Journal of Xenobiotics最新文献

Foundries represent complex exposure scenarios where metals, particulate matter, and combustion by-products coexist, posing potential cumulative biological effects. Urinary metabolic profiles from 64 foundry workers and 78 residents living in surrounding areas were investigated using multivariate statistical modeling. Differences in urinary metabolite patterns were observed between the two groups, including lower levels of several amino acids (e.g., valine, alanine, tyrosine, and tryptophan) and tricarboxylic acid intermediates (e.g., citrate and succinate), together with higher levels of selected branched-chain amino acid catabolites (e.g., 3-hydroxyisobutyrate and erythro-2,3-dihydroxybutyrate) in workers. Variations in gut microbiota-related metabolites, such as phenylacetylglycine and p-cresol sulphate, were also detected. Based on these metabolic patterns, potential molecular mechanisms related to energy metabolism, oxidative stress and host-microbiome interaction are discussed as interpretative hypotheses. The comparison between workers and residents was interpreted, taking into account differences in demographic and lifestyle characteristics between groups. Overall, the results indicate that occupational exposure in foundries is associated with measurable differences in urinary metabolic profiles, demonstrating that the applied NMR-based metabolomic strategy is capable of capturing early biological effects and supporting its potential as a non-invasive and holistic biomonitoring tool for evaluating the health impact of complex occupational exposures.

Cancer cases have been estimated that will increase in the next years with consequent increase of antineoplastic (AD) drug treatments and workers handling these hazardous chemicals. We aimed to evaluate genotoxic/oxidative effects of AD exposure by fpg-comet assay on a large size sample of workers (214 exposed and 164 controls) involved in preparation; administration, including Hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC); and disposal. With the final aim to identify suitable early biomarkers of genotoxic effect useful to health surveillance, we correlated fpg-comet assay (blood) and Buccal Micronucleus Cytome (BMCyt) assay data. Fpg-comet parameters resulted higher in the exposed group vs. controls, demonstrating direct and oxidative DNA damage in workers handling ADs. Fpg-comet direct DNA damage and genotoxic parameters of BMCyt assay demonstrated a weak statistically significant correlation. This cross-sectional study is one of the few available evaluating both direct and oxidative DNA damage due to ADs on a large sample size of workers and correlating fpg-comet and BMCyt assay results. It highlights the need to evaluate genotoxic effects by both the biomarkers and furnishes a contribution to their validation. Moreover, we demonstrate for the first time oxidative DNA damage on workers performing HIPEC and PIPAC administration.

The rising levels of Co(II) in aquatic environments present considerable risks, thereby necessitating the development of effective remediation strategies. This study introduces an innovative pre-hydration method for synthesizing carbonated calcined clay dolomite (CCCD) to efficiently remove Co(II) from contaminated water. This pre-hydration treatment successfully reduced the complete carbonation temperature of the material from 500 °C to 400 °C, significantly enhancing energy efficiency. The Co(II) removal performance was systematically investigated by varying key parameters such as contact time, initial Co(II) concentration, pH, and solid/liquid ratio. Optimal removal was achieved at 318 K with pH of 4 and a solid/liquid ratio of 0.5 g·L^-1. Continuous flow column experiments confirmed the excellent long-term stability of CCCD, maintaining a consistent Co(II) removal efficiency of 99.0% and a stable effluent pH of 8.5 over one month. Isotherm and kinetic models were used to empirically describe concentration-dependent and time-dependent uptake behavior. The equilibrium data were best described by the Langmuir model, while kinetics followed a pseudo-second-order model. An apparent maximum removal capacity of 621.1 mg g^-1 was obtained from Langmuir fitting of equilibrium uptake data. Mechanistic insights from Visual MINTEQ calculations and solid phase characterizations (XRD, XPS, and TEM) indicate that Co(II) removal is dominated by mineral water interface precipitation. The gradual hydration of periclase (MgO) forms Mg(OH)₂, which creates localized alkaline microenvironments at particle surfaces and drives Co(OH)₂ formation. Carbonate availability further favors CoCO₃ formation and retention on CCCD. Importantly, this localized precipitation pathway maintains a stable, mildly alkaline effluent pH (around 8.5), reducing downstream pH adjustment demand and improving operational compatibility. Overall, CCCD combines high Co(II) immobilization efficiency, strong long-term stability, and an energy-efficient preparation route, supporting its potential for scalable remediation of Co(II) contaminated water.

Human carboxylesterases (CES) are enzymes that play a central role in the metabolism and biotransformation of diverse endogenous substances and xenobiotics. The two most relevant isoforms, CES1 and CES2, are crucial in clinical pharmacotherapy as they catalyze the hydrolysis of numerous approved drugs and prodrugs. Elucidating the structural basis of CES isoform substrate specificity is essential not only for understanding and anticipating the biological fate of administered drugs, but also for designing prodrugs with optimized site-specific bioactivation. Additionally, this knowledge is also important for the design of biomedically useful molecules such as subtype-targeted CES inhibitors and fluorescent probes. In this context, both experimental and computational methodologies have been used to explore the mechanistic and thermodynamic properties of CES-mediated catalysis. Experimental designs commonly employ recombinant CES or human tissue microsomes as enzyme sources, utilizing quantification methods such as spectrophotometry (UV and fluorescence) and mass spectrometry. Computational approaches fall into two categories: (1) modeling substrate: CES recognition and affinity (molecular docking, molecular dynamics simulation, and free-energy binding calculations), and (2) modeling substrate: CES reaction coordinates (hybrid QM/MM simulations). While experimental and theoretical approaches are highly synergistic in studying the catalytic properties of CES subtypes, they represent distinct technical and scientific fields. This review aims to provide an integrated discussion of the key concepts and the interplay between the most commonly used wet-lab and dry-lab strategies for investigating CES catalytic activity. We hope this report will serve as a concise resource for researchers exploring CES isoform specificity, enabling them to effectively utilize both experimental and computational methods.

Background: Pesticide toxicity to insects is an important adverse effect with a potentially large ecological impact when considering the effect on beneficial insects, as pollinators. The assessment of this endpoint is necessary to avoid applying ecologically dangerous pesticides. Aim of the study: Assessment of the availability of the Monte Carlo method for the development of a model for toxicity (pLD50) towards bees and other pollinators. In addition, the index of ideality of correlation is examined as a possibility to increase the statistical quality of quantitative structure-activity relationships (QSARs) for the toxicity of pesticides to pollinators. Main results and novelty: models with good performance on the toxic effect of pesticides towards different pollinators, wrapping acute and chronic effects, using the Monte Carlo method for QSAR analysis.

Cisplatin, a platinum-based compound, is a cornerstone of modern chemotherapy and remains widely used against a variety of solid tumors, including testicular, ovarian, lung, bladder, and head and neck cancers. Its anticancer activity is primarily attributed to the formation of DNA crosslinks, which obstruct replication and repair, ultimately leading to apoptosis. However, the clinical value of cisplatin is constrained by two major challenges: its toxic profile and the development of resistance. Cisplatin toxicity arises from its interaction not only with tumor DNA but also with proteins and nucleic acids in healthy tissues, resulting in a range of adverse effects, including, but not limited to, nephrotoxicity, ototoxicity, neurotoxicity, and gastrointestinal injury. In pediatric patients, permanent hearing loss represents a particularly debilitating complication. On the other hand, tumor cells can evade cisplatin cytotoxicity through diverse mechanisms, including reduced intracellular drug accumulation, enhanced DNA repair, detoxification by thiol-containing molecules, and alterations in apoptotic signaling. These resistance pathways severely compromise treatment outcomes and often necessitate alternative or combination strategies. This review examines the chemical structure of cisplatin, the molecular mechanisms of cisplatin cytotoxicity and cisplatin-induced resistance, as well as the main applications in cancer management and the complications associated with its clinical use.

Agricultural biomass has potential as a renewable and versatile carbon feedstock for developing eco-friendly and biodegradable polymers capable of replacing conventional petrochemical plastics. To address the growing environmental concerns associated with plastic waste and carbon emissions, lignocellulosic residues, edible crop by-products, and algal biomass were utilized as sustainable raw materials. These biomasses provided carbohydrate-, lipid-, and lignin-rich fractions that were deconstructed through optimised physical, chemical, and enzymatic pretreatments to yield fermentable intermediates, such as reducing sugars, organic acids, and fatty acids. The intermediates were subsequently converted through tailored microbial fermentation processes into biopolymer precursors, primarily polyhydroxyalkanoates (PHAs) and lactate-based monomers. The resulting monomers underwent polymerization via polycondensation and ring-opening reactions to produce high-performance biodegradable plastics with tunable structural and mechanical properties. Additionally, the direct extraction and modification of naturally occurring polymers, such as starch, cellulose, and lignin, were explored to develop blended and functionalized bioplastic formulations. Comparative evaluation revealed that these biomass-derived polymers possess favourable physical strength, thermal stability, and biodegradability under composting conditions. Life-cycle evaluation further indicated a significant reduction in greenhouse gas emissions and improved carbon recycling compared to fossil-derived counterparts. The study demonstrates that integrating agricultural residues into bioplastic production not only enhances waste valorization and rural bioeconomy but also supports sustainable material innovation for packaging, farming, and consumer goods industries. These findings position agriculture-based biodegradable polymers as a critical component of circular bioeconomy strategies, contributing to reduced plastic pollution and improved environmental sustainability.

Endocrine disruptors, including bisphenol A, S, AF, and F, have been demonstrated to exhibit endocrine-disrupting activity. This phenomenon has been associated with a variety of health problems, including (but not limited to) neurological and reproductive disorders. Given the potential hazards, it is essential to have effective tools to assess their toxicity. The nematode Caenorhabditis elegans has become a widely used model organism for studying bisphenols because of its genetic simplicity and the conservation of its fundamental biological processes. This review article summarizes current knowledge of bisphenol toxicity and the use of the model organism C. elegans as a high-throughput system for investigating the toxicological profiles of BPA and its emerging alternatives. Furthermore, we highlight the specific methodologies for assessing the toxic effects of bisphenols in C. elegans. While highlighting its advantages, we critically discuss its limitations, including the absence of specific metabolic organs, which constrain direct extrapolation to mammalian systems. Based on available evidence, we conclude that C. elegans serves as an essential bridge between in vitro assays and mammalian models, offering a powerful platform for the early hazard identification and mechanistic screening of bisphenol analogues.

Heracleum sosnowskyi Manden., or H. sosnowskyi, of the Apiaceae was first cultivated in the USSR in 1947 as a potential fodder plant. Due to the development of cold-resistant cultivars and the characteristics of H. sosnowskyi, it quickly became feral. As a result, H. sosnowskyi began to spread as an aggressive invasive species in the 1970s and 1980s. By the 90s it had become an ecological disaster. As well as forming monocultures and displacing native species, H. sosnowskyi contains furanocoumarins, photosensitizing compounds that increase skin sensitivity to ultraviolet rays and cause severe burns. In addition, furanocoumarins have cytotoxic, genotoxic, mutagenic and estrogenic effects. H. sosnowskyi also contains essential oils, which are particularly active during flowering and can irritate the mucous membranes of the eyes and respiratory tract, as well as cause allergic reactions in the form of bronchospasm in people with asthma and hypersensitivity. When released in high concentrations, these biologically active compounds have an allelopathic effect on native plant species, displacing them and reducing biodiversity. As H. sosnowskyi is not native; the biologically active compounds it secretes have a xenobiotic effect, causing serious damage to the ecosystems it occupies. However, in parallel with these negative properties, furanocoumarins have been found to be effective in the treatment of cancer and skin diseases. Furanocoumarins possess antimicrobial antioxidant osteo- and neuroprotective properties. Essential oils containing octyl acetate, carboxylic acid esters, and terpenes can be used in the pharmaceutical industry as antiseptic and anti-inflammatory agents. Additionally, essential oils can be used as biofumigants and natural herbicides. A comprehensive approach allows H. sosnowskyi to be viewed in two ways. On the one hand, it is an aggressive alien species that causes significant damage to ecosystems and poses a threat to human health. On the other hand, it is a potentially valuable natural resource whose biomass can be used within the principles of the circular economy. It is hoped that the use of H. sosnowskyi for economic interests can be a partial compensation for the problem of its aggressive invasion, which is of anthropogenic origin.

Background: Chemical Intolerance (CI), Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactive Disorder (ADHD) are conditions with rising incidence rates not fully explained by greater awareness or changes in diagnostic practices. It is now generally accepted that the interaction between genetic and environmental exposures plays a role in all of these conditions. Prior studies show that these conditions co-occur. This study seeks to explore previous findings using an international sample.

Methods: A five-country (N = 5000) stratified panel survey was used to assess self-reported CI in themselves, and ASD and ADHD in their children. A generalized linear model was used to estimate Odds Ratios. Age- and sex-adjusted logistic models used CI as a predictor of ASD and ADHD in separate models.

Results: Compared to those classified as Low CI, High levels of CI were associated with greater Odds Ratios (OR) of reporting a child with ASD and ADHD in all countries except Japan. Italy, India, and the USA had over twice the OR of reporting a child with ASD. Mexico had over 1.9 times the OR. The results with ADHD are similar to the ASD results.

Conclusions: The results of this study are consistent with two prior U.S. studies, showing an association between ASD and ADHD among women who have CI. However, cross-cultural comparisons, especially prevalence estimates for ASD and ADHD, cannot be interpreted as epidemiologic rates due to serious limitations of the survey methodology. No causal relationship should be inferred from this study.