Uncovering hidden dangers: The combined toxicity of abamectin and lambda-cyhalothrin on honey bees.

Studying the toxic effects of pesticides on bees has consistently been a prominent area of interest for researchers. Nonetheless, existing research has predominantly concentrated on individual toxicity assessments, leaving a gap in our understanding of mixed toxicity. This study delves into the individual and combined toxic effects of abamectin (ABA) and lambda-cyhalothrin (LCY) on honey bees (Apis mellifera) in laboratory settings. We discovered that ABA (96 h-LC50 value of 0.079 mg/L) exhibited greater acute toxicity to honey bees compared to LCY (96 h-LC50 value of 9.177 mg/L). Moreover, the mixture of ABA and LCY presented an acute antagonistic effect on honey bees. Additionally, our results indicated that exposure to LCY, at medium concentration, led to a reduction in the abundance of gut core bacterium Snodgrassella. However, an increase in the abundance of Bifidobacterium was noted when exposed to a medium concentration of LCY and its mixture with ABA. Transcriptomic analysis revealed significant regulation of certain genes in the medium concentration of all three treatments compared to the control group, primarily enriching in metabolism and immune-related pathways. Following chronic exposure to field-relevant concentrations of ABA, LCY, and their mixture, there were significant alterations in the activities of immunity-related enzyme polyphenol oxidase (PPO) and detoxification enzymes glutathione S-transferase (GST) and carboxylesterase (CarE). Additionally, the expression of four genes (abaecin, cyp9e2, cyp302a1, and GstD1) associated with immune and detoxification metabolism was significantly altered. These findings suggest a potential health risk posed by the insecticides ABA and LCY to honey bees. Despite exhibiting acute antagonistic effect, mixed exposure still induced damage to bees at all levels. This study advances our knowledge of the potential adverse effects of individual or combined exposure to these two pesticides on non-target pollinators and offers crucial guidance for the use of insecticides in agricultural production.

Prenatal exposure to fenvalerate causes depressive-like behavior in adulthood by inhibiting brain-derived 5-HT synthesis.

The developmental toxicity of fenvalerate, a representative pyrethroid insecticide, is well documented. The present study aimed to explore whether prenatal exposure to fenvalerate causes depression-like behavior in adulthood. Pregnant mice were orally administrated with either corn oil or fenvalerate (2 or 20 mg/kg) during pregnancy. Depressive-like behaviors were assessed by tail suspension test (TST), forced swim test (FST) and sucrose preference test (SPT). Immobility times in TST and FST were increased in offspring whose mothers were exposed to fenvalerate throughout pregnancy. By contrast, sugar preference index, as determined by SPT, was decreased in fenvalerate-exposed offspring. Prefrontal PSD95, a postsynaptic membrane marker, was downregulated in fenvalerate-exposed adulthood offspring. Fenvalerate-induced reduction of prefrontal PSD95 began at GD18 fetal period. Accordingly, prefrontal 5-HT, a neurotransmitter for synaptogenesis, was also reduced in fenvalerate-exposed GD18 fetuses. Tryptophan hydroxylase 2 (TPH2), a key enzyme for 5-HT synthesis, was downregulated in the midbrain of fenvalerate-exposed GD18 fetuses. Additional experiment showed that GRP78 and p-eIF2α, two endoplasmic reticulum stress-related proteins, were increased in the midbrain of fenvalerate-exposed fetal mice. The present results suggest that prenatal exposure to fenvalerate causes depressive-like behavior in adulthood, partially by inhibiting brain-derived 5-HT synthesis.

Sub-lethal effects of deltamethrin and permethrin resulted in ultrastructural alterations in scales and oxygen uptake changes of Anabas testudineus (Bloch, 1792).

The present study used scanning electron microscopy (SEM) to assess the toxicity of sub-lethal concentrations of deltamethrin (0.035, 0.007 and 0.0007 mg L-1) and permethrin (0.93, 0.093 and 0.0093 mg L-1) on the ultrastructure of the scales of Anabas testudineus (Bloch, 1792) during a 21 day exposure. The oxygen uptake of the fish during deltamethrin (0.007 and 0.0007 mg L-1) and permethrin (0.093 and 0.0093 mg L-1) exposure was also investigated. The SEM studies revealed abnormal morphological alterations and modifications of fish scales, which were concentration-dependent. Deltamethrin-exposed fish showed severe deformation and fusion of two circuli in different rows, thereby disrupting the normal radii pattern. This fusion was probably caused by the cyanide moiety of the pesticide. On the other hand, permethrin characteristically produced a thick mucus layer over the scale surface. The different concentrations of both the pesticides affected circuli pattern with severe breakage of circuli and loss of lepidonts present over their ridges. Erythrocyte extrusions were also seen at several places over the scale surface. There was significant reduction of oxygen uptake in fish exposed to permethrin at both the concentrations, but in deltamethrin treatments significant reduction occurred only at the higher concentration of 0.007 mg L-1, though this was less than the lower permethrin concentration of 0.0093 mg L-1, and moreover effects of both the pyrethroids on oxygen consumption increased at higher concentrations.

Beta-cyfluthrin impairs implantation process by inducing mitochondrial defects and changes in reactive oxygen species-mediated signaling pathways in porcine trophectoderm and uterine luminal epithelial cells.

Pyrethroid insecticides, such as beta-cyfluthrin, are used extensively globally, including in households and agriculture, and have been detected in the milk and urine of humans and cattle. Beta-cyfluthrin exhibits toxic effects, including neurotoxicity and male reproductive toxicity; however, few studies have investigated female reproductive toxicity despite its wide environmental distribution. The present study investigates effects of beta-cyfluthrin on implantation in porcine cells (pTr from the trophectoderm and pLE from the endometrial luminal epithelium). To identify the various physiological changes induced by beta-cyfluthrin, such as apoptosis and lipid peroxidation, flow cytometry analysis and immunofluorescence were performed with various reagents. In addition, the expression of genes and proteins associated with intracellular changes was confirmed using qRT-PCR and western blotting. Beta-cyfluthrin induced cell-cycle arrest and altered intracellular calcium flux. It also disrupted the mitochondrial function and promoted reactive oxygen species (ROS) production, leading to lipid peroxidation. Moreover, ROS induced by beta-cyfluthrin altered mitogen-activated protein kinase (MAPK) pathways and decreased cell migration capability. The expression levels of genes that are significant during early pregnancy were altered by beta-cyfluthrin in both cell lines. The changes resulted in apoptosis and diminished cell proliferation of pTr and pLE. Collectively, the results imply that beta-cyfluthrin disrupts the implantation process by affecting the physiology of the trophectoderm and endometrial luminal epithelial cells. The present study is the first to reveal the cellular mechanisms of beta-cyfluthrin on the female reproductive system and highlights the need for further in-depth research into its hazards.

The toxicity and health risk of chlorothalonil to non-target animals and humans: A systematic review.

Chlorothalonil (CTL), an organochloride fungicide applied for decades worldwide, has been found to be present in various matrixes and even accumulates in humans or other mammals through the food chain. Its high residue and diffusion in the environment have severely affected food security and public health. More and more research has considered CTL as a possible toxin to environmental non-target organisms, via influencing multiple systems such as metabolic, developmental, endocrine, genetic, and reproductive pathways. Aquatic organisms and amphibians are the most vulnerable species to CTL exposure, especially during the early period of development. Under experimental conditions, CTL can also have toxic effects on rodents and other non-target organisms. As for humans, CTL exposure is most often reported to be relevant to allergic reactions to the skin and eyes. We hope that this review will improve our understanding of the hazards and risks that CTL poses to non-target organisms and find a strategy for rational use.

A relaxin receptor gene RpGPCR41 is involved in the resistance of Rhopalosiphum padi to pyrethroids.

Rhopalosiphum padi is a global pest that poses a significant threat to wheat crops and has developed resistance to various insecticides. G protein-coupled receptors (GPCRs), known for their crucial role in signaling and biological processes across insect species, have recently gained attention as a potential target for insecticides. GPCR has the potential to contribute to insect resistance through the regulation of P450 gene expression. However, GPCRs in R. padi remained unexplored until this study. We identified a total of 102 GPCRs in R. padi, including 81 receptors from family A, 10 receptors from family B, 8 receptors from family C, and 3 receptors from family D. Among these GPCR genes, 16 were up-regulated in both lambda-cyhalothrin and bifenthrin-resistant strains of R. padi (LC-R and BIF-R). A relaxin receptor gene, RpGPCR41, showed the highest up-regulated expression in both the resistant strains, with a significant increase of 14.3-fold and 22.7-fold compared to the susceptible strain (SS). RNA interference (RNAi) experiments targeting the relaxin receptor significantly increase the mortality of R. padi when exposed to the LC50 concentration of lambda-cyhalothrin and bifenthrin. The expression levels of five P450 genes (RpCYP6CY8, RpCYP6DC1, RpCYP380B1, RpCYP4CH2, and RpCYP4C1) were significantly down-regulated following knockdown of RpGPCR41 in LC-R and BIF-R strains. Our results highlight the involvement of GPCR gene overexpression in the resistance of R. padi to pyrethroids, providing valuable insights into the mechanisms underlying aphid resistance and a potential target for aphid control.

Z-scheme heterojunction composed of Fe-doped g-C3N4 and Bi2MoO6 for photo-fenton degradation of antibiotics over a wide pH range: Activity and toxicity assessment.

In photo-Fenton technology, the narrower pH range limits its practical application for antibiotic wastewater remediation. Therefore, in this study, a Z-scheme heterojunction photo-Fenton catalyst was constructed by Fe-doped graphite-phase carbon nitride in combination with bismuth molybdate for the degradation of typical antibiotics. Fe doping can shorten the band gap and increase visible-light absorption. Simultaneously, the constructed Z-scheme heterojunction provides a better charge transfer pathway for the photo-Fenton reaction. Within 30 min, Fe3CN/BMO-3 removed 95.54% of tetracycline hydrochloride (TC), and its remarkable performance was the higher Fe3+/Fe2+ conversion efficiency through the decomposition of H2O2. The Fe3CN/BMO-3 catalyst showed remarkable photo-Fenton degradation performance in a wide pH range (3.0-11.0), and it also had good stability in the treatment of TC wastewater. Furthermore, the order of action of the active species was h+ > ·O2- > 1O2 > ·OH, and the toxicity assessment suggested that Fe3CN/BMO-3 was effective in reducing the biotoxicity of TC. The catalyst proved to be an economically feasible and applicable material for antibiotic photo-Fenton degradation, and this study provides another perspective on the application of elemental doping and constructed heterojunction photo-Fenton technology for antibiotic water environmental remediation.

From growth inhibition to ultrastructural changes: Toxicological assessment of lambda cyhalothrin and fosetyl aluminium against Bacillus subtilis and Pseudomonas aeruginosa.

In modern agricultural practices, agrochemicals and pesticides play an important role in protecting the crops from pests and elevating agricultural productivity. This strategic utilization is essential to meet global food demand due to the relentless growth of the world's population. However, the indiscriminate application of these substances may result in environmental hazards and directly affect the soil microorganisms and crop production. Considering this, an in vitro study was carried out to evaluate the pesticides' effects i.e. lambda cyhalothrin (insecticide) and fosetyl aluminum (fungicide) at lower, recommended, and higher doses on growth behavior, enzymatic profile, total soluble protein production, and lipid peroxidation of bacterial specimens (Pseudomonas aeruginosa and Bacillus subtilis). The experimental findings demonstrated a concentration-dependent decrease in growth of both tested bacteria, when exposed to fosetyl aluminium concentrations exceeding the recommended dose. This decline was statistically significant (p < 0.000). However, lambda cyhalothrin at three times of recommended dose induces 10% increase in growth of Pseudomonas aeruginosa (P. aeruginosa) and 76.8% decrease in growth of Bacillus subtilis (B. subtilis) respectively as compared to control. These results showed the stimulatory effect of lambda cyhalothrin on P. aeruginosa and inhibitory effect on B. subtilis. Pesticides induced notable alterations in biomarker enzymatic assays and other parameters related to oxidative stress among bacterial strains, resulting in increased oxidative stress and membrane permeability. Generally, the maximum toxicity of both (P. aeruginosa and B. subtilis) was shown by fosetyl aluminium, at three times of recommended dose. Fosetyl aluminium induced morphological changes like cellular cracking, reduced viability, aberrant margins and more damage in both bacterial strains as compared to lambda cyhalothrin when observed under scanning electron microscope (SEM). Conclusively the, present study provide an insights into a mechanistic approach of pyrethroid insecticide and phosphonite fungicide induced cellular toxicity towards bacteria.

Contribution of Immune Responses to the Cardiotoxicity and Hepatotoxicity of Deltamethrin in Early Life Stage Zebrafish (Danio rerio).

Deltamethrin (DM) is a widely used insecticide that has demonstrated developmental toxicity in the early life stages of fish. To better characterize the underlying mechanisms, embryos from Tg(cmlc2:RFP), Tg(apo14:GFP), and Tg(mpx:GFP) transgenic strains of zebrafish were exposed to nominal DM concentrations of 0.1, 1, 10, 25, and 50 µg/L until 120 h post-fertilization (hpf). Heart size increased 56.7%, and liver size was reduced by 17.1% in zebrafish exposed to 22.7 and 24.2 µg/L DM, respectively. RNA sequencing and bioinformatic analyses predicted that key biological processes affected by DM exposure were related to inflammatory responses. Expression of IL-1 protein was increased by 69.0% in the 24.4 µg/L DM treatment, and aggregation of neutrophils in cardiac and hepatic histologic sections was also observed. Coexposure to resatorvid, an anti-inflammatory agent, mitigated inflammatory responses and cardiac toxicity induced by DM and also restored liver biomass. Our data indicated a complex proinflammatory mechanism underlying DM-induced cardiotoxicity and hepatotoxicity which may be important for key events of adverse outcomes and associated risks of DM to early life stages of fish.

Predictions of tissue concentrations of myclobutanil, oxyfluorfen, and pronamide in rat and human after oral exposures via GastroPlusTM physiologically based pharmacokinetic modelling.

Heritage agrochemicals like myclobutanil, oxyfluorfen, and pronamide, are extensively used in agriculture, with well-established studies on their animal toxicity. Yet, human toxicity assessment relies on conventional human risk assessment approaches including the utilization of animal-based ADME (Absorption, Distribution, Metabolism, and Excretion) data. In recent years, Physiologically Based Pharmacokinetic (PBPK) modelling approaches have played an increasing role in human risk assessment of many chemicals including agrochemicals. This study addresses the absence of PBPK-type data for myclobutanil, oxyfluorfen, and pronamide by generating in vitro data for key input PBPK parameters (Caco-2 permeability, rat plasma binding, rat blood to plasma ratio, and rat liver microsomal half-life), followed by generation of PBPK models for these three chemicals via the GastroPlusTM software. Incorporating these experimental input parameters into PBPK models, the prediction accuracy of plasma AUC (area under curve) was significantly improved. Validation against rat oral administration data demonstrated substantial enhancement. Steady-state plasma concentrations (Css) of pronamide aligned well with published data using measured PBPK parameters. Following validation, parent-based tissue concentrations for these agrochemicals were predicted in humans and rats after single or 30-day repeat exposure of 10 mg/kg/day. These predicted concentrations contribute valuable information for future human toxicity risk assessments of these agrochemicals.

Biochemical and molecular-level effects of co-exposure to chlorpyrifos and lambda-cyhalothrin on the earthworm (Eisenia fetida).

Farmland soil organisms frequently encounter pesticide mixtures presented in their living environment. However, the underlying toxic mechanisms employed by soil animals to cope with such combined pollution have yet to be explored. This investigation aimed to reveal the changes in cellular and mRNA levels under chlorpyrifos (CPF) and lambda-cyhalothrin (LCT) co-exposures in earthworms (Eisenia fetida). Results exhibited that the combination of CPF and LCT triggered an acute synergistic influence on the animals. Most exposures resulted in significant alterations in the activities of total superoxide dismutase (T-SOD), copper/zinc superoxide dismutase (Cu/Zn-SOD), caspase 3, and carboxylesterase (CarE) compared to the basal level. Moreover, when exposed to chemical mixtures, the transcription levels of four genes [heat shock protein 70 (hsp70), gst, sod, and calreticulin (crt)] also displayed more pronounced changes compared with their individual exposures. These changes in determined parameters indicated the occurrence of oxidative stress, cell death, detoxification dysfunction, and endoplasmic reticulum damage after co-exposure to CPF and LCT in E. fetida. The comprehensive examination of mixture toxicities of CPF and LCT at different endpoints would help to understand the overall toxicity they cause to soil invertebrates. The augmented deleterious effect of these pesticides in a mixture suggested that mixture toxicity assessment was necessary for the safety evaluation and application of pesticide mixtures.

Myclobutanil induces neurotoxicity by activating autophagy and apoptosis in zebrafish larvae (Danio rerio).

Myclobutanil (MYC), a typical broad-spectrum triazole fungicide, is often detected in surface water. This study aimed to explore the neurotoxicity of MYC and the underlying mechanisms in zebrafish and in PC12 cells. In this study, zebrafish embryos were exposed to 0, 0.5 and 1 mg/L of MYC from 4 to 96 h post fertilization (hpf) and neurobehavior was evaluated. Our data showed that MYC decreased the survival rate, hatching rate and heart rate, but increased the malformation rate and spontaneous movement. MYC caused abnormal neurobehaviors characterized by decreased swimming distance and movement time. MYC impaired cerebral histopathological morphology and inhibited neurogenesis in HuC:egfp transgenic zebrafish. MYC also reduced the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and downregulated neurodevelopment related genes (gfap, syn2a, gap43 and mbp) in zebrafish and PC12 cells. Besides, MYC activated autophagy through enhanced expression of the LC3-II protein and suppressed expression of the p62 protein and autophagosome formation, subsequently triggering apoptosis by upregulating apoptotic genes (p53, bax, bcl-2 and caspase 3) and the cleaved caspase-3 protein in zebrafish and PC12 cells. These processes were restored by the autophagy inhibitor 3-methyladenine (3-MA) both in vivo and in vitro, indicating that MYC induces neurotoxicity by activating autophagy and apoptosis. Overall, this study revealed the potential autophagy and apoptosis mechanisms of MYC-induced neurotoxicity and provided novel strategies to counteract its toxicity.

Lambda-cyhalothrin alters locomotion, mood and memory abilities in Swiss mice.

Lambda-cyhalothrin (LCT) is a type II pyrethroid widely used in agriculture for plant protection against pests. However, pyrethroids represents a risk for rural female farmworkers, and few studies addressed LCT-behavioural alterations in mice. The present study evaluates the effect of LCT on behaviour of eight weeks aged female mice. Mice were divided into three groups including treated mice that received through gavage (i) 0.5 mg/kg bw and (ii) 2 mg/kg of LCT dissolved in corn oil, and (iii) the vehicle controls. Behavioural tests assess the locomotor activity using open field test, the anxiety by the dark-light box test, the learning memory with novel object recognition test, the memory retention by the elevated plus maze test, and the spatial working memory using the Y-maze test. Subacute treatment with low doses of LCT decreases total distance travelled, induces anxiogenic effect by reducing the time spent in the enlightened compartment, alters memory retention by increasing the latency time, and also affects learning memory by reducing the recognition index parameter. However, LCT does not significantly alter spatial working memory. In conclusion, LCT-treated female mice show an alteration in locomotor activity, mood state and memory abilities probably related to oxidative stress and altered neurotransmission.

Co-exposure to deltamethrin and cyazofamid: variations in enzyme activity and gene transcription in the earthworm (Eisenia fetida).

Pesticide formulations are typically applied as mixtures, and their synergistic effects can increase toxicity to the organisms in the environment. Despite pesticide mixtures being the leading cause of pesticide exposure incidents, little attention has been given to assessing their combined toxicity and interactions. This survey purposed to reveal the cumulative toxic effects of deltamethrin (DEL) and cyazofamid (CYA) on earthworms (Eisenia fetida) by examining multiple endpoints. Our findings revealed that the LC50 values of DEL for E. fetida, following 7- and 14-day exposures, ranged from 887.7 (728-1095) to 1552 (1226-2298) mg kg-1, while those of CYA ranged from 316.8 (246.2-489.4) to 483.2 (326.1-1202) mg kg-1. The combinations of DEL and CYA induced synergistic influences on the organisms. The contents of Cu/Zn-SOD and CarE showed significant variations when exposed to DEL, CYA, and their combinations compared to the untreated group. Furthermore, the mixture administration resulted in more pronounced alterations in the expression of five genes (hsp70, tctp, gst, mt, and crt) associated with cellular stress, carcinogenesis, detoxification, and endoplasmic reticulum compared to single exposures. In conclusion, our comprehensive findings provided detailed insights into the cumulative toxic effects of chemical mixtures across miscellaneous endpoints and concentration ranges. These results underscored the importance of considering mixture administration during ecological risk evaluations of chemicals.

Daily temperature fluctuation interacts with the mean temperature to increase the toxicity of a pyrethroid insecticide in a moth.

Climate change complicates ecotoxicology studies because species responses to pesticides depend on temperature. Classically illustrated by the effect of constant laboratory temperatures, a recent review revealed that the toxicity of pesticides is also often increased by daily temperature fluctuations. Here, we investigated the combined effects of daily temperature fluctuation and mean temperature on the toxicity of two insecticides in the moth Spodoptera littoralis. Our study tested the toxicity of chlorpyrifos and deltamethrin on larvae of six experimental groups that crossed three treatments of daily temperature fluctuations (0, 5 or 10 °C) and two treatments of mean temperatures (25 or 33 °C). We showed that daily temperature fluctuation increased larval mortality induced by chlorpyrifos and deltamethrin. However, the response differed between the organophosphorus insecticide chlorpyrifos and the pyrethroid insecticide deltamethrin. The increase in chlorpyrifos toxicity by daily temperature fluctuation did not differ between mean temperatures of 25 and 33 °C. Remarkably, the increase in deltamethrin toxicity by daily temperature fluctuation was dependent on the crossed effects of the amplitude of daily fluctuation and mean temperature. This increase in deltamethrin toxicity occurred with a daily fluctuation of only 5 °C for larvae reared at 25 °C and a daily fluctuation of 10 °C in larvae reared at 33 °C. To confidently quantify the responses of insecticide toxicity to temperature, future ecotoxicology studies will have to evaluate the generality of the interaction between the effects of daily temperature fluctuation and mean temperature.

Combined toxic effects of polyethylene microplastics and lambda-cyhalothrin on gut of zebrafish (Danio rerio).

Microplastics (MPs), which are prevalent and increasingly accumulating in aquatic environments. Other pollutants coexist with MPs in the water, such as pesticides, and may be carried or transferred to aquatic organisms, posing unpredictable ecological risks. This study sought to assess the adsorption of lambda-cyhalothrin (LCT) by virgin and aged polyethylene MPs (VPE and APE, respectively), and to examine their influence on LCT's toxicity in zebrafish, specifically regarding acute toxicity, oxidative stress, gut microbiota and immunity. The adsorption results showed that VPE and APE could adsorb LCT, with adsorption capacities of 34.4 mg∙g-1 and 39.0 mg∙g-1, respectively. Compared with LCT exposure alone, VPE and APE increased the acute toxicity of LCT to zebrafish. Additionally, exposure to LCT and PE-MPs alone can induce oxidative stress in the zebrafish gut, while combined exposure can exacerbate the oxidative stress response and intensify intestinal lipid peroxidation. Moreover, exposure to LCT or PE-MPs alone promotes inflammation, and combined exposure leads to downregulation of the myd88-nf-κb related gene expression, thus impacting intestinal immunity. Furthermore, exposure to APE increased LCT toxicity to zebrafish more than VPE. Meanwhile, exposure to PE-MPs and LCT alone or in combination has the potential to affect gut microbiota function and alter the abundance and diversity of the zebrafish gut flora. Collectively, the presence of PE-MPs may affect the toxicity of pesticides in zebrafish. The findings emphasize the importance of studying the interaction between MPs and pesticides in the aquatic environment.