[Two cases of pyridaben poisoning were successfully treated by blood purification].

Pyridaben is a broad-spectrum acaricide widely used in agriculture, accidental or self-administration of large doses of pyridaben can cause multiple organ failure in patients. Due to its damage to multiple organs and no specific antidote, the mortality rate is high. This paper reports two patients who took a large amount of pyridaben, developed severe metabolic acidosis, hyperlactatemia, toxic encephalopathy, and liver, kidney, heart and digestive tract damage. After timely gastric lavage, catharsis, organ support andblood purification treatment, the condition improved and discharged. It is expected to provide clinical ideas for the treatment of pyridaben poisoning.

Pyridaben induces apoptosis and inflammation in bovine mammary epithelial cells by disturbance of calcium homeostasis and upregulation of MAPK cascades.

Pyridaben is a widely used pyridazinone insecticide used to protect crops against insects and mites. The toxicity of pyridaben has been reported in mice, zebrafish, the human reproductive system, nervous system, and respiratory system. Pyridaben can also be ingested by dairy cattle through feed. However, the toxicity of pyridaben in cattle has not been investigated on. Thus, this study focuses on demonstrating the toxicity of pyridaben in the bovine mammary glands and with the generation milk in the bovine mammary epithelial cells, as it is crucial to the continuance of the amount and the quality of the milk produced. We started by analyzing the intracellular toxicity along with the impact of pyridaben on the cell cycle distribution and the transcription of associated genes. Pyridaben treatment induced cell cycle arrest accompanied the disruption in G1 and S phases with imbalanced cytosolic and mitochondrial calcium ion homeostasis, and caused a destruction of mitochondrial membrane potential. This eventually led to apoptosis of MAC-T cells. We also investigated in the impact that pyridaben has on MAPK signaling proteins, where phosphorylation of ERK1/2, JNK, and p38 were upregulateed. Moreover, examination of the effect of pyridaben in the inflammatory genes revealed hyperactivation of the inflammatory gene transcription. This is the first research to assess the negative outcomes that pyridaben could impose on dairy cattle and milk production.

Pyridaben impaired cell cycle progression through perturbation of calcium homeostasis and PI3K/Akt pathway in zebrafish hepatocytes.

Environmental pollution caused by pesticides is a growing concern. Pyridaben, a widely used organochlorine insecticide, is a representative water pollutant. Owing to its extensive usage, it has been detected in various aquatic ecosystems, including rivers and oceans. Pyridaben is highly toxic to aquatic organisms; however, the mechanism of its toxicity in the liver, which is important in toxicant metabolism, has not been studied. Therefore, we employed zebrafish and its well-characterized liver cell line, ZFL to assess pyridaben hepatotoxicity and explore its potential mechanisms of action. Pyridaben led to reduction of the liver size and fluorescence intensity of dsRed-labeled Tg (fabp10a:dsRed) zebrafish. It reduced the viability and proliferation of ZFL cells in vitro by inducing apoptosis and cell cycle arrest. These changes might be primarily linked to uncontrolled intracellular calcium flow in ZFL cells exposed to pyridaben. Additionally, it also downregulates the PI3K/Akt signaling cascade, leading to the inactivation of Gsk3ß and nuclear translocation of ß-catenin. Taken together, our findings suggest that pyridaben could have hepatotoxic effects on aquatic organisms. This study is the first to provide insight into the hepatotoxic mechanism of pyridaben using both in vivo and in vitro models.

CYP4CL2 Confers Metabolic Resistance to Pyridaben in the Citrus Pest Mite Panonychus citri.

The citrus red mite Panonychus citri has developed strong resistance to acaricides. Cytochrome P450 monooxygenases (P450s) can detoxify pesticides and are involved in pesticide resistance in many insects. Here, a pyridaben-resistant P. citri strain showed cross-resistance to cyenopyrafen, bifenazate, fenpyroximate, and tolfenpyrad. Piperonyl butoxide, a P450 inhibitor, significantly increased the toxicity of pyridaben to resistant (Pyr_Rs) and susceptible (Pyr_Control) P. citri strains. P450 activity was significantly higher in Pyr_Rs than in Pyr_Control. Analyses of RNA-Seq data identified a P450 gene (CYP4CL2) that is potentially involved in pyridaben resistance. Consistently, it was up-regulated in two field-derived resistant populations (CQ_WZ and CQ_TN). RNA interference-mediated knockdown of CYP4CL2 significantly decreased the pyridaben resistance in P. citri. Transgenic Drosophila melanogaster expressing CYP4CL2 showed increased pyridaben resistance. Molecular docking analysis showed that pyridaben could bind to several amino acids at substrate recognition sites in CYP4CL2. These findings shed light on P450-mediated pyridaben resistance in pest mites.

Residue levels and risk assessment of acetamiprid-pyridaben mixtures in cabbage under various open field conditions.

Acetamiprid and pyridaben are highly efficient insecticides widely used to protect leafy vegetables against various pests, such as Phyllotreta striolata, but analyses of their residual behaviors applied in mixtures in cabbage fields are primarily lacking. Herein, field trials were performed by spraying 50% acetamiprid-pyridaben wettable powder (50% WP) once at a dose of 150 g of active ingredient per hectare in 12 representative provinces of China under Good Agricultural Practices. The residues of acetamiprid and pyridaben were detected using modified Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) and liquid chromatography-tandem mass spectrometry, together with an assessment of their dietary risks. The average recoveries of the two insecticides were 84.6-104%, and the relative standard deviations were 0.898-10.1%. The residual concentrations of acetamiprid and pyridaben at the preharvest interval of 7 days were <0.364 and 0.972 mg/kg, respectively, and less than their maximum residue limits in cabbage (0.5 mg/kg for acetamiprid and 2 mg/kg for pyridaben) in China. The chronic and acute risk values of acetamiprid and pyridaben were 0.0787-33.3%, implying acceptable health hazards to Chinese consumers. In conclusion, applying 50% WP in cabbage fields under Good Agricultural Practices is acceptable. These results provide essential data for using mixtures of acetamiprid and pyridaben in cabbage fields.

Acetamiprid and pyridaben poisoning: A case report.

Background: The agricultural industry has experienced beneficial outcomes by implementing contemporary synthetic pesticides, specifically, the mixture of acetamiprid and pyridaben. However, concerns regarding public health have arisen due to the increased number of suicides caused by insecticide poisoning. Nevertheless, limited reports of human exposure to these pesticides have reported various adverse clinical effects. In this study, we present the case of an individual who consumed the acetamiprid and pyridaben mixture for suicidal purposes, and subsequently developed central nervous system depression, hyperlactacidemia, and metabolic acid poisoning, which thus required clinical management. Case report: A 74-year-old woman was transported to our hospital after ingesting a combination of 30 mL of acetamiprid 5 % and pyridaben 5 %. The patient displayed nausea and vomiting symptoms, followed by confusion. An arterial blood gas analysis revealed metabolic acidosis and hyperlactacidemia. The patient was carefully monitored for vital signs and treated with gastric lavage, purgation, and proton pump inhibitors to reduce gastric acid, blood volume, and electrolyte resuscitation. In addition, the patient received 24 h of hemoperfusion (HP) and continuous renal replacement therapy (CRRT). As a result of these interventions, the patient had a speedy recovery and was discharged 10 days later. Conclusion: This case report provided the details of a rare instance of acute poisoning in humans resulting from exposure to newer synthetic pesticides, specifically acetamiprid and pyridaben. The report described the clinical manifestations and effective supportive therapy management. Future clinicians may find the results of this report valuable for identifying clinical symptoms and treating acute poisoning caused by newer synthetic pesticides.

Hematological, biochemical, genotoxic, and histopathological changes induced by pyridaben.

The current work examined the genotoxic effects of pyridaben (PDB) in male Sprague Dawley rats. Twenty Sprague Dawley rats were divided into four equal groups; the first group was used as a control group; the other three groups were exposed to 19, 28.5, and 57 mg/kg b.w PDB by oral gavage for 4 weeks. Blood samples were collected for hematological and biochemical parameters; femoral bone marrow was flushed for chromosomal aberrations (CA) assay and liver samples were used for the analysis of gene expression of IL-6 and Casp-3 as well as histopathological and immunhistochemical investigation for Casp-3. The results showed that PDB exposure lead to non-significant changes in hematological parameters in all PDB administrated groups while malondialdehyde, glutathione peroxidase, aspartate aminotransferase, and alkaline phosphatase were significantly increased in 19 and 57 mg/kg PDB doses groups Also, gene expression of IL-6 and Casp-3 revealed a significant increase in 28.5 and 57 mg/kg PDB doses groups as compared with the control. However, there was no significant change in the percentage of CAs in bone marrow cells in all PDB-exposed groups. The histopathological and immunhistochemical examination showed focal areas of inflammatory cellular infiltration with fibrosis in 57 mg/kg b.w PDB dose group accompanied by the severe positive reaction of caspase3 in the liver.

Monoclonal Antibody-Based Colorimetric Lateral Flow Immunoassay for the Detection of Pyridaben in the Environment.

Pyridaben, a broad-spectrum pyridazinone acaricide that is widely used in agricultural production, can induce neurotoxicity and reproductive abnormalities, and is highly toxic to aquatic organisms. In this study, a pyridaben hapten was synthesized and used to prepare monoclonal antibodies (mAbs), among which 6E3G8D7 showed the highest sensitivity in indirect competitive enzyme-linked immunosorbent assay, with a 50% inhibitory concentration (IC50) of 3.49 ng mL-1. The mAb, 6E3G8D7, was further applied to a gold nanoparticle-based colorimetric lateral flow immunoassay (CLFIA) for pyridaben detection, according to the signal intensity ratio of the test line to the control line, which showed a visual limit of detection of 5 ng mL-1. The CLFIA also showed high specificity and achieved excellent accuracy in different matrices. In addition, the amounts of pyridaben in blind samples detected by the CLFIA, were consistent with high-performance liquid chromatography. Therefore, the developed CLFIA is considered a promising, reliable, and portable method for pyridaben on-site detection in agro-products and environmental samples.

Evaluation of confirmatory data following Article 12 MRL review and modification of the existing MRLs in pome fruits for pyridaben.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Nissan Chemical Europe SAS submitted a request to the competent national authority in the Czech Republic to modify the existing maximum residue levels (MRLs) in pome fruits and to evaluate the confirmatory data identified in the framework of the MRL review under Article 12 of Regulation (EC) No 396/2005 as not available. To address the data gaps on residue trials, new trials according to the Good Agricultural Practices (GAPs) on apples, pears, medlars, quinces, loquats/Japanese medlars, apricots, peaches and beans with pods evaluated during the MRL review were not provided. These data gaps are not addressed. However, residue trials on apples and pears for an alternative GAP were provided and resulted by extrapolation in an MRL proposal for pome fruits lower than the current (tentative) MRL in EU legislation. The provided information may require a revision of the existing MRLs for pome fruits, apricots, peaches and beans with pods. Information on storage temperature of samples from the feeding study and a validated analytical method for animal commodities were submitted. The two data gaps on animal commodities were satisfactorily addressed. Adequate analytical methods for enforcement are available to control the residues of pyridaben in plant matrices under consideration and in all animal matrices, where currently an limit of quantification (LOQ) of 0.02 mg/kg is considered at the validated LOQ of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the uses of pyridaben according to the reported agricultural practices is unlikely to present a risk to consumer health.

Sublethal and transgenerational effects of pyridaben exposure on the fitness and gene expression of Panonychus citri.

BACKGROUND: Panonychus citri is a globally dominant citrus plant pest mite. Pesticide-induced population resurgence is a concern for mite control. Exposure to sublethal concentrations of pesticides has stimulated reproduction and outbreak risks in many pests. Pyridaben, a mitochondrial electron transport inhibitor, has been frequently used worldwide in mite control. In the study, sublethal and transgenerational effects of pyridaben exposure on Pyr_Rs (resistant) and Pyr_Control (susceptible) strains were systematically investigated in both exposed parental generation (F0 ) and unexposed offspring generations (F1 and F2 ) by evaluating life-table and physiological parameters. RESULTS: After exposure to pyridaben, the fecundity of both strains was significantly reduced in F0 generation while significantly induced in F1 generation. Interestingly, these effects also stimulated the fecundity of the F2 generation in Pyr_Control strain while no significant effects occurred for Pyr_Rs strain. The intrinsic rate of increase (r) and finite rate of increase (λ) were significantly decreased only in F1 generation of Pyr_Control strain after exposure treatment. Meanwhile, the population projection indicated a smaller population size in F1 generation of Pyr_Control strain while a population increase for Pyr_Rs strain after sublethal treatment. Subsequent detoxification enzyme assays indicated that only P450 activities in F0 generation were significantly activated by LC30 exposure to pyridaben in both strains. Significant downregulation of reproduction-related (Pc_Vg) genes was observed in the F0 generations of both strains. Significant upregulation of P450 (CYP4CL2) and Pc_Vg of the F1 generation in both strains suggested the presence of delayed hormesis effects on the reproduction and developed tolerance to pyridaben, although the effects did not last over a longer period (F2 generation). CONCLUSION: These results provide evidence for transgenerational hormesis effects of low concentrations of pyridaben exposure that may lead to population increase and resurgence risks of resistant-mites in natural settings by stimulating reproduction. © 2023 Society of Chemical Industry.

Resistance of Panonychus citri (McGregor) (Acari: Tetranychidae) to pyridaben in China: monitoring and fitness costs.

BACKGROUND: Panonychus citri is a major citrus pest worldwide. The short life cycle and high reproductive potential of P. citri, combined with heavy acaricide use, have led to high levels of resistance to acaricides, posing a threat to global resistance management programs. Here, resistance monitoring was established to determine the pyridaben resistance status of ten P. citri populations in China from 2014 to 2021 using a leaf-dipping assay. Four characterized strains-the susceptible strain (Lab_S), the resistant strain (Pyr_R), as well as the segregated resistant strain (Pyr_Rs) and the segregated susceptible strain (Pyr_Control) derived from the crossing of the Lab_S and Pyr_R strains, were used to evaluate the life-history characteristics using age-stage, two-sex life tables. RESULTS: Most P. citri populations developed high resistance to pyridaben. Resistance levels exceeded 1000-fold in Yuxi, Anyue, Nanning, and Ganzhou populations compared with the Lab_S strain. Compared with Pyr_Control, two key fitness cost criteria, developmental period and fecundity, showed significant differences in Pyr_Rs under consistent conditions. The intrinsic rate of increase, net reproductive rate and gross reproductive rate were lower in the resistant strain compared with the Pyr_Control strain. The Pyr_Rs strain had a lower relative fitness of 0.934 compared with the Pyr_Control. Moreover, the life-history traits and population parameters of the Pyr_R strain also showed significant differences compared with the Lab_S strain. CONCLUSION: The resistance levels to pyridaben varied greatly among the different P. citri populations and showed regional differences. Substantial fitness costs are associated with pyridaben resistance. This study provides potential implications for developing strategies for resistance management in P. citri. © 2022 Society of Chemical Industry.

Pyridoxal 5'-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring.

Pyridaben (PY) is a widely used organochlorine acaricide, which can be detected in the peripheral blood of pregnant women. Available evidence suggests that PY has reproductive toxicity. However, it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring. Here, we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg-1 day-1 via gavage and observed anxiety-like behaviors in PY offspring aged five weeks. We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism. Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected, and the pyridoxal 5'-phosphate (PLP) concentration and the active form of vitamin B6 was significantly reduced. Moreover, the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated. Meanwhile, there was a decreasing trend in the concentration of GABA in the hippocampal DG region. Next, we supplemented PLP at a dose of 20 mg kg-1 day-1 to the PY offspring via intraperitoneal injection at three weeks. We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors. This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism, reduce the concentration of PLP, down-regulate the expression levels of Pdxk and Gad1, inhibit the production of GABA, and ultimately lead to anxiety-like behaviors in offspring.

Setting of an import tolerance for pyridaben in grapefruits.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Nissan Chemical Europe S.A.S. submitted a request to the competent national authority in the Netherlands to set an import tolerance for the active substance pyridaben in grapefruits imported from the United States of America. The data submitted in support of the requests were found to be sufficient to derive an MRL proposal of 0.5 mg/kg for grapefruits. Adequate analytical methods for enforcement are available to control the residues of pyridaben on the commodity under consideration, at or above the validated LOQ of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the uses of pyridaben on imported grapefruits from United States according to the reported agricultural practices, is unlikely to present a risk to consumer health.

An overview on the green synthesis and removal methods of pyridaben.

Pyridaben is an acaricide widely used around the world to control phytophagous mites, white flies, aphids, and thrips. It is highly toxic to nontarget organisms such as predatory mites, bees, and fishes. Therefore, the occurrence and removal of pyridaben in food and the environment are worthy of concern. This mini-review focuses on pyridaben residue levels in crops, aquatic systems, and soils, as well as the green synthesis and removal of pyridaben. During the period of 2010-2022, pyridaben was reported in monitoring studies on fruits, vegetables, herbs, bee products, aquatic systems, and soils. Vegetable and agricultural soil samples exhibited the highest detection rates and residue levels. One-pot synthesis offers a green chemistry and sustainable alternative for the synthesis of pyridaben. Among traditional home treatments, peeling is the most effective way to remove pyridaben from crops. Magnetic solid-phase extraction technology has emerged as a powerful tool for the adsorption and separation of pyridaben. Photocatalytic methods using TiO2 as a catalyst were developed as advanced oxidation processes for the degradation of pyridaben in aqueous solutions. Current gaps in pyridaben removal were proposed to provide future development directions for minimizing the exposure risk of pyridaben residues to human and nontarget organisms.

Susceptibility to Acaricides and the Frequencies of Point Mutations in Etoxazole- and Pyridaben-Resistant Strains and Field Populations of the Two-Spotted Spider Mite, Tetranychus urticae (Acari: Tetranychidae).

The two-spotted spider mite Tetranychus urticae Koch is a major agricultural pest worldwide and is known to rapidly develop resistance to pesticides. In the present study, we explored a field strain that was collected in 2000 and 2003 and has been exhibiting resistance to etoxazole and pyridaben over the last 16 years. The resistance ratios of the etoxazole- and pyridaben-resistant strains (ER and PR) to etoxazole or pyridaben were more than 5,000,000- and 4109.6-fold higher than that of the susceptible strain, respectively. All field-collected populations showed resistance to etoxazole and pyridaben. The ER and PR strains showed cross-resistance to several acaricides. Both I1017F and H92R point mutations were detected in 7 out of 8 field groups. Spirodiclofen and spiromesifen resulted in more than 77.5% mortality in the 8 field groups. In addition, the genotype frequency of the I1017F point mutation was 100.0% in the ER strain, and that of the H92R point mutation was 97.0% in the PR strain. All of the field populations were found to have a high frequency of I1017F. These results suggest that the observation of resistance patterns will help in designing a sustainable IPM program for T. urticae.

Pyridaben induced cardiotoxicity during the looping stages of zebrafish (Danio rerio) embryos.

Pyridaben is a widely used acaricide in agriculture and reaches a high concentration (97 µg/L) in paddy water for a short time when pyridaben was applied to rice. However, its toxicity to aquatic organisms is still poorly understood. Therefore, we assessed the pyridaben cardiotoxicity to aquatic organisms using the zebrafish (Danio rerio) model. We found that pyridaben is highly toxic to aquatic organisms, and LC50 of pyridaben for zebrafish at 72 hpf was 100.6 µg/L. Pyridaben caused severe cardiac malformations and functional abnormalities. Morphologic abnormity included severe pericardial edema, cardiomegaly, decreased cardiomyocytes, thinning of the myocardial layer, linear heart, and increased the distance between sinus venous and bulbus arteriosus (SV-BA). Functional failure included arrhythmia, heart failure, and reduced pumping efficiency. The genes involved in heart development, WNT signaling, BMP signaling, ATPase, and cardiac troponin C were abnormally expressed in the pyridaben treatment group. Exposure to pyridaben increased oxidative stress and induced cell apoptosis. The above causes may lead to cardiac toxicity. The results suggest that pyridaben exposure induced elevated oxidative stress through the WNT signaling pathway, which in turn led to apoptosis in the heart and cardiotoxicity. Besides, pyridaben exposure at the critical stage of cardiac looping (24-36 hpf) resulted in the greatest cardiotoxicity. The chorion reduced the entry of pyridaben and protected zebrafish embryos, resulting in cardiotoxicity second only to the stage of cardiac looping. The study should provide valuable information that pyridaben exposure causes cardiotoxicity in zebrafish embryos and have potential health risks for other aquatic organisms and humans.

Residue behavior and dietary risk assessment of six pesticides in pak choi using QuEChERS method coupled with UPLC-MS/MS.

A reliable and simple modified QuEChERS method with UPLC-MS/MS was developed for the simultaneous determination of six pesticides (dimethomorph, imidaclothiz, lufenuron, methoxyfenozide, pyridaben, spinetoram) and their metabolites in pak choi. Method validation indicated good linearity (R2 ≥ 0.99), accuracy (recoveries of 75%-112%), sensitivity (limits of quantification, 0.002-0.01 mg kg-1), and precision (relative standard deviations ≤ 21%), and matrix effects were -36-28%. The half-lives of the six pesticides in pak choi were 2.2-12 d under open field and greenhouse conditions. Considering the short growth cycle of pak choi, the terminal residue levels (0.046-7.8 mg kg-1) and the relevant maximum residue limits (MRLs) of some countries, 5 d was recommended as the pre-harvest interval for the six pesticides on pak choi. Dietary risk assessment revealed that the risk quotients were 3.1%-58% for different gender and age groups in China, indicating none unacceptable public health risk for general population. The results showed that all the six pesticides degraded faster and the terminal residues were much lower under open field conditions than those under greenhouse conditions, which was mainly due to the influence of rainfall, sunlight and other environmental factors. This work was thus significant in assessing the dissipation fate and food safety risks of the six pesticides on pak choi and facilitated the establishment of maximum residue limits.

Pyridaben induces mitochondrial dysfunction and leads to latent male reproductive abnormalities.

As an organochloride pesticide, pyridaben (PDB) has been used on various plants, including fruiting plants and other crops. Because of emerging concerns regarding exposure to pesticides, the deleterious effects of PDB, including neuronal disease and reproductive abnormalities, have been determined. However, the intracellular mechanisms that contribute to the effects of PDB on the male reproductive system are still unknown. Therefore, we investigated the effects of PDB on the male reproductive organ, focusing on the testes using mouse testicular cells. We demonstrated that PDB suppressed cellular proliferation of mouse Leydig (TM3) and Sertoli (TM4) cells. Additionally, PDB disturbed calcium homeostasis via mitochondrial dysfunction and activation of endoplasmic reticulum stress. Furthermore, PDB inhibited transcriptional gene expression regarding the cell cycle, as well as steroidogenesis and spermatogenesis, which are the primary functions of TM3 and TM4 cells. Moreover, we verified via western blot analysis that PDB dysregulated the intracellular cell signaling pathways in mitochondrial-associated membranes and the Mapk/Pi3k pathway. Lastly, we confirmed that PDB efficiently suppressed the spheroid formation of TM3 and TM4 cells mimicking an in vivo environment. Collectively, the current results indicate that PDB induces testicular toxicity and male reproductive abnormalities by inducing mitochondrial dysfunction, endoplasmic reticulum stress and calcium imbalance.

Pyridaben leads to inhibition of cell growth and induction of cell death through intracellular mechanisms in early pregnancy.

Recently, infertility has become a major global issue. It is crucial to identify environmental factors that lead to infertility. The prevalent use of pesticides in agriculture results in the exposure of livestock and humans to these pesticides. Studies have reported the harmful effects of pesticides on pregnancy. Pyridaben, a pesticide that inhibits mitochondrial complex 1, has been reported to have detrimental effects on neurons, spermatogenesis, hormonal balance, and embryonic development. However, the effect of pyridaben on the female reproductive system has not yet been studied. Therefore, in this study, we evaluated the effects of pyridaben on early pregnancy in porcine reproductive cell lines, which are known to mimic the female reproductive system. Results demonstrated that pyridaben decreased cell growth in porcine endometrial luminal epithelial and porcine trophectoderm cell lines through inhibition of cell signal transduction. Further, pyridaben increased subG1 phase and late apoptosis through the induction of reactive oxygen species production, mitochondrial dysfunction, calcium unbalances, pro-apoptotic signals, and endoplasmic reticulum (ER) stress. Moreover, we found that pyridaben induced autophagy and inhibition of placentation through the regulation of ER-mitochondria axis proteins. Overall, pyridaben was found to be harmful in early pregnancy in pigs and may have similar effects in human pregnancy.

Modification of the existing maximum residue level for pyridaben in sweet pepper/bell pepper and setting of an import tolerance in tree nuts.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Nissan Chemical Europe S.A.S. submitted two requests to the competent national authority in the Netherlands, respectively to modify the existing maximum residue level (MRL) in sweet pepper/bell pepper and to set an import tolerance in tree nuts for the active substance pyridaben. The data submitted in support of the requests were found to be sufficient to derive the MRL proposals of 0.3 mg/kg for sweet peppers/bell peppers and of 0.05* mg/kg for tree nuts. Adequate analytical methods for enforcement are available to control the residues of pyridaben in the commodities under consideration, at or above the validated limits of quantification (LOQs) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of pyridaben on imported tree nuts from United States and from the indoor use on sweet peppers/bell peppers according to the reported agricultural practices, is unlikely to present a risk to consumer health. The reliable end points, appropriate for use in regulatory risk assessment are presented.