Neonicotinoid Insecticides Research Articles

Ecological risks caused by neonicotinoid pesticides in sediments: A case study of freshwater basins in China.

Neonicotinoid insecticides (NNIs) are extensively used in agricultural production in China due to their selective neurotoxicity towards target insects. In recent years, the rapid development of agriculture has increased the use and residue of NNIs. Consequently, the sediment environment, serving as the ultimate sink, is significantly impacted by NNIs. Upon release into the environment, NNIs can enter the human body through the food chain, posing potential ecological and human health risks. This study analyzed 79 sediment samples from two major river basins in North and South China, the Liaohe River basin in Liaoning Province and the Jianjiang River basin in Guangdong Province. The content, composition, distribution, and source of eight NNIs were analyzed, and assess the ecological and human health risks of the target compounds in these regions. The results indicated that the average concentration of NNIs in the sediments of the Jianjiang River basin (2.34 μg/kg) is slightly higher than that of the Liaohe River basin (2.32 μg/kg), and the sources of NNIs in the two areas were different, with differences in the sources of NNIs likely attributable to varying types of agricultural production. The risk assessment revealed that the ecotoxicological and public health risks were more pronounced in the Jianjiang River basin compared to the Liaohe River basin, underscoring the critical need for surveillance and management of hazardous substances like NNIs. The insights findings from this study can provide scientific guidance for the risk evaluation and environmental management of NNIs.

Transcriptome analysis reveals the molecular mechanisms of neonicotinoid acetamiprid in Leydig cells.

At present, the reproductive toxicology of neonicotinoids has received greater attention, however, its potential mechanisms are still not fully understood. Acetamiprid (ACE) is a new-generation neonicotinoid and has become a ubiquitous contaminant in the environment. This study aimed to investigate the toxic effects of ACE in TM3 Leydig cells based on transcriptome analysis. The viability and apoptosis of TM3 cells exposed to different concentrations of ACE were assessed by CCK8 and flow cytometry, respectively. After ACE exposure, transcriptome analysis was performed to screen differential expression genes (DEGs), followed by qPCR verification. Results showed that ACE exposure resulted in a time- and dose-dependent decrease in the viability of TM3 cells (p < .05). ACE also exerted a dose-dependent pro-apoptotic effect on TM3 cells. Results of RNA-seq showed that 1477 DEGs were obtained, of which 539 DEGs were up-regulated and 938 DEGs were down-regulated. GO and KEGG analyses of DEGs showed that DNA replication and cell cycle might be the key mechanisms for the cytotoxicity of ACE. qPCR results demonstrated that Mdm2, Cdkn1a (p21) and Gadd45 were significantly increased, and Pcna, Ccna2 (CycA), Ccnb1 (CycB), Ccne1 (CycE), and Cdk1 were significantly decreased, indicating that ACE exposure might promote G1/S and G2/M cell cycle arrest. Additionally, FoxO, p53, and HIF-1 signaling pathways and ferroptosis might play important roles in ACE-induced reproductive toxicity. Collectively, this study provides new perspectives into the mechanism of ACE-induced reproductive toxicity and lays a theoretical foundation for the in-depth study of non-target toxicity mechanisms of neonicotinoid insecticides.

Unraveling the acute sublethal effects of acetamiprid on honey bee neurological redox equilibrium.

Understanding the off-target effects of neonicotinoid insecticides, including acetamiprid, which is the most commonly applied agricultural chemical, is crucial as it may be an important factor of negative impact on pollinator insects causing a number of problems such as colony collapse disorder (CCD) of honey bees. While CCD is known as a multifactorial disease, the role of pesticides in this context is not negligible. Therefore, it is essential to gain a deeper comprehension of the mechanisms through which they function. The aim of this research was to study the effects of sublethal acetamiprid doses on honey bees, specifically focusing on the redox homeostasis of the brain. According to our findings, it can be confirmed that acetamiprid detrimentally impacts the redox balance of the brain increasing hydrogen peroxide and malondialdehyde levels, suggesting consequential lipid peroxidation and membrane damage as consequences. Moreover, acetamiprid had negative effects on the glutathione system and total antioxidant capacity, as well as key enzymes involved in the maintenance of redox homeostasis. In summary, it can be concluded that acetamiprid adversely affected the redox balance of the central nervous system of honey bees in our study. Our findings could potentially contribute to a better understanding of pesticide-related consequences and to improvement of bee health.

Photodegradation of Neonicotinoid Insecticides Nitenpyram, Thiacloprid, and Acetamiprid in Water and Soil Environments.

The photodegradations of three selected neonicotinoid insecticides nitenpyram, thiacloprid, and acetamiprid were investigated in both water and soil samples under natural sunlight, UVA light, and UVB light. The results indicate that these insecticides undergo significant degradations when subjected to sunlight, whether they are in deionized (DI) water, tap water, and DI water containing 100mg/L humic acids or in soil. The degradation half-lives of nitenpyram, thiacloprid, and acetamiprid in tap water under sunlight were found to be 3.7, 4.7, and 8.9h, respectively, in DI water 5.4, 6.3, 9.1h, respectively, in DI water containing 100mg/L humic acids 3.6, 3.3, 6.5h, respectively, and in soil 7.5, 7.9, and 15.9h, respectively. The degradation due to hydrolysis was found insignificant as compared to photodegradation. The examination of the effects of light source revealed that the UVB in the sunlight plays a major role in the photodegradation of these three neonicotinoids, and the effects of UVA and visible light are negligible. The analysis on the degradation products indicated that the nitroguanidine group in these insecticides is unstable and prone to break up under sunlight. A total of nine degradation products were detected, of which the health effects and the fate and transport in the environment need to be further studied.

Microbial degradation mechanisms of the neonicotinoids acetamiprid and flonicamid and the associated toxicity assessments

Extensive use of the neonicotinoid insecticides acetamiprid (ACE) and flonicamid (FLO) in agriculture poses severe environmental and ecological risks. Microbial remediation is considered a feasible approach to address these issues. Many ACE-and FLO-degrading microorganisms have been isolated and characterized, but few reviews have concentrated on the underlying degradation mechanisms. In this review, we describe the microbial degradation pathways of ACE and FLO and assess the toxicity of ACE, FLO and their metabolites. Especially, we focus on the enzymes involved in degradation of ACE and FLO, including cytochrome P450s, nitrile hydratases, amidases, and nitrilases. Those studies reviewed here further our understanding of the enzymatic mechanisms of microbial degradation of ACE and FLO, and aid in the application of microbes to remediate environmental ACE and FLO contamination.

Disruption of exploratory behavior and olfactory memory in cockroaches exposed to sublethal doses of the neonicotinoid Thiamethoxam

Neonicotinoid insecticides (NNI) are agonists of insect nicotinic acetylcholine receptors (nAChR) that induce non-elucidate mechanisms of abnormal behavior in insects. In this work, we investigated the effects of sublethal doses of the neonicotinoid thiamethoxam (TMX) on neurochemical and physiological parameters in cockroaches. Sublethal doses of TMX (0.01–10 ng.g−1 body mass) caused significant alterations in most of the neurophysiological parameters evaluated. TMX reduced sustained locomotor activity by 19.9–25.8 %, depending on the dose. Leg grooming activity increased by 124.5 ± 3.4 %, 158.7 ± 3.5 %, 168.3 ± 3.4 %, and 160.4 ± 3.4 % (mean ± SEM) with TMX doses of 0.01, 0.1, 1, and 10 ng.g−1, respectively. Exploratory activity was significantly reduced only at the lowest TMX dose (0.01 ng.g−1) – the time spent immobile increased from 30 % to ~45 %, whereas none of the doses affected the walking speed. Treatment with TMX (0.01 ng.g−1) markedly reduced the olfactory sensitivity of the cockroaches and also reduced the mechanosensory action potential amplitude, rise time and decay time by 61.2 ± 19 %, 50 ± 4 %, and 76.8 ± 9.5 %, respectively. In semi-isolated heart preparations, TMX caused positive chronotropism (increases of 34.7 ± 15.9 %, 26.8 ± 7.8 %, 43.0 ± 16.5 %, and 19.0 ± 13.7 % for 0.01, 0.1, 1, and 10 ng of TMX, respectively). TMX attenuated the activity of glutathione-S-transferase by 35.1 ± 6.4 % at the highest dose tested (10 ng.g−1). TMX caused alterations in the metal ion content of cockroach brains that varied with the dose tested and the ion examined. These findings indicate that sublethal doses of TMX can interfere with normal neurological function in cockroaches and disrupt brain metal ion homeostasis.

Antiparasitic effect of imidacloprid on the copepodite and adult stages of Caligus rogercresseyi

In Chile, there are currently eight authorized pharmaceutical chemical compounds for the control of sea lice (Caligus rogercresseyi), namely emamectin benzoate, diflubenzuron, lufenuron, hexaflumuron, hydrogen peroxide, deltamethrin, cypermethrin and azamethiphos; however, being this range of tools considered scarce, moreover, loss of sensitivity to some of these compounds have been described in previous studies. Imidacloprid is a neonicotinoid synthetic insecticide that was authorized in Norway in 2021 and has revealed good efficacy in controlling Lepeophtheirus salmonis on salmon farms; however, it has not been authorized for use in Chile. Therefore, in this study, we investigated the efficacy of imidacloprid on the copepodite and adult stages of C. rogercresseyi, which, to our knowledge, has not been investigated in previous studies. We observed that imidacloprid immobilized the parasite at both stages; however, adults were able to recover after the exposure, with 50 % of the adults exposed to concentrations <40 ppm for 24 h recovering, suggesting that a concentration > 20 ppm is required for 100 % mortality of this parasite. In contrast, the copepodite stage was immobilized at 20 ppm, suggesting that copepodites are more sensitive to imidacloprid than the adults. Further studies are required to understand the biological responses of the different stages of C. rogercresseyi to design effective control strategies, improve our understanding of the mechanisms of imidacloprid, and determine the optimal concentrations for control of the parasite.

High-performance ratiometric magnetic electrochemical sensor for acetamiprid detection using Ag@PDA@Fe3O4 nanocomposites

Acetamiprid (AAP) is a renowned neonicotinoid insecticide for swift insect control that is prone to residue in agricultural products and threatens human health. Magnetic electrochemical sensor (MES) was developed for high-precision detection of AAP based on silver nanoparticle (AgNPs) and polydopamine (PDA) modified Fe3O4 nanocomposites (Ag@PDA@Fe3O4). The electrochemical signals generated by AAP hydrolysis and AgNPs oxidation are respectively used as two special signal sources. An increase in AAP concentration led to a proportional increase in the signal from AAP hydrolysis at +0.9 V (IAAP), while the signal from AgNPs oxidation at +0.27 V (IAg) correspondingly decreased. The output signal ΔIAAP/ΔIAg (R2=0.9890) demonstrates a superior linear relationship compared to ΔIAAP (R2=0.9790) or ΔIAg (R2=0.9740) alone. MES demonstrated a broad linear detection range from 0.01 to 2.00 mg L−1 and an impressive limit of detection (LOD, 3S/M) at 3.6 µg L−1. The incorporation of magnetic glassy carbon electrodes (MGCE) significantly mitigates the detachment of nanomaterials. MES has excellent stability and selectivity, and can successfully detect AAP in actual cowpea samples. This study provides pivotal insights into the design of nanomaterial-based ratiometric electrochemical sensors for the sensitive and selective detection of AAP.

Prenatal exposure to neonicotinoid insecticides, fetal endocrine hormones and birth size: Findings from SMBCS

BackgroundNeonicotinoid insecticides (NNIs) were reported to be endocrine disruptors and cause adverse health effects in human. However, epidemiological evidence about the effect of prenatal NNIs exposure on birth outcome and hormones remains limited. ObjectivesThis study aimed to explore the effects of prenatal NNIs exposure on neonatal birth size and endocrine hormones, and assess the potential mediating role of hormones. MethodsThe study included 860 mother–child pairs from the Sheyang Mini Birth Cohort Study. 12 parent NNIs (p-NNIs) and 6 metabolites of NNIs (m-NNIs) were measured in maternal urine samples collected on their delivery days, and 5 thyroid hormones and 2 sex hormones were analyzed in cord serum. The concentrations of p-NNIs and its specific metabolite(s) were summed to characterize the role of each class of NNIs. Generalized linear model and weighted quantile sum regression were used to examine the impact of prenatal NNIs exposure on birth size and endocrine hormones, and potential mediating roles of hormones were further explored using mediation analysis. ResultsHigher detection frequencies of m-NNIs were observed than those in p-NNIs. A decrease in neonatal head circumference for gestation age z-score was associated with a 10-fold increase in 5-OH-IMI (β = -0.15, 95 %CI: −0.26, −0.03), ∑DIN (β = -0.22, 95 %CI: −0.40, −0.03), ∑IMI (β = -0.20, 95 %CI: −0.35, −0.06) and ∑NNIs (β = -0.23, 95 %CI: −0.42, −0.04). ∑IMI and ∑DIN were the major contributors to the significantly negative mixture effect and no sex-specific effect was observed. Negative associations were observed between ∑DIN and TT3 (β = -0.013, 95 %CI: −0.025, −0.002), ∑IMI and T (β = -0.035, 95 %CI: −0.065, −0.004), respectively. Furthermore, TT3 and T demonstrated 6.7 % and 6.1 % mediating effects on the negative association of prenatal ∑DIN and ∑IMI exposure with head circumference. ConclusionsOur findings suggested the potential endocrine disruptive properties of NNIs and their impacts on head circumference. Endocrine hormones may partly mediate these associations.

Formation of reactive nitrogen species promoted by iron ions through the photochemistry of a neonicotinoid insecticide

Abstract. Nitrous acid (HONO) and nitrogen oxides (NOx=NO+NO2) are important atmospheric pollutants and key intermediates in the global nitrogen cycle, but their sources and formation mechanisms are still poorly understood. Here, we investigated the effect of soluble iron (Fe3+) on the photochemical behavior of a widely used neonicotinoid (NN) insecticide, nitenpyram (NPM), in the aqueous phase. The yields of HONO and NOx increased significantly when NPM solution was irradiated in the presence of iron ions (Fe3+). We propose that the enhanced HONO and NO2 emissions from the photodegradation of NPM in the presence of iron ions result from the redox cycle between Fe3+ and Fe2+ and the generated reactive oxygen species (ROS) by electron transfer between the excited triplet state of NPM and molecular oxygen (O2). Using the laboratory-derived parameterization based on kinetic data and gridded downward solar radiation, we estimate that the photochemistry of NPM induced by Fe3+ releases 0.50 and 0.77 Tg N yr−1 of NOx and HONO, respectively, into the atmosphere. This study suggests a novel source of HONO and NOx during daytime and potentially helps to narrow the gap between field observations and model outcomes of HONO in the atmosphere. The suggested photochemistry of NPM can be an important contribution to the global nitrogen cycle affecting the atmospheric oxidizing capacity and climate change.

Effects of tillage intensity and pesticide treated seeds on epigeal arthropod communities and weed seed predation in a maize-soybean rotation

Tillage practices and the use of pesticide seed treatments (PST) both have the potential to influence epigeal arthropod communities and the ecosystem services they provide, yet few studies have examined both factors in conjunction. A three-year field study (2017–2019) was conducted to assess the independent and interactive effects of tillage and pesticide seed treatments on epigeal arthropod communities and weed seed predation in a long-term row crop tillage intensity experiment located in southeastern New Hampshire, USA. Throughout the study, maize and soybean were planted in rotation with and without pesticide seed treatments (seed coatings containing a mixture of systemic and contact fungicides and neonicotinoid insecticides) under three tillage systems (full-, strip-, and no-till) in a randomized complete block design with four replications. Epigeal arthropod communities were sampled with pitfall traps from September to October 2018–2019 and weed seed predation was assessed over the same period each year from 2017–2019. A total of 1669 individual arthropods, representing 47 taxonomic groups, were observed over the course of the study. In 2018, epigeal arthropod communities differed based only on pesticide seed treatment. The opposite response was observed in 2019, as epigeal arthropod communities differed based only on tillage. Activity densities of Pterostichus melanarius (Illiger) were higher in the strip-till compared to full-till treatment in 2018. Annual levels of post-dispersal weed seed predation by invertebrates (% total seeds removed) varied based on tillage treatment in 2017 and 2019, but not in 2018, and ranged from as low as 6.1 % to as much as 27.2 % depending on year and treatment. These data provide evidence that both pesticide seed treatments and tillage systems can influence the communities of epigeal arthropods that inhabit annual row crop agroecosystems relatively late in the growing season, when the majority of pesticide residues have likely dissipated, and that the weed seed predation services provided by members of this community can be strongly negatively impacted by intensive tillage.

Theoretical and Experimental Study of the Stability of Thiamethoxam Under Different Environmental Conditions

The neonicotinoid insecticide thiamethoxam (TMX) is widely applied in agriculture, owing to its high spectrum of target pests. Its frequent use contributed to its accumulation in the environment, mainly in water; therefore, its natural degradation mechanisms are relevant to understand the physicochemical factors that can accelerate its decomposition. So, this study evaluated the stability of TMX against variations in pH, temperature, and exposure time to solar radiation, with the purpose of assessing the natural mechanisms of its degradation in water. Further, simulations of the reaction mechanisms at the molecular level were performed. It was observed that the degradation of TMX in the environment is favored by its exposure to solar radiation for several days and in more acidic pH conditions. However, TMX degradation did not result in reduced ecotoxicity. Basic pH values also help in the degradation of TMX, but by a lower percentage than that in an acid medium. Although exposure of TMX to solar radiation promotes heating of the compound, the isolated effect of thermal energy (temperature) is not sufficient for its degradation. The computer simulations showed the regions with higher electron densities and that the TMX structure is stable, preventing the bonds from breaking with increasing temperature, up to 60 °C. The HO− and H3O+ ions do not interact significantly with the molecule to the point of modifying its structure. With solar radiation, an electron can change to the excited state, contributing to TMX degradation due to a triplet configuration that allows it to react with the ions in the solution. In this way, the present work contributed to jointly present a theoretical and experimental study of the forms of natural degradation of the TMX contaminant.

Identifying and modeling the impact of neonicotinoid exposure on honey bee colony profit

Abstract Pollination by the European honey bee, Apis mellifera, is essential for the production of many crops, including highbush blueberries (Vaccinum corymbosum). To understand the impact of agrochemicals (specifically, neonicotinoids, a class of synthetic, neurotoxic insecticides) on these pollinators, we conducted a field study during the blueberry blooms of 2020 and 2021 in British Columbia (B.C.). Forty experimental honey bee colonies were placed in the Fraser Valley: half of the colonies were located within 1.5 km of highbush blueberry fields (“near” colonies) and half were located more than 1.5 km away (“far” colonies). We calculated risk quotients for these compounds using their chronic lethal dietary dose (LDD50) and median lethal concentration (LC50). Pesticide risk was similar between colonies located near and far from blueberry forage, suggesting that toxicity risks are regionally ubiquitous. Two systemic neonicotinoid insecticides, clothianidin and thiamethoxam, were found at quantities that exceeded chronic international levels of concern. We developed a profit model for a pollinating beekeeper in B.C. that was parameterized by: detected pesticide levels; lethal and sublethal bee health; and economic data. For colonies exposed to neonicotinoid pesticides in and out of the blueberry forage radii, there were economic consequences from colony mortality and sublethal effects such as a loss of honey production and compromised colony health. Further, replacing dead colonies with local bees was more profitable than replacing them with imported packages, illustrating that beekeeping management selection of local options can have a positive effect on overall profit.

A New approach for simultaneous detection and photocatalytic degradation of imidacloprid and dinotefuran in water using terbium-based fluorometry and mixed-phase TiO2

This study explores a novel method for detecting neonicotinoid insecticides, imidacloprid (IMD) and dinotefuran (DNT), in water using terbium (Tb3+) ions photo probe. The optimal excitation and emission wavelengths for Tb3+ luminescence were identified at 310 nm and 545 nm, respectively. The influence of pH and solvent on Tb-complex fluorescence was investigated. Results indicate a significant enhancement of luminescence intensity at pH 6 for IMD in DMF and pH 7.0 for DNT in DMSO. The fluorescence intensity exhibited a linear relationship with IMD and DNT concentrations ranging from 0.1 to 20 µg/mL (R2 > 0.99). Limits of quantitation (LOQ) were determined as 0.1 µg/mL for IMD and 0.05 µg/mL for DNT. This newly developed photo probe demonstrates the potential for monitoring photolysis and photocatalytic degradation of these neonicotinoids using TiO2 as a catalyst under controlled photoreactor conditions. The method offers a promising alternative for rapidly and sensitively detecting these prevalent insecticides in water samples.

An overview on the fate and behavior of imidacloprid in agricultural environments.

This review provides an overview on the fate and behavior of imidacloprid, a neonicotinoid insecticide, in agricultural environments. The study focuses on four key aspects: adsorption and leaching of imidacloprid in soil, degradation and hydrolysis of imidacloprid in soil and water, uptake and persistence of imidacloprid in plants, and volatilization of imidacloprid to the atmosphere. The review presents the latest findings from research on each of these topics. While imidacloprid is highly effective at controlling pests, it is also known to persist in the environment, posing risks to non-target organisms such as bees, birds, and aquatic life. Moreover, there is increasing concern about its potential to accumulate in the soil and water systems, which may have long-term effects on the ecosystem. The review suggests that better understanding of the behavior and fate of imidacloprid in agricultural environments is essential for developing effective strategies to minimize its environmental impact.

Contamination profile and hazards of neonicotinoid insecticides in honey from apiaries in Beijing, China.

The residues of neonicotinoid insecticides in honey have raised global concern for their adverse effects on non-target organisms. However, information on the presence of neonicotinoids in raw honey in China is limited. Our study investigated the distribution profiles of neonicotinoids in raw honey samples collected from apiaries in plain and mountainous areas surrounding Beijing City. At least one of four neonicotinoids, imidacloprid, thiamethoxam, acetamiprid, or clothianidin, was found in 46.9% of samples. Neonicotinoids in multi-floral honey in plain areas exhibited higher concentrations and prevalence than in uni-floral honey collected from mountainous areas. These results indicated that neonicotinoid residues in honey were linked to the agricultural ecosystems influenced by geographies, particularly the intensity of agriculture and nectariferous plant types. The dietary risks to adult and children health from neonicotinoid exposure were deemed de minimis, while risks to honeybees at the maximum concentration level require much attention through refined, higher-tier assessments and possible mitigation measures for the use of these products.

Acetamiprid elicits oxidative stress, pro-inflammatory response, and cellular proliferation in human bronchial epithelial cells in vitro and in silico: alleviative implications of the mixture of heat-killed Lactobacillus strains

BackgroundAcetamiprid (ACE), a neonicotinoid insecticide, has been extensively used to control pests in agricultural and industrial environments. It has been reported that ACE is detrimental to the lungs. Nevertheless, the extent to which the activation of oxidative stress, inflammation, and cellular proliferation contributes to the pulmonary toxicity induced by ACE exposure remains insufficiently understood. This study explored the mechanism of toxicological consequences after ACE exposure in bronchial epithelial cells (BEAS-2B cells). The research also examined the potential ameliorative effects of the mixture of heat-killed Lactobacillus delbrueckii and Lactobacillus fermentum (HKL) on the toxicities of ACE.ResultsFollowing 14 days of exposure to ACE at 0.5 and 1 μM, oxidative stress was induced, as evidenced by the decreased levels of reduced glutathione, catalase, glutathione peroxidase, and superoxide dismutase, along with increased levels of malondialdehyde. Also, ACE exposure results in overexpression and raised protein levels of the IL-25, NF-κB1, NF-κB2, IL-33, TSLP, and NF-κB target genes, which induce inflammatory responses. In addition, ACE boosted Ki-67-positive BEAS-2B cells. The molecular docking of ACE with target genes and their proteins demonstrated a potent binding affinity, further supported by the presence of hydrophobic contacts, electrostatic interactions, and hydrogen bonds. The post-treatment of HKL following the ACE (1 μM) exhibited its antioxidant, anti-inflammatory, and antiproliferative activities in suppressing ACE-induced toxicity.ConclusionsOur research revealed that ACE toxicity in BEAS-2B cells is caused by driving oxidative stress, pro-inflammatory response, and cellular proliferation. This study would give us a strategy to alleviate ACE-induced lung impairment by heat-killed probiotic supplements. As a result, dietary supplements that contain these microorganisms may potentially be beneficial in countries with high levels of pesticide contamination.

Associations between Neonicotinoid, Pyrethroid, and Organophosphate Insecticide Metabolites and Neurobehavioral Performance in Ecuadorian Adolescents.

Organophosphate and pyrethroid insecticides can affect children's neurodevelopment and increase inflammation. Limited evidence exists among adolescents and on whether inflammation may mediate pesticide-neurobehavior associations. We examined the associations between insecticide metabolite concentrations and neurobehavior among adolescents in Ecuadorian agricultural communities. We included 520 participants aged 11-17 years. We measured urinary insecticide metabolites (mass spectrometry) and neurobehavior (NEPSY-II). Associations were adjusted for socio-demographic and anthropometric characteristics. The associations of insecticide mixtures with neurobehavior were evaluated using PLS regression, and mediation by inflammatory biomarkers (TNF-α, IL-6, CRP, SAA, sICAM-1, sVCAM-1 and sCD-14) was conducted. Among organophosphates, para-nitrophenol (PNP) and 3,5,6-Trichloro-2-pyridinol (TCPy) were inversely associated with Social Perception (score difference per 50% increase [β 50% ] = -0.26 [95%CI: - 1.07, -0.20] and -0.10 [-0.22, 0.01], respectively). PNP and TCPy also had significant inverse associations with Attention/Inhibitory Control at concentrations >60 th percentile (β 50% = -0.26 [95%CI: -0.51, -0.01] and β 50% = -0.22 [95%CI: -0.43, -0.00], respectively). The pyrethroid, 3-phenoxybenzoic acid (3-PBA), was inversely associated with Language (β 50% = -0.13 [95%CI: -0.19, -0.01]) and had a negative quadratic association with Attention/Inhibitory Control. The neonicotinoid 5-Hydroxy imidacloprid (OHIM) was positively associated with Memory/Learning (β 50% = 0.20 [95%CI: 0.04, 0.37]). Mixtures of all insecticides were significantly negatively related to all domains, except for Memory/Learning, which was positively associated. No mediation by inflammatory markers on these associations was observed. Concurrent organophosphate, pyrethroid, and the mixtures of all metabolites were associated with lower performance in all domains except for Memory/Learning. Neonicotinoids were positively associated with Memory/Learning and Social Perception scores.

Paralysis caused by dinotefuran at environmental concentration via interfering the Ca2+-ROS-mitochondria pathway in Chironomus kiiensis.

Dinotefuran as the third-generation of neonicotinoid insecticides is extensively used in agriculture worldwide, posing a potential toxic threat to non-target animals and humans. However, the chronic toxicity mechanism related to mitochondria damage of dinotefuran to non-target animals at environmental concentration is unclear. In this study, the mitochondria damage and oxidative stress of dinotefuran on Chironomus kiiensis were investigated at environmental concentrations by long-term exposure. At the same time, relevant gene expressions of these toxicity indexes were measured as sensitive ecotoxicity biomarkers to reflect the toxic effects of dinotefuran on Chironomidae. Our present study showed that chronic exposure to environmental concentrations of dinotefuran resulted in behavioral inhibition in the larvae of Chironomidae. For burrowing inhibition of 10 days, the lowest observed-effect concentration (LOEC) and 50% inhibitory concentration (IC50) were 0.01 (0.01-0.04) and 0.60 (0.44-0.82) μg/L, respectively. Dinotefuran promoted the release of intracellular calcium ions (Ca2+) in Chironomidae via dysregulating the gene expressions of atp2b, camk ii, and calm. Subsequently, the disruption of the Ca2+ signaling pathway induced oxidative stress by raising reactive oxygen species (ROS), hydrogen peroxide (H2O2), and malonaldehyde (MDA) levels. Thus, the over-release of Ca2+ and ROS disordered the normal functioning of mitochondrial-related pathways by dysregulating the expressions of mitochondria-related genes of atpef0a, sdha, and cyt b. Our findings showed that low environmental concentrations of dinotefuran caused paralysis of the midge via interfering the Ca2+-ROS-mitochondria pathway. These results provided data support for assessing the potential environmental risk of dinotefuran.

Cytotoxicity induced by three commercial neonicotinoid insecticide formulations in differentiated human neuroblastoma SH-SY5Y cells.

Neonicotinoid insecticides are used worldwide for crop protection. They act as agonists at postsynaptic nicotinic acetylcholine receptors (nAChRs), disrupting normal neurotransmission in target insects. Human exposure is high due to the widespread use of neonicotinoids and their residues in food. This study aimed to evaluate the in vitro neurotoxicity of three neonicotinoid commercial formulations Much 600 FS® (imidacloprid 600gL-1), Evidence 700 WG® (imidacloprid 700gkg-1), and Actara 250 WG® (thiamethoxam 250gkg-1) in differentiated human neuroblastoma SH-SY5Y cell line. Cells were incubated with the pesticides for 96h, and the cytotoxicity was evaluated through the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium·bromide (MTT) reduction and neutral red (NR) uptake assays. Toxicological pathways such as reactive oxygen (ROS) and nitrogen species (RNS) production, mitochondrial membrane potential, cell death mode, and the expression of the pro-apoptotic protein Bax were also evaluated. EC50 values of 266.4, 4,175, and 653.2mgL-1 were found for Much®, Evidence® and Actara®, respectively. Significant increases in ROS and RNS generation were observed for all pesticides, while mitochondrial membrane potential and Bax protein expression showed no significant changes. Analysis of cell death mode revealed an increase in early apoptotic cells. Therefore, neonicotinoid insecticides are potentially neurotoxic, reinforcing concerns about human exposure to these commercial formulations.