Journal of Xenobiotics最新文献

Exposure to environmental pollutants, including toxic metals, volatile organic compounds (VOCs), and per- and polyfluoroalkyl substances (PFAS), has been increasingly linked to impaired kidney function. However, the combined effects of these exposures, along with essential elements, on kidney health remain poorly understood. This study aimed to evaluate the independent and cumulative or mixture effects of toxic metals (cadmium, lead, and mercury), essential elements (iron, manganese, and selenium), PFAS (PFOA and PFOS), and VOCs (m-/p-xylene and o-xylene) on kidney function as measured by estimated glomerular filtration rate (eGFR). Using data from the National Health and Nutrition Examination Survey (NHANES), we applied multiple imputation to address missing data and implemented statistical techniques, including Bayesian Kernel Machine Regression (BKMR), quantile g-computation, and Weighted Quantile Sum Regression (WQSR) to assess complex exposure-response relationships, including non-linear, potential synergistic, and antagonistic effects. The results indicated that several exposures were correlated, particularly o-xylene with m-/p-xylene (r = 0.77), Cd with Pb (r = 0.46), and PFOS with PFOA (r = 0.61). eGFR was negatively associated with Pb, PFOS, PFOA, and Hg. In the BKMR analysis, overall posterior inclusion probabilities (PIPs) highlighted PFOS, Cd, Se, Mn, and Fe as the most influential exposures. Quantile g-computation highlighted Cd and Mn as major contributors, while WQSR modeling confirmed Mn as a key contributor. The findings underscore the importance of considering complex interactions in environmental exposure assessments. While essential elements may offer protective effects, toxic metals, PFAS, and VOCs remain critical contributors to kidney dysfunction. These insights highlight the need for integrative risk assessment approaches and public health strategies aimed at mitigating harmful exposures while promoting optimal nutrient balance.

Alternaria mycotoxins represent a significant and emerging concern in the field of food safety due to their widespread occurrence in diverse food and feed commodities, including cereals, tomatoes, oilseeds, and dried fruits. Among these, alternariol (AOH), alternariol monomethyl ether (AME), tenuazonic acid (TeA), and altertoxin-I (ATX-I) are the most frequently detected, often co-occurring at varying concentrations, thereby increasing the complexity of exposure and risk assessment. The gastrointestinal tract (GIT) is a crucial target of these toxins, as well as the liver, particularly considering its detoxifying role. Nevertheless, despite being a source of possible gastrointestinal and hepatic toxicity, there is still scarce data on the toxicokinetics of Alternaria toxins, on their mode of action, and respective toxic effects. To date, in vitro studies have shown that different Alternaria mycotoxins exhibit diverse toxicological effects, which may be dependent on their chemical structure. AOH and ATX-I have shown genotoxicity and cytotoxicity, mainly through interaction with the DNA and apoptosis, respectively. Tentoxin (TEN) has displayed hepatotoxic potential via impairment of detoxification pathways, and altenuene (ALT) has revealed lower toxicity. In vivo, AME and ATX-II revealed genotoxicity, while AOH and ATX-I showed context-dependent variability in their effects. Altogether, this review emphasizes that there is still a great lack of knowledge on these mycotoxins and an urgent need for more comprehensive toxicological and occurrence data to support proper risk assessment and, ultimately, regulatory decision-making.

Triclosan (TCS) is a widely used antimicrobial agent found in personal care products and household cleaners. While valued since the 1960s for its ability to inhibit bacterial fatty acid synthesis, its environmental persistence, ecotoxicity, and bioaccumulative potential have raised significant global concern. The increased use of disinfectants during the COVID-19 pandemic has further exacerbated its prevalence as an aquatic pollutant. In the environment, TCS is distributed through water bodies and sediments, undergoing processes such as biodegradation and photochemical degradation. Its bioaccumulation poses a substantial threat to aquatic organisms, particularly fish. A growing body of research indicates that TCS acts as an endocrine disruptor and developmental toxicant, with documented adverse effects encompassing impaired embryonic and larval development, skeletal malformations, and induction of oxidative stress, mitochondrial dysfunction, DNA damage, and inflammatory responses. Furthermore, TCS exposure is linked to reproductive toxicity, including altered sex hormone levels and diminished reproductive capacity. This review consolidates current knowledge on the chemical properties, environmental fate, biodegradation pathways, and ecotoxicological impacts of TCS, with a specific emphasis on its multifaceted health risks to fish. The synthesis aims to provide a foundation for future research, inform environmental risk assessments, and support the development of evidence-based regulatory measures.

Pharmacological compounds can disrupt glucose homeostasis, leading to impaired glucose tolerance, hyperglycemia, or newly diagnosed diabetes, as well as worsening glycemic control in patients with pre-existing diabetes. Traditional risk factors alone cannot explain the rapidly growing global incidence of diabetes. Therefore, prevention of insulin resistance could represent an effective strategy. Achieving this goal requires a deeper understanding of the mechanisms underlying the development of insulin resistance, with particular attention to the aryl hydrocarbon receptor (AhR). AhR, a transcription factor functioning as a xenobiotic sensor, plays a key role in various molecular pathways regulating normal homeostasis, organogenesis, and immune function. Activated by a range of exogenous and endogenous ligands, AhR is involved in the regulation of glucose and lipid metabolism as well as insulin sensitivity. However, current findings remain contradictory regarding whether AhR activation exerts beneficial or detrimental effects. This narrative review summarizes recent studies exploring the role of the AhR pathway in insulin secretion and glucose homeostasis across different tissues, and discusses molecular mechanisms involved in this process. Considering that several drugs act as AhR ligands, the review also compares how these ligands affect metabolic pathways of glucose and lipid metabolism and insulin sensitivity, producing either positive or negative effects.

This paper explores the evolving integration of the One Health framework into the European regulatory landscape for plant protection products, focusing on key scientific and procedural challenges. The analysis addresses three fundamental components of risk evaluation-regulatory complexity, hazard identification, and characterisation-and exposure assessment, while providing an up-to-date overview of emerging policies and challenges affecting the sustainable use of plant protection products in Europe. Addressing these issues requires interdisciplinary collaboration among toxicologists, epidemiologists, ecologists, regulatory authorities, industry stakeholders, and public health experts, working synergistically to tackle complex risks. It emphasises that transitioning to more sustainable and resilient agricultural systems in line with One Health principles requires critically reviewing existing policies. By integrating evolving scientific knowledge with communication and agricultural production needs across diverse European contexts, this approach offers valuable insights to inform future policy development and risk management innovation.

This study investigates the relationship between kidney function and exposure to low-level cadmium (Cd) and lead (Pb) in individuals with and without diabetes. Specifically, it tests the hypothesis that the nephrotoxicity of Cd and Pb reduces the tubular degradation of filtered proteins, namely β₂-microglobulin (β₂M). Data were obtained from a Thai cohort of 137 people, of which 65 were diagnosed with diabetes. Blood Cd, blood Pb, and urinary excretion of Cd (E_Cd) were used as exposure indicators, while urinary N-acetylglucosaminidase (E_NAG) and fractional tubular degradation of β₂M (FrTD_β2M) reflected kidney tubular cell injury and the function of tubular cells, respectively. Spearman's rank correlation revealed that FrTD_β2M varied directly with the estimated glomerular filtration rate (eGFR; r = 0.434), and inversely with fasting plasma glucose (r = -0.215), E_Cd (r = -0.527), E_NAG (r = -0.536), and Cd/Pb exposure (r = -0.249). In a multiple regression model analysis adjusting for potential confounders, the association between FrTD_β2M and eGFR in those with diabetes was particularly strong (β = 0.476) compared to controls (β = 0.360), whereas an inverse association of FrTD_β2M and E_Cd (β = -0.295) was found only in those with diabetes, along with a positive association of E_NAG with E_Cd (R² = 0.071). A mediation analysis has revealed that tubular injury (E_NAG) mediated 26% of the FrTD_β2M decrease associated with Cd/Pb exposure. These findings suggested that tubular protein degradation pathways may be compromised under combined metabolic and environmental stressors, Cd, and Pb.

Volatile organic compounds (VOCs) emitted from indoor surface coatings can significantly impact indoor air quality and health. This study compared emissions from water-based polyurethane (PUR) and acrylate-polyurethane (ACR-PUR) coatings, identifying 94 VOCs across 16 chemical classes. Time-resolved concentrations were analysed via Principal Component Analysis (PCA), which revealed distinct temporal emission patterns and chemically coherent clusters. Aromatic hydrocarbons, alcohols, esters, and isocyanates dominated the emission profiles, with ACR-PUR releasing markedly higher concentrations of symptom-relevant compounds. Acute exposure was linked to toluene, styrene, phenol, and methyl butyl ketone (MBK), which decreased sharply within 60 days, while compounds such as 1,3-dioxolane, isopropylbenzene, and ethenyl acetate exhibited persistent emissions, suggesting increased chronic risk. Although total VOC levels remained below the German UBA "excellent" threshold (<200 µg/m³), neurotoxic and carcinogenic compounds remained detectable. The combination of PCA-based temporal insights with toxicological profiling and emission transfer dynamics offers a refined framework for indoor air risk assessment. These results underscore the need to complement total VOC indices with symptom-oriented, time-resolved screening protocols to better evaluate SBS risk in indoor environments using water-based coatings.

Lichens are complex symbiotic systems known for synthesizing diverse secondary metabolites with documented antimicrobial, antioxidant, and antiproliferative activities. The present study focused on Pseudevernia furfuracea, a species widely distributed across Moroccan habitats. Two hydrodistillation-derived extracts (HE1 and HE2) were analyzed through ultra-high-Performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) to characterize their metabolite composition, and their effects were evaluated on Jurkat cells, a representative human cell line of the immune system. As the results of the characterization, the main compounds identified were Caprolactam, N,N-Diethylaniline, Erucamide, and 4-Isopropylaniline. Cytotoxicity assessment revealed that both HE1 and HE2 decreased the viability of Jurkat cells in a concentration-dependent manner. The mean effective concentrations (EC₅₀) after 24 h of treatment were 53.79 ± 2.92 µg/mL for HE1 and 59.76 ± 2.01 µg/mL for HE2. Cell death mechanisms were further examined by flow cytometry, revealing that apoptosis predominated after 24 h of treatment, progressing mainly to late apoptotic stages after 48 h. In parallel, the expression levels of key cytokine genes, including IL-2, TNF-α, and IFN-γ, were quantified at the mRNA level to evaluate potential immunomodulatory effects. Up-regulation was observed in IL-2 after exposure to both extracts for 24 and 48 h, and in the case of IFN-γ after exposure to HE2 for 24 h; in contrast, HE1 and HE2 produced down-regulation in TNF-α at 24 h. These findings suggest that HE1 and HE2 have immunomodulatory activity in Jurkat cells. Further investigations are needed to elucidate the underlying mechanisms and to clarify how HE1 and HE2 influence immune responses in human systems.

There is an urgent need to evaluate the toxicity of xenobiotics and environmental mixtures for preventing loss in water quality for the sustainability of aquatic ecosystems. A simple prebiotic chemical pathway based on malate formation from pyruvate (pyr) and glyoxalate (glyox) is proposed as a quick and cheap screening tool for toxicity assessment. The assay is based on the pyr and glyox (aldol) condensation reactions, leading to biologically relevant precursors such as oxaloacetate and malate. Incubation of pyr and glyox at 40-70 °C in the presence of reduced iron Fe(II) led to malate formation following the first 3 h of incubation. The addition of various xenobiotics/contaminants (silver, copper, zinc, cerium IV, samarium III, dibutylphthalate, 1,3-diphenylguanidine, carbon-walled nanotube, nanoFe₂O₃ and polystyrene nanoparticles) led to inhibitions in malate synthesis at various degrees. Based on the concentration inhibiting malate concentrations by 20% (IC20), the following potencies were observed: silver < copper ~ 1.3-diphenylguanidine ~ carbon-walled nanotube < zinc ~ samarium < dibutylphthalate ~ samarium < Ce(IV) < nFeO₃ < polystyrene nanoplastics. The IC20 values were also significantly correlated with the reported trout acute lethality data, suggesting its potential as an alternative toxicity test. The pyr-glyox pathway was also tested on surface water extracts (C18), identifying the most contaminated sites from large cities and municipal wastewater effluents dispersion plume. The inhibition potencies of the selected test compounds revealed that not only pro-oxidants but also chemicals hindering enolate formation, nucleophilic attack of carbonyls and dehydration involved in aldol-condensation reactions were associated with toxicity. The pyr-glyox pathway is based on prebiotic chemical reactions during the emergence of life and represents a unique tool for identifying toxic compounds individually and in complex mixtures.

Indoor exposure to polybrominated diphenyl ethers (PBDEs), particularly those bound to fine particulate matter (PM₁, particles < 1 µm), may pose a health concern, especially in light of prolonged indoor occupancy and the capacity of ultrafine particles to reach the lower respiratory tract. This study investigates indoor exposure to PBDEs associated with PM₁ in residential homes in Zagreb, Croatia, across warm and cold seasons. BDE-47 was consistently detected in all samples, while BDE-183 was consistently absent. Elevated concentrations and increased detection frequencies of BDE-99 and BDE-100 were observed during the colder season. Consequently, total PBDE (ΣPBDE) levels in the cold season were approximately 2.5 times higher than in the warm season. Although estimated daily inhalation intakes were below established oral reference doses, the potential for deep pulmonary deposition and systemic distribution underscores the need for further investigation. These findings represent the first reported data on indoor PM₁-associated PBDEs in Europe, emphasizing the impact of seasonal dynamics on inhalation exposure due to variation on indoor contaminant levels.