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Background: Despite evidence of atrazine toxicity in developing organisms from experimental studies, few studies—and fewer epidemiologic investigations—have examined the potential effects of prenatal exposure. Objectives: We assessed the association between adverse birth outcomes and urinary biomarkers of prenatal atrazine exposure, while taking into account exposures to other herbicides used on corn crops (simazine, alachlor, metolachlor, and acetochlor). Methods: This study used a case-cohort design nested in a prospective birth cohort conducted in the Brittany region of France from 2002 through 2006. We collected maternal urine samples to examine pesticide exposure biomarkers before the 19th week of gestation. Results: We found quantifiable levels of atrazine or atrazine mercapturate in urine samples from 5.5% of 579 pregnant women, and dealkylated and identified hydroxylated triazine metabolites in 20% and 40% of samples, respectively. The presence versus absence of quantifiable levels of atrazine or a specific atrazine metabolite was associated with fetal growth restriction [odds ratio (OR) = 1.5; 95% confidence interval (CI), 1.0-2.2] and small head circumference for sex and gestational age (OR = 1.7; 95% CI, 1.0-2.7). Associations with major congenital anomalies were not evident with atrazine or its specific metabolites. Head circumference was inversely associated with the presence of quantifiable urinary metolachlor. Conclusions: Ulis study is the first to assess associations of birth outcomes with multiple urinary biomarkers of exposure to triazine and chloroacetanilide herbicides. Evidence of associations with adverse birth outcomes raises particular concerns for countries where atrazine is still in use.

The thermal characterisation and toxicity profile of a class of disubstituted heterofused triazinones were revealed in this article for the first time. The thermal behaviour of molecules 1–12 was investigated by means of TG and DSC analyses performed in an air atmosphere and by the coupled TG/FTIR technique in a nitrogen atmosphere. The heating atmosphere affects both the stability of compounds and the degradation mechanism. A two-step degradation occurs in air, while a one-step degradation takes place in nitrogen, both preceded by a melting process. Compound 3 shows the highest thermal stability, while molecule 10—the lowest. The thermal decomposition of the studied heterocyclic molecules begins with the degradation of the bicyclic system, resulting in the formation of volatile gaseous products such as ammonia/hydrazine, hydrogen cyanide, carbon dioxide, and isocyanates. In the further stage, mainly aromatic compounds are released, and their chemical composition depends on the presence and type of substituents at the phenyl and benzyl moieties. In addition, the toxicity profiles of molecules were assessed in the animal (zebrafish) and cellular (erythrocytes) models, and the antihaemolytic activity was evaluated in the AAPH- and H2O2-induced haemolysis inhibition assays. It was found that all the tested compounds are safe for the developing zebrafish and red blood cells, and they are able to effectively protect erythrocytes from oxidative damage. These favourable properties make them promising drug candidates suitable for further in vivo studies.

Baloxavir has emerged as a breakthrough anti-influenza therapy, owing to its single-dose regimen and rapid viral clearance. Nevertheless, clinical adverse effects have been reported, while the underlying cellular mechanisms remain unclear. In this study, we demonstrate that baloxavir acid rapidly induces mitochondrial morphological abnormalities. This mitochondrial dysfunction subsequently initiates a cascade of cellular events, including G0/G1 cell cycle arrest mediated by the downregulation of cyclin D3 and CDK4, and apoptosis via the Bak-caspase-3 pathway. Co-treatment with the antioxidant N-acetylcysteine alleviated baloxavir-induced mitochondrial abnormalities and the decreased expression level of cyclin D3. In contrast, the prodrug baloxavir marboxil exhibited minimal mitochondrial toxicity, underscoring the advantage of the prodrug strategy in reducing adverse effects. Our findings identify mitochondrial impairment as a key mechanism for baloxavir-induced cytotoxicity and provide molecular insights that may help explain its clinical adverse profile.

The red flour beetle, Tribolium castaneum (Herbst) is a cosmopolitan insect pest that causes severe loss in broad range of stored commodities worldwide. Chemical control has been considered as major preventive measure to manage this dangerous pest. Therefore, we have evaluated 22 different insecticides against T. castaneum collected from five districts of southern Punjab, Pakistan. Bioassays were performed to assess the LC 50 values of considered insecticides. Our results showed that emamectin benzoate was the most toxic insecticide among all the insecticides. There was non-significant difference in toxicity of deltamethrin and triazophos to all tested populations based on overlapping 95% confidence interval of LC 50 . The spinosad was more toxic as compared with the spinetoram. In case of ketoenoles, spirotetramat was more toxic as compared with the spiromesifen. In case of acetamaprid and nitenpyram, there is non- significant difference in LC 50 values of the all tested strains of T. castaneum based on overlapping 95%CI. We used four insect growth regulators (IGRS) including methoxyfenozide, pyriproxyfen, lufenuron and cyromazine as larvicides. The lufenuron was more toxic as compared with the pyriproxyfen, methoxyfenozide and cyromazine in most of the studied populations. Methoxyfenozide was moderately toxic. These results will provide help in establishing an effective management program for T. castaneum .

Background: A major food safety incident in China was made public in September 2008. Kidney and urinary tract effects, including kidney stones, affected about 300,000 Chinese infants and young children, with six reported deaths. Melamine had been deliberately added at milk-collecting stations to diluted raw milk ostensibly to boost its protein content. Subsequently, melamine has been detected in many milk and milk-containing products, as well as other food and feed products, which were also exported to many countries worldwide. Objectives: The melamine event represents one of the largest deliberate food contamination incidents. We provide a description and analysis of this event to determine the global implications on food and feed safety. Discussions: A series of factors, including the intentional character of the milk contamination, the young age of the population affected, the large number of potentially contaminated products, the global distribution of these products, and the delay in reporting led this event to take on unexpected proportions. This incident illustrated the complexity of international trade of food products and food ingredients that required immediate actions at international level. Conclusion: Managing food-safety events should be done internationally and early on as soon as multinational consequences are expected. Collaboration between food-safety authorities worldwide is needed to efficiently exchange information and to enable tracking and recalling of affected products to ensure food safety and to protect public health.

Pseudomonas spp. are bacteria known for their ability to degrade various pesticides, acting as natural biofilters. Despite their widespread use, the degradation of metribuzin—a herbicide commonly applied in agriculture—by these bacterial strains remains undocumented. This investigation aims to assess the capacity of Pseudomonas spp. to alleviate metribuzin-induced stress in different wheat cultivars under precisely controlled environmental conditions, offering insights into potential bioremediation strategies. This experiment was conducted as factorial in a completely randomized design with three replications. It included varying concentrations of metribuzin (0, 5, 10, 15, 20, and 30 mg/kg), bacterial treatments (control, P. fluorescens , and P. aeruginosa ), and wheat cultivars (Pishtaz, Chamran, and Sivand). The evaluation focused on plant growth and biochemical responses, monitored at ten-day intervals starting 14 days after planting (DAP). A strong dose-dependent inhibition of plant growth was observed with increasing metribuzin concentrations. Growth reduction intensified at concentrations above 20 mg/kg, but near-complete inhibition (EC90) generally required higher concentrations, depending on cultivar and bacterial treatment. Pishtaz demonstrated the highest level of herbicide tolerance, with EC90 values in the non-inoculated treatment ranging from 23 to 107 mg/kg across growth stages. Increases in antioxidant enzyme activities and decreases in malondialdehyde levels were observed, indicating the stress mitigation capabilities of Pseudomonas spp. through biodegradation, which also led to enhanced plant growth and increased bacterial colony numbers in the soil. Variability in metribuzin sensitivity was observed among the cultivars, with Pishtaz being notably tolerant, Chamran semi-sensitive, and Sivand sensitive. P. fluorescens , in particular, showed a marked ability to reduce metribuzin’s detrimental effects, underscoring the potential of employing microbial strategies for managing pesticide stress in wheat cultivation.

Conventional photosystem II (PSII) herbicides applied in agriculture can pose significant environmental risks to aquatic environments. In response to the frequent detection of these herbicides in the Great Barrier Reef (GBR) catchment area, transitions towards ‘alternative’ herbicides are now widely supported. However, water quality guideline values (WQGVs) for alternative herbicides are lacking and their potential ecological impacts on tropical marine species are generally unknown. To improve our understanding of the risks posed by some of these alternative herbicides on marine species under tropical conditions, we tested the effects of four herbicides on the widely distributed diatom Chaetoceros muelleri. The PSII herbicides diuron, propazine, and tebuthiuron induced substantial reductions in both 24 h effective quantum yields (ΔF/F m ′) and 3-day specific growth rates (SGR). The effect concentrations, which reduced ΔF/F m ′ by 50% (EC 50 ), ranged from 4.25 µg L −1 diuron to 48.6 µg L −1 propazine, while the EC 50 s for SGR were on average threefold higher, ranging from 12.4 µg L −1 diuron to 187 µg L −1 tebuthiuron. Our results clearly demonstrated that inhibition of ΔF/F m ′ in PSII is directly linked to reduced growth (R 2  = 0.95) in this species, further supporting application of ΔF/F m ′ inhibition as a valid bioindicator of ecological relevance for PSII herbicides that could contribute to deriving future WQGVs. In contrast, SGR and ΔF/F m ′ of C. muelleri were nonresponsive to the non-PSII herbicide haloxyfop at the highest concentration tested (4570 µg L −1 ), suggesting haloxyfop does not pose a risk to C. muelleri . The toxicity thresholds (e.g. no effect concentrations; NECs) identified in this study will contribute to the derivation of high-reliability marine WQGVs for some alternative herbicides detected in GBR waters and support future assessments of the cumulative risks of complex herbicide mixtures commonly detected in coastal waters.

Several findings have highlighted the importance of diet and ecotoxic compounds on aging. Melamine (Mel), a widely documented food adulterant, has demonstrated toxicity in multiple organs of the human body, including the brain. However, its neurotoxic effects on aging neurons remain unexplored. This study aims to bridge this gap by investigating the in-vitro neurotoxic impact of Mel in a D-galactose (DG)-induced aging model of neuronal SH-SY5Y cells. In the present study, the SH-SY5Y cells were administered a toxic dose of Mel and DG individually and in combination (Mel + DG) to determine their potential for neurotoxicity. The analysis involved measuring cell viability through MTT assay and morphological examination via neurite length assessment. Furthermore, we evaluated the antioxidant status of the cells by examining catalase (CAT), superoxide dismutase (SOD), and total antioxidant activities. Subsequent investigations of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and caspase-3 (Casp3) activity were also performed. The co-administration with Mel and DG resulted in the highest cell death compared to individual treatments of Mel or DG and control untreated cells. The combined exposure of Mel and DG also led to significant neurite shrinkage and ROS accumulation, indicating exacerbated toxicity. Moreover, SOD, CAT, and total antioxidant levels were significantly reduced in the co-treatment (Mel + DG) group than in Mel-only or DG-only treated group, showing excessively hampered antioxidant state. Additionally, the Casp3 activity was markedly elevated in the cell group jointly treated with Mel and DG, as compared to Mel or DG alone treated groups, signifying a heightened apoptotic reaction. This study provides early insights into the increased neurotoxic potential of Melamine (Mel) in an aging model of neuronal cells. The outcomes reveal that Mel consumption in the elderly may contribute to a higher risk of neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases.

As an effective herbicide, 1, 3, 5-Triazine herbicides (S-THs) are used widely in the pesticide market. However, due to their chemical properties, S-THs severely threaten the environment and human health (e.g., human lung cytotoxicity). In this study, molecular docking, Analytic Hierarchy Process—Technique for Order Preference by Similarity to the Ideal Solution (AHP-TOPSIS), and a three-dimensional quantitative structure-active relationship (3D-QSAR) model were used to design S-TH substitutes with high herbicidal functionality, high microbial degradability, and low human lung cytotoxicity. We discovered a substitute, Derivative-5, with excellent overall performance. Furthermore, Taguchi orthogonal experiments, full factorial design of experiments, and the molecular dynamics method were used to identify three chemicals (namely, the coexistence of aspartic acid, alanine, and glycine) that could promote the degradation of S-THs in maize cropping fields. Finally, density functional theory (DFT), Estimation Programs Interface (EPI), pharmacokinetic, and toxicokinetic methods were used to further verify the high microbial degradability, favorable aquatic environment, and human health friendliness of Derivative 5. This study provided a new direction for further optimizations of novel pesticide chemicals.