Journal Description
Journal of Xenobiotics
Journal of Xenobiotics
is an international, peer-reviewed, open access journal on xenobiotics published bimonthly online by MDPI (from Volume 10, Issue 1 - 2020).
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, ESCI (Web of Science), PubMed, PMC, CAPlus / SciFinder, Embase, and other databases
- Journal Rank: JCR - Q1 (Toxicology) / CiteScore - Q2 (Pharmacology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 27.6 days after submission; acceptance to publication is undertaken in 2.9 days (median values for papers published in this journal in the first half of 2025).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review and reviewer names are published annually in the journal.
Impact Factor:
4.4 (2024);
5-Year Impact Factor:
5.7 (2024)
Latest Articles
Influence of Pristine and Photoaging Polystyrene Microspheres on Sperm Quality and DNA Integrity of the Sand Dollars Scaphechinus mirabilis
J. Xenobiot. 2025, 15(6), 176; https://doi.org/10.3390/jox15060176 - 23 Oct 2025
Abstract
Plastic pollution represents a significant emerging environmental problem. Micro-sized particles of synthetic polymers—microplastics (MPs)—have been identified in all parts of marine ecosystems. In the marine environment, organisms are exposed to MPs, which undergo a constant process of physicochemical and biological degradation. Utilization of
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Plastic pollution represents a significant emerging environmental problem. Micro-sized particles of synthetic polymers—microplastics (MPs)—have been identified in all parts of marine ecosystems. In the marine environment, organisms are exposed to MPs, which undergo a constant process of physicochemical and biological degradation. Utilization of UV irradiation as the optimal exposure factor in the simulation of fundamental natural conditions is a widely accepted approach. This enables the study of the harmful effects of such particles when interacting with aquatic organisms. This study aimed to investigate the effect of pristine and photoaging primary polystyrene microspheres (µPS) at three concentrations on the viability and DNA integrity of the sperm of the sand dollars Scaphechinus mirabilis. The results of the investigation demonstrated that IR spectroscopy revealed structural changes in polystyrene, confirming the oxidative degradation of the polymer under UV irradiation. The study demonstrated that artificially aged µPS exhibited a more pronounced effect than pristine particles, as evidenced by reduced sperm viability and increased DNA damage. Thus, the resazurin test showed that after exposure to UV-irradiated µPS, sperm viability decreased to 83–85% at concentrations of 10 and 100 particles and to 70% at a concentration of 1000. In addition, the Comet assay showed that the particles increased the percentage of DNA in the tail from 20% to 30% in a dose-dependent manner. The findings substantiate and augment the existing body of experimental data of the toxicity of aged plastic fragments, thereby underscoring the need for further study into the toxicity of aged MPs on marine invertebrates.
Full article
(This article belongs to the Special Issue (Micro)plastic Pollution: From Monitoring to Toxicity in All Environments)
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Open AccessArticle
Insights into Hepatic, Neuronal, and hERG Channel Safety of Plant-Derived Active Compounds
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Yosita Kasemnitichok, Sion Lee, Oh Bin Kwon, Tullayakorn Plengsuriyakarn and Kesara Na-Bangchang
J. Xenobiot. 2025, 15(6), 175; https://doi.org/10.3390/jox15060175 - 22 Oct 2025
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Curcumin (CUR), atractylodin (ATD), α-mangostin (αMG), ethyl-p-methoxycinnamate (EPMC), ligustilide (LIG), and β-eudesmol (BEU) are commonly used in Thai traditional medicine formulations. This study evaluated the cytotoxic effects of these compounds in HepG2 liver cancer cells and ReNcell VM neural progenitor cells using the
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Curcumin (CUR), atractylodin (ATD), α-mangostin (αMG), ethyl-p-methoxycinnamate (EPMC), ligustilide (LIG), and β-eudesmol (BEU) are commonly used in Thai traditional medicine formulations. This study evaluated the cytotoxic effects of these compounds in HepG2 liver cancer cells and ReNcell VM neural progenitor cells using the resazurin assay, as well as their potential for hERG inhibition in hERG-overexpressing HEK293 cells, utilizing the automated patch-clamp technique. αMG and CUR significantly reduced HepG2 cell viability (IC50 = 5.5 and 21 µM, respectively). In undifferentiated ReNcell VM cells, αMG was the most potent inhibitor of cell viability (IC50 = 2.1 µM), followed by CUR (IC50 = 21.1 µM), while in differentiated ReNcell VM cells, only αMG exhibited significant neurotoxicity (IC50 = 6.0 µM). Other compounds showed no significant effects on these cells. ATD, BEU, LIG, and EPMC demonstrated low inhibition of hERG channels (IC50 = 26.4, 33.4, 37.3, and 53 µM, respectively), while CUR and αMG displayed weak inhibitory effects (IC50 > 100 µM). αMG may have cytotoxic effects on hepatocytes and neurons at concentrations much higher than when used as medicine or food supplements. At regular clinical doses, αMG, ATD, BEU, EPMC, LIG, and CUR are unlikely to cause significant side effects. However, if these compounds are considered for drug development, their potential effects on hERG channels should be carefully assessed to avoid possible cardiotoxicity. Pharmacokinetics, both preclinical and clinical studies, are necessary to understand the relationship between the plasma concentration profile of EPMC and its potential risks for hepatotoxicity, neurotoxicity, cardiotoxicity, and drug interactions.
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Open AccessArticle
Integrated Monitoring of Water Quality, Metal Ions, and Antibiotic Residues, with Isolation and Optimization of Enrofloxacin-Degrading Bacteria in American Shad (Alosa sapidissima) Aquaculture Systems
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Yao Zheng, Jiajia Li, Ampeire Yona, Xiaofei Wang, Xue Li, Julin Yuan and Gangchun Xu
J. Xenobiot. 2025, 15(6), 174; https://doi.org/10.3390/jox15060174 - 22 Oct 2025
Abstract
This study investigated water quality, metal ion concentrations, and antibiotic residues specifically enrofloxacin (ENR) and its metabolite ciprofloxacin (CIP), across six American shad (Alosa sapidissima) aquaculture sites over a one-year period. Water and sediment samples were analyzed to determine contamination levels,
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This study investigated water quality, metal ion concentrations, and antibiotic residues specifically enrofloxacin (ENR) and its metabolite ciprofloxacin (CIP), across six American shad (Alosa sapidissima) aquaculture sites over a one-year period. Water and sediment samples were analyzed to determine contamination levels, and ENR-degrading bacteria were isolated from the culture environment to explore their potential use in bioremediation. Findings showed that NH3-N and total suspended solids (TSS) exceeded recommended standards at all sampling sites. Elevated levels of Li, Na (except S1), Fe, Ni (except S2 and S4), Sr, and Cu were found at site S3. Site S5 recorded the highest concentrations of Al, As, and Pb, while Cd was most abundant at S6. In sediments, S5 showed higher levels of Mg, K (except S3), Ca, Cr, Mn, Fe, Ni, As, Pb, Cu, and Zn (except S3). ENR and CIP were detected in all water and sediment samples, with a 100% detection rate. The highest ENR (16.68–3215.95 mg·kg−1) and CIP (3.90–459.60 mg·kg−1) concentrations in water occurred at site S6, following a seasonal pattern of autumn > winter > summer > spring. In sediments, the maximum ENR (41.43–133.67 mg·kg−1) and CIP (12.36–23.71 mg·kg−1) levels were observed in spring. Two ENR-degrading bacterial strains were successfully isolated and identified as Enterococcus and Bacillus. Optimal degradation was achieved at 30 °C, pH 8.0, 6% inoculum, and 3000 Lux, resulting in a 64.2% reduction in ENR after 72 h. Under slightly different conditions (25 °C, pH 10), degradation reached 58.5%. This study provides an efficient strain resource for the bioremediation of ENR pollution in the aquaculture water of American shad.
Full article
(This article belongs to the Topic Aquatic Emerging Contaminants and Their Ecotoxicological Consequences, 2nd Edition)
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Open AccessReview
Scientific and Regulatory Perspectives on Chemical Risk Assessment of Pesticides in the European Union
by
Fabio Buonsenso
J. Xenobiot. 2025, 15(5), 173; https://doi.org/10.3390/jox15050173 - 21 Oct 2025
Abstract
People are exposed to pesticides daily through food, drinking water, and the environment, both in urban and rural settings. These chemicals, while offering economic and agricultural benefits through pest control and increased productivity, may pose a growing risk to human health and ecosystem
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People are exposed to pesticides daily through food, drinking water, and the environment, both in urban and rural settings. These chemicals, while offering economic and agricultural benefits through pest control and increased productivity, may pose a growing risk to human health and ecosystem biodiversity. While the European regulatory framework offers a robust foundation for risk assessment, significant limitations persist, especially in addressing cumulative exposure, low-dose effects, and chemical mixtures. This review focuses on selected scientific and regulatory challenges by reviewing recent European Food Safety Authority (EFSA) conclusions, Organization for Economic Co-operation and Development (OECD) test guidelines updates, and current European legislative approaches. Particular attention is given to the regulation of endocrine-disrupting and reprotoxic substances, highlighting progress and remaining gaps in implementation. A brief mention will also be made of immuno-toxic substances, for which no specific hazard class has yet been established. Building on official reports and peer-reviewed literature, this review provides a structured evaluation of the scientific and regulatory landscape, including underexplored issues like the transition to animal-free toxicology and integration of biomonitoring with health data. The goal is to propose realistic, evidence-based improvements to current frameworks using integrated, interdisciplinary approaches that connect toxicology, policy, and implementation science. A shift to a holistic, systems-based, and precautionary paradigm is vital to address emerging challenges and ensure strong protection of health and environment, as well as supporting the needs of the agricultural sector.
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(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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Open AccessArticle
Association Between Antibiotic Exposure and the Risk of Male Infertility: A Case–Control Study
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Friday E. Okonofua, Lorretta Favour C. Ntoimo, Titus A. M. Msagati, Oladiran Ayodeji, Michael Aziken, Akhere Omonkhua, Victor Ohenhen, Celestina Olafusi and Moses O. Alfred
J. Xenobiot. 2025, 15(5), 172; https://doi.org/10.3390/jox15050172 - 21 Oct 2025
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Irregular use of antibiotics is widespread in Nigeria, which has been reported to be associated with the prevalence of antibiotic resistance. As antibiotics have been reported to be associated with declining male infertility in animal models, we investigated the association between exposure to
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Irregular use of antibiotics is widespread in Nigeria, which has been reported to be associated with the prevalence of antibiotic resistance. As antibiotics have been reported to be associated with declining male infertility in animal models, we investigated the association between exposure to antibiotics and sperm quality. The study was a prospective case–control study involving 136 infertile men and 154 fertile men recruited from five hospitals in southern Nigeria. Semen analysis was carried out, while Liquid Chromatography Mass Spectrometry was used to assay for various antibiotics in urinary samples. Three antibiotics showed an independent association with sperm quality in the regression analysis. Urinary ampicillin was associated with more than a 3 mL decline in sperm count in the cases, with no significant effects shown in the control group. Similarly, a significant association of urinary chloramphenicol with sperm motility and sperm morphology was shown in cases of infertility. In contrast, an independent association of urinary tetracycline with increased sperm motility in men with infertility was found, but no significant association was shown in fertile men. We conclude that urinary antibiotics—ampicillin, tetracycline, and chloramphenicol—may be associated with varying sperm characteristics and sperm quality in Nigerian men.
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Open AccessArticle
Four-Year Monitoring Survey of Pesticide Residues in Tomato Samples: Human Health and Environmental Risk Assessment
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Alessandro Atzei, Hamza Bouakline, Francesco Corrias and Alberto Angioni
J. Xenobiot. 2025, 15(5), 171; https://doi.org/10.3390/jox15050171 - 20 Oct 2025
Abstract
A four-year survey was conducted to monitor the presence of multiple pesticide residues contaminating tomatoes, with the aim of evaluating the potential health and environmental risks. A multiresidue liquid chromatography–triple mass spectrometry with a multiple reaction monitoring (LC-MS/MS-MRM) method was fully validated and
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A four-year survey was conducted to monitor the presence of multiple pesticide residues contaminating tomatoes, with the aim of evaluating the potential health and environmental risks. A multiresidue liquid chromatography–triple mass spectrometry with a multiple reaction monitoring (LC-MS/MS-MRM) method was fully validated and used to test 252 pesticides in 360 samples analysed. According to SANTE guidelines, the proposed method was considered suitable for the purpose. Dietary risk assessment was conducted using the Hazard Quotient (HQ) approach and the European Food Safety Authority (EFSA) Pesticide Residue Intake Model; meanwhile, the cumulative environmental risk assessment was conducted using the Concentration Addition (CA) and Independent Action (IA) methods. Data obtained revealed multiple contaminations in most fields examined over the years. Twenty-two pesticide residues were identified, comprising 68.2% fungicides, 27.3% insecticides, and the remaining 4.5% acaricides. Higher levels were detected for Boscalid in 2022 in three fields, with an average value of 0.42 mg/kg. Multi-residue contamination occurred each year; the lowest abundance was detected in 2023 (3.9%), and the highest in 2022 (12.3%), with 5 pesticide residues as the maximum number of compounds detected in one sample in 2022. The consumer risk assessment identified no potential health concerns for adults or toddlers, and the combined risk was considered acceptable. The environmental assessment showed maximum cumulative ratio (MCR) values that were always ≥1, indicating a contribution to the toxicity of the mixture, only slightly higher than that of the single compound with the highest toxicity. The results of this study highlight the critical need to include cumulative dietary exposure assessments in pesticide risk evaluations, especially for food products that are susceptible to contamination by multiple residues.
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(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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Open AccessArticle
Estrogen Degradation Metabolites: Some Effects on Heart Mitochondria
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Cristina Uribe-Alvarez, Elizabeth Lira-Silva, Lilia Morales-García, Natalia Chiquete-Felix, Francisco Javier Roldán-Gómez, Jesús Vargas-Barrón, José J. García-Trejo, Alejandro Silva-Palacios, Salvador Uribe-Carvajal and Natalia Pavón
J. Xenobiot. 2025, 15(5), 170; https://doi.org/10.3390/jox15050170 - 18 Oct 2025
Abstract
Mitochondria play crucial roles in various cellular functions, including ATP production, apoptosis, and calcium homeostasis. Signaling pathways and hormones such as estrogens regulate the mitochondrial network through genetic, epigenetic, and metabolic processes. Estrogens increase the efficiency of mitochondrial oxidative phosphorylation by preventing uncoupling.
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Mitochondria play crucial roles in various cellular functions, including ATP production, apoptosis, and calcium homeostasis. Signaling pathways and hormones such as estrogens regulate the mitochondrial network through genetic, epigenetic, and metabolic processes. Estrogens increase the efficiency of mitochondrial oxidative phosphorylation by preventing uncoupling. Upon reaching menopause, when estrogen levels decrease, impaired mitochondrial function (uncoupled oxidative phosphorylation, lower ATP yields) is observed. Like all hormones in the body, estrogens undergo metabolic processing, resulting in estrogenic degradation metabolites (EDMs). These metabolites can form adducts with genomic and mitochondrial DNA and are of particular interest due to their potential role as carcinogens. Given that estradiol influences mitochondrial function, it is possible that EDMs may have an impact on heart mitochondria. To investigate this, we used isolated heart mitochondria from control and oophorectomized (mimicking menopausal stage) female Wistar rats of the same age. We found that mitochondria exposed to EDMs exhibited reduced coupling of oxidative phosphorylation and diminished ATP production, while increasing reactive oxygen species generation. Furthermore, these effects were significantly stronger in mitochondria from oophorectomized rats than in mitochondria from control (intact) rats. In addition, mitochondrial oxidative phosphorylation complex activities were differentially affected: complex I and ATPase activities decreased, while complex IV remained unaffected. We propose that exposure to EDMs promotes mitochondrial dysfunction in rats and that these effects are exacerbated by oophorectomy, a procedure commonly used to model the effects of menopause in women.
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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Open AccessArticle
Heavy Metals Affect the Antioxidant Defences in the Soil Ciliate Rigidohymena tetracirrata
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Govindhasamay R. Varatharajan, Antonio Calisi, Santosh Kumar, Daizy Bharti, Arnab Ghosh, Shikha Singh, Amit C. Kharkwal, Martina Coletta, Francesco Dondero and Antonietta La Terza
J. Xenobiot. 2025, 15(5), 169; https://doi.org/10.3390/jox15050169 - 17 Oct 2025
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In this study, we evaluated the cytotoxicity and antioxidant activity of the soil ciliate Rigidohymena tetracirrata (Gellért, 1942) Berger 2011, exposed to single and bimetallic mixtures of heavy metals (HMs) for 24 h. Ecotoxicological tests showed LC20 values of 0.16, 19.86 and
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In this study, we evaluated the cytotoxicity and antioxidant activity of the soil ciliate Rigidohymena tetracirrata (Gellért, 1942) Berger 2011, exposed to single and bimetallic mixtures of heavy metals (HMs) for 24 h. Ecotoxicological tests showed LC20 values of 0.16, 19.86 and 0.68 mg L−1 to Copper (Cu), Zinc (Zn), and Cadmium (Cd), respectively, and LC50 values of 0.25, 44.12 and 1.12 mg L−1, respectively. Furthermore, it was observed that the mixture of Cd and Zn exhibited antagonism in comparison to other mixtures, (Cd + Cu and Cu + Zn). In the total phenolic content (TPC) assay, a higher phenolic content was observed for the LC20 of extracellular Cu (p ≤ 0.01) and the LC20 of intracellular Cd (p ≤ 0.001). The LC50 values for Cd and Zn in both extracellular and intracellular contents demonstrated increased α,α-diphenyl-β-picrylhydrazyl (DPPH) scavenging activity with significant values of p ≤ 0.05, respectively. Regarding hydroxyl scavenging activity (HRSA), the LC50 of extracellular Cd (p ≤ 0.001) and LC50 of intracellular Cu (p ≤ 0.001) exhibited higher antioxidant activity. Therefore, the present study suggests that R. tetracirrata holds considerable potential as bioindicators and could be used as a model organism in ecotoxicological studies of soil polluted by HMs.
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Open AccessArticle
Two-Step Air/Water Oxidation Process for the Long-Lasting Photoluminescence and Biological Viability (MTT Assay) of Porous Silicon Particles
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Claudia Castillo Calvente, María F. Gilsanz-Muñoz, Javier Pérez-Piñeiro, Arisbel Cerpa-Naranjo, Rodrigo Blasco, Elvira Bragado-García, María S. Fernández-Alfonso and Darío Gallach-Pérez
J. Xenobiot. 2025, 15(5), 168; https://doi.org/10.3390/jox15050168 - 17 Oct 2025
Abstract
Due to their visible photoluminescence (PL) at room temperature, porous silicon particles (PSps) have gained interest for their potential biomedical applications, making them promising biological markers for in vivo or in vitro use. This study explores the PL evolution and stabilization of PSps
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Due to their visible photoluminescence (PL) at room temperature, porous silicon particles (PSps) have gained interest for their potential biomedical applications, making them promising biological markers for in vivo or in vitro use. This study explores the PL evolution and stabilization of PSps following a two-step oxidation process involving air annealing and chemical oxidation in deionized water. PS layers were fabricated by electrochemical etching of p+-Si wafers and then annealed in air at 300 °C and 600 °C for five minutes. The layers were then stored in deionized water and sonicated to produce PSps. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were used to analyze the morphology and composition of the particles, and spectrofluorimetry was used to monitor the PL over several weeks. Samples annealed at 300 °C exhibited a transition from nearly complete PL quenching to strong yellow–red emission. In contrast, the 600 °C sample showed no PL emission. The cytotoxicity of the PSps was evaluated using an MTT assay on human endothelial cells (EA.Hy926) with PSps and polyethylene glycol (PEG)-coated PSps at concentrations of (3.5–125 µg/mL) in both serum-free and fetal bovine serum (FBS)-containing media over 24, 48, and 72 h. Cell viability was significantly affected by both exposure time and particle concentration; however, this effect was prevented under conditions mimicking the physiological plasma environment.
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(This article belongs to the Section Nanotoxicology and Nanopharmacology)
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Open AccessArticle
DNA Damage and Bisphenol Levels in Chronic Kidney Disease Patients Undergoing Hemodialysis
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Cesar Emilio Ruiz, Lourdes Vela, Martí Nadal, Neus González, Ricard Marcos, Alba Hernández, Susana Pastor and Elisabeth Coll
J. Xenobiot. 2025, 15(5), 167; https://doi.org/10.3390/jox15050167 - 17 Oct 2025
Abstract
Bisphenol (BP) compounds are widely present in the environment, primarily due to their use as plastic additives. These substances involve health risks, particularly as endocrine disruptors. While the general population is chronically exposed, patients with end-stage chronic kidney disease undergoing hemodialysis (HD-CKD) represent
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Bisphenol (BP) compounds are widely present in the environment, primarily due to their use as plastic additives. These substances involve health risks, particularly as endocrine disruptors. While the general population is chronically exposed, patients with end-stage chronic kidney disease undergoing hemodialysis (HD-CKD) represent a particularly vulnerable group. This is due to both impaired renal clearance of circulating BPs and potential contamination from plastic-containing dialyzers used in extracorporeal blood circulation. In this longitudinal study, from the 35 HD-CKD patients initially selected, 25 changed their conventional dialyzers to BPA-free dialyzers for 6 months. Blood serum samples were collected, at baseline and after the intervention, to quantify levels of five BP analogues: Bisphenol A (BPA), Bisphenol AF (BPAF), Bisphenol F (BPF), Bisphenol B (BPB), and Bisphenol S (BPS). Genotoxicity was assessed using the comet assay and the micronucleus test on peripheral white blood cells. Among the analyzed BPs, only BPAF showed a statistically significant reduction when using BPA-free dialyzers. In terms of genotoxicity, a significant decrease was observed only in primary DNA damage (mainly DNA strand breaks), with no notable changes in chromosomal damage. This is the first study to detect multiple BP analogues in HD-CKD patients, beyond BPA, and to associate human exposure to BPs with DNA damage biomarkers. The observed reduction in DNA damage in parallel with decreased BPAF levels highlights the importance of monitoring and minimizing BP exposure of this high-risk population.
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(This article belongs to the Section Emerging Chemicals)
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Open AccessArticle
QSAR Models for Predicting Oral Bioavailability and Volume of Distribution and Their Application in Mapping the TK Space of Endocrine Disruptors
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Guillaume Ollitrault, Marco Marzo, Alessandra Roncaglioni, Emilio Benfenati, Olivier Taboureau and Enrico Mombelli
J. Xenobiot. 2025, 15(5), 166; https://doi.org/10.3390/jox15050166 - 15 Oct 2025
Abstract
Toxicokinetic (TK) properties are essential in the framework of chemical risk assessment and drug discovery. Specifically, a TK profile provides information about the fate of chemicals in the human body. In this context, Quantitative Structure–Activity Relationship (QSAR) models are convenient computational tools for
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Toxicokinetic (TK) properties are essential in the framework of chemical risk assessment and drug discovery. Specifically, a TK profile provides information about the fate of chemicals in the human body. In this context, Quantitative Structure–Activity Relationship (QSAR) models are convenient computational tools for predicting TK properties. Here, we developed QSAR models to predict two TK properties: oral bioavailability and volume of distribution at steady state (VDss). We collected and curated two large sets of 1712 and 1591 chemicals for oral bioavailability and VDss, respectively, and compared regression and classification (binary and multiclass) models with the application of several machine learning algorithms. The best predictive performance of the models for regression (R) prediction was characterized by a Q2F3 of 0.34 with the R-CatBoost model for oral bioavailability and a geometric mean fold error (GMFE) of 2.35 with the R-RF model for VDss. The models were then applied to a list of potential endocrine-disrupting chemicals (EDCs), highlighting chemicals with a high probability of posing a risk to human health due to their TK profiles. Based on the results obtained, insights into the structural determinants of TK properties for EDCs are further discussed.
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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Open AccessReview
Endocrine-Disrupting Chemicals and Male Infertility: Mechanisms, Risks, and Regulatory Challenges
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Sofoklis Stavros, Nikolaos Kathopoulis, Efthalia Moustakli, Anastasios Potiris, Ismini Anagnostaki, Spyridon Topis, Nefeli Arkouli, Konstantinos Louis, Charalampos Theofanakis, Themos Grigoriadis, Nikolaos Thomakos and Athanasios Zikopoulos
J. Xenobiot. 2025, 15(5), 165; https://doi.org/10.3390/jox15050165 - 13 Oct 2025
Abstract
Male reproductive health is increasingly threatened by endocrine-disrupting chemicals (EDCs), which interfere with hormonal homeostasis and reproductive physiology. Rising rates of male infertility have been linked to greater exposure to pollutants such as heavy metals, phthalates, pesticides, and bisphenol A. These compounds act
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Male reproductive health is increasingly threatened by endocrine-disrupting chemicals (EDCs), which interfere with hormonal homeostasis and reproductive physiology. Rising rates of male infertility have been linked to greater exposure to pollutants such as heavy metals, phthalates, pesticides, and bisphenol A. These compounds act through multiple mechanisms, including oxidative stress, apoptosis, receptor-mediated disruption of estrogenic and androgenic signaling, alterations in the hypothalamic–pituitary–gonadal (HPG) axis, and heritable epigenetic changes. Such disruptions impair key outcomes like sperm concentration, motility, morphology, DNA integrity, and steroidogenesis. Evidence from animal studies and human epidemiology consistently demonstrates these harmful effects, with biomarkers of EDC exposure correlating with reduced semen quality, hormonal imbalances, and infertility. Beyond individual health, infertility linked to EDCs carries significant social and economic costs. This review evaluates regulatory frameworks, highlights methodological challenges in risk assessment, and synthesizes mechanistic and clinical evidence. Particular attention is given to unresolved issues such as non-monotonic dose responses, mixture effects, low-dose exposures, and transgenerational impacts. Future priorities include refining biomonitoring, addressing mixture risks, and strengthening international regulation. By integrating mechanistic, clinical, and policy insights, this review underscores the urgent need for strategies to mitigate EDC-related threats to male reproductive health.
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(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health: 2nd Edition)
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Open AccessArticle
Determination of Artificial Sweeteners in Commercial Beverages: Do We Know What We Are Consuming?
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Mar Castellanos and Juan M. Sanchez
J. Xenobiot. 2025, 15(5), 164; https://doi.org/10.3390/jox15050164 - 11 Oct 2025
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Non-nutritive artificial sweeteners (NASs) are xenobiotics widely used in the food industry as sugar substitutes, since they provide few to no calories compared to sucrose. While NASs are considered safe at the acceptable daily intake (ADI) established by regulatory agencies, there is increasing
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Non-nutritive artificial sweeteners (NASs) are xenobiotics widely used in the food industry as sugar substitutes, since they provide few to no calories compared to sucrose. While NASs are considered safe at the acceptable daily intake (ADI) established by regulatory agencies, there is increasing controversy regarding their potential ability to promote metabolic derangements, especially to disrupt the gut microbiome balance. In this study, we analyzed a large cohort of the most commonly consumed beverages in Spain, categorizing them by the type of soda to determine the composition and content of the most frequently used NASs in the food industry. All commercial NAS formulations analyzed contained mixtures of different NASs. The NAS contents were always within regulated limits, although some samples yielded values close to these thresholds. Most soda samples analyzed contained NASs, even though the majority were not labeled as “zero sugars”, “no sugar added”, or “reduced calories”, which may mislead consumers. A preliminary statistical evaluation of the obtained results (cluster analysis) suggests that beverages can be grouped into three distinct clusters based on the total amount of NAS present in the samples. Differences in the total NAS content were significant among the three groups, with one cluster showing two- and four-fold higher levels than the others.
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Open AccessArticle
Advanced Characterization of Environmental Pollutant Metabolism in Human Skin
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Rafael Reis, Martine Zanini, Guillaume Lereaux, Ariane Dimitrov and Samia Boudah
J. Xenobiot. 2025, 15(5), 163; https://doi.org/10.3390/jox15050163 - 11 Oct 2025
Abstract
Ultrafine particles (UFPs) containing polycyclic aromatic hydrocarbons (PAHs) benzo[a]pyrene (BaP), are linked to pollution-induced health concerns, with skin being highly susceptible to contamination. Understanding the metabolic fate of these environmental pollutants in the skin is crucial. Moreover, traditional in vitro models often lack
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Ultrafine particles (UFPs) containing polycyclic aromatic hydrocarbons (PAHs) benzo[a]pyrene (BaP), are linked to pollution-induced health concerns, with skin being highly susceptible to contamination. Understanding the metabolic fate of these environmental pollutants in the skin is crucial. Moreover, traditional in vitro models often lack metabolic competency, while animal testing raises ethical concerns. This study introduces a novel approach combining stable isotope labeling (SIL) and liquid chromatography–high-resolution mass spectrometry (LC-HRMS) to investigate BaP metabolism. The physiologically relevant 3D reconstructed human epidermis (RHE) model was used. RHE models were exposed to BaP and deuterium-labeled BaP (BaP-d12). These analyses, followed by data analysis incorporating stable isotope filtering, revealed the presence of five distinct BaP phase I metabolites, including mono-hydroxylated, dihydroxylated, and quinone derivatives. This study demonstrates the power of coupling stable isotope labeling with LC-HRMS for the comprehensive characterization of BaP metabolic pathways in human skin. The identification of specific metabolites enhances our understanding of BaP detoxification mechanisms and their potential adverse effects. This analytical approach holds promise for investigating the metabolic fate of various other environmental pollutants.
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(This article belongs to the Topic Exploring the Interplay of Agriculture, Analytical Chemistry, Environments and Toxics)
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Open AccessReview
Effects of Endocrine-Disrupting Chemicals in the Brain: The Example of Neurodevelopment Alterations upon Exposure In Utero to Synthetic Sex Hormones
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Charles Sultan, Laura Gaspari and Marie-Odile Soyer-Gobillard
J. Xenobiot. 2025, 15(5), 162; https://doi.org/10.3390/jox15050162 - 10 Oct 2025
Abstract
Endocrine disruptors contaminate indoor and outdoor air, water, and food. Besides modifications of the androgen/estrogen balance, endocrine disruptors can alter thyroid function, metabolic balance, immune defenses, and brain development during fetal life, childhood, and adolescence. Among the consequences of fetal exposure to endocrine
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Endocrine disruptors contaminate indoor and outdoor air, water, and food. Besides modifications of the androgen/estrogen balance, endocrine disruptors can alter thyroid function, metabolic balance, immune defenses, and brain development during fetal life, childhood, and adolescence. Among the consequences of fetal exposure to endocrine disruptors, neurobehavioral disorders, particularly psychiatric disorders (for example, schizophrenia and bipolar disorder), attention deficit disorders, and mood disorders, occupy a special place. Therefore, endocrine disruptors are also neuroendocrine disruptors. This review article first summarizes the direct and transgenerational effects of endocrine disruptors. Then, data from a French national cohort of patients whose mothers were treated with synthetic hormones (estrogens and/or progestogens) during their pregnancy(ies) are used to describe the psychiatric disorders developed by children exposed in utero and the multigenerational and potentially transgenerational impacts.
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(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health: 2nd Edition)
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Open AccessArticle
The Antiproliferative Activity of Tatridin A Against Prostate Cancer Cells Is Lost in Acid Medium by Transformation to Desacetyl-β-Cyclopyrethrosin
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Cecilia Villegas, Rebeca Pérez, Camilo Céspedes-Méndez, Viviana Burgos, Ricardo Baggio, Sebastián Suárez, Bernd Schmidt and Cristian Paz
J. Xenobiot. 2025, 15(5), 161; https://doi.org/10.3390/jox15050161 - 9 Oct 2025
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Background: Prostate cancer (PC) progression is strongly driven by dysregulated signaling pathways, with NF-κB playing a central role. Sesquiterpene lactones have been reported to modulate this pathway. This study evaluated and compared the cytotoxic effects of two structurally distinct sesquiterpene lactones: Tatridin A,
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Background: Prostate cancer (PC) progression is strongly driven by dysregulated signaling pathways, with NF-κB playing a central role. Sesquiterpene lactones have been reported to modulate this pathway. This study evaluated and compared the cytotoxic effects of two structurally distinct sesquiterpene lactones: Tatridin A, a germacranolide, and desacetyl-β-cyclopyrethrosin, a eudesmanolide derivative. Their mechanisms of action were also examined, focusing on oxidative stress induction and NF-κB modulation. Methods: Chemical structures were confirmed by NMR and X-ray crystallography. Cytotoxicity was assessed in DU-145 and 22Rv1 PC cells using real-time cell analysis. Reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were measured with fluorometric assays. NF-κB activity was determined in THP-1 reporter cells and by Western blot of IκBα phosphorylation. Results: Tatridin A markedly reduced viability, showing lower IC50 values (81.4 ± 2.7 µM in DU-145 and 50.7 ± 1.9 µM in 22Rv1 cells) than desacetyl-β-cyclopyrethrosin (166.9 ± 3.2 µM and 290.3 ± 8.3 µM, respectively). It also inhibited proliferation at markedly lower concentrations, with clonogenic IC50 values of 7.7 µM in DU-145 and 5.24 µM in 22Rv1cells. Both compounds increased ROS, but tatridin A induced earlier and stronger responses and ΔΨm loss. Furthermore, tatridin A more effectively inhibited NF-κB signaling than classical inhibitors. Conclusions: Tatridin A exerts cytotoxic effects through oxidative stress, mitochondrial impairment, and NF-κB inhibition, supporting the therapeutic potential of germacranolides for the treatment of advanced PC.
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A Synergistic Approach with Doxycycline and Spirulina Extracts in DNBS-Induced Colitis: Enhancing Remission and Controlling Relapse
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Meriem Aziez, Mohamed Malik Mahdjoub, Tahar Benayad, Ferroudja Abbas, Sarah Hamid, Hamza Moussa, Ibrahima Mamadou Sall, Hichem Tahraoui, Abdeltif Amrane and Noureddine Bribi
J. Xenobiot. 2025, 15(5), 160; https://doi.org/10.3390/jox15050160 - 3 Oct 2025
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Background: Chronic relapsing colitis involves immune dysregulation and oxidative stress, making monotherapies often insufficient. This study investigates a therapeutic strategy combining doxycycline (Dox), an immunomodulatory antibiotic, with Arthrospira platensis extracts to enhance anti-inflammatory and antioxidant effects, improving remission and controlling relapse. Methods: Ethanolic
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Background: Chronic relapsing colitis involves immune dysregulation and oxidative stress, making monotherapies often insufficient. This study investigates a therapeutic strategy combining doxycycline (Dox), an immunomodulatory antibiotic, with Arthrospira platensis extracts to enhance anti-inflammatory and antioxidant effects, improving remission and controlling relapse. Methods: Ethanolic (ES) and aqueous (AS) extracts of A. platensis were chemically characterized by GC-MS after derivatization. Colitis was induced in mice using two intrarectal DNBS administrations spaced 7 days apart, with oral treatments (Dox, ES, AS, or combinations) given daily between doses. Disease progression was evaluated through clinical monitoring, histological scoring, and biochemical analysis, including MPO and CAT activities, as well as NO, MDA, and GSH levels. Results: GC-MS identified 16 bioactive compounds in each extract. ES contained mainly fatty acids and amino acids, whereas AS was rich in polysaccharides and phytol. Combined doxycycline and A. platensis extracts significantly enhanced recovery in reactivated DNBS colitis compared to monotherapies. Each treatment alone reduced disease severity, but their combination showed synergistic effects, significantly reducing disease activity index (p < 0.001), restoring mucosal integrity, and modulating inflammatory and oxidative markers (p < 0.001). Conclusion: Doxycycline potentiates the anti-colitic effects of A. platensis extracts via complementary mechanisms, offering a promising combination for managing relapsing colitis.
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The Potential Release of Chemicals from Crumb Rubber Infill Material—A Literature Review
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Federica Ghelli, Samar El Sherbiny, Giulia Squillacioti, Nicoletta Colombi, Valeria Bellisario and Roberto Bono
J. Xenobiot. 2025, 15(5), 159; https://doi.org/10.3390/jox15050159 - 2 Oct 2025
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End-of-life tyre (ELT) management is still a hot topic due to implications for sustainability and human health. This review aims to summarise the findings concerning the chemicals’ bio-accessibility/availability from the granular tyre-derived infill material used in sport surfaces. We included 14 original research
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End-of-life tyre (ELT) management is still a hot topic due to implications for sustainability and human health. This review aims to summarise the findings concerning the chemicals’ bio-accessibility/availability from the granular tyre-derived infill material used in sport surfaces. We included 14 original research articles and 5 reports (grey literature). The results included the analysis concerning volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), phthalates, metal(loid)s and other substances. The release of some dangerous chemicals was demonstrated, even though results must be considered critically. However, the chemicals’ bioaccessibility shows a highly nuanced picture and is not, per se, sufficient to determine the risk for the exposed subjects. The lack of bioavailability and epidemiological studies analysing the exposures in real scenarios resulted in one of the main issues concerning a proper evaluation of the potential risks for human health.
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Coffee Waste as a Green Precursor for Iron Nanoparticles: Toward Circular, Efficient and Eco-Friendly Dye Removal from Aqueous Systems
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Cristina Rodríguez-Rasero, Juan Manuel Garrido-Zoido, María del Mar García-Galán, Eduardo Manuel Cuerda-Correa and María Francisca Alexandre-Franco
J. Xenobiot. 2025, 15(5), 158; https://doi.org/10.3390/jox15050158 - 2 Oct 2025
Abstract
In this study, the use of spent coffee waste as a green precursor of polyphenolic compounds, which are subsequently employed as reducing agents for the synthesis of zero-valent iron nanoparticles (nZVI) aimed at the efficient removal of dyes from aqueous systems, has been
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In this study, the use of spent coffee waste as a green precursor of polyphenolic compounds, which are subsequently employed as reducing agents for the synthesis of zero-valent iron nanoparticles (nZVI) aimed at the efficient removal of dyes from aqueous systems, has been investigated. The nanoparticles, generated in situ in the presence of controlled amounts of hydrogen peroxide, were applied in the removal of organic dyes—including methylene blue, methyl orange, and orange G—through a heterogeneous Fenton-like catalytic process. The synthesized nZVI were thoroughly characterized by nitrogen adsorption at 77 K, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and powder X-ray diffraction (XRD). A statistical design of experiments and response surface methodology were employed to evaluate the effect of polyphenol, Fe(III), and H2O2 concentrations on dye removal efficiency. Results showed that under optimized conditions, a 100% removal efficiency could be achieved. This work highlights the potential of nZVI synthesized from agro-industrial waste through sustainable routes as an effective solution for water remediation, contributing to circular economy strategies and environmental protection.
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(This article belongs to the Special Issue Integrative Studies on Environmental Toxicity, Bioaccumulation and Remediation Strategies for Hazardous Substances)
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Methylphenidate and Its Impact on Redox Balance and Behavior
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George Jîtcă, Ingrid Evelin Mehelean, Ana Natalia Maier and Carmen-Maria Jîtcă
J. Xenobiot. 2025, 15(5), 157; https://doi.org/10.3390/jox15050157 - 30 Sep 2025
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Methylphenidate (MPH) and its active enantiomer, dexmethylphenidate, are widely prescribed as first-line therapies for attention deficit hyperactivity disorder (ADHD), yet their increasing non-medical use highlights significant clinical and toxicological challenges. MPH blocks dopamine (DAT) and norepinephrine (NET) transporters, thereby elevating synaptic catecholamine levels.
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Methylphenidate (MPH) and its active enantiomer, dexmethylphenidate, are widely prescribed as first-line therapies for attention deficit hyperactivity disorder (ADHD), yet their increasing non-medical use highlights significant clinical and toxicological challenges. MPH blocks dopamine (DAT) and norepinephrine (NET) transporters, thereby elevating synaptic catecholamine levels. While this underpins therapeutic efficacy, prolonged or abusive exposure has been associated with mitochondrial impairment, disrupted bioenergetics, and excessive reactive oxygen species (ROS) production, which collectively contribute to neuronal stress and long-term neurotoxicity. Growing evidence suggests that the gut–brain axis may critically influence MPH outcomes: diet-induced shifts in microbiome composition appear to regulate oxidative stress, neuroinflammation, and drug metabolism, opening potential avenues for dietary or probiotic interventions. From a forensic perspective, the detection and monitoring of MPH misuse require advanced methodologies, including enantioselective LC–MS/MS and analysis of alternative matrices such as hair or oral fluids, which enable retrospective exposure assessment and improves abuse surveillance. Despite its established therapeutic profile, MPH remains a compound with a narrow balance between clinical benefit and toxicological risk. Future directions should prioritize longitudinal human studies, biomarker identification for abuse monitoring, and the development of mitochondria-targeted therapies to minimize adverse outcomes and enhance safety in long-term treatment.
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