrafish larvae. In conclusion, S-ACT significantly influences zebrafish larval neurodevelopment by inhibiting the Wnt/ß-catenin signaling pathway, distinguishing it from R-ACT neurotoxic effects.

Computation-Directed Molecular Design, Synthesis, and Fungicidal Activity of Succinate Dehydrogenase Inhibitors.

Succinate dehydrogenase inhibitors (SDHIs) are a class of fungicides targeting the pathogenic fungi mitochondrial SDH. Here, molecular docking, three-dimensional quantitative structure-activity relationship (3D-QSAR), and molecular dynamics (MD) simulations were used to guide SDHI innovation. Molecular docking was performed to explore the binding modes of SDH and its inhibitors. 3D-QSAR models were carried out on 33 compounds with activity against Rhizoctonia cerealis (R. cerealis); their structure-activity relationships were analyzed using comparative molecular field analysis and comparative molecular similarity indices analysis. MD simulations were used to assess the stability of the complexes under physiological conditions, and the results were consistent with molecular docking. Binding free energy was calculated through the molecular mechanics generalized born surface area method, and the binding free energy was decomposed. The results are consistent with the activity of bioassay and indicate that van der Waals and lipophilic interactions contribute the most in the molecular binding process. Afterward, we designed and synthesized 12 compounds under the guidance of the above-mentioned analyses, bioassay found that F9 was active against R. cerealis with the EC50 value of 9.43 µg/mL, and F4, F5, and F9 were active against Botrytis cinerea with an EC50 values of 5.80, 3.17, and 1.63 µg/mL, respectively. They all showed good activity between positive controls of pydiflumetofen and thifluzamide. Our study provides new considerations for effective SDHIs discovery.

3D-QSAR Combination with Molecular Dynamics Simulations to Effectively Design the Active Ryanodine Receptor Agonists against Spodoptera frugiperda.

Computer-aided molecular modeling was applied to design a series of Spodoptera frugiperda RyR agonists. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used to generate 3D-QSAR models. MD simulations in the complex with S. frugiperda native, mutant RyR, and mammalian RyR1 under physiological conditions were used to validate the detailed binding mechanism. Binding free energy calculation by molecular mechanics generalized surface area (MM-GBSA) explained the role of key amino acid residues in ligand-receptor binding. Therefore, 14 new compounds were effectively designed and synthesized, and a bioassay indicated that compounds A-2 and A-3 showed comparable activity to that of chloranthraniliprole with LC50 values of 0.27, 0.18, and 0.20 mg L-1, respectively, against S. frugiperda. Most target compounds also displayed good activity against Mythinma separata at 0.1 mg L-1. Molecular docking and MM-GBSA calculations demonstrated that A-3 had a better binding capacity with native and mutant S. frugiperda RyRs.

Novel Acaricidal Silico-Containing Pyrazolyl Acrylonitrile Derivatives Identified through Rational Carbon-Silicon Bioisosteric Replacement Strategy.

The identification of novel pyrazolyl acrylonitrile acaricides with improved properties is of great value for the control of phytophagous mites. A series of innovative silicon-containing pyrazolyl acrylonitriles were rationally designed by applying a bioisosteric carbon-silicon replacement strategy and prepared based on novel synthetic methodology. As a result of our research, we discovered compound A25 which possesses outstanding acaricidal activity. With an LC50 value of 0.062 mg/L, compound A25 was found to be 2.3-fold and 1.9-fold more potent than the commercial acaricides cyenopyrafen and cyetpyrafen, respectively. Enzymatic inhibitory assay indicated that the active principle M1 of compound A25 possesses an IC50 value of 2.32 µM against Tetranychus cinnabarinus SDH, which was about twofold superior compared to the active metabolites of cyenopyrafen (IC50 = 4.72 µM). Molecular docking study showed that the active metabolites 2 and 3 and their corresponding silicon counterparts form H-bonds and cation-π interaction with the residues of Trp165, Tyr433, and Arg279.

Discovery of Novel Diamides Scaffold Containing Monofluoro-acrylamides Activating the Insect Ryanodine Receptor.

The research and development of organofluorine chemistry has flourished; in particular, monofluoroalkene has aroused considerable interest from medicinal and organic chemists. It is a significant attempt to introduce monofluoroalkene into agrochemicals. In this study, monofluoroalkene was introduced into diamide molecules and inserted between the aliphatic amide and benzene ring, and 44 compounds have been successfully synthesized. The bioassay results showed that compounds with monofluoro-acrylamide moiety (Z-isomers) had excellent larvicidal activity against lepidopteran pests at 5 mg·L-1. The LC50 values of compounds B16, B18, and B21 against Mythimna separata were 1.02, 1.32, and 0.78 mg·L-1, respectively. 3D-QSAR analysis including the CoMFA model and the CoMSIA model was conducted to illustrate the contributions of steric, electrostatic, hydrophobic, and hydrogen bond fields on the bioactivity. Moreover, typical symptoms caused by chlorantraniliprole including dehydration, shrinkage, and blackening were also observed on the test larvae treated with monofluoro-acrylamide diamide compounds. M. separata central neurons calcium imaging experiment of compound B18 indicated that the monofluoro-acrylamide diamide compounds were potential insect ryanodine receptor activators. The molecular docking was performed in the CHL binding domain of Plutella xylostella RyR and revealed that the predicted binding mode of compound B21 was slightly different from that of CHL. The MM|GBSA dG Bind values of B21 and CHL with P. xylostella RyR were respectively -85.797 and -95.641 kcal·mol-1. The present work explored the insecticidal properties of a new diamide scaffold containing a monofluoro-acrylamide fragment and extended the application of monofluoroalkene in the agrochemical field.

The effects of Spinosad on zebrafish larvae and THP-1 cells: Associated with immune cell damage and NF-kappa B signaling pathway activation.

Spinosad is a highly effective macrolide insecticide with a wide range of applications. However, few studies have been reported on the effects of Spinosad on immune cells. The immune system is an important line of defense in the human body and plays an important role in maintaining the normal functioning of the organism. Meanwhile, macrophages, neutrophils and Thymic T cells are an important component of the immune system. We studied the immunotoxicity of Spinosad using zebrafish and THP-1 cells. In vivo, Spinosad (0-20 µM) did not cause developmental toxicity in zebrafish, but induced damage to immune cells. In vitro, Spinosad (0-20 µM) inhibited THP-1 cells viability and induced mitochondrial damage and oxidative stress production. In further studies, it impaired phagocytosis of THP-1 cells and interfered with lipid metabolism. In addition, we found that Spinosad can promote the formation of the inflammatory body NLRP3 (NLR family, pyrin domain-containing 3) and activate the NF-kappa B (NF-κB) signaling pathway. These results suggest that Spinosad has a potential risk for inducing immunotoxicity. This study has drawn attention to Spinosad-induced immunotoxicity.

Developmental toxicity and estrogenicity of glyphosate in zebrafish in vivo and in silico studies.

As the most heavily used herbicide globally, glyphosate (GLY) has been detected in a variety of environments and has raised concerns about its ecological and health effects. There is debate as to whether GLY may disrupt the endocrine system. Here, we investigated the developmental toxicity of GLY in zebrafish based on deep learning-enabled morphometric analysis (DLMA). In addition, the estrogenic activity of GLY was assessed by endocrine disruption prediction, docking study and in vivo experiments. Results showed that exposure to environmental concentrations of GLY negatively impacted zebrafish development, causing yolk edema and pericardial edema. Endocrine disruption prediction suggested that GLY may target estrogen receptors (ER). Molecular docking analysis revealed binding of GLY to three zebrafish ER. In vivo zebrafish experiment, GLY enhanced the protein levels of ERα and the mRNA levels of cyp19a, HSD17b1, vtg1, vtg2, esr1, esr2a and esr2b. These results suggest that GLY may act as an endocrine disruptor by targeting ER, which warrants further attention for its potential toxicity to aquatic animals.

Molecular mechanisms of cardiotoxicity induced by acetamide and its chiral isomers.

Acetamide (ACT) is used in a racemic form, and the considerable residues of this compound in the environment raise potential safety concerns for human health. We investigated the toxicity of ACT and its chiral isomers on human cardiomyocyte (AC16) cell line and zebrafish embryonic heart, and found that (+)-S-ACT was the main component causing cardiac toxicity. Our findings indicate that the IC50 of (±)-Rac-ACT on AC16 cells was 20.19 µg/mL. (-)-R-ACT, (±)-Rac-ACT, and (+)-S-ACT caused DNA damage and apoptosis in AC16 cells at this concentration. The underlying molecular mechanism may involve the induction of reactive oxygen species (ROS). The accumulation of ROS results in a decline in mitochondrial membrane potential (MMP) and prompts the release of cytochrome c (cyt c) from the mitochondria. This cascade of events ultimately activates the caspase-3 and caspase-9 signaling pathways, resulting in apoptosis. Furthermore, in vivo observations in zebrafish hearts demonstrated caspase-3 activation and the presence of the DNA damage marker (γH2AX), indicating that (+)-S-ACT is more toxic to cardiomyocytes than (-)-R-ACT and (±)-Rac-ACT. These findings suggest that (+)-S-ACT may be the primary component responsible for the toxicity of (±)-Rac-ACT in AC16 cells. Overall, these findings raise public awareness regarding the risks associated with chiral isomeric pesticides and provide a scientific foundation for their appropriate use.

Design, Synthesis, and Biological Activities of Novel Phenylpyrazole Derivatives Containing a Trifluoromethylselenyl Moiety.

Phenylpyrazole insecticides are widely used for crop protection and public sanitation by blocking gamma-aminobutyric acid (GABA)-gated chloride channels and glutamate-gated chloride (GluCl) channels. Herein, 36 novel phenylpyrazole derivatives containing a trifluoromethylselenyl moiety were designed and synthesized based on the strategy of introducing a selenium element. All derivative structures were characterized by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). The insecticidal activity results indicated that some derivatives had good insecticidal activities against Aedes albopictus (A. albopictus) and Plutella xylostella (P. xylostella). The larvicidal activity against mosquitos of compounds 5, 5a, 5k, and 5l at 0.5 mg/L was 60-80%. At a concentration of 500 mg/L, compounds 5, 5a, 5h, 5k, 5l, 5r, 6, 6j, 6k, and 7 showed a 70-100% mortality against P. xylostella. Among them, derivatives 5 and 6 had a better insecticidal effect with mortality rates of 87 and 93% at 50 mg/L, respectively. It was summarized that the different binding poses of fipronil and compounds 5 and 6 in the Musca domestica (M. domestica) GABARs might lead to the disparity in bioactivity from docking studies. Toxicity tests on zebrafish suggested that compound 6 may be slightly less toxic to the embryos than fipronil on hatching rate.

Design, Synthesis, and Insecticidal Evaluation of Neonicotinoids with Conjugated Diene.

Neonicotinoid insecticides acting on the insect nicotinic acetylcholine receptors (nAChRs) play an essential role in contemporary pest control. In the present study, a series of novel neonicotinoid analogues with conjugated diene were synthesized. Bioassays indicated that compounds A3 and A12 had LC50 values of 1.26 and 1.24 mg/L against Myzus persicae, respectively, which were comparable to that of imidacloprid (IMI, LC50 = 0.78 mg/L). Density functional theory (DFT) calculations were performed to explain the differences in the insecticidal activities of target compounds. Molecular docking results indicate that compounds A3 and A12 interact favorably with Lymnaea stagnalis AChBP. The hydrolysis experiments confirmed that the stability of compounds A3 and A12 was enhanced in water.

Developmental and cardiovascular toxicities of acetochlor and its chiral isomers in zebrafish embryos through oxidative stress.

Acetochlor (ACT) is a widely used pesticide, yet the environmental and health safety of its chiral isomers remains inadequately evaluated. In this study, we evaluated the toxicity of ACT and its chiral isomers in a zebrafish model. Our findings demonstrate that ACT and its chiral isomers disrupt early zebrafish embryo development, inducing oxidative stress, abnormal lipid metabolism, and apoptosis. Additionally, ACT and its chiral isomers lead to cardiovascular damage, including reduced heart rate, decreased red blood cell (RBC) flow rate, and vascular damage. We further observed that (+)-S-ACT has a significant impact on the transcription of genes involved in cardiac and vascular development, including tbx5, hand2, nkx2.5, gata4, vegfa, dll4, cdh5, and vegfc. Our study highlights the potential risk posed by different conformations of chiral isomeric pesticides and raises concerns regarding their impact on human health. Overall, our results suggest that the chiral isomers of ACT induce developmental defects and cardiovascular toxicity in zebrafish, with (+)-S-ACT being considerably more toxic to zebrafish than (-)-R-ACT.

Glyphosate Causes Vascular Toxicity through Cellular Senescence and Lipid Accumulation.

The health risks associated with glyphosate (GLY) have recently received increasing attention. However, its potential vascular toxic effects in occupationally exposed populations remain unclear. This study assessed the effects of GLY on human aortic vascular smooth muscle cells (HAVSMCs) and the relationship between GLY and atherosclerosis. The results demonstrate that GLY induces a relatively larger and more flattened cell morphology, which is typical of cellular senescence and promotes senescence-associated ß-galactosidase activity, as well as the expression of p53, p21, and p16 proteins in HAVSMCs. Regarding toxic effects, GLY induces the accumulation of reactive oxygen species, DNA damage, and mitochondrial damage in HAVSMCs. Mechanistically, the nuclear factor erythroid 2-related factor 2-Kelch-like ECH-associated protein 1 pathway is activated in response to oxidative stress produced by GLY. In an in vivo model, GLY led to dyslipidemia and macrophage recruitment in zebrafish vasculature. In conclusion, our results demonstrate that GLY induces vascular toxicity and may be a potential risk for atherosclerosis. These findings highlight the need for concern about cardiovascular risk in occupational populations chronically exposed to GLY.