Toxics最新文献

Cholangiocarcinoma (CCA) is a rare and highly aggressive cancer of the biliary tract, associated with poor clinical outcomes due to late diagnosis, extensive metastasis, drug resistance, and limited treatment options. Apigenin, a natural flavonoid, has been found to exhibit anticancer properties in several types of human cancer cells. Therefore, apigenin may be relevant to developing chemotherapeutic agents for cancer treatment. In this study, we examined the effects of apigenin on cell viability, cell cycle distribution, apoptosis, and cell migration in human CCA cell lines (KKU-M055) under in vitro conditions. The results demonstrate that apigenin significantly suppressed specific CCA cell proliferation by inducing cell cycle arrest at the G2/M phase and promoting cell apoptosis in KKU-M055 cells while exhibiting low toxicity in immortalized MMNK1 cells. Apigenin enhanced apoptotic features, including nuclear fragmentation and the loss of mitochondrial membrane potential. Furthermore, apigenin induced the apoptosis of KKU-M055 cells in both extrinsic and intrinsic pathways by activating caspase-8, -9, and -3/7. Moreover, apigenin inhibited KKU-M055 migration. Our study suggests apigenin as a promising candidate for treating CCA, and these findings provide theoretical support for the further development and potential application of apigenin in clinical CCA therapy.

Bisphenols (BPs) are ubiquitous environmental endocrine disruptors that cause various human health hazards and pollute water, soil, and the atmosphere to varying degrees. Although various studies have investigated the pollution characteristics and health hazards of BPs in different media, a systematic review of BPs in the broader environmental context is still lacking. This study highlights the pollution characteristics, detection methods, and risk assessment status of BPs by combining relevant studies from both domestic and international sources, and their environmental distribution characteristics are summarized. The results show that BP pollution is a widespread and complex global phenomenon. Bisphenol A (BPA) remains the predominant component of BPs, which can damage the nervous and reproductive systems. At present, high-performance liquid chromatography-tandem mass spectrometry, high-performance liquid chromatography, and liquid chromatography-tandem mass spectrometry are the main detection methods used for BPs. BPs can also damage the reproductive system, leading to germ cell apoptosis and ovarian damage. Future research should focus on expanding the BP testing repertoire, advancing rapid detection techniques, elucidating toxic mechanisms, conducting comprehensive safety assessments, and developing systematic health risk assessment methods. These efforts will provide a scientific foundation for preventing and controlling emerging pollutants.

Risk assessment for cosmetics in the European Union (EU) are triggered by a ban on animal testing and concerns of endocrine disruption (ED). The risk assessment focuses on healthy populations and, for potential ED, includes specific developmental stages as vulnerable due to specific concerns on endocrine effects. However, the assessment focuses on healthy individuals and does not consider that some pathologies may increase dermal absorption and even vulnerability to endocrine disruptors. Data from the EU risk assessment, human pharmacokinetic studies and ToxCast bioactivity were combined in a hypothesis-driven Next-Generation Risk Assessment to identify possible risk drivers for vulnerable populations including oncological patients and atopic dermatitis. In vitro effects are observed at concentration in the order of measured plasmatic levels under normal use patterns. The induction of hepatic enzymes is the most relevant bioactivity endpoint, in line with animal findings. The information on endocrine potential is inconclusive, and the possibility for skin effects and endocrine mechanism linked to tumor induction require further elucidation. The information on octocrylene (CAS number: 6197-30-4) bioactivity is limited, lacking information on the metabolites and the immunotoxicity potential, particularly relevant for oncological patients.

Copper accumulation in neurons induces oxidative stress, disrupts mitochondrial activity, and accelerates neuronal death, which is central to the pathophysiology of neurodegenerative diseases like Wilson disease. Standard treatments for copper toxicity, such as D-penicillamine, trientine, and chloroquine, are frequently associated with severe side effects, creating a need for safer therapeutic alternatives. To address this, we developed a curcumin-loaded nanoemulsion (CUR-NE) using the spontaneous emulsification technique, aimed at enhancing the bioavailability and therapeutic efficacy of curcumin. The optimized nanoemulsion displayed a particle size of 76.42 nm, a zeta potential of -20.4 mV, and a high encapsulation efficiency of 93.69%, with a stable and uniform structure. The in vitro tests on SH-SY5Y neuroblastoma cells demonstrated that CUR-NE effectively protected against copper-induced toxicity, promoting significant cellular uptake. Pharmacokinetic studies revealed that CUR-NE exhibited a longer half-life and extended circulation time compared to free curcumin. Additionally, pharmacodynamic evaluations, including biochemical assays and histopathological analysis, confirmed that CUR-NE provided superior neuroprotection in copper overload conditions. These results emphasize the ability of CUR-NE to augment the therapeutic effects of curcumin, presenting a novel approach for managing copper-induced neurodegeneration. The study highlights the effectiveness of nanoemulsion-based delivery platforms in improving chelation treatments for neurological diseases.

The antioxidant properties of resveratrol (RES) against oxidative toxicity induced by testicular toxicants are well documented. The current study aimed to investigate the probable beneficial role of RES on male reproduction in adult rats following prepubertal exposure to perfluorooctanoic acid (PFOA). Healthy rats of the Wistar strain (23 days old) were allocated into four groups. Rats in group I did not receive any treatment, while rats in groups II, III, and IV received RES, PFOA, and RES + PFOA, respectively, between days 23 and 56 and were monitored for up to 90 days. Exposure to PFOA resulted in a significant reduction in spermiogram parameters, testicular 3β- and 17β-HSD activity levels, and circulatory levels of testosterone. A significant elevation in LPx, PCs, H₂O₂, and O₂^-, associated with a concomitant reduction in SOD, CAT, GPx, GR, and GSH, was noticed in the testes, as well as region-specific changes in pro- and antioxidants in the epididymides of exposed rats compared to controls. A significant increase in serum FSH and LH, testicular cholesterol levels, and caspase-3 activity was observed in PFOA-exposed rats compared to controls. Histological analysis revealed that the integrity of the testes was deteriorated in PFOA-exposed rats. Transcriptomic profiling of the testes and epididymides revealed 98 and 611 altered genes, respectively. In the testes, apoptosis and glutathione pathways were disrupted, while in the epididymides, glutathione and bile secretion pathways were altered in PFOA-exposed rats. PFOA exposure resulted in the down-regulation in the testes of 17β-HSD, StAR, nfe2l2, ar, Lhcgr, and mRNA levels, associated with the up-regulation of casp3 mRNA, and down-regulation of alpha 1 adrenoceptor, muscarinic choline receptor 3, and androgen receptor in the epididymides of exposed rats compared to the controls. These events might lead to male infertility in PFOA-exposed rats. In contrast, restoration of selected reproductive variables was observed in RES plus PFOA-exposed rats compared to rats exposed to PFOA alone. Taken together, we postulate that prepubertal exposure to PFOA triggered oxidative damage and altered genes in the testes and epididymides, leading to suppressed male reproductive health in adult rats, while RES, with its steroidogenic, antiapoptotic, and antioxidant effects, restored PFOA-induced fertility potential in rats.

The increasing importance of waste materials utilization with the necessary modification to remove various pollutants from industrial wastewater has been a research focus over the past few decades. Using waste material from one industry to solve pollution problems in another ultimately leads toward sustainable and circular approaches in environmental engineering, solving waste management and wastewater treatment issues simultaneously. In contemporary research and industry, there is a notable trend toward utilizing industrial wastes as precursors for adsorbent formation with a wide application range. In line with this trend, red mud, a byproduct generated during alumina production, is increasingly viewed as a material with the potential for beneficial reuse rather than strictly a waste. One of the potential uses of red mud, due to its specific composition, is in the removal of heavy metal and radionuclide ions. This study summarizes red mud's potential as an adsorbent for wastewater treatment, emphasizing techno-economic analysis and sorption capacities. An overview of the existing research includes a critical evaluation of the adsorption performance, factors influencing efficiency rather than efficacy, and the potential for specific pollutant adsorption from aqueous solutions. This review provides a new approach to a circular economy implementation in wastewater treatment while guiding future research directions for sustainable and cost-effective solutions.

Di-isopropyl methyl phosphonate (DIMP) has no major commercial uses but is a by-product or a precursor in the synthesis of the nerve agent sarin (GB). Also, DIMP is utilized as a simulant compound for the chemical warfare agents sarin and soman in order to test and calibrate sensitive IMS instrumentation that warns against the deadly chemical weapons. DIMP was measured from 2 ppb_v (15 μg m^-3) to 500 ppb_v in the air using a pocket-held ToF ion mobility spectrometer, model LCD-3.2E, with a non-radioactive ionization source and ammonia doping in positive ion mode. Excellent sensitivity (LoD of 0.24 ppb_v and LoQ of 0.80 ppb_v) was noticed; the linear response was up to 10 ppb_v, while saturation occurred at >500 ppb_v. DIMP identification by IMS relies on the formation of two distinct peaks: the monomer M·NH₄⁺, with a reduced ion mobility K₀ = 1.41 cm² V^-1 s^-1, and the dimer M₂·NH₄⁺, with K₀ = 1.04 cm² V^-1 s^-1 (where M is the DIMP molecule); positive reactant ions (Pos RIP) have K₀ = 2.31 cm² V^-1 s^-1. Quantification of DIMP at trace levels was also achieved by GC-MS over the concentration range of 1.5 to 150 μg mL^-1; using a capillary column (30 m × 0.25 mm × 0.25 μm) with a TG-5 SilMS stationary phase and temperature programming from 60 to 110 °C, DIMP retention time (RT) was ca. 8.5 min. The lowest amount of DIMP measured by GC-MS was 1.5 ng, with an LoD of 0.21 μg mL^-1 and an LoQ of 0.62 μg mL^-1 DIMP. Our results demonstrate that these methods provide robust tools for both on-site and off-site detection and quantification of DIMP at trace levels, a finding which has significant implications for forensic investigations of chemical agent use and for environmental monitoring of contamination by organophosphorus compounds.

Biomonitoring allows for the assessment of internal exposure to various pesticides and metabolites. Following PRISMA guidelines, this systematic review aims to summarise innovative biomonitoring techniques for assessing pesticide exposure in agricultural workers, their advantages and limitations, and their applicability. The search of the Medline/PubMed, ScienceDirect, Scopus, and Web of Science databases identified 14 articles dealing with new techniques for biomonitoring pesticide exposure in agricultural workers. These new methodologies have identified several biomarkers associated with exposure to organophosphates. Most of the included studies combine and/or improve traditional methods to overcome their limitations. This leads to more sensitive, specific, and precise techniques with lower detection and quantification limits. Therefore, it is necessary to thoroughly analyse and test new biomonitoring methods for assessing pesticide exposure. These techniques can complement qualitative risk assessments and aid in developing strategies to protect public health and the environment.

Examining contaminant concentrations in birds in Arctic environments is important for managing species for assessing long-term trends. Recent reports on mercury (Hg) concentrations in Arctic species of seabirds has identified a need for data from missing regions or species. We measured arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb), manganese (Mn), Hg and selenium (Se) in the body feathers of Atlantic Puffin (Fratercula arctica) from four colonies in Iceland in 2011 and one in 2009. Puffins forage on small fish at an intermediate trophic concentration. We found that (1) concentrations examined in the colony in 2009 were lower than in 2011 for all metals except As and Hg, and (2) concentrations of Cd and Se varied significantly among colonies for feathers collected in 2011. Pb concentrations in Puffin feathers in one colony were 14-fold higher in 2009 than in 2011 (mean of 805 ng.g^-1 vs. 58 ng.g^-1). The highest mean Hg concentration in 2011 was 362 ng.g^-1 and was 4880 ng.g^-1 for Se. The concentrations of Hg in the Atlantic Puffins reported in this study were similar to, or lower than those reported for the same species elsewhere and for Tufted Puffin from the Pacific.

In this study, a human health risk assessment was performed on the ingestion route of groundwater containing polyvinyl chloride (PVC) microplastics (MPs), and the carcinogenic and non-carcinogenic risks of di(2-ethylhexyl) phthalate (DEHP), a representative additive, were determined. In particular, the impact of volume diversity according to the shape (morphology) of PVC MP (fragment, fiber, film) on the risk characterization was intensively explored. Firstly, a continuous particle size distribution following a power function was derived using the abundance ratio of PVC MPs by size in the investigated groundwater, and human health risk assessment for DEHP in the PVC MPs was performed through the volume distribution according to the shape of MPs. DEHP human health risk assessment showed an excess cancer risk (ECR) of below 10^-6 for a 95% cumulative probability for all MP shapes, but the values varied depending on the shape. Sensitivity analysis showed that the parameter that most affected human health risk was MP volume, second to concentration, which is dependent on MP shape. Therefore, it is necessary to consider the variety of MP shapes during human health risk assessment, and it can be achieved through probabilistic risk assessment utilizing the probability distribution for size and shape of MPs.