Journal of Applied Toxicology最新文献

This study investigates the effects of occupational carbon dioxide (CO₂) exposure on corneal tissue through Fourier transform infrared (FTIR) spectroscopy and chemometric analysis. Human activities have significantly increased atmospheric CO₂ levels, leading to potential health risks, particularly in confined environments such as mining, submarines, and enclosed workspaces. While CO₂ exposure is commonly associated with respiratory and cardiovascular effects, its impact on ocular health remains underexplored. Rats were exposed to three different CO₂ concentrations (3%, 5%, and 10%) in a controlled chamber for 8 h per day over a 30-day period. Second derivative analysis of corneal FTIR spectra revealed significant alterations in protein secondary structures, lipid composition, and phosphate group alterations, indicating CO₂-induced biochemical changes. Notably, exposure led to a shift in the amide I band from 1650 to 1643 cm^-1, suggesting a transition from α-helix to random coil structures in corneal proteins, which compromises tissue integrity. Changes in lipid hydrocarbon chain vibrations and increased gauche rotamers indicated disruptions in membrane order and fluidity. Additionally, phospholipid and nucleic acid modifications were observed, potentially affecting cellular stability. The study provides valuable insights into corneal bio-molecular alterations due to CO₂ exposure, contributing to a deeper understanding of environmental and occupational eye health risks.

Fentanyl, an ultra-potent synthetic opioid, has traditionally been characterized by its acute toxic effects, particularly respiratory depression. However, accumulating research indicates that its neurobiological influence extends far beyond its short pharmacological window, intersecting with several core mechanisms implicated in major neurodegenerative disorders. This review integrates multiscale evidence to propose a unified conceptual framework in which fentanyl may function not only as an acute neurotoxin but also as a putative accelerator of long-term neurodegenerative vulnerability. Drawing from molecular signaling, cellular stress pathways, glial-neuronal cross-talk, neurovascular regulation, synaptic architecture, and large-scale neural networks, we highlight fentanyl's capacity to trigger a convergent cascade encompassing hypoxic-metabolic reprogramming, mitochondrial fragmentation, TLR4-NF-κB-driven inflammation, NLRP3 inflammasome activation, complement-mediated synaptic pruning, astrocytic EAAT2 downregulation, and blood-brain barrier compromise. These alterations propagate through recursive cross-talk loops that progressively diminish neuronal resilience, destabilize oscillatory coherence, and weaken circuit-level adaptability. Importantly, mechanistic overlaps with Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis suggest that fentanyl exposure may be mechanistically associated with processes capable of accelerating disease onset, exacerbating progression, or unmasking latent vulnerabilities, particularly in genetically or metabolically predisposed individuals. By reframing fentanyl as a systems-level destabilizer capable of imprinting persistent neurobiological changes, this model underscores the need for comprehensive biomarker development, longitudinal risk assessment, and targeted neuroprotective interventions. The integrative framework presented herein offers a foundation for predicting the long-term neurological consequences of fentanyl exposure and calls for urgent reconsideration of its role in population-level neurodegenerative risk.

Azo dyes, like Eriochrome Black T (EBT), enter freshwater ecosystems through textile effluent, posing potential risks to fish, which are key bioindicators and significant aquaculture resources. Despite the widespread use of azo dyes, toxicological data about their effects on air-breathing organs (ABOs) is scarce. This study examines the impacts of EBT on two catfish species, Heteropneustes fossilis and Clarias batrachus, selected for their distinctive ABO morphologies, which facilitate interspecific comparison to EBT intoxication. To achieve this goal, acclimatized fishes (both species) were exposed to three sublethal concentrations of the median LC50_96h value of EBT (1, 10, and 20 mg L^-1) for 96 h. Both species showed significantly higher accumulation of EBT, with the ABO of C. batrachus showing more significant accumulation. EBT exposure caused higher levels of lipid peroxidation and a substantial increase in the activities of antioxidant enzymes (such as SOD, GPx, and GR), while reducing catalase (CAT) activity. Histological examination showed structural damage and signs of respiratory distress in the ABOs of both species. Histochemical analysis also showed changes in number, percent area occupancy, and size of mucous cells, highlighting the deteriorating impact of EBT on fishes. Moreover, a careful assessment of the results demonstrated that C. batrachus manifested greater sensitivity to all concentrations of EBT in comparison with H. fossilis. These findings illustrate the susceptibility of fish respiratory organs to dye exposure and highlight the necessity of monitoring azo dye contamination for protecting aquaculture species and freshwater ecosystems.

Sturgeons are particularly vulnerable to the bioaccumulation of trace elements due to their longevity, benthic habits, and slow metabolic turnover. As aquaculture has become the primary global source of caviar, updated information on essential and toxic elements in farmed sturgeon products is needed to assess food safety. Twelve Acipenser baerii at reproductive stage 4 were sampled from a commercial farm in Tehran Province. Caviar was digested using acid-assisted mineralization, and essential (Zn, Cu, Fe, Se) and toxic (Cd, Pb, Cr, As, Hg) elements were quantified. Zinc was the most abundant element (31.0-35.9 mg/kg), while iron (3.0-4.9 mg/kg), copper (0.9-1.8 mg/kg), and selenium (0.38-0.64 mg/kg) fell within expected physiological ranges for farmed sturgeons. Concentrations of toxic elements were consistently low, Cd (0.01-0.07 mg/kg), Pb (0.12-0.20 mg/kg), As (0.07-0.15 mg/kg), Cr (0.14-0.31 mg/kg), and Hg (0.01-0.05 mg/kg), and remained below international safety thresholds. Overall, the trace-element profile of farmed A. baerii caviar indicates low contaminant levels and compliance with current food-safety standards. These results provide updated baseline information for Iranian sturgeon aquaculture and support the safety of caviar produced under controlled farming conditions.

The teratogenic potential of dapagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, widely used in managing type 2 diabetes, remains poorly characterized. This study investigates the dose-dependent developmental effects of dapagliflozin using a chick embryo model to provide critical insights into its safety during early developmental stages. Fertilized eggs were incubated under controlled conditions, and dapagliflozin was administered at concentrations of 1.0-2.5 mg/mL on embryonic Day 3. Morphometric analysis revealed significant reductions in body weight (up to 47%) in higher-dose groups compared to controls, with survival rates declining sharply (40% mortality) in the 2.5 mg/mL group. Histological examination demonstrated hepatic steatosis, pulmonary emphysema, and cardiac inflammation, alongside neural apoptosis and vascular abnormalities. Reactive oxygen species (ROS) levels, measured via DPPH (2,2-diphenyl-1-picrylhydrazyl), superoxide dismutase (SOD), and chloramphenicol acetyltransferase (CAT) assays, results from DPPH assay showed up to 94.7% of radical scavenging activity in heart tissue, while intracellular oxidative stress is confirmed by SOD and CAT assays, implicating oxidative stress as a central mediator of these abnormalities. This study provides the first comprehensive evidence of dapagliflozin's dose-dependent teratogenicity in a nonmammalian vertebrate model. The findings underscore the need for caution in prescribing dapagliflozin during pregnancy and warrant further investigations in mammalian systems to evaluate its potential implications for human health.

In recent years, one of the most striking consequences of overpopulation and consumption activities worldwide has been the rapid increase in environmental pollutants. Sodium pyrithione (NaPT) is an organosulfur compound commonly used for its antimicrobial and antifungal properties in industrial and personal care products. The primary objective of this study was to determine the impact of NaPT exposure on whole-body vitellogenin (Vtg) levels in adult male zebrafish, a highly relevant model for toxicological studies. As Vtg functions as a key estrogen-responsive biomarker, its induction serves as a critical indicator for assessing endocrine disruption, thereby justifying its selection as the primary endpoint. The adaptation period completed, stocked zebrafish were transferred to experimental aquariums and exposed to 1 and 5 μg/L concentrations of NaPT for 24, 72, 96 h, and 7 days. Commercial ELISA kits determined Vtg levels. The whole-body zebrafish Vtg analysis revealed that Vtg levels were increased at all time intervals, regardless of dose differences, compared to the control group (p < 0.05). Only at 24 h, low and high doses of NaPT had significantly different Vtg levels (p = 0.009). Biocidal products, among the environmental pollutants, have been found to affect time-dependent levels, especially in non-target organisms. The results suggested that NaPT exposure leads to significant alterations in Vtg expression, indicating its potential to interfere with endocrine function in fish. The observed endocrine-disrupting effects of NaPT directly underscore the potential risks marine pollution poses to ecosystem health and, consequently, to human well-being through shared environmental pathways.

Thiram is a dithiocarbamate fungicide that protects turf, fruits and ornamental plants. The purpose of this experiment was to ascertain the toxico-pathological effects of thiram induced toxicity in Cyprinus carpio. The fish were divided into four groups: Group A was kept as control, compared to groups B, C, and D exposed to 40, 80, and 120 μg/L thiram, respectively. The results indicated a significant (p < 0.05) reduction in body weight, while both the absolute and relative weights of gills increased significantly (p < 0.05) in fish exposed to a higher concentration of thiram. Hematological parameters showed significant (p < 0.05) reduction in RBCs, Hb, HCT, LYM, MCV, MCHC, and platelet counts, while neutrophils and leukocytes were significantly (p < 0.05) increased. Oxidative stress parameters (TBARS and ROS) were significantly (p < 0.05) increased, while antioxidant enzymes (GSH, POD, CAT, and SOD) were significantly (p < 0.05) decreased. Moreover, comet assay showed significantly (p < 0.05) higher percentile rate of DNA damage in gills tissues of treated fish exposed to 80 and 120 μg/L thiram compared to control fish. Moreover, results showed severe histopathological changes in the gills like aneurysm, degeneration of cartilaginous cores, disruption of primary lamellae, necrosis of lamellar pillars and atrophy of lamellae. Hence, thiram demonstrates severe detrimental effects on physical and hematological parameters, induces oxidative stress, affects anti-oxidant enzyme activity, causes DNA damage and leads to histopathological alterations in the gills tissues of the freshwater fish.

Microplastics (MPs) are emerging contaminants in aquatic ecosystems and are able to modify the bioavailability and toxicity of co-occurring chemicals. In the present study, it was investigated whether high-density polyethylene (HDPE)-MPs exacerbate the toxicological effects of the pyrethroid insecticide deltamethrin in juvenile common carp (Cyprinus carpio). Fish (n = 270; 25 ± 5 g) were randomly allocated to a 2 × 3 factorial design (three replicates per group; 15 fish per tank) and exposed for 30 days to sub-lethal deltamethrin (12.5 μg/L; 10% of 96-h LC₅₀) and/or HDPE-MPs (0, 350, or 700 μg/L; 200-250 μm). Hepatic detoxification- and antioxidant-related gene expression was quantified, together with redox status, oxidative damage, and plasma biochemical biomarkers of organ function and injury. Deltamethrin and MPs alone altered transcriptional and biochemical endpoints, while co-exposure (particularly with 700 μg/L MPs) produced the most pronounced responses, including stronger induction of detoxification/metal-binding genes, reduced overall antioxidant capacity, and marked increases in lipid peroxidation and protein oxidation. Plasma activities of AST, ALT, ALP, LDH, GGT, and CK increased, and butyrylcholinesterase was inhibited, indicating cellular membrane damage and multi-organ dysfunction. Changes in circulating metabolites and creatinine further supported hepatic and renal impairment, and significant interaction effects for multiple endpoints suggested potentiation of deltamethrin toxicity by MPs. Overall, HDPE MPs act as relevant co-stressors that intensify deltamethrin-driven toxicity in fish, underscoring the need for mixture-aware monitoring and risk assessment in contaminated freshwater environments.

This work presents the first demonstration of a tube-based droplet microfluidic implementation of the Ames test, bridging single-droplet resolution with regulatory genotoxicity testing. The Ames test is a cornerstone assay for detecting mutagenicity, but conventional plate- and well-based formats suffer from high reagent consumption, low throughput, and limited automation. We report a droplet-based microfluidic Ames test assay using Salmonella typhimurium TA98, combining nanoliter compartmentalization with multiparameter optical detection. Cell density screening identified an optimal inoculum range of 10⁶-10⁷ cells/mL that maximized sensitivity while limiting spontaneous revertants. Dose-response analysis with the reference mutagen 4-nitro-o-phenylenediamine (4-NOPD) revealed clear increases in the fraction of droplets with growth of revertants, followed by a cytotoxic suppression at ≥ 8 μg/mL. A threshold-based evaluation enabled robust quantification of stochastic mutation events at single-droplet resolution. Compared with the classical fluctuation assay, the microfluidic format reduced reagent consumption by > 90%, generated statistically powerful datasets within 48 h, and eliminated subjective scoring. This study establishes segmented-flow microfluidics as a scalable, sensitive, and resource-efficient platform for mutagenicity testing, with applications in regulatory toxicology, environmental monitoring, and high-throughput chemical screening.

Taizhou City in Zhejiang Province was once one of China's largest e-waste-polluted areas. We assessed the effects of perinatal exposure to multiple heavy metals and dioxins on serum steroid levels in children from this area. We recruited 42 pairs of mothers and infants, collected breast milk and blood samples from the children, and detected dioxins and heavy metals in the breast milk, as well as steroid hormones in the serum. We employed multiple analytical approaches, including multivariable linear regression (MLR) model and Bayesian kernel machine regression (BKMR) models, to investigate the relationship between heavy metals, dioxins, and the serum steroid hormone levels in these children. In a separate exposure model using MLR, total polychlorinated dibenzofurans (PCDFs) (β: -0.930, 95% CI: -1.837, -0.023) and total polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/DFs) (β: -0.578, 95% CI: -1.142, -0.013) were negatively associated with DHEA. Within the MLR mixed exposure model, a negative association was observed between cadmium (Cd) and progesterone (β: -0.225, 95% CI: -0.447, -0.004), while a positive association was found between 2,3,7,8-TeCDD (TCDD) and dehydroepiandrosterone (DHEA) (β: 0.841, 95% CI: 0.196, 1.485). However, based on the BKMR results, these associations were attenuated. Perinatal exposure to heavy metals and dioxins may disrupt sex hormone levels and may have an impact on later reproductive health.