Journal of Applied Toxicology最新文献

The study evaluates the biosafety of a novel chitosan-based nanohybrid fertilizer (NHF), formulated with poly (methacrylic acid) (PMAA) and encapsulating NPK and micronutrients (Fe, Mg), across multiple trophic levels to assess its suitability for sustainable agriculture. Following OECD guidelines, the eco-toxicological impact was tested on terrestrial organisms (earthworms: Eudrilus eugeniae; pollinators: Apis cerana indica, Trichogramma chilonis), aquatic organisms (fish: Poecilia reticulata), and beneficial microbes (Bacillus subtilis, Trichoderma viride, Pseudomonas fluorescens). No mortality was observed in honey bees or fish across all NHF concentrations (1%, 1.5%, 2%), indicating high biocompatibility. Earthworms exhibited near-100% survival and significant growth (weight and length increases) across treatments, suggesting no acute or sublethal toxicity. T. chilonis showed high adult emergence (88%-96%) and parasitisation efficiency (87%-94%), classified as "harmless" per IOBC standards. Microbial assays revealed dose-dependent effects: B. subtilis and T. viride exhibited reduced growth compared to controls, but NHF treatments were less inhibitory than chitosan alone, with T. viride recovering to control levels by 96 h. Cytotoxicity assays (LDH, MTT) on P. fluorescens indicated lower cell death and higher viability at higher NHF concentrations, attributed to nutrient enrichment. These findings highlight NHF's minimal ecological impact and compatibility with sustainable farming, offering a safer alternative to conventional fertilizers while supporting soil health, pollination, and aquatic ecosystems.

It has indicated that arsenic exhibits toxicity to skeletal muscle; however, the specific characteristics of arsenic-induced skeletal muscle damage and associated risk indicators remain unclear. Our previous research has demonstrated that arsenite-induced skeletal muscle atrophy exhibits a susceptibility in middle-aged rats, and other studies have shown that glucocorticoids play a significant role in maintaining skeletal muscle mass. This study was aimed at investigating the relationship between alterations in serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels and indicators of arsenic-induced skeletal muscle aging in mice. In this study, 24 male C57BL/6J mice were randomly assigned to a control group and three arsenite exposure groups with low dose (0.01 mg/L), medium dose (0.1 mg/L), and high dose (1 mg/L). The results showed that in the 0.1 and 1 mg/L arsenite exposure groups compared to the control group, a shortening in relative telomere length and a decreased ratio of type II/I myofibers were observed in the gastrocnemius muscle. Additionally, serum levels of ACTH and CORT were elevated, alongside increased indicators of oxidative stress (SOD, GSH, and MDA) as well as inflammatory factors (TNF-α, IL-1β, and IL-6) within the gastrocnemius muscle. In addition, mice exposed to 1 mg/L arsenite exhibited a significant decline in limb grip strength and skeletal muscle atrophy. The serum levels of ACTH and CORT in arsenite exposure groups exhibited a significant negative correlation with limb grip strength, gastrocnemius muscle index, and the relative length of telomeres in the gastrocnemius muscle. This study demonstrated that long-term exposure to arsenite could accelerate skeletal muscle aging in middle-aged mice, potentially linked to the dysregulation of the HPA axis.

The diamondback moth, Plutella xylostella (L.), is a major pest of cruciferous crops with a remarkable capacity to develop insecticide resistance. The present study evaluated the susceptibility, resistance ratios, and detoxification mechanisms of field populations collected from Andhra Pradesh, India, against tolfenpyrad 15 EC and emamectin benzoate 5 SG. Laboratory selection studies revealed declining LC₅₀ values over successive generations reared without insecticide pressure, indicating partial recovery of susceptibility. Field bioassays showed resistance ratios ranging from 9.8 to 13.1 for tolfenpyrad and 5.3 to 10.2 for emamectin benzoate, with the Ponnur population exhibiting the highest resistance levels. Biochemical assays demonstrated that tolfenpyrad resistance was primarily associated with increased glutathione-S-transferase (GST) activity, while emamectin benzoate resistance was largely mediated by elevated carboxylesterase (CarE) activity, supported by moderate induction of mixed-function oxidases (MFOs). Specifically, GST activity increased by 2.06-fold and CarE activity by 1.90-fold in resistant populations compared with the susceptible strain, confirming the role of detoxification enzymes in resistance development. These findings highlight distinct enzymatic pathways involved in insecticide resistance and emphasize the importance of regular resistance monitoring. Adoption of insecticide rotation with different modes of action, combined with non-chemical pest management strategies, is recommended to prolong the efficacy of these insecticides in crucifer pest management programs.

Gentamicin (GET) is a commonly prescribed aminoglycoside antibiotic used to treat severe bacterial infections, but its therapeutic effectiveness is limited by its cardiotoxicity, which is mainly caused by oxidative damage and inflammation. This study investigated the cardioprotective role of vincamine (VIN) against GET-induced cardiac injury. Adult male rats were divided into four groups and treated for 7 days with either CMC (control), VIN, GET, or a combination of GET and VIN. Measurements included oxidative stress markers (TAC and MDA), gene expression of inflammatory cytokines and apoptosis markers (TNF-α, IL-6, Bax, Bcl-2) by qRT-PCR, protein levels of signaling molecules (Nrf2/HO-1, WNT-4, pGSK-3β, β-catenin, pERK, Klotho) by qRT-PCR and ELISA, and NF-κB protein quantification via Western blot. Cardiac tissue was also examined histologically for structural changes. Results demonstrated that VIN significantly reduced GET-induced cardiac damage by modulating crucial signaling pathways and markedly diminished the tissue structural alterations caused by GET. These findings suggest that VIN may serve as a promising cardioprotective agent against GET-induced toxicity through the regulation of pathways including Nrf2/HO-1, pERK/NF-κB, WNT-4/pGSK-3β/β-catenin, and Bax/Bcl-2.

Long-term exposure to rare earth elements has been shown to induce neurotoxicity; however, research on neurotoxicity during the early developmental stages is limited, and the underlying mechanisms remain poorly understood. This study investigated the effects of prenatal and lactational exposure to neodymium nitrate on hippocampal function in rat offspring. Through behavioral assessments, pathological staining methods, and analysis of apoptosis-associated variables (Bax, Bcl-2, Caspase-3, and Cyt-c) in the hippocampal tissue of the offspring, we elucidated the mechanisms underlying impaired learning and cognitive abilities. Furthermore, high-throughput sequencing revealed the differential expression of long noncoding RNA gene LncMSTRG.5686.1 in the hippocampus of exposed offspring rats, providing insights into its regulatory role in hippocampal neuronal apoptosis following prenatal and lactational exposure to neodymium nitrate. In vitro experiments demonstrated a dose-dependent upregulation of LncMSTRG.5686.1 expression in Nd (NO₃)₃-treated SH-SY5Y cells, accompanied by the induction of mitochondrial apoptosis. Fluorescence in situ hybridization localized LncMSTRG.5686.1 to the cytoplasm, suggesting its potential involvement in the competitive endogenous RNA network. Subsequent experiments revealed that LncMSTRG.5686.1 binds to and regulates let-7a-5p expression, which in turn modulates the mitochondrial apoptosis pathway in Nd (NO₃)₃-treated SH-SY5Y cells by competitive binding with LncMSTRG.5686.1.

The widespread use of the chloroacetanilide herbicide S-metolachlor has raised concerns about its ecotoxicological impact on aquatic organisms, yet tissue-specific effects in fish remain poorly understood. To address this, juvenile rainbow trout (Oncorhynchus mykiss) were exposed to environmentally relevant concentrations (0.0123, 0.0615, and 0.123 mg/L) for 7, 14, and 21 days, and biomarkers were assessed in the liver, kidney, gill, muscle, and brain. Antioxidant defenses were generally stimulated, particularly in the muscle and gill, while oxidative damage markers increased across tissues, accompanied by protein depletion. These alterations were mechanistically linked to suppression of ATPase activity in the gill and kidney, indicating a cascade from oxidative stress to impaired osmoregulation. Brain tissue showed only modest responses, and acetylcholinesterase activity was not significantly affected. The integrated biomarker response (IBR) index synthesized these outcomes, highlighting gill and muscle as the most vulnerable tissues. Disturbances at this level serve as sensitive early-warning indicators that, if sustained, can compromise individual performance traits such as growth, survival, and reproductive capacity. At the population level, these impairments may lower resilience to additional environmental stressors, while at the ecosystem scale, they have the potential to alter community dynamics and energy flow. Collectively, the findings establish a mechanistic basis for connecting sublethal biomarker responses to ecologically relevant adverse outcomes, thereby enhancing the predictive utility of biomarker-based approaches in environmental risk assessment.

Synthetic dye, auramine O (AO) commonly utilized in food, textile, and leather manufacturing industries, has raised health concerns; however, its chronic hepatotoxic effects remain underexplored. The current study was designed to assess the chronic hepatotoxic effects of AO using zebrafish as an in vivo model. Zebrafish embryos were exposed to AO (1-100 mg/L) for developmental toxicity assessment, whereas adults and larvae were subjected to environmentally relevant concentrations, 5 and 10 mg/L of AO for 28 days, alongside bisphenol A (BPA, 225 μg/L) serving as a positive control. Oxidative stress and apoptosis were evaluated in 5-day-old larvae using DCFH-DA and acridine orange staining, whereas adult liver samples underwent biochemical, histological, and gene expression analysis. Also, AO accumulation was quantified in the adult liver tissue using high-performance liquid chromatography (HPLC) analysis. AO exposure led to dose-dependent increases in reactive oxygen species (ROS) (24.31% ± 0.17%), apoptosis (17.19% ± 0.35%), lipid peroxidation (27.37 ± 1.90 nmol/mg), LDH (1.71 ± 0.012 U/mL), ALT (0.68 ± 0.001 U/mL), and AST (0.82 ± 0.008 U/mL), with concurrent reductions in superoxide dismutase and catalase activity activities. Metabolic disruption was evident from elevated glucose (131.3 ± 0.88 mg/dL), cholesterol (3.26 ± 0.16 mmol/L), and triglycerides (2.31 ± 0.03 mmol/L) at 10 mg/L. Gene expression analysis showed upregulation of COX-2, iNOS, TNF-α, FAS, and BAX and downregulation of PIK3CD and BCL-2, indicating inflammation and impaired survival signaling. Histopathology showed considerable changes in liver morphology. Also, oil red O and toluidine blue staining indicated that the lipid was significantly increased (37.35% ± 2.20%) and mast cell degranulation occurred (83.41% ± 1.94%) in the group treated with the highest levels of AO. AO liver concentrations were measured by HPLC and demonstrated a dose-dependent association. These data indicate that AO dye alters the antioxidant defense system by increasing oxidative stress, hepatic inflammation, and altering metabolic function; however, regulation and further toxicological testing are necessary based on these results.

The use of organochlorine (OCP) and non-organochlorine pesticides in paddy soils is widespread in wetland and lowland rice systems, with implications for soil health and food safety. This study assessed pesticide residues in soils (0-15 and 15-30 cm) collected from uphill, hill-wash, and valley-bottom locations during pre-sowing and post-harvest periods, as well as in rice sampled at five post-harvest stages: harvested, dried, stored, dehusked, and parboiled. Gas chromatography revealed that before sowing, dichlorophenyltrichloroethane (0.7600 mg/kg) was significantly higher (p < 0.05) in valley-bottom subsoil, while post-harvest glyphosate (1.1562 mg/kg) was similarly elevated. In rice, dichlorvos (0.3899 mg/kg) peaked in dehusked grains. Detected residues included OCPs (e.g., lindane, hexachlorobenzene, aldrin, heptachlor, and DDT derivatives) and non-OCPs (glyphosate, 2,4-D, carbofuran, profenofos, and dichlorvos). Health risk assessment showed hazard quotients and indices below unity for most pesticides, indicating negligible non-carcinogenic risks, except for OCPs. However, lifetime cancer risks for aldrin, heptachlor, and γ-chlordane exceeded the USEPA's acceptable range (10^-6-10^-4) emphasizing long-term concerns from persistent OCPs. Comparisons with other tropical regions confirm modern pesticides rarely exceed Codex MRLs, but legacy OCPs persist. The findings highlight the need for integrated pest management and continuous monitoring to ensure soil health, rice safety, and consumer protection.

Di(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, crosses the placental barrier and disrupts fetal development, though its precise mechanisms remain poorly defined. To assess its placental effects, pregnant mice were treated daily with 40 μg/kg DEHP, and placental alterations were systematically evaluated through histopathological examination, Western blot analysis, and whole-transcriptome sequencing. DEHP exposure reduced the total placental area, disrupted the decidual and spongiotrophoblast layers, and disorganized vascular structures. Concurrently, protein levels of Bax, p53, and Caspase-3 were significantly elevated, while Bcl-2 expression decreased, indicating mitochondrial apoptosis mediated by the PI3K/Akt-p53 pathway. Transcriptomic profiling further revealed widespread dysregulation of mRNAs and noncoding RNAs, enriched in processes involving the Notch signaling pathway, cholesterol metabolism, hormone response, and oxygen transport. Construction of a ceRNA network suggested that miR-6538 may contribute to placental dysfunction by regulating Tmcc2 and Susd2. These findings elucidate a novel mechanism through which DEHP impairs placental structure and function via apoptotic signaling and RNA regulatory networks, offering important insights into its reproductive toxicity.