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J. Xenobiot., Volume 16, Issue 1 (February 2026) – 38 articles

Cover Story (view full-size image): Europium (Eu), found in acid mine drainage as well as in effluents from mining, phosphor-related, and electronics-related industries, represents both an emerging aquatic contaminant and a valuable resource. The marine macroalga Ulva lactuca demonstrated high Eu biosorption capacity with limited oxidative damage, as lipid peroxidation remained near control levels except at the highest exposure concentration. These findings identify U. lactuca as a resilient, nature-based system for Eu removal and recovery, while also providing insight into Eu toxicity and cellular partitioning in marine macroalgae. View this paper
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39 pages, 1877 KB  
Article
Rare Earth Elements and Technology-Related Trace Metals in Paediatric Scalp Hair: A 2001 Urban Baseline from Spain
by Antonio Peña-Fernández, Manuel Higueras, Roberto Valiente Borox and M. Carmen Lobo-Bedmar
J. Xenobiot. 2026, 16(1), 38; https://doi.org/10.3390/jox16010038 - 23 Feb 2026
Cited by 1 | Viewed by 593
Abstract
Rare earth elements (REEs) and technology-related trace elements are increasingly used in modern products and processes, but biomonitoring data in healthy children and adolescents remain scarce; scalp hair provides a practical, integrative matrix for assessing multi-element patterns over time. Scalp hair collected in [...] Read more.
Rare earth elements (REEs) and technology-related trace elements are increasingly used in modern products and processes, but biomonitoring data in healthy children and adolescents remain scarce; scalp hair provides a practical, integrative matrix for assessing multi-element patterns over time. Scalp hair collected in April–May 2001 from children (6–9 years; n = 120) and adolescents (13–16 years; n = 97) living in Alcalá de Henares (Spain) was retrieved from archival storage and analysed in 2025 using a single QA/QC-controlled ICP–MS workflow. Seven REEs (Ce, La, Pr, Nd, Gd, Er, and Y) and nine technology-related trace elements (Bi, Sb, Th, U, Pd, Pt, Rh, Ir, and Rb) were quantified after rigorous decontamination; left-censored data were treated using Kaplan–Meier, regression on order statistics, and maximum-likelihood approaches, and population reference values were derived as percentile-based upper limits (P95, 95% CI). In children, REEs were frequently detected and showed strong within-suite covariation, with medians in the low ng g−1 range (e.g., Ce ≈ 0.011 µg g−1; La ≈ 0.007 µg g−1), whereas in adolescents, most REEs were near reporting limits. Sb and U were ubiquitous in both age groups, while platinum-group elements were largely undetected. Shale-normalised REE patterns were subparallel across normalisers, La/Ce anomalies were centred below unity, and weak soil–hair correlations suggested multiple microenvironmental exposure pathways. These data provide a robust pre-diffusion baseline for REE metals in European youth, offering a benchmark for future urban exposome assessments. Full article
(This article belongs to the Section Emerging Chemicals)
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29 pages, 4828 KB  
Article
Identification, Quantification, and Characterization of Microplastics in Skincare and Treatment Creams: A Potential Health Concern Related to the Exposure Pathway
by Raluca Maria Stirbescu, Cristiana Radulescu, Raluca Maria Bucur (Popa), Andreea Laura Banica, Ioan Alin Bucurica and Ioana Daniela Dulama
J. Xenobiot. 2026, 16(1), 37; https://doi.org/10.3390/jox16010037 - 22 Feb 2026
Cited by 1 | Viewed by 733
Abstract
This research aimed to quantify and investigate the morphology of microplastics in skincare and treatment creams related to their chemical composition and the potential risks to human health associated with exposure to microplastics by dermal contact. A total of 21 skincare and treatment [...] Read more.
This research aimed to quantify and investigate the morphology of microplastics in skincare and treatment creams related to their chemical composition and the potential risks to human health associated with exposure to microplastics by dermal contact. A total of 21 skincare and treatment cream samples, indicating the target audience (men, women, and children) for each product, and potential diseases were analyzed in terms of the hidden risk of microplastics. To determine the exact number of microplastics to which adults and children are exposed over the course of a year, in-depth research was conducted on the cosmetic care and treatment products used by over 354 respondents from Romania. This study used a free, self-reported questionnaire method, which took into account consumer habits and preferences, as well as any potential medical conditions that could affect exposure. Optical microscopy and micro-FTIR revealed a total of 109 microplastics, with different sizes, colors, and shapes (i.e., fragments and fibers) and various chemical compositions, including mixtures of polymeric and natural structures, as well as 100% synthetic materials, e.g., polyethylene and polyester. The potential health risk of exposure to microplastics in certain cosmetic formulations for adults was assessed by calculating various risk indices, such as the polymer risk index (H), pollution load index (PLI), dermal plastic absorption (DPA), chronic daily dermal exposure (CDDE), risk to human health from dermal absorption (RHHDA), and estimated annual dermal absorption (EADA). These indices were calculated based on the medical conditions and application areas indicated on the labels of the analyzed creams (i.e., skincare and treatment), for both adult and children’s categories, using the fingertip unit (FTU) method for estimating the cream amount. The plastic toxicity of the analyzed samples was assessed using the H and PLI indices. The risk of microplastics to human health from dermal exposure was assessed using the DPA, CDDE, RHHDA, and EADA indices, which showed concerning results regarding the presence of these particles in cosmetic formulations. Full article
(This article belongs to the Special Issue Microplastics in the Environment: Intake Through the Food Chain and Cosmeceuticals, Human Exposure, and Health Concerns)
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15 pages, 1143 KB  
Article
Indole-3-Acetic Acid and Skatole Exert Opposing Effects on MDR1 Proteostasis in Human Colonic Epithelial Cells: A Molecular Basis for the Gut Microbial Metabolic Switch
by Kazuma Naito, Ayame Tomii, Katsunori Ishii and Hidehisa Shimizu
J. Xenobiot. 2026, 16(1), 36; https://doi.org/10.3390/jox16010036 - 18 Feb 2026
Viewed by 635
Abstract
The escalating consumption of red meat is a potent environmental risk factor for inflammatory bowel disease (IBD), which is characterized by compromised expression of the xenobiotic transporter P-glycoprotein (MDR1/ABCB1). While gut microbiota metabolize dietary tryptophan into diverse indole derivatives [...] Read more.
The escalating consumption of red meat is a potent environmental risk factor for inflammatory bowel disease (IBD), which is characterized by compromised expression of the xenobiotic transporter P-glycoprotein (MDR1/ABCB1). While gut microbiota metabolize dietary tryptophan into diverse indole derivatives that function as aryl hydrocarbon receptor (AhR) ligands, their differential regulation of MDR1 remains an unresolved AhR paradox. Here, we investigated the mechanisms by which two distinct metabolites, indole-3-acetic acid (IAA) and skatole, regulate MDR1 expression in human colonic epithelial Caco-2 cells. We observed that IAA selectively enhances MDR1 protein stability via an AhR-dependent pathway without inducing de novo transcription, suggesting a mechanism we term enhanced proteostasis mediated by the AhR-Hsp90 complex. Conversely, skatole, a toxic dysbiotic metabolite linked to red meat intake, triggered a time-dependent depletion of MDR1 and potently abrogated the protective efficacy of IAA. Our findings are consistent with a model in which skatole acts as a putative structural disruptor, potentially destabilizing the chaperone complex essential for MDR1 integrity. This destruction is facilitated by a key bacterial enzyme, indoleacetate decarboxylase (IAD), which is a pH-dependent metabolic switch in the gut. The modern Western diet, characterized by high protein and low fiber content, elevates colonic pH, thereby activating IAD to convert protective IAA into toxic skatole. These findings provide a molecular framework for the red meat–microbiome–barrier failure axis and highlight the restoration of the IAA/skatole balance through dietary intervention as a promising therapeutic strategy. Full article
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8 pages, 220 KB  
Editorial
New Challenges in the Monitoring, Risk Assessment, and Management of Pesticides and Biocides in the “One Health Era”
by Teresa D’Amore
J. Xenobiot. 2026, 16(1), 35; https://doi.org/10.3390/jox16010035 - 14 Feb 2026
Viewed by 589
Abstract
Pesticides and biocides remain indispensable chemicals for agriculture, food safety, public health, and industrial applications, as they safeguard crop yields, control disease vectors, and maintain high hygiene standards [...] Full article
(This article belongs to the Special Issue New Challenges in the Monitoring, Risk Assessment and Management of Pesticides and Biocides in the “One Health Era”)
12 pages, 807 KB  
Systematic Review
Micro- and Nanoplastics as a Potential Risk Factor for Stroke: A Systematic Review
by Jakub Kufel, Miłosz Korbaś, Julita Janiec, Zofia Pankowska, Marta Młynek, Aleksandra Gaweł and Adam Mitręga
J. Xenobiot. 2026, 16(1), 34; https://doi.org/10.3390/jox16010034 - 14 Feb 2026
Viewed by 673
Abstract
Environmental pollution with micro- and nanoplastics (MNPs) is an escalating global health concern. Despite growing evidence of MNPs’ presence in the human body, their impact on cerebrovascular diseases remains poorly understood. This study aimed to systematically assess the presence of MNPs in the [...] Read more.
Environmental pollution with micro- and nanoplastics (MNPs) is an escalating global health concern. Despite growing evidence of MNPs’ presence in the human body, their impact on cerebrovascular diseases remains poorly understood. This study aimed to systematically assess the presence of MNPs in the vascular system and their association with the risk and progression of stroke. A systematic review was conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420251272759). PubMed, Scopus, Web of Science, and Embase databases were searched for original research articles published in the last 10 years. Five studies were included (2 human observational, 3 animal in vivo), comprising 287 patients and rodent models. Methodological quality was assessed using ROBINS-E and SYRCLE’s RoB tools. The analysis confirmed the presence of MNPs, particularly polyethylene and polyvinyl chloride, in key human pathological structures, including carotid atherosclerotic plaques and stroke thrombi. Notably, the presence of MNPs in plaques was associated with a 4.5-fold increase in the risk of major cardiovascular events and death. Animal model studies provided a biological rationale for these observations, demonstrating that MNP exposure may lead to microembolization in cerebral circulation, blood–brain barrier disruption, and exacerbated ischemic injury. Importantly, MNP burden may reflect cumulative environmental exposure and vascular disease severity rather than a direct causal factor in stroke pathogenesis. Nevertheless, MNPs may still represent a novel, modifiable risk factor for stroke through their association with adverse vascular outcomes. Available evidence confirms their accumulation in the cardiovascular system and suggests an association with adverse clinical outcomes. Due to the limited number of studies, further standardized research on larger populations is required to establish whether a causal relationship exists. Full article
(This article belongs to the Special Issue (Micro)plastic Pollution: From Monitoring to Toxicity in All Environments)
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16 pages, 3860 KB  
Article
Protective Effects of Eugenol Against Monosodium Glutamate-Induced Reproductive Toxicity in Male Wistar Rats
by Kouthulgama Veekshith Reddy, Majid Shafi, Abhinav Madari, Sharath Chandra Goud, Shayaib Ahmad Kamil, Akeel Bashir, Masood Saleem Mir, Mir Nadeem Hassan, Mudasir Ali Rather, Zahoor Ahmad Wani, Showkeen Muzamil Bashir, Atif Khurshid Wani and Showkat Ahmad Shah
J. Xenobiot. 2026, 16(1), 33; https://doi.org/10.3390/jox16010033 - 13 Feb 2026
Viewed by 527
Abstract
Monosodium glutamate (MSG), a widely used flavor enhancer, has been implicated in oxidative stress-mediated systemic and reproductive toxicity, particularly affecting the male gonadal system. This study evaluated the ameliorative potential of eugenol, a phenolic compound with potent antioxidant properties, against MSG-induced reproductive toxicity [...] Read more.
Monosodium glutamate (MSG), a widely used flavor enhancer, has been implicated in oxidative stress-mediated systemic and reproductive toxicity, particularly affecting the male gonadal system. This study evaluated the ameliorative potential of eugenol, a phenolic compound with potent antioxidant properties, against MSG-induced reproductive toxicity in male Wistar rats. Thirty rats were randomly divided into five groups: group 1 (control), group 2 (MSG 2.5 g/kg), group 3 (eugenol 200 mg/kg), group 4 (MSG + eugenol 100 mg/kg), and group 5 (MSG + eugenol 200 mg/kg). Treatments were administered orally for 28 days. Hematological, biochemical, hormonal, antioxidant, gross, and histopathological assessments were conducted after sacrifice on Day 29. MSG exposure significantly reduced testicular weight, testosterone levels, TEC, Hb, PCV, serum proteins, and testicular GSH and SOD, while markedly elevating TLC, AST, ALT, BUN, creatinine, and TBARS. Severe testicular degeneration, vascular congestion, germ-cell loss, and disrupted seminiferous tubules were observed histologically. Co-administration of eugenol resulted in significant and dose-dependent amelioration of MSG-induced alterations, restoring hematological and biochemical parameters, improving antioxidant status, and elevating testosterone levels. Gross pathology and histopathology demonstrated progressive structural recovery, with the higher eugenol dose showing near-normal testicular architecture and active spermatogenesis. Eugenol alone produced no adverse effects and remained comparable to the control group across all parameters. The findings indicate that eugenol confers strong protective effects against MSG-induced reproductive toxicity, primarily through its antioxidant and cytoprotective actions. Eugenol may serve as a promising natural therapeutic agent for mitigating chemically induced male reproductive impairments. Full article
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15 pages, 1342 KB  
Article
In Vivo Passive Sampling Implantation in Fish for Monitoring of PAHs: Calibration and Kinetics
by Jhon Fredy Narváez Valderrama, Juan José García Londoño, Daniel Gil Ramírez, Clara S. Arias-Monsalve and Jorge L. Gallego
J. Xenobiot. 2026, 16(1), 32; https://doi.org/10.3390/jox16010032 - 10 Feb 2026
Viewed by 514
Abstract
Polycyclic aromatic hydrocarbons (PAHs) can enter water bodies and bioaccumulate in fish, leading to biomagnification; therefore, their monitoring is necessary. Passive sampling is easy to handle and shows potential for this purpose. However, studies in vivo are scarce, and kinetic parameters governing analyte [...] Read more.
Polycyclic aromatic hydrocarbons (PAHs) can enter water bodies and bioaccumulate in fish, leading to biomagnification; therefore, their monitoring is necessary. Passive sampling is easy to handle and shows potential for this purpose. However, studies in vivo are scarce, and kinetic parameters governing analyte partitioning between tissue and samplers remain poorly characterized. In this study, the silicone rubber membranes (SRMs) were exposed to fish fillet from common carp (Cyprinus carpio) to determine bioaccumulation parameters based on dissipation modelling using performance reference compounds (PRCs). The SRM was implanted in vivo in fish, and the dissipated PRCs were measured and applied to a mono-compartmental model. The results in fish fillet showed a pseudo-first kinetic order, and the plateau was attained at a time > 30 h. However, the equilibrium may not be ensured because of the low lipid fraction (fl) in fish (4.5%), which could lead to a local saturation of the tissue in contact with the SRM. The ratio between elimination and uptake constants (Ke/Ku) showed faster PAHs–SRM sorption than PAHs-fish tissue sorption (200 times); thus, fish with low fl will lead to faster SRM sorption. By contrast, in fish with higher fl, the long-term exposures will be necessary. The percentage of released deuterated PAHs from SRM during in vivo fish exposure was 1.6 times higher than that observed in the fish fillet, indicating an active clearance process. Therefore, during implantation, the rate of clearance and the fl should be considered to ensure detectable levels for applying the integrative equation based on dissipation modelling. Full article
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13 pages, 901 KB  
Article
Effects of Pharmacological and Agrochemical Endocrine Disruptors on Human Sperm Mitochondrial Respiration: Evidence from Ex Vivo Bioenergetic Profiling
by Graziana Assalve, Paola Lunetti, Vincenzo Zara and Alessandra Ferramosca
J. Xenobiot. 2026, 16(1), 31; https://doi.org/10.3390/jox16010031 - 9 Feb 2026
Viewed by 433
Abstract
Background: Human exposure to endocrine-disrupting chemicals (EDCs) is increasingly linked to male reproductive dysfunction, but underlying mechanisms remain unclear. This study aimed to evaluate how selected pharmacological (dihydroxyflutamide, 2OH-FTA; bicalutamide, BIC) and agrochemical (lindane, βHCH; permethrin, PERM; mancozeb, MNZ; tributyltin oxide, TBTO) EDCs [...] Read more.
Background: Human exposure to endocrine-disrupting chemicals (EDCs) is increasingly linked to male reproductive dysfunction, but underlying mechanisms remain unclear. This study aimed to evaluate how selected pharmacological (dihydroxyflutamide, 2OH-FTA; bicalutamide, BIC) and agrochemical (lindane, βHCH; permethrin, PERM; mancozeb, MNZ; tributyltin oxide, TBTO) EDCs affect mitochondrial function in human spermatozoa with parameters within World Health Organization (WHO) reference ranges. Methods: Human sperm cells were exposed ex vivo to 0.1–1000 nM of each compound. Mitochondrial respiration was measured using polarography, assessing oxygen consumption in active (V3) and resting (V4) states, and the respiratory control ratio (RCR) was calculated as an index of mitochondrial coupling. Results: Both 2OH-FTA and BIC reduced RCR in a concentration-dependent manner, mainly due to increases in V4, with BIC showing the strongest effect. βHCH produced a similar pattern, elevating V4 and decreasing RCR. In contrast, PERM, MNZ, and TBTO caused near-complete collapse of both V3 and V4 even at sub-nanomolar concentrations, indicating severe, concentration-independent mitochondrial toxicity. Conclusions: Sperm mitochondria are highly sensitive to EDCs, and distinct compounds exert different bioenergetic effects. Mitochondrial respiration assays provide a useful tool for ex vivo toxicological screening and risk assessment. Full article
(This article belongs to the Topic Disease Risks and Toxic Pathway from Environmental Chemical Exposure)
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17 pages, 485 KB  
Review
The Impact of Endocrine-Disrupting Chemicals on Embryonic Recurrent Implantation Failure: A Narrative Review
by Anastasios Potiris, Panagiotis Antsaklis, Panagiotis Christopoulos, Nikolaos Kathopoulis, Efthalia Moustakli, Ismini Anagnostaki, Eirini Drakaki, Nefeli Arkouli, Aikaterini-Lydia Vogiatzoglou, Athanasios Zikopoulos, Sofoklis Stavros and Charalampos Theofanakis
J. Xenobiot. 2026, 16(1), 30; https://doi.org/10.3390/jox16010030 - 8 Feb 2026
Viewed by 653
Abstract
A significant and persistent issue in assisted reproduction is recurrent implantation failure (RIF), which is often observed even after the transfer of embryos of high morphological and/or genetic quality. Accumulating data suggest that exposure to chemicals with endocrine-disrupting effects (EDCs) may be associated [...] Read more.
A significant and persistent issue in assisted reproduction is recurrent implantation failure (RIF), which is often observed even after the transfer of embryos of high morphological and/or genetic quality. Accumulating data suggest that exposure to chemicals with endocrine-disrupting effects (EDCs) may be associated with adverse implantation outcomes. Many environmentally widespread substances have the potential to interfere with the regulation of the endocrine system, affecting critical mechanisms involved in implantation, such as endometrial receptivity, steroid hormone receptor signaling, immune tolerance at the maternal–fetal interface, and the epigenetic regulation of genes that are essential for successful implantation. Experimental studies have shown that exposure to EDCs can alter gene expression in the endometrium, inflammatory pathways, and the dynamics of early embryonic development, while clinical and epidemiological data have associated increased levels of EDCs in the body with lower implantation rates in assisted reproductive technology (ART) cycles. This narrative review examines the implications of these findings in reproductive medicine, summarizes recent experimental and clinical data, and highlights the molecular mechanisms linking exposure to endocrine disruptors with recurrent implantation failure. Recognizing environmental chemical exposure as a potentially modifiable risk factor may offer new perspectives for the prevention of RIF and the development of more personalized therapeutic strategies. Full article
(This article belongs to the Special Issue Environmental Exposures and Their Impact on Reproduction)
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21 pages, 9532 KB  
Article
Sodium Nitroprusside as a Xenobiotic Model of Oxidative and Nitrosative Stress in Cellular and Zebrafish Systems
by Carlos Alberto-Silva, Felipe Assumpção da Cunha e Silva, Brenda Rufino da Silva, Leticia Ribeiro de Barros, Adolfo Luis Almeida Maleski and Maricilia Silva Costa
J. Xenobiot. 2026, 16(1), 29; https://doi.org/10.3390/jox16010029 - 6 Feb 2026
Viewed by 1003
Abstract
Oxidative and nitrosative stress are central mechanisms in the pathogenesis of neurodegenerative diseases, where excessive production of reactive oxygen and nitrogen species (ROS/RNS) leads to mitochondrial dysfunction, membrane damage, and neuronal death. In this study, we established and compared short-term (2 h) and [...] Read more.
Oxidative and nitrosative stress are central mechanisms in the pathogenesis of neurodegenerative diseases, where excessive production of reactive oxygen and nitrogen species (ROS/RNS) leads to mitochondrial dysfunction, membrane damage, and neuronal death. In this study, we established and compared short-term (2 h) and long-term (20 h) exposure paradigms to sodium nitroprusside (SNP), used as a xenobiotic nitric oxide donor, in two neuronal cell lines (mHippoE-18 and PC12) and zebrafish larvae, aiming to provide a preclinical framework for neurodegenerative drug discovery. In vitro, SNP exposure caused concentration-dependent reductions in viability and alterations in oxidative balance, with mHippoE-18 cells exhibiting higher susceptibility than PC12 cells. In the short-term exposure paradigm, cytotoxicity was primarily associated with membrane disruption at higher concentrations, whereas oxidative stress contributed more strongly at intermediate doses. In the long-term exposure, mHippoE-18 cells showed strong integrated correlations between ROS, LDH release, and viability loss, highlighting their increased vulnerability to nitrosative stress. In zebrafish, SNP exposure impaired metabolic activity and swimming behavior in both paradigms. Long-term exposure led to consistent dose-dependent increases in ROS, accompanied by locomotor deficits tightly linked to energy metabolism. Overall, the higher sensitivity of mHippoE-18 cells compared with PC12 cells, together with the dose-dependent metabolic and behavioral impairments observed in zebrafish, indicates that cellular responses partially mirror in vivo outcomes. This integrative approach underscores the value of combining neuronal cell lines with zebrafish larvae to capture complementary aspects of SNP-induced neurotoxicity and to strengthen preclinical evaluation of candidate compounds with protective or therapeutic potential. These findings support the use of SNP as a xenobiotic model to probe nitrosative stress-driven neurotoxicity across cellular and organismal systems. Full article
(This article belongs to the Special Issue Xenobiotics in Aquatic Ecosystems: Fate, Toxicity, and Sustainable Remediation)
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16 pages, 1082 KB  
Systematic Review
Genetic Modulation of Mercury Exposure on Perinatal and Birth Outcomes: A Systematic Review and Meta-Analysis of Gene-Environment Interactions
by Aqsa Aufa Syauqi Sadana, Saekhol Bakri, Shinji Tokonami, Eka Djatnika Nugraha, Hasnawati Amqam and Muflihatul Muniroh
J. Xenobiot. 2026, 16(1), 28; https://doi.org/10.3390/jox16010028 - 6 Feb 2026
Viewed by 688
Abstract
Genetic polymorphisms can modulate susceptibility to mercury (Hg) toxicity by altering metabolic and detoxification pathways. This review evaluated the association between genetic variants, Hg exposure, and obstetric outcomes. A systematic search of Scopus, PubMed and ScienceDirect through May 2025 identified 12 eligible studies [...] Read more.
Genetic polymorphisms can modulate susceptibility to mercury (Hg) toxicity by altering metabolic and detoxification pathways. This review evaluated the association between genetic variants, Hg exposure, and obstetric outcomes. A systematic search of Scopus, PubMed and ScienceDirect through May 2025 identified 12 eligible studies (n = 4995), conducted in accordance with PRISMA guidelines, with methodological quality assessed using the Newcastle–Ottawa Scale. Meta-analysis was selectively performed only for genetically and methodologically comparable studies. The most frequently examined genes were GSTP1, GCLC, GCLM, GPX1, MT1A, ALAD, and APOE. Meta-analysis of GSTP1 rs1695, showed no statistically significant association between the Val105 allele and hair mercury concentrations (MD = −0.08 µg/g; 95% CI: −0.18 to 0.02; p = 0.13), although the direction of effect suggested a potential protective trend. Polymorphisms in other glutathione-related genes (GCLC, GCLM, and GPX1) were consistently associated with increased risks of small-for-gestational-age infants, preeclampsia, and impaired neurodevelopmental outcomes in offspring. In contrast, the APOE ε4 allele appeared to be associated with reduced fetal mercury burden, whereas polymorphisms in ALAD and MT1A were linked to higher mercury levels and adverse pregnancy-related outcomes. By integrating epidemiological evidence with mechanistic insights within a gene–environment interaction framework, this review helps to address important gaps in the existing literature. These findings underscore the importance of incorporating genetic susceptibility into Hg risk assessment and precision-based prenatal interventions. Full article
(This article belongs to the Special Issue Xenobiotics in the Perinatal and Early Childhood Stages: Sources of Exposure and Effects)
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38 pages, 1367 KB  
Review
Genetic and Environmental Factors Shaping Hearing Loss: Xenobiotics, Mechanisms and Translational Perspectives
by Francisco Esteves and Helena Caria
J. Xenobiot. 2026, 16(1), 27; https://doi.org/10.3390/jox16010027 - 5 Feb 2026
Viewed by 793
Abstract
The central mechanistic hypothesis underlying multifactorial hearing loss posits that genetic susceptibility and environmental exposures act synergistically to disrupt cochlear homeostasis through redox imbalance, mitochondrial dysfunction, and pro-inflammatory mechanisms. This gene–environment paradigm has significant translational implications: elucidating the molecular crosstalk between genetic variants [...] Read more.
The central mechanistic hypothesis underlying multifactorial hearing loss posits that genetic susceptibility and environmental exposures act synergistically to disrupt cochlear homeostasis through redox imbalance, mitochondrial dysfunction, and pro-inflammatory mechanisms. This gene–environment paradigm has significant translational implications: elucidating the molecular crosstalk between genetic variants and environmental factors may enable precision risk stratification and the development of targeted otoprotective strategies. The present review provides a comprehensive examination of the major determinants implicated in hearing loss. The manuscript is organized into six main sections that encompass the most relevant domains of current research. First, it offers (I) an overview of epidemiological patterns and the multifactorial nature of hearing impairment. This is followed by (II) a background synthesis of the complex genetic architecture underlying hearing loss. Next, the authors present (III) an outline of environmental determinants and exposure profiles associated with auditory dysfunction, highlighting prominent pollutant/xenobiotic classes (e.g., organic solvents and volatile aromatic hydrocarbons, heavy metals, pesticides, and especially organophosphates and persistent organochlorine compounds), followed by (IV) an analysis of oxidative stress, mitochondrial impairment, and inflammatory pathways involved in cochlear injury. Subsequently, (V) translational perspectives and integrated therapeutic approaches are discussed, with emphasis on epidemiological prevention and precision-based interventions. Finally, (VI) this review addresses current challenges and future directions in elucidating gene–environment interactions in hearing loss. Full article
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13 pages, 810 KB  
Article
Toxicokinetic and Partial Mass Balance Assessment of 14C-Alpha Olefins in Rats
by Quan Shi, Jamie Dunn, Juan-Carlos Carrillo, Michael G. Penman, Robert H. Powrie, Corinne Haines, Hua Shen, Yuan Tian, Sophie Jia, Fabienne Hubert and Peter J. Boogaard
J. Xenobiot. 2026, 16(1), 26; https://doi.org/10.3390/jox16010026 - 2 Feb 2026
Viewed by 440
Abstract
Higher olefins are a class of alkenes widely used as intermediates in the production of essential consumer and industrial products. This radiolabel disposition and partial mass balance study investigated the distribution and excretion of four 14C-radiolabelled alpha higher olefins (i.e., 1-octene, 1-decene, [...] Read more.
Higher olefins are a class of alkenes widely used as intermediates in the production of essential consumer and industrial products. This radiolabel disposition and partial mass balance study investigated the distribution and excretion of four 14C-radiolabelled alpha higher olefins (i.e., 1-octene, 1-decene, 1-hexadecene, and 1-eicosene) in male Wistar rats following a single oral dose (100 mg/kg). Blood, liver, kidney, adipose tissue, urine, and faeces were collected and analysed for total 14C-derived radioactivity. Urinary elimination was rapid, with approximately 70% and 90% of total radioactivity recovered in urinary excreted within 24 and 48 h, respectively. Excretion patterns showed a clear chain-length-dependent trend: shorter-chain olefins (C8, C10) exhibited higher urinary excretion, indicating greater systemic absorption, while longer-chain olefins (C16, C20) were primarily eliminated via faeces, suggesting limited intestinal uptake. Tissue distribution was minimal in blood, liver, and kidney, but adipose tissue retention increased with chain length. Total recovery of administered radioactivity in the analysed matrices was low, ranging from 17% to 60%. Importantly, because exhaled 14CO2 and volatile parent compounds were not captured, the missing fraction cannot be quantified and the balance cannot be considered closed. All in all, the current study describes the partial disposition of higher olefins and highlights the influence of molecular size and lipophilicity on the biological fat, though further studies are required to fully characterise their metabolic profile and total elimination kinetics. Full article
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37 pages, 5817 KB  
Article
Structural and Dynamic Insights into Podocalyxin–Ezrin Interaction as a Target in Cancer Progression
by Mila Milutinovic, Stuart Lutimba and Mohammed A. Mansour
J. Xenobiot. 2026, 16(1), 25; https://doi.org/10.3390/jox16010025 - 2 Feb 2026
Viewed by 1114
Abstract
Cancer metastasis, the spread of tumour cells from the primary site to distant organs, is responsible for over 90% of cancer deaths, yet effective treatments remain elusive due to incomplete understanding of the molecular drivers involved. Podocalyxin (PODXL), a protein overexpressed in many [...] Read more.
Cancer metastasis, the spread of tumour cells from the primary site to distant organs, is responsible for over 90% of cancer deaths, yet effective treatments remain elusive due to incomplete understanding of the molecular drivers involved. Podocalyxin (PODXL), a protein overexpressed in many aggressive cancers, links the cell membrane to the internal skeleton through its interaction with Ezrin, an actin cytoskeleton cross-linker. Despite its therapeutic relevance, the PODXL–Ezrin interface remains structurally uncharacterised and pharmacologically intractable. Here, we employed an integrated computational approach combining protein–protein docking, molecular dynamics (MD) simulations, and virtual screening to investigate the structural basis of the PODXL–Ezrin interaction. Using AlphaFold-predicted structures, we modelled PODXL and Ezrin complexes, revealing that PODXL’s cytoplasmic domain stabilises upon Ezrin binding, with Arg495 mediating temporally distinct electrostatic interactions essential for initial complex assembly. Particularly, we characterised the R495W missense mutation in PODXL’s Ezrin-binding domain, demonstrating that substitution of arginine with bulky, hydrophobic tryptophan may allosterically destabilise Ezrin’s dormant conformation. This mutation slightly increases the intramolecular distance between the F3 subdomain and C-terminal domain from 2.59 Å to 3.40 Å, thus leading to potential partial unmasking of the Thr567 phosphorylation site that could plausibly prime Ezrin for activation. Molecular dynamics simulations in the WT state with a total simulation time of 100 ns revealed enhanced structural rigidity and reduced radius of gyration fluctuations in the mutant complex, consistent with a potential “locked,” activation-prone state that amplifies oncogenic signalling. Through virtual screening, we identified NSC305787 as a selective destabiliser of the R495W mutant complex by disrupting key Trp495–pre-C-terminal loop Ezrin interactions and causing steric hindrance to PIP2 recruitment. Our findings identified mutation-dependent changes in drug binding that can guide the development and repurposing of compounds for targeting PODXL-related cancers and improve patient outcomes in PODXL-altered malignancies. Full article
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32 pages, 2498 KB  
Article
Enhanced Diclofenac Biodegradation by Bacterial Strains and a Microbial Consortium from Activated Sludge: Toxicity Assessment and Insights into Microbial Community Dynamics
by Alba Lara-Moreno, Belen Rodriguez-Morillo, Fernando Madrid, Pedro M. Martin-Sanchez, Jaime Villaverde, Carmen Mejías, Esteban Alonso, Juan Luis Santos and Esmeralda Morillo
J. Xenobiot. 2026, 16(1), 24; https://doi.org/10.3390/jox16010024 - 2 Feb 2026
Viewed by 570
Abstract
Diclofenac (DCF) is a widely used non-steroidal anti-inflammatory drug whose presence in environmental matrices has led to its classification as an emerging contaminant. Developing effective and sustainable removal strategies is therefore essential. In this study, Pseudomonas aeruginosa CSWD.1, Pseudomonas sp. CSWD.2, and a [...] Read more.
Diclofenac (DCF) is a widely used non-steroidal anti-inflammatory drug whose presence in environmental matrices has led to its classification as an emerging contaminant. Developing effective and sustainable removal strategies is therefore essential. In this study, Pseudomonas aeruginosa CSWD.1, Pseudomonas sp. CSWD.2, and a microbial consortium (MC) were isolated from activated sludge through enrichment cultures with DCF and employed as laboratory models to investigate DCF biodegradation capacity under a biosafety-aware framework. Biodegradation assays supplemented with glucose showed limited removal (45.5%) by CSWD.1, whereas CSWD.2 and the MC achieved complete elimination (100%) of 10 mg L−1 DCF in 21 and 5 days, respectively. Three extracellular metabolites, 4’-hydroxy-diclofenac (4’-OH-DCF), 5-hydroxy-diclofenac (5-OH-DCF), and putative NO2-DCF, were detected, with concentrations varying during degradation. Persistence of 4’-OH-DCF and tentatively identified NO2-DCF after 28 days was potentially associated with increased toxicity relative to the abiotic control. Overall, the results suggest that evaluating metabolites and their toxicity is essential, requiring isolation of additional microorganisms able to degrade 4’-OH-DCF and NO2-DCF to combine with the microorganisms isolated in this study. Metabarcoding analysis of the microbial consortium after bioremediation revealed the dominant bacterial population of Burkholderia (88.9% relative abundance) and a predominant fungal genus Talaromyces (80.1%), indicating that both bacteria and fungi may be associated with DCF transformation. These results provide insights into microbial community dynamics and their potential application in designing effective consortia for DCF bioremediation. Full article
(This article belongs to the Topic Aquatic Emerging Contaminants and Their Ecotoxicological Consequences, 2nd Edition)
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28 pages, 6228 KB  
Article
The Freshwater Ciliate Coleps hirtus as a Model Organism for Metal and Nanoparticle Toxicity: Mixture Interactions and Antioxidant Responses
by Govindhasamay R. Varatharajan, Martina Coletta, Santosh Kumar, Daizy Bharti, Arnab Ghosh, Shikha Singh, Amit C. Kharkwal, Francesco Dondero and Antonietta La Terza
J. Xenobiot. 2026, 16(1), 23; https://doi.org/10.3390/jox16010023 - 1 Feb 2026
Viewed by 837
Abstract
Heavy metals (HMs) and metal-oxide nanoparticles (NPs) frequently co-occur in freshwater systems, yet their combined effects on microbial predators remain poorly understood. Here, the freshwater ciliate Coleps hirtus was used to evaluate the cytotoxicity of single and binary mixtures of HMs (Cd, Cu, [...] Read more.
Heavy metals (HMs) and metal-oxide nanoparticles (NPs) frequently co-occur in freshwater systems, yet their combined effects on microbial predators remain poorly understood. Here, the freshwater ciliate Coleps hirtus was used to evaluate the cytotoxicity of single and binary mixtures of HMs (Cd, Cu, Zn) and NPs (ZnO, CuO, TiO2, SiO2), and to characterize associated antioxidant responses. Acute toxicity was assessed after 24 h by estimating LC20 and LC50 values, while mixture toxicity for Cd + Zn and Cd + ZnO was analyzed using the Toxic Unit approach and the MixTOX framework. Non-enzymatic (TPC, DPPH, HRSA) and enzymatic (CAT, GST, GPx, SOD) antioxidants were quantified as sublethal biomarkers at concentrations below lethal thresholds. HMs were markedly more toxic than NPs, with a toxicity ranking of Cu > Cd >> Zn, whereas NPs followed ZnO > CuO >> TiO2 >> SiO2. Cd + Zn mixtures showed predominantly antagonistic or non-interactive effects, while Cd + ZnO mixtures exhibited strong synergistic toxicity with a non-linear dependence on mixture composition, as supported by MixTox modeling. Exposure to HMs and NPs induced significant and often coordinated changes in antioxidant biomarkers, with binary mixtures eliciting stronger responses than single contaminants. Together, these findings indicate that mixture composition strongly influences both toxicity outcomes and oxidative stress responses in C. hirtus. The combination of clear, mixture-dependent toxicity patterns and robust oxidative stress responses makes C. hirtus a promising bioindicator for freshwater environments impacted by HMs and NPs. Full article
(This article belongs to the Special Issue Xenobiotics in Aquatic Ecosystems: Fate, Toxicity, and Sustainable Remediation)
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17 pages, 3099 KB  
Article
Microplastics and Nitrite Stress Affect Physiological and Metabolic Functions of the Hepatopancreas in Marine Shrimp
by Yi-Fu Xing, Xuan-Yi Zhu, Hong-Biao Dong, Jian-Hua Huang, Ya-Fei Duan and Jia-Song Zhang
J. Xenobiot. 2026, 16(1), 22; https://doi.org/10.3390/jox16010022 - 27 Jan 2026
Viewed by 632
Abstract
Nitrite is a common toxic substance in aquaculture, and microplastics are environmental pollutants capable of adsorbing small molecules/particles. Shrimp rely mainly on the hepatopancreas to accomplish detoxification metabolism. In this study, we investigated the individual and combined effects of nitrite and microplastics on [...] Read more.
Nitrite is a common toxic substance in aquaculture, and microplastics are environmental pollutants capable of adsorbing small molecules/particles. Shrimp rely mainly on the hepatopancreas to accomplish detoxification metabolism. In this study, we investigated the individual and combined effects of nitrite and microplastics on the physiological function of the P. vannamei hepatopancreas. The results demonstrated that both nitrite and microplastics induced morphological damage, with the combined stress exacerbating tissue damage. Oxidative stress biochemical indicators were disrupted, and most enzyme activities and gene expression levels were upregulated to varying degrees in each experimental group. The expression levels of immune genes (cytC, CASP-3, Crus, ALF, and proPO), detoxification metabolism genes (CYP450, EH1, SULT, and UGT), and oxidative-stress-related genes (ROMO1, SOD, GPx, and Trx) exhibited different fluctuations. Nitrite and microplastic stress resulted in altered hepatopancreatic function, mainly involving amino acid biosynthesis and metabolism, ABC transporters, oxidative phosphorylation, and the mTOR pathway. We identified 17 metabolic biomarkers, including 6 lipids (Oleic acid, Prostaglandin G2, Linoleic acid, Palmitic acid, Docosahexaenoic acid, Docosapentaenoic acid), 6 amino acids (L-Leucine, Agmatine, L-Arginine, L-Tyrosine, Ornithine, N-Acetylornithine), and 5 carbohydrates (Glyceric acid, Citric acid, D-Mannose, Sorbitol, Fumaric acid). These findings suggest that nitrite and microplastic stresses cause hepatopancreatic tissue damage and induce oxidative stress, physiological and metabolic dysfunction in the shrimp P. vannamei, thereby impacting its normal physiological functions. Full article
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13 pages, 882 KB  
Review
Potential Role of Mosses in Evaluating Airborne Microplastic Deposition in Terrestrial Ecosystems
by Roberto Bargagli and Emilia Rota
J. Xenobiot. 2026, 16(1), 21; https://doi.org/10.3390/jox16010021 - 24 Jan 2026
Cited by 1 | Viewed by 520
Abstract
The deposition of airborne microplastics (MPs) poses potential risks to human health and terrestrial ecosystems. Therefore, suitable mitigation efforts are needed, as is knowledge of their deposition patterns in inhabited and remote regions. Currently, there are no standardized protocols for monitoring airborne MPs, [...] Read more.
The deposition of airborne microplastics (MPs) poses potential risks to human health and terrestrial ecosystems. Therefore, suitable mitigation efforts are needed, as is knowledge of their deposition patterns in inhabited and remote regions. Currently, there are no standardized protocols for monitoring airborne MPs, and implementing and managing automatic monitoring systems would be costly and feasible only in a few fixed locations. Over the past few decades, several species of cryptogams have proven to be reliable biomonitors of persistent atmospheric contaminants. Due to the lack of standardized methodologies, the results of preliminary biomonitoring surveys for MPs have been inconsistent and difficult to compare. However, they clearly indicate higher MP concentrations in epigeic mosses than in epiphytic lichens (collected at the same site or experimentally exposed in parallel in bags). This review discusses the morphophysiological features that favor the entrapment and retention of intercepted MPs in mosses, as well as the field and laboratory activities necessary to determine whether these organisms progressively accumulate airborne MPs as a function of the exposure time. Steps for future research needed to develop a cost-effective, reliable and easily applicable biomonitoring methodology are suggested. Evaluating the advantages of active moss biomonitoring over sampling atmospheric bulk deposition or exposing suitable commercial materials is recommended. Full article
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17 pages, 627 KB  
Article
Remediation Potential of Ulva lactuca for Europium: Removal Efficiency, Metal Partitioning and Stress Biomarkers
by Saereh Mohammadpour, Thainara Viana, Rosa Freitas, Eduarda Pereira and Bruno Henriques
J. Xenobiot. 2026, 16(1), 20; https://doi.org/10.3390/jox16010020 - 24 Jan 2026
Viewed by 512
Abstract
As demand for rare earth elements (REEs) rises and environmental concerns about the extraction of primary resources grow, biological methods for removing these elements have gained significant attention as eco-friendly alternatives. This study assessed the ability of the green macroalga Ulva lactuca to [...] Read more.
As demand for rare earth elements (REEs) rises and environmental concerns about the extraction of primary resources grow, biological methods for removing these elements have gained significant attention as eco-friendly alternatives. This study assessed the ability of the green macroalga Ulva lactuca to remove europium (Eu) from aqueous solutions, evaluated the cellular partition of this element and investigated the toxicological effects of Eu exposure on its biochemical performance. U. lactuca was exposed to variable concentrations of Eu (ranging from 0.5 to 50 mg/L), and the amount of Eu in both the solution and algal biomass was analyzed after 72 h. The results showed that U. lactuca successfully removed 85 to 95% of Eu at low exposure concentrations (0.5–5.0 mg/L), with removal efficiencies of 75% and 47% at 10 and 50 mg/L, respectively. Europium accumulated in algal biomass in a concentration-dependent manner, reaching up to 22 mg/g dry weight (DW) at 50 mg/L. The distribution of Eu between extracellular and intracellular fractions of U. lactuca demonstrated that at higher concentrations (5.0–50 mg/L), 93–97% of Eu remained bound to the extracellular fraction, whereas intracellular uptake accounted for approximately 20% at the lowest concentration (0.5 mg/L). Biochemical analyses showed significant modulation of antioxidant defenses. Superoxide dismutase activity increased at 10 and 50 mg/L, while catalase and glutathione peroxidase activities were enhanced at lower concentrations (0.5–1.0 mg/L) and inhibited at higher exposures. Lipid peroxidation levels remained similar to controls at most concentrations, with no evidence of severe membrane damage except at the highest Eu level. Overall, the results demonstrate that U. lactuca is an efficient and resilient biological system for Eu removal, combining high sorption capacity with controlled biochemical responses. These findings highlight its potential application in environmentally sustainable remediation strategies for REE-contaminated waters, while also providing insights into Eu toxicity and cellular partitioning mechanisms in marine macroalgae. Full article
(This article belongs to the Special Issue Xenobiotics in Aquatic Ecosystems: Fate, Toxicity, and Sustainable Remediation)
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32 pages, 5535 KB  
Article
Comparative Hepatic Toxicity of Pesticides in Common Carp (Cyprinus carpio Linnaeus, 1758): An Integrated Histopathological, Histochemical, and Enzymatic Biomarker Approach
by Vesela Yancheva, Stela Stoyanova, Elenka Georgieva, Eleonora Kovacheva, Bartosz Bojarski, László Antal, Ifeanyi Emmanuel Uzochukwu and Krisztián Nyeste
J. Xenobiot. 2026, 16(1), 19; https://doi.org/10.3390/jox16010019 - 22 Jan 2026
Viewed by 530
Abstract
The intensive use of pesticides in agriculture poses serious risks to aquatic ecosystems and non-target organisms, yet toxicological data remain limited. This study evaluated the acute effects of three widely used pesticides—pirimiphos-methyl (10 and 60 μg/L), propamocarb hydrochloride (40 and 80 μg/L), and [...] Read more.
The intensive use of pesticides in agriculture poses serious risks to aquatic ecosystems and non-target organisms, yet toxicological data remain limited. This study evaluated the acute effects of three widely used pesticides—pirimiphos-methyl (10 and 60 μg/L), propamocarb hydrochloride (40 and 80 μg/L), and 2,4-D (50 and 100 μg/L)—on the liver of common carp (Cyprinus carpio Linnaeus, 1758), a sentinel species in aquaculture, but also a species equally important in risk assessment and environmental monitoring. Fish were exposed for 96 h under controlled conditions, and histopathological, histochemical, and biochemical biomarkers were analyzed. All tested pesticides induced significant histopathological alterations, predominantly circulatory and degenerative changes, with severity increasing at higher concentrations. Propamocarb hydrochloride and 2,4-D caused more pronounced and partly irreversible hepatotoxicity compared to pirimiphos-methyl. The histochemical assessment revealed altered glycogen metabolism, while the biochemical assays showed inhibition of key liver enzymes, including ALAT, ASAT, ChE, and LDH, indicating disrupted metabolic processes. These findings highlight the vulnerability of aquatic organisms to pesticide exposure and support the use of fish liver biomarkers as effective tools in ecotoxicology research. The study also emphasizes the need for stricter regulation and environmental monitoring of pesticide contamination in aquatic ecosystems. Full article
(This article belongs to the Special Issue Xenobiotics in Aquatic Ecosystems: Fate, Toxicity, and Sustainable Remediation)
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16 pages, 1926 KB  
Article
From Aquifer to Tap: Comprehensive Quali-Quantitative Evaluation of Plastic Particles Along a Drinking Water Supply Chain of Milan (Northern Italy)
by Andrea Binelli, Alberto Cappelletti, Cristina Cremonesi, Camilla Della Torre, Giada Caorsi and Stefano Magni
J. Xenobiot. 2026, 16(1), 18; https://doi.org/10.3390/jox16010018 - 22 Jan 2026
Viewed by 508
Abstract
This study presents the first evaluation of plastic particle contamination along a complete drinking water supply chain within the distribution system of Milan, Northern Italy. Fourteen grab water samples were collected from various points, including groundwater extraction, post-treatment stages, a public fountain, and [...] Read more.
This study presents the first evaluation of plastic particle contamination along a complete drinking water supply chain within the distribution system of Milan, Northern Italy. Fourteen grab water samples were collected from various points, including groundwater extraction, post-treatment stages, a public fountain, and ten household taps. Plastic particles were identified using µFTIR spectroscopy and characterized by polymer type, shape, size, and color. Overall, low concentrations of plastic particles were detected, ranging from 0.3 ± 0.5 particles/L in the accumulation tank to an average of 1.9 ± 1.4 particles/L in household tap water, with no significant increase observed along the supply chain. The entire data set was dominated by cellulose particles (76%), as plastics accounted for only 8%. Microplastics (1 µm–1 mm) were the most commonly detected (90%), while the remaining 10% were large microplastics (1–5 mm). Qualitatively, polyester fibers were the most prevalent particles identified. However, greater variability and higher concentrations were found in private residence samples, suggesting that internal plumbing systems may be a primary source of contamination. Estimated human exposure through this supply system, based on a current theoretical model, was minimal compared to global benchmarks. These findings highlight the necessity of integrating private distribution infrastructure into future regulatory frameworks to assist stakeholders in making informed decisions to mitigate potential plastic contamination. Full article
(This article belongs to the Special Issue (Micro)plastic Pollution: From Monitoring to Toxicity in All Environments)
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29 pages, 1636 KB  
Article
Geochemical Patterns and Human Health Risks of Less-Regulated Metal(loid)s in Historical Urban and Industrial Topsoils from Alcalá de Henares, Spain
by Antonio Peña-Fernández, Manuel Higueras, Gevorg Tepanosyan, M. Ángeles Peña Fernández and M. C. Lobo
J. Xenobiot. 2026, 16(1), 17; https://doi.org/10.3390/jox16010017 - 21 Jan 2026
Cited by 1 | Viewed by 485
Abstract
Nine technology-related metal(loid)s (Ag, Co, Fe, Mo, Pt, Rh, Sb, Se and Y) were monitored in 137 topsoil samples from urban parks, industrial areas and gardens in Alcalá de Henares (Spain) using ICP–MS. Selenium was not detected, while Mo, Sb and Rh showed [...] Read more.
Nine technology-related metal(loid)s (Ag, Co, Fe, Mo, Pt, Rh, Sb, Se and Y) were monitored in 137 topsoil samples from urban parks, industrial areas and gardens in Alcalá de Henares (Spain) using ICP–MS. Selenium was not detected, while Mo, Sb and Rh showed a high proportion of values below the detection limit, indicating generally low contamination. In contrast, Fe, Co and Y were detected in all samples, with industrial soils showing about two-fold higher median Co and Fe than urban soils. Garden soils displayed marked silver enrichment (median 0.439 vs. 0.068 mg kg−1 in urban soils), with Ag pollution indices up to 71 and enrichment factors up to 69; around 17% of garden samples exceeded EF > 40, and more than one-quarter had EF > 10. Principal component analysis suggested a predominantly geogenic association for Co, Fe and Y and an anthropogenic component for Ag, Mo, Rh and Sb, while Pt was mainly linked to vehicular emissions. Under standard US EPA exposure scenarios applied to the 2001 topsoil concentrations, oral and inhalation hazard quotients for elements with available benchmarks remained <0.2 and inhalation cancer risks for Co were ≤2.5 × 10−7, indicating low estimated risk within the model assumptions. However, quantitative risk characterisation remains constrained by benchmark gaps for Pt and Rh and by limited consensus toxicity values for Y, which introduces uncertainty for these technology-related elements. These results should therefore be interpreted primarily as a baseline (2001) in surface soils for Alcalá de Henares rather than as a direct representation of current exposure conditions. Full article
(This article belongs to the Section Emerging Chemicals)
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17 pages, 1126 KB  
Article
Long-Term Per- and Polyfluoroalkyl Substances Exposure and Kidney Function in Taiwanese Adolescents and Young Adults: A 10-Year Prospective Cohort Study
by Chien-Yu Lin, Hui-Ling Lee and Ta-Chen Su
J. Xenobiot. 2026, 16(1), 16; https://doi.org/10.3390/jox16010016 - 21 Jan 2026
Cited by 1 | Viewed by 574
Abstract
Background and hypothesis: Per- and polyfluoroalkyl substances (PFAS) are highly persistent synthetic chemicals that can accumulate in renal tissue and potentially disrupt kidney function. Most prospective studies on PFAS–renal associations have focused on middle-aged or older adults, leaving uncertainty about whether similar [...] Read more.
Background and hypothesis: Per- and polyfluoroalkyl substances (PFAS) are highly persistent synthetic chemicals that can accumulate in renal tissue and potentially disrupt kidney function. Most prospective studies on PFAS–renal associations have focused on middle-aged or older adults, leaving uncertainty about whether similar patterns exist in younger populations. Methods: We investigated decade-long trajectories of plasma concentrations of 11 PFAS and their longitudinal associations with estimated glomerular filtration rate (eGFR) among 529 Taiwanese adolescents and young adults (aged 12–30 years) enrolled in the prospective YOung TAiwanese Cohort (YOTA), with measurements obtained in 2006–2008 and 2017–2019. Results: Nearly all plasma PFAS declined significantly over the 10-year period. Despite these reductions, higher baseline levels and greater annualized increases (Δln-PFAS/Δt) in linear perfluorooctanoic acid (PFOA), linear and branched perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were consistently associated with larger eGFR gains over time (β = 0.33–0.40, q < 0.05). In complementary models using follow-up eGFR as the outcome, both baseline and cumulative PFAS changes (Δln-PFAS) remained positively associated with higher eGFR (β = 1.71–3.84, q < 0.05). Polynomial analyses further indicated mild non-linear exposure–response patterns for several PFAS, suggesting that renal effects may deviate from linearity across exposure ranges. The composite PFAS exposure index (mean of standardized ln-PFAS concentrations) was robustly associated with higher eGFR across sensitivity analyses excluding participants with chronic conditions. These associations were more pronounced among individuals with greater metabolic or physiological vulnerability. Conclusions: Higher PFAS exposure was associated with elevated eGFR in young adults, which may be consistent with early glomerular hyperfiltration or other renal hemodynamic alterations. These findings raise the hypothesis of early renal stress in early life and underscore the need for ongoing biomonitoring and longitudinal follow-up with additional kidney injury markers to clarify long-term renal consequences. Full article
(This article belongs to the Topic Environmental Toxicology and Human Health—2nd Edition)
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17 pages, 641 KB  
Article
Evaluation of Plasticiser Levels, Phthalates and Bisphenols in Bahraini Subjects with and Without Type-2 Diabetes
by Edwina Brennan, Priya Das, Pearl Wasif, Xianyu F. Wang, Jochen F. Mueller, Chang He, Jean V. Varghese, Alexandra E. Butler, Stephen L. Atkin and Naji Alamuddin
J. Xenobiot. 2026, 16(1), 15; https://doi.org/10.3390/jox16010015 - 19 Jan 2026
Viewed by 458
Abstract
Background: Plasticisers with endocrine-disrupting potential are ubiquitous and associate with obesity and type-2 diabetes (T2D), with higher levels reported in the Middle East. However, no data exist on plasticiser exposure in Bahrain where T2D affects 15% of the national population. Methods: An observational [...] Read more.
Background: Plasticisers with endocrine-disrupting potential are ubiquitous and associate with obesity and type-2 diabetes (T2D), with higher levels reported in the Middle East. However, no data exist on plasticiser exposure in Bahrain where T2D affects 15% of the national population. Methods: An observational exploratory study in T2D (n = 60) and controls (n = 96), analysed for 24 h urinary plasticiser levels (liquid chromatography tandem mass spectrometry (LC-MS/MS)). Correlation and generalised linear model (GLM) analyses were employed to examine associations. Results: T2D were older (p < 0.001), had higher body mass index (BMI) (p < 0.001), body weight (p < 0.001) and glycosylated haemoglobin A1c (HbA1c) (p < 0.001). Correlation analysis revealed differences in inter-plasticiser, and plasticiser and biomarker relationships, with loss or reversal in T2D compared to controls. Mono-n-butyl phthalate (MnBP) levels were higher in T2D (p = 0.04); however, regression analysis revealed significant association with age. The GLM analyses demonstrated marked differences in the levels of mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), monoethyl phthalate (MEP) and bisphenol S (BPS), with lower levels in T2D versus controls (B = −3.41, p = 0.01; B = −5.28, p < 0.001; B = −8.94, p < 0.001; B = −6.09, p = 0.006, respectively); however, these contrasts appeared to be substantially confounded by BMI and/or age. Positive influence of age and negative influence of BMI when observed across the full dataset were generally reversed in T2D. Levels were complementary to those previously reported for the Middle East. Conclusions: The study indicates the phthalate levels in Bahrain are elevated though complementary to studies of phthalates in the Middle East; within those levels, the study indicates differential exposure–response relationships with plasticisers, influenced by age and BMI, in those with T2D compared to healthy controls. Full article
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12 pages, 740 KB  
Article
Urinary Metabolomics as a Window into Occupational Exposure: The Case of Foundry Workers
by Michele De Rosa, Silvia Canepari, Giovanna Tranfo, Ottavia Giampaoli, Adriano Patriarca, Agnieszka Smolinska, Federico Marini, Lorenzo Massimi, Fabio Sciubba and Mariangela Spagnoli
J. Xenobiot. 2026, 16(1), 14; https://doi.org/10.3390/jox16010014 - 15 Jan 2026
Viewed by 860
Abstract
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 [...] Read more.
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. Full article
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17 pages, 3706 KB  
Article
Carbonation of Calcined Clay Dolomite for the Removal of Co(II): Performance and Mechanism
by Can Wang, Jingxian Xu, Tingting Gao, Xiaomei Hong, Fakang Pan, Fuwei Sun, Kai Huang, Dejian Wang, Tianhu Chen and Ping Zhang
J. Xenobiot. 2026, 16(1), 13; https://doi.org/10.3390/jox16010013 - 13 Jan 2026
Viewed by 498
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Tracking the Environmental Fate of Heavy Metals: Migration, Accumulation, and Detection Techniques)
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20 pages, 1057 KB  
Article
Cross-Sectional Multicenter Biomonitoring Study on Genotoxicity and Oxidative DNA Damage in Oncology Healthcare Workers from Seven Italian Hospitals
by Cinzia Lucia Ursini, Giorgia Di Gennaro, Giuliana Buresti, Raffaele Maiello, Anna Maria Fresegna, Aureliano Ciervo, Marco Gentile, Virginia Di Basilio, Sabrina Beltramini, Daniela Gaggero, Nicoletta Rigamonti, Erica Maccari, Giorgia Zorzetto, Piera Maiolino, Pasquale Di Filippo, Maria Concetta Bilancio, Paolo Baldo, Valeria Martinello, Andrea Di Mattia, Chiara Esposito, Patrizia Nardulli, Mariarita Laforgia, Maria Vittoria Visconti, Matteo Vitali, Emanuela Omodeo-Salè and Delia Cavalloadd Show full author list remove Hide full author list
J. Xenobiot. 2026, 16(1), 12; https://doi.org/10.3390/jox16010012 - 13 Jan 2026
Cited by 1 | Viewed by 495
Abstract
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 [...] Read more.
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. Full article
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26 pages, 2593 KB  
Review
Experimental and In Silico Approaches to Study Carboxylesterase Substrate Specificity
by Sergio R. Ribone and Mario Alfredo Quevedo
J. Xenobiot. 2026, 16(1), 11; https://doi.org/10.3390/jox16010011 - 12 Jan 2026
Cited by 1 | Viewed by 762
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Topic Phase I and Phase II Xenobiotic-Metabolizing Enzymes: Structure, Function, and Regulation)
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28 pages, 1194 KB  
Review
Cisplatin as a Xenobiotic Agent: Molecular Mechanisms of Actions and Clinical Applications in Oncology
by Monia Cecati, Valentina Pozzi, Veronica Pompei, Valentina Schiavoni, Stefania Fumarola, Alice Romagnoli, Giovanni Tossetta, Angelo Montana, Alessandro Polizzi, Davide Sartini and Roberto Campagna
J. Xenobiot. 2026, 16(1), 9; https://doi.org/10.3390/jox16010009 - 8 Jan 2026
Cited by 1 | Viewed by 1837
Abstract
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 [...] Read more.
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. Full article
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18 pages, 1025 KB  
Article
Simulation of the Impact of Pesticides on Pollinators Under Different Conditions Using Correlation Weighting of Quasi-SMILES Components Together with the Index of Ideality of Correlation (IIC)
by Alla P. Toropova, Andrey A. Toropov, Sofia Mescieri, Alessandra Roncaglioni and Emilio Benfenati
J. Xenobiot. 2026, 16(1), 10; https://doi.org/10.3390/jox16010010 - 8 Jan 2026
Viewed by 750
Abstract
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: [...] Read more.
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. Full article
(This article belongs to the Special Issue Integrative Studies on Environmental Toxicity, Bioaccumulation and Remediation Strategies for Hazardous Substances, 2nd Edition)
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