Journal of Xenobiotics

21 pages, 420 KB

Open AccessArticle

Evaluation of Endocrine Disruptome and VirtualToxLab for Predicting Per- and Polyfluoroalkyl Substances Binding to Nuclear Receptors

by Nina Franko, Manca Vetrih and Marija Sollner Dolenc

J. Xenobiot. 2025, 15(5), 136; https://doi.org/10.3390/jox15050136 - 22 Aug 2025

Abstract

This study investigated whether the Endocrine Disruptome and VirtualToxLab in silico platforms are suitable for predicting the endocrine disrupting effects of per- and polyfluoroalkyl substances (PFASs)—in particular, for interactions with oestrogen receptors (ERs) and androgen receptor (AR). Compounds included in the U.S. Environmental [...] Read more.

This study investigated whether the Endocrine Disruptome and VirtualToxLab in silico platforms are suitable for predicting the endocrine disrupting effects of per- and polyfluoroalkyl substances (PFASs)—in particular, for interactions with oestrogen receptors (ERs) and androgen receptor (AR). Compounds included in the U.S. Environmental Protection Agency’s PFAS working list were analysed with both models, and the results were compared with the available in vitro data regarding their modulation of nuclear receptors. Based on the identified prediction parameters, such as sensitivity, specificity, accuracy, and Mathews’ correlation coefficient, VirtualToxLab was found to be a reliable model for predicting the reactivity of PFASs with AR, while a positive consensus approach of both platforms provided reliable predictions of the PFAS reactivity with ERα and ERβ. This study provides the evidence that Endocrine Disruptome and VirtualToxLab can be used as a tier 1 screening tool for assessment of the endocrine disrupting effect of PFASs. Furthermore, it demonstrates that the likelihood of endocrine disrupting properties increases with the lipophilicity of PFASs and identifies the understudied PFHpS, PFNS, PFDS, 9-Cl, NMeFOSAA, NEtFOSAA, 4:2 FTS, 6:2 FTS, 8:2 FTS, 6:2 monoPAP, 8:2 monoPAP, and 5:3 acid as potential ligands of AR and/or ERs. Full article

(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health: 2nd Edition)

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44 pages, 1673 KB

Open AccessReview

Managing PFAS in Sewage Sludge: Exposure Pathways, Impacts, and Treatment Innovations

by Luoana Florentina Pascu, Valentina Andreea Petre, Ioana Antonia Cimpean, Iuliana Paun, Florinela Pirvu and Florentina Laura Chiriac

J. Xenobiot. 2025, 15(4), 135; https://doi.org/10.3390/jox15040135 - 21 Aug 2025

Abstract

Per- and polyfluoroalkyl substances (PFAS) are a global concern due to their persistence, ubiquity, and accumulation in living organisms. Found in soils, biosolids, water, and the food chain, they pose health risks such as hormone disruption, immune damage, reproductive issues, and cancer. Regulations [...] Read more.

Per- and polyfluoroalkyl substances (PFAS) are a global concern due to their persistence, ubiquity, and accumulation in living organisms. Found in soils, biosolids, water, and the food chain, they pose health risks such as hormone disruption, immune damage, reproductive issues, and cancer. Regulations mainly target older PFAS like PFOA and PFOS, while many newer PFAS, including breakdown products, are poorly understood in terms of distribution, behavior, and toxicity. To address this complex issue, this review offers a detailed overview of human exposure to PFAS and their toxic effects. It highlights biosolids as a key, understudied source of PFAS in the environment. The review also discusses limitations of testing, missing long-term cleanup data, and regulatory issues that neglect total exposure and vulnerable populations. Additionally, it evaluates, in the specific context of biosolids management, the effectiveness, scalability, benefits, and drawbacks of various treatment technologies, such as thermal processes (pyrolysis, incineration, smoldering combustion), advanced oxidation, adsorption, hydrothermal liquefaction, and biological degradation. This work combines environmental science, toxicology, and engineering to outline PFAS management in biosolids and proposes a research and policy plan. Focusing on regulating PFAS as a group, validating real-world results, and employing adaptable treatment strategies underscores the need for a coordinated, science-based effort to reduce PFAS risks worldwide. Full article

(This article belongs to the Section Emerging Chemicals)

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20 pages, 2087 KB

Open AccessReview

Lead Poisoning in the Americas: Sources, Regulations, Health Impacts, and Molecular Mechanisms

by Blanca Miriam Torres-Mendoza, Asbiel Felipe Garibaldi-Ríos, Lourdes Del Carmen Rizo De La Torre, Ana María Puebla-Pérez, Luis E. Figuera, Guillermo Moisés Zúñiga-González, Belinda Claudia Gómez-Meda, Itzae Adonai Gutiérrez-Hurtado, Elvia Harumi Scott-López, Verónica Vázquez-González, Celeste Patricia Gazcón-Rivas and Martha Patricia Gallegos-Arreola

J. Xenobiot. 2025, 15(4), 134; https://doi.org/10.3390/jox15040134 - 20 Aug 2025

Abstract

Lead poisoning is a significant public health issue, contributing to 0.6% of the global disease burden and disproportionately affecting developing countries. Vulnerable populations, such as children, pregnant women, and low-income communities, remain at high risk, often exposed to lead levels exceeding safe thresholds. [...] Read more.

Lead poisoning is a significant public health issue, contributing to 0.6% of the global disease burden and disproportionately affecting developing countries. Vulnerable populations, such as children, pregnant women, and low-income communities, remain at high risk, often exposed to lead levels exceeding safe thresholds. While the problem is global, this review focuses specifically on the Americas, regions with diverse regulatory landscapes and persistent environmental lead exposure. Regulatory frameworks vary widely, and the lack of global consensus on acceptable blood lead levels leaves important gaps in protection. This review compiles and updates knowledge on emerging sources of lead exposure in the region, evaluates advancements in regulatory approaches, and analyzes the molecular impacts of lead on human health. Using the Comparative Toxicogenomics Database (CTD), lead was found to interact with 3448 genes, including those linked to inflammation and oxidative stress, and is associated with 4401 diseases and 799 disrupted pathways. These findings emphasize the need for regionally tailored interventions, strengthened policies, and further research on its health impacts. Full article

(This article belongs to the Topic Environmental Toxicology and Human Health—2nd Edition)

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29 pages, 583 KB

Open AccessReview

Harnessing Engineered Microbial Consortia for Xenobiotic Bioremediation: Integrating Multi-Omics and AI for Next-Generation Wastewater Treatment

by Prabhaharan Renganathan, Lira A. Gaysina, Cipriano García Gutiérrez, Edgar Omar Rueda Puente and Juan Carlos Sainz-Hernández

J. Xenobiot. 2025, 15(4), 133; https://doi.org/10.3390/jox15040133 - 19 Aug 2025

Abstract

The global increase in municipal and industrial wastewater generation has intensified the need for ecologically resilient and technologically advanced treatment systems. Although traditional biological treatment technologies are effective for organic load reduction, they often fail to remove recalcitrant xenobiotics such as pharmaceuticals, synthetic [...] Read more.

The global increase in municipal and industrial wastewater generation has intensified the need for ecologically resilient and technologically advanced treatment systems. Although traditional biological treatment technologies are effective for organic load reduction, they often fail to remove recalcitrant xenobiotics such as pharmaceuticals, synthetic dyes, endocrine disruptors (EDCs), and microplastics (MPs). Engineered microbial consortia offer a promising and sustainable alternative owing to their metabolic flexibility, ecological resilience, and capacity for syntrophic degradation of complex pollutants. This review critically examines emerging strategies for enhancing microbial bioremediation in wastewater treatment systems (WWTS), focusing on co-digestion, biofilm engineering, targeted bioaugmentation, and incorporation of conductive materials to stimulate direct interspecies electron transfer (DIET). This review highlights how multi-omics platforms, including metagenomics, transcriptomics, and metabolomics, enable high-resolution community profiling and pathway reconstructions. The integration of artificial intelligence (AI) and machine learning (ML) algorithms into bioprocess diagnostics facilitates real-time system optimization, predictive modeling of antibiotic resistance gene (ARG) dynamics, and intelligent bioreactor control. Persistent challenges, such as microbial instability, ARG dissemination, reactor fouling, and the absence of region-specific microbial reference databases, are critically analyzed. This review concludes with a translational pathway for the development of next-generation WWTS that integrate synthetic microbial consortia, AI-mediated biosensors, and modular bioreactors within the One Health and Circular Economy framework. Full article

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18 pages, 1185 KB

Open AccessArticle

Ecotoxicological Assessment of Sediment Samples Impacted by Wastewater Treatment Plant Effluents Transporting Contaminants of Emerging Concern

by Carlos Silva, Ana Ré, Nelson Abrantes, Fernando J. M. Gonçalves and Joana Luísa Pereira

J. Xenobiot. 2025, 15(4), 132; https://doi.org/10.3390/jox15040132 - 15 Aug 2025

Abstract

Wastewater treatment plant (WWTP) effluents can be important sources of contaminants of emerging concern (CEC) for riverine ecosystems, with some accumulation in sediments. This study investigated the ecotoxicological effects of sediment samples collected near three WWTPs. Sediment elutriates, simulating resuspension conditions, and whole [...] Read more.

Wastewater treatment plant (WWTP) effluents can be important sources of contaminants of emerging concern (CEC) for riverine ecosystems, with some accumulation in sediments. This study investigated the ecotoxicological effects of sediment samples collected near three WWTPs. Sediment elutriates, simulating resuspension conditions, and whole sediment samples were tested. Results showed that sediments were toxic to some organisms and beneficial to others. Elutriates from one site significantly reduced luminescence in the bacterium Aliivibrio fischeri, though this was not consistently linked to sediment contaminant levels. Significant noxious effects of elutriates were recorded for the macrophyte Lemma minor (yield reductions up to 48%) and the microalgae Raphidocelis subcapitata (yield reductions up to 25%). Exposure to elutriates resulted in increased Daphnia magna reproduction and increased biomass yield of Chironomus riparius exposed to sediments directly. Overall, there were no major toxicity variations in samples collected upstream and downstream of the effluent outfall. Suggesting limited hazardous potential of the effluent and a potential masking effect of background contamination (mostly metals and polycyclic aromatic hydrocarbons). The complexity of effluent-sourced contamination, coupled with the realistic testing approach, renders this work a valuable contribution to understanding the role of WWTP effluents in surface freshwaters contamination and their effects, especially concerning CECs. Full article

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35 pages, 2122 KB

Open AccessReview

Xenobiotic Toxicants and Particulate Matter: Effects, Mechanisms, Impacts on Human Health, and Mitigation Strategies

by Tamara Lang, Anna-Maria Lipp and Christian Wechselberger

J. Xenobiot. 2025, 15(4), 131; https://doi.org/10.3390/jox15040131 - 14 Aug 2025

Abstract

Particulate matter (PM), a complex mixture of solid particles and liquid droplets, originates from both natural sources, such as sand, pollen, and marine salts, and anthropogenic activities, including vehicle emissions and industrial processes. While PM itself is not inherently toxic in all its [...] Read more.

Particulate matter (PM), a complex mixture of solid particles and liquid droplets, originates from both natural sources, such as sand, pollen, and marine salts, and anthropogenic activities, including vehicle emissions and industrial processes. While PM itself is not inherently toxic in all its forms, it often acts as a carrier of xenobiotic toxicants, such as heavy metals and organic pollutants, which adhere to its surface. This combination can result in synergistic toxic effects, significantly enhancing the potential harm to biological systems. Due to its small size and composition, PM can penetrate deep into the respiratory tract, acting as a physical “shuttle” that facilitates the distribution and bioavailability of toxic substances to distant organs. The omnipresence of PM in the environment leads to unavoidable and constant exposure, contributing to increased morbidity and mortality rates, particularly among vulnerable populations like the elderly, children, and individuals with pre-existing health conditions. This exposure also imposes a substantial financial burden on healthcare systems, as treating PM-related illnesses requires significant medical resources and leads to higher healthcare costs. Addressing these challenges necessitates effective mitigation strategies, including reducing PM exposure, improving air quality, and exploring novel approaches such as AI-based exposure prediction and nutritional interventions to protect public health and minimize the adverse effects of PM pollution. Full article

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24 pages, 15698 KB

Open AccessArticle

Cardioprotective Effects of SAR Through Attenuating Cardiac-Specific Markers, Inflammatory Markers, Oxidative Stress, and Anxiety in Rats Challenged with 5-Fluorouracil

by Roza Haroon Rasheed and Tavga Ahmed Aziz

J. Xenobiot. 2025, 15(4), 130; https://doi.org/10.3390/jox15040130 - 10 Aug 2025

Abstract

This study aimed to evaluate the cardioprotective effects of two different doses of saroglitazar (SAR) in an animal model of cardiotoxicity induced by 5-fluorouracil (5-FU). Thirty-five rats were randomly allocated into five groups: the negative control, which received distilled water; the 5-FU (150 [...] Read more.

This study aimed to evaluate the cardioprotective effects of two different doses of saroglitazar (SAR) in an animal model of cardiotoxicity induced by 5-fluorouracil (5-FU). Thirty-five rats were randomly allocated into five groups: the negative control, which received distilled water; the 5-FU (150 mg/kg as I.P.) group; the N-acetylcysteine (100 mg/kg) group; and the SAR (0.5 and 5 mg/kg) groups. The last three groups received 5-FU on day 10 along with their treatment. An open field test was performed at zero-time and at the end of the study. On day eleven the animals were euthanized and blood samples were used for measuring troponin I, CK-MB, natriuretic peptide, lipid profile, LDH, ALT, AST, CRP, ESR, TNF-α, IL1β, MDA, and total antioxidant capacity (TAOC). Cardiac tissues were sent for histopathological examination. The study revealed that 5-FU elevated the levels of cardiac-specific and injury-related biomarkers, inflammatory and oxidative stress markers, and that the use of SAR, particularly the high dose, decreased all the cardiac- and other injury-related biomarkers as well as attenuating inflammatory and oxidative stress biomarkers. SAR-treated groups exhibited a significant increase in locomotor activity and a decrease in anxiety-like behavior, indicated by a reduction in time spent in one square and an increase in total movement time. Additionally, the histopathological findings greatly supported the biochemical results evidenced by stopping the detrimental effects caused by 5-FU through structural and functional alterations of cardiac tissues manifested as ameliorating congestion, inflammation, degeneration, arterial wall thinning, and endothelial loss. The dual-acting PPAR agonist SAR demonstrated cardiac protection activity, particularly the high dose, by attenuating cardiac-specific and nonspecific injury biomarkers along with anti-inflammatory and antioxidant activities and attenuated anxiety induced by 5-FU. These findings render SAR a promising candidate to be tested in clinical trials. Further studies are warranted with other cardiotoxicants to confirm these findings. Full article

(This article belongs to the Section Drug Therapeutics)

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23 pages, 9644 KB

Open AccessReview

Xenobiotics and Broiler Microbiota: Molecular Insights into Bacterial Antimicrobial Resistance and Food Safety Implications for Human Health

by Marta Gonçalves, Nuno Vale, Paulo Martins da Costa and Paula Silva

J. Xenobiot. 2025, 15(4), 129; https://doi.org/10.3390/jox15040129 - 8 Aug 2025

Abstract

Antibiotics have played an evolving role in poultry production, generally transitioning from widespread use to more precise and controlled applications. Despite this shift, the long-term consequences of earlier practices continue to affect current and future generations. This review aims to explore the multifaceted [...] Read more.

Antibiotics have played an evolving role in poultry production, generally transitioning from widespread use to more precise and controlled applications. Despite this shift, the long-term consequences of earlier practices continue to affect current and future generations. This review aims to explore the multifaceted consequences of antibiotic use in poultry production, with particular emphasis on the growing challenge of antimicrobial resistance (AMR). Evidence demonstrates that antibiotic use affects the gut microbiome, often resulting in long-lasting decreased diversity and restructuring of the bacterial communities. Moreover, consequences extend to the surrounding environment, including the airborne microbiome, water systems, and poultry litter, where alterations in microbial communities tend to be more subtle, whereas changes in genetic elements related to resistance are often more pronounced (drift). The emergence and persistence of resistance in these environments facilitate the spread of resistance genes across ecological boundaries, contributing to the broader dissemination of AMR. These findings highlight the complex, interconnected nature of AMR, underscoring the urgent need for responses grounded in the One Health framework. Such approaches are essential for safeguarding both public and environmental health while maintaining sustainable poultry production practices. Full article

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17 pages, 6121 KB

Open AccessArticle

The Gut Microbiota Metabolite Urolithin B Mitigates Cholestatic Liver Injury in Mice via Modulating the Crosstalk Between PPARα, Nrf2, and NF-κB Signaling Pathways

by Hani M. Alrawili, Mahmoud Elshal, Marwa S. Serrya and Dina S. El-Agamy

J. Xenobiot. 2025, 15(4), 128; https://doi.org/10.3390/jox15040128 - 8 Aug 2025

Abstract

Urolithin (Uro)-B, a gut microbiota metabolite of ellagic acid, has recently gained considerable attention due to its beneficial bioactivities. This study investigated the potential hepatoprotective effect of Uro-B against alpha-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury (CLI) in mice and explored the possible involved [...] Read more.

Urolithin (Uro)-B, a gut microbiota metabolite of ellagic acid, has recently gained considerable attention due to its beneficial bioactivities. This study investigated the potential hepatoprotective effect of Uro-B against alpha-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury (CLI) in mice and explored the possible involved mechanisms. Mice were treated with Uro-B (50 and 100 mg/kg) for four days and received ANIT (75 mg/kg) once on the second day. Our data revealed that Uro-B reduced elevated serum transaminases, alkaline phosphatase, lactate dehydrogenase, and total bilirubin levels associated with ANIT injection. Histopathologically, Uro-B effectively ameliorated ANIT-induced disruption of the hepatic architecture as represented by repressed necro-inflammation and bile duct proliferation. Uro-B also maintained oxidant/antioxidant status that was dysregulated by ANIT. Mechanistically, Uro-B markedly activated Kelch-like ECH-associated protein 1 (Keap-1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling with subsequent upregulation of hepatic heme oxygenase-1 expression. On the other hand, Uro-B suppressed the ANIT-induced expression of nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Interestingly, Uro-B repressed peroxisome proliferator-activated receptor alpha (PPARα) expression in the liver. These findings indicate a promising hepatoprotective effect of Uro-B against ANIT-induced CLI in mice. Uro-B modulated the interplay between Keap1/Nrf2, NF-κB/TNF-α, and PPARα signaling pathways, resulting in powerful antioxidant and anti-inflammatory effects. Full article

(This article belongs to the Section Drug Therapeutics)

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21 pages, 3236 KB

Open AccessArticle

The Plasticizer Dibutyl Phthalate (DBP) Impairs Pregnancy Vascular Health: Insights into Calcium Signaling and Nitric Oxide Involvement

by Ana R. Quelhas, Melissa Mariana and Elisa Cairrao

J. Xenobiot. 2025, 15(4), 127; https://doi.org/10.3390/jox15040127 - 6 Aug 2025

Abstract

Dibutyl phthalate (DBP) is used as a plasticizer to enhance flexibility in several household products, cosmetics, and food-contact materials. Due to its harmful effects, DBP is restricted or banned in children’s products and food items, particularly in Europe. Due to its endocrine disruptor [...] Read more.

Dibutyl phthalate (DBP) is used as a plasticizer to enhance flexibility in several household products, cosmetics, and food-contact materials. Due to its harmful effects, DBP is restricted or banned in children’s products and food items, particularly in Europe. Due to its endocrine disruptor properties and considering its ability to cross the placental barrier, it is imperative to study DBP’s vascular effects in pregnancy, given the vulnerability of this period. Thus, this study investigated the potential effects of DBP on the cardiovascular system using umbilical arteries from healthy pregnant women. Specifically, the impact of DBP on the vascular reactivity after both rapid and 24 h DBP exposure was analyzed, as well as the contractility and the cell viability of vascular smooth muscle cells (VSMC). DBP did not exhibit overt cytotoxic effects on VSMCs, possibly due to its adsorption onto polystyrene surfaces, potentially limiting bioavailability. Interestingly, DBP induced vasorelaxation in a concentration-dependent manner. Although mechanistic insights remain to be fully elucidated, the results suggest the involvement of pathways associated with nitric oxide signaling and calcium handling. Overall, DBP exposure appears to modulate arterial tone regulation, which may have implications for vascular function during pregnancy. Full article

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27 pages, 2559 KB

Open AccessReview

Virgin Coconut Oil and Its Lauric Acid, Between Anticancer Activity and Modulation of Chemotherapy Toxicity: A Review

by Debalina Bose, Adetayo Olorunlana, Rania Abdel-Latif, Ademola C. Famurewa and Eman M. Othman

J. Xenobiot. 2025, 15(4), 126; https://doi.org/10.3390/jox15040126 - 5 Aug 2025

Abstract

Virgin coconut oil (VCO) has emerged as a functional food oil with considerable health benefits and wide applications in the food, pharmaceutical, and cosmetic industries due to its resident bioactive compounds, including lauric acid (LA). LA is the most abundant saturated medium-chain fatty [...] Read more.

Virgin coconut oil (VCO) has emerged as a functional food oil with considerable health benefits and wide applications in the food, pharmaceutical, and cosmetic industries due to its resident bioactive compounds, including lauric acid (LA). LA is the most abundant saturated medium-chain fatty acid in VCO and has been associated with several pharmacological activities. The literatures show the pharmacological effects of VCO and LA on chronic pathologies, infectious diseases, and metabolic disorders. A robust body of evidence shows that LA and other phenolic compounds are responsible for the VCO protection against toxicities and pharmacological efficacies. This review elucidates the anticancer mechanisms of VCO/LA and their modulation of the chemotherapy-induced side effect toxicity. VCO, LA, and their nanomaterial/encapsulated derivatives promote ROS generation, antiproliferation, apoptosis, cell cycle arrest, the inhibition of metastasis, and the modulation of cancer-related signaling pathways for cancer cell death in vivo and in vitro. VCO mitigates oxidative inflammation and apoptosis to block the underlying mechanisms of the side effect toxicity of chemotherapy. However, the possible beneficial effect of LA on the toxicity of chemotherapy is currently unknown. The available evidence emphasizes the anticancer effect and mechanism of VCO and LA, and the VCO potential to combat adverse side effects of chemotherapy. Thus, VCO and LA are potential adjuvant therapeutic agents in the management of various cancers. Nevertheless, future studies should be targeted at elucidating cancer-related molecular mechanisms to bridge the gap in knowledge. Full article

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23 pages, 1730 KB

Open AccessArticle

Prioritization and Sensitivity of Pesticide Risks from Root and Tuber Vegetables

by Milica Lučić and Antonije Onjia

J. Xenobiot. 2025, 15(4), 125; https://doi.org/10.3390/jox15040125 - 3 Aug 2025

Abstract

This study investigated pesticide residues in 580 vegetable samples collected from markets in Serbia, encompassing potatoes, carrots, celery, radishes, horseradish, ginger, onions, and leeks. In total, 33 distinct pesticides were detected using validated HPLC-MS/MS and GC-MS/MS analytical methods. Multiple residues were identified in [...] Read more.

This study investigated pesticide residues in 580 vegetable samples collected from markets in Serbia, encompassing potatoes, carrots, celery, radishes, horseradish, ginger, onions, and leeks. In total, 33 distinct pesticides were detected using validated HPLC-MS/MS and GC-MS/MS analytical methods. Multiple residues were identified in 19 samples, while 29 samples exceeded established maximum residue levels (MRLs). Acute and chronic dietary risks were assessed for both adults and children. Although individual hazard quotients (HQs) for adults and children remained below the threshold of concern (HQ < 1), the cumulative acute risk reached up to 63.1% of the Acute Reference Dose (ARfD) for children and 51.1% ARfD for adults, with ginger and celery posing the highest risks. Similarly, cumulative chronic risks remained below the safety threshold, with the Acceptable Daily Intake (ADI) percentages reaching a maximum of 5.9% ADI for adults and increased vulnerability of 11.0% ADI among children. Monte Carlo simulations were applied to account for variability and uncertainty in chronic exposure estimates. The hazard index (HI) results showed that adverse health effects for both population groups remained within acceptable safety limits (HI < 1), although higher susceptibility was observed in children. Sensitivity analysis identified body weight and vegetable consumption rates as the most influential factors affecting chronic risk variability. 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”)

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18 pages, 2003 KB

Open AccessArticle

Spatial Gradient Effects of Metal Pollution: Assessing Ecological Risks Through the Lens of Fish Gut Microbiota

by Jin Wei, Yake Li, Yuanyuan Chen, Qian Lin and Lin Zhang

J. Xenobiot. 2025, 15(4), 124; https://doi.org/10.3390/jox15040124 - 3 Aug 2025

Abstract

This comprehensive study investigates the spatial distribution of metals in surface water, their accumulation in fish tissues, and their impact on the gut microbiome dynamics of fish in the Qi River, Huanggang City, Hubei Province. Three distinct sampling regions were established: the mining [...] Read more.

This comprehensive study investigates the spatial distribution of metals in surface water, their accumulation in fish tissues, and their impact on the gut microbiome dynamics of fish in the Qi River, Huanggang City, Hubei Province. Three distinct sampling regions were established: the mining area (A), the transition area (B), and the distant area (C). Our results revealed that metal concentrations were highest in the mining area and decreased with increasing distance from it. The bioaccumulation of metals in fish tissues followed the order of gut > brain > muscle, with some concentrations exceeding food safety standards. Analysis of the gut microbiota showed that Firmicutes and Proteobacteria dominated in the mining area, while Fusobacteriota were more prevalent in the distant area. Heavy metal pollution significantly altered the composition and network structure of the gut microbiota, reducing microbial associations and increasing negative correlations. These findings highlight the profound impact of heavy metal pollution on both fish health and the stability of their gut microbiota, underscoring the urgent need for effective pollution control measures to mitigate ecological risks and protect aquatic biodiversity. Future research should focus on long-term monitoring and exploring potential remediation strategies to restore the health of affected ecosystems. Full article

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32 pages, 995 KB

Open AccessArticle

Phytotoxic Effects and Agricultural Potential of Nanofertilizers: A Study Using Zeolite, Zinc Oxide, and Titanium Dioxide Under Controlled Conditions

by Ezequiel Zamora-Ledezma, Glenda Leonela Loor Aragundi, Willian Stalyn Guamán Marquines, Michael Anibal Macías Pro, José Vicente García Díaz, Henry Antonio Pacheco Gil, Julián Mauricio Botero Londoño, Mónica Andrea Botero Londoño and Camilo Zamora-Ledezma

J. Xenobiot. 2025, 15(4), 123; https://doi.org/10.3390/jox15040123 - 1 Aug 2025

Abstract

Nanofertilizers (NFs) and engineered nanoparticles (NPs) are increasingly used in agriculture, yet their environmental safety remains poorly understood. This study evaluated the comparative phytotoxicity of zinc oxide (ZnO), titanium dioxide (TiO₂), and clinoptilolite nanoparticles, three commercial nanofertilizers, and potassium dichromate (K [...] Read more.

Nanofertilizers (NFs) and engineered nanoparticles (NPs) are increasingly used in agriculture, yet their environmental safety remains poorly understood. This study evaluated the comparative phytotoxicity of zinc oxide (ZnO), titanium dioxide (TiO₂), and clinoptilolite nanoparticles, three commercial nanofertilizers, and potassium dichromate (K₂Cr₂O₇) using Lactuca sativa seeds under adapted OECD-208 protocol conditions. Seeds were exposed to varying concentrations of each xenobiotic material (0.5–3% for NFs; 10–50% for NPs), with systematic assessment of seedling survival, root and hypocotyl length, dry biomass, germination index (GI), and median effective concentration (EC₅₀) values. Nanofertilizers demonstrated significantly greater phytotoxicity than engineered nanoparticles despite lower application concentrations. The toxicity ranking was established as NF1 > NF3 > NF2 > NM2 > NM1 > NM3, with NF1 being most toxic (EC₅₀ = 1.2%). Nanofertilizers caused 45–78% reductions in root length and 30–65% decreases in dry biomass compared with controls. GI values dropped to ≤70% in NF1 and NF3 treatments, indicating concentration-dependent growth inhibition. While nanofertilizers offer agricultural benefits, their elevated phytotoxicity compared with conventional nanoparticles necessitates rigorous pre-application safety assessment. These findings emphasize the critical need for standardized evaluation protocols incorporating both physiological and ecotoxicological endpoints to ensure safe xenobiotic nanomaterial deployment in agricultural systems. Full article

(This article belongs to the Special Issue Integrative Studies on Environmental Toxicity, Bioaccumulation and Remediation Strategies for Hazardous Substances)

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22 pages, 2376 KB

Open AccessReview

Hypertension in People Exposed to Environmental Cadmium: Roles for 20-Hydroxyeicosatetraenoic Acid in the Kidney

by Soisungwan Satarug

J. Xenobiot. 2025, 15(4), 122; https://doi.org/10.3390/jox15040122 - 1 Aug 2025

Abstract

Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension. By 2040, CKD is predicted to be the fifth-leading cause of years of life lost. Developing strategies to [...] Read more.

Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension. By 2040, CKD is predicted to be the fifth-leading cause of years of life lost. Developing strategies to prevent CKD and to reduce its progression to kidney failure is thus of great public health significance. Hypertension is known to be both a cause and a consequence of kidney damage and an eminently modifiable risk factor. An increased risk of hypertension, especially among women, has been linked to chronic exposure to the ubiquitous food contaminant cadmium (Cd). The mechanism is unclear but is likely to involve its action on the proximal tubular cells (PTCs) of the kidney, where Cd accumulates. Here, it leads to chronic tubular injury and a sustained drop in the estimated glomerular filtration rate (eGFR), a common sequela of ischemic acute tubular necrosis and acute and chronic tubulointerstitial inflammation, all of which hinder glomerular filtration. The present review discusses exposure levels of Cd that have been associated with an increased risk of hypertension, albuminuria, and eGFR ≤ 60 mL/min/1.73 m² (low eGFR) in environmentally exposed people. It highlights the potential role of 20-hydroxyeicosatetraenoic acid (20-HETE), the second messenger produced in the kidneys, as the contributing factor to gender-differentiated effects of Cd-induced hypertension. Use of GFR loss and albumin excretion in toxicological risk calculation, and derivation of Cd exposure limits, instead of β₂-microglobulin (β₂M) excretion at a rate of 300 µg/g creatinine, are recommended. Full article

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20 pages, 1266 KB

Open AccessSystematic Review

A Systematic Review on Contamination of Marine Species by Chromium and Zinc: Effects on Animal Health and Risk to Consumer Health

by Alexandre Mendes Ramos-Filho, Paloma de Almeida Rodrigues, Adriano Teixeira de Oliveira and Carlos Adam Conte-Junior

J. Xenobiot. 2025, 15(4), 121; https://doi.org/10.3390/jox15040121 - 1 Aug 2025

Abstract

Potentially toxic elements, such as chromium (Cr) and zinc (Zn), play essential roles in humans and animals. However, the harmful effects of excessive exposure to these elements through food remain unknown. In this sense, this study aimed to evaluate the anthropogenic contamination of [...] Read more.

Potentially toxic elements, such as chromium (Cr) and zinc (Zn), play essential roles in humans and animals. However, the harmful effects of excessive exposure to these elements through food remain unknown. In this sense, this study aimed to evaluate the anthropogenic contamination of chromium and zinc in aquatic biota and seafood consumers. Based on the PRISMA protocol, 67 articles were selected for this systematic review. The main results point to a wide distribution of these elements, which have familiar emission sources in the aquatic environment, especially in highly industrialized regions. Significant concentrations of both have been reported in different fish species, which sometimes represent a non-carcinogenic risk to consumer health and a carcinogenic risk related to Cr exposure. New studies should be encouraged to fill gaps, such as the characterization of the toxicity of these essential elements through fish consumption, determination of limit concentrations updated by international regulatory institutions, especially for zinc, studies on the influence of abiotic factors on the toxicity and bioavailability of elements in the environment, and those that evaluate the bioaccessibility of these elements in a simulated digestion system when in high concentrations. Full article

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23 pages, 2437 KB

Open AccessArticle

From Farmworkers to Urban Residents: Mapping Multi-Class Pesticide Exposure Gradients in Morocco via Urinary Biomonitoring

by Zineb Ben Khadda, Andrei-Flavius Radu, Souleiman El Balkhi, Fagroud Mustapha, Yahya El Karmoudi, Gabriela Bungau, Pierre Marquet, Tarik Sqalli Houssaini and Sanae Achour

J. Xenobiot. 2025, 15(4), 120; https://doi.org/10.3390/jox15040120 - 23 Jul 2025

Abstract

Pesticide exposure gradients between occupational, para-occupational, and general populations remain poorly characterized in North African agricultural contexts. This study evaluates urinary pesticide levels among farmers, indirectly exposed individuals, and a control group in Morocco’s Fez-Meknes region. A cross-sectional survey measured pesticide concentrations using [...] Read more.

Pesticide exposure gradients between occupational, para-occupational, and general populations remain poorly characterized in North African agricultural contexts. This study evaluates urinary pesticide levels among farmers, indirectly exposed individuals, and a control group in Morocco’s Fez-Meknes region. A cross-sectional survey measured pesticide concentrations using LC-MS/MS in urine samples collected from 154 adults residing in both rural and urban areas. A questionnaire was used to gather information from participants regarding factors that may elevate the risk of pesticide exposure. The results revealed that farmers exhibited the highest concentrations of pesticides in their urine, including compounds classified as Ia/Ib by the World Health Organization. Indirectly exposed individuals showed moderate levels of contamination, with notable detections such as dichlofluanid (22.13 µg/L), while the control group had residual traces of neonicotinoids, notably imidacloprid (2.05 µg/L). Multivariate analyses revealed several sociodemographic factors significantly associated with increased pesticide exposure. The main risk factors identified included low education, residence in an agricultural area, and the consumption of untreated water (wells/rivers). Conversely, wearing personal protective equipment was associated with reduced urinary concentrations. This study highlights intense occupational exposure among farmers, secondary environmental contamination among residents living near treated areas, and the widespread dispersion of pesticide residues into urban areas. 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”)

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22 pages, 1643 KB

Open AccessArticle

Skin Wound Healing: The Impact of Treatment with Antimicrobial Nanoparticles and Mesenchymal Stem Cells

by Pavel Rossner, Eliska Javorkova, Michal Sima, Zuzana Simova, Barbora Hermankova, Katerina Palacka, Zuzana Novakova, Irena Chvojkova, Tereza Cervena, Kristyna Vrbova, Anezka Vimrova, Jiri Klema, Andrea Rossnerova and Vladimir Holan

J. Xenobiot. 2025, 15(4), 119; https://doi.org/10.3390/jox15040119 - 18 Jul 2025

Abstract

An investigation into the biological mechanisms initiated in wounded skin following the application of mesenchymal stem cells (MSCs) and nanoparticles (NPs) (Ag, ZnO), either alone or combined, was performed in mice, with the aim of determining the optimal approach to accelerate the healing [...] Read more.

An investigation into the biological mechanisms initiated in wounded skin following the application of mesenchymal stem cells (MSCs) and nanoparticles (NPs) (Ag, ZnO), either alone or combined, was performed in mice, with the aim of determining the optimal approach to accelerate the healing process. This combined treatment was hypothesized to be beneficial, as it is associated with the production of molecules supporting the healing process and antimicrobial activity. The samples were collected seven days after injury. When compared with untreated wounded animals (controls), the combined (MSCs+NPs) treatment induced the expression of Sprr2b, encoding small proline-rich protein 2B, which is involved in keratinocyte differentiation, the response to tissue injury, and inflammation. Pathways associated with keratinocyte differentiation were also affected. Ag NP treatment (alone or combined) modulated DNA methylation changes in genes involved in desmosome organization. The percentage of activated regulatory macrophages at the wound site was increased by MSC-alone and Ag-alone treatments, while the production of nitric oxide, an inflammatory marker, by stimulated macrophages was decreased by both MSC/Ag-alone and MSCs+Ag treatments. Ag induced the expression of Col1, encoding collagen-1, at the injury site. The results of the MSC and NP treatment of skin wounds (alone or combined) suggest an induction of processes accelerating the proliferative phase of healing. Thus, MSC-NP interactions are a key factor affecting global mRNA expression changes in the wound. Full article

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42 pages, 8737 KB

Open AccessReview

Environmental Xenobiotics and Epigenetic Modifications: Implications for Human Health and Disease

by Ana Filipa Sobral, Andrea Cunha, Inês Costa, Mariana Silva-Carvalho, Renata Silva and Daniel José Barbosa

J. Xenobiot. 2025, 15(4), 118; https://doi.org/10.3390/jox15040118 - 13 Jul 2025

Abstract

Environmental xenobiotics, including heavy metals, endocrine-disrupting chemicals (EDCs), pesticides, air pollutants, nano- and microplastics, mycotoxins, and phycotoxins, are widespread compounds that pose significant risks to human health. These substances, originating from industrial and agricultural activities, vehicle emissions, and household products, disrupt cellular homeostasis [...] Read more.

Environmental xenobiotics, including heavy metals, endocrine-disrupting chemicals (EDCs), pesticides, air pollutants, nano- and microplastics, mycotoxins, and phycotoxins, are widespread compounds that pose significant risks to human health. These substances, originating from industrial and agricultural activities, vehicle emissions, and household products, disrupt cellular homeostasis and contribute to a range of diseases, including cancer and neurodegenerative diseases, among others. Emerging evidence indicates that epigenetic alterations, such as abnormal deoxyribonucleic acid (DNA) methylation, aberrant histone modifications, and altered expression of non-coding ribonucleic acids (ncRNAs), may play a central role in mediating the toxic effects of environmental xenobiotics. Furthermore, exposure to these compounds during critical periods, such as embryogenesis and early postnatal stages, can induce long-lasting epigenetic alterations that increase susceptibility to diseases later in life. Moreover, modifications to the gamete epigenome can potentially lead to effects that persist across generations (transgenerational effects). Although these modifications represent significant health risks, many epigenetic alterations may be reversible through the removal of the xenobiotic trigger, offering potential for therapeutic intervention. This review explores the relationship between environmental xenobiotics and alterations in epigenetic signatures, focusing on how these changes impact human health, including their potential for transgenerational inheritance and their potential reversibility. Full article

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